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Definition of Inflammation, Causes of Inflammation and Possible Anti-inflammatory Strategies
Abstract
Current definition of inflammation by its cardinal signs is obsolete and unsuitable for guiding adequate therapeutic strategies. Furthermore, present theory of the inflammatory process regarding vascular phenomena as essential for generation of cardinal signs is invalid and unable to explain well established empirical facts, particularly the extent of the osmotic pressure and temperature variations within the inflamed tissue.
... Inflammation is part of the complex biological response by the vascular tissues to harmful stimuli, such as damaged cells, pathogens, or irritants. Inflammation is a protective mechanism by the organism to remove injurious stimuli and initiate a healing process (Stankov, 2012). In an acute inflammatory process, there are various ways that the physical signs and symptoms of inflammation can be observed and felt (Szade et al., 2015). ...
... The following sequence of events that occurs in a specific type of tissue is designed to get rid of a pathogen (an agent causing disease) or repair some form of trauma, usually in a characteristic pattern. Essentially, an inflammatory response is a defense mechanism that protects an organism from infection and helps to heal any damage caused by the infection and other forms of irritation (Stankov, 2012). Two types of inflammation can be distinguished, acute and chronic, with each having its own characteristic pattern of response (Blázquez-Prieto et al., 2018). ...
... Extrinsic causes include those causing inflammation by physical agents or those causing inflammation by living agents. Inflammation from physical agents can be caused by trauma, frostbite, burns, X-rays, and various forms of environmental pollution (Stankov, 2012). The most significant inflammatory problems today are caused by living agents, resulting in infections. ...
... Inflammation is part of the complex biological response by the vascular tissues to harmful stimuli, such as damaged cells, pathogens, or irritants. Inflammation is a protective mechanism by the organism to remove injurious stimuli and initiate a healing process (Stankov, 2012). In an acute inflammatory process, there are various ways that the physical signs and symptoms of inflammation can be observed and felt (Szade et al., 2015). ...
... The following sequence of events that occurs in a specific type of tissue is designed to get rid of a pathogen (an agent causing disease) or repair some form of trauma, usually in a characteristic pattern. Essentially, an inflammatory response is a defense mechanism that protects an organism from infection and helps to heal any damage caused by the infection and other forms of irritation (Stankov, 2012). Two types of inflammation can be distinguished, acute and chronic, with each having its own characteristic pattern of response (Blázquez-Prieto et al., 2018). ...
... Extrinsic causes include those causing inflammation by physical agents or those causing inflammation by living agents. Inflammation from physical agents can be caused by trauma, frostbite, burns, X-rays, and various forms of environmental pollution (Stankov, 2012). The most significant inflammatory problems today are caused by living agents, resulting in infections. ...
... It is characterized by key features at the injury site commonly known as the cardinal signs of inflammation. These features include redness (rubor), swelling (tumor), heat (calor), pain (dolor) and loss of function (functio laesa) [84,85]. The redness and heat result from vasodilatation and increased blood flow to the inflamed site, the swelling is caused by increased vessel permeability causing leakage of fluid and plasma proteins into the interstitial area and the pain is due to an intensive sensation of harmful stimulus [84,86,87]. ...
... These features include redness (rubor), swelling (tumor), heat (calor), pain (dolor) and loss of function (functio laesa) [84,85]. The redness and heat result from vasodilatation and increased blood flow to the inflamed site, the swelling is caused by increased vessel permeability causing leakage of fluid and plasma proteins into the interstitial area and the pain is due to an intensive sensation of harmful stimulus [84,86,87]. ...
... Infection by microorganisms such as bacteria, viruses and fungi can cause inflammation [88]. Noninfectious causes of inflammation can be categorized as physical (burns, frostbites, physical injury, foreign bodies, trauma), chemical (hydrolytic enzymes, glucose, acids, toxins,) and biological [84,88]. The immune system recognizes noxious stimuli, both infectious and non-infectious, using PRR [86]. ...
Chronic wounds are a silent epidemic threatening the lives of many people worldwide. They are associated with social, health care and economic burdens and can lead to death if left untreated. The treatment of chronic wounds is very challenging as it may not be fully effective and may be associated with various adverse effects. New wound healing agents that are potentially more effective are being discovered continuously to combat these chronic wounds. These agents include silver nanoformulations which can contain nanoparticles or nanocomposites. To be effective, the discovered agents need to have good wound healing properties which will enhance their effectiveness in the different stages of wound healing. This review will focus on the process of wound healing and describe the properties of silver nanoformulations that contribute to wound healing.
... 23 Description of the spread of inflammatory cells Lymphocytes, macrophages and plasma are signs of chronic inflammation in a disease. 24 The H. pylori-positive sample found the most spread of inflammatory cells in grade 3, as many as 24 samples (27.59%). As for the H. pylori-negative sample, the most spread of inflammatory cell infiltration was in grade 1, as many as 28 samples (32.18%). ...
... Acute inflammation can turn chronic if the cause of inflammation persists or the normal healing process is disrupted. 24 Chronic inflammation in the absence of neutrophils has cytotoxic Tlymphocyte activity that damages the mucosa and glands in some types of gastritis. This is why chronic inflammation is almost always found in the histopathological picture of gastritis patients. ...
Background Helicobacter pylori (H. pylori) is a bacterium which could reason chronic gastritis and then has the capability to purpose gastric mucosal atrophy. The modifications within the degree of gastric mucosal atrophy have been appreciably correlated with the degree of risk of gastric cancer. The purpose of the observe turned into to research the relationship among H. pylori and the spread of inflammatory cellular infiltration and gastric mucosal atrophy in gastritis patients in Banjarmasin. Method The study was carried out in September-November 2021 using a cross-sectional method with purposive sampling, that is as many as 87 samples of histopathological slides of gastritis patients in the anatomical pathology laboratory of Sari Mulia Hospital, Banjarmasin for the period 2019. Research analysis used Kolmogorov-Smirnov. Slide preparations were stained with immunohistochemistry (IHC) and hematoxylin-eosin (HE). Inflammatory cellular clearance was measured the use of a scale from revised Sydney system and gastric mucosal atrophy become measured the use of the OLGA staging system. Results The results showed as many as 40 (45.98%) H.pylori-positive patients with the most chronic inflammatory cell infiltration in 24 (60%) patients at grade 3 (p<0.001) and for gastric mucosal atrophy as many as 29 (72, 50%) of patients at various stages (p<0.001). Conclusion H. pylori has a significant relationship with inflammatory cell infiltration and gastric mucosal atrophy. H. pylori-positive causes a growth within the severity of inflammatory cellular irritation and mucosal atrophy in gastritis patients.
... Mefenamic acid's precision in targeting COX-2 is essential in drug development, sparing constitutive COX-1 responsible for gastric integrity and platelet regulation. In the complex field of anti-inflammatory drug development, COX-2 inhibition, exemplified by mefenamic acid, plays a pivotal role in managing inflammatory conditions [23][24][25]. Licorice root extract, with over 300 compounds, is a promising anti-inflammatory candidate, primarily due to glycyrrhizin. Research supports its potential for managing inflammatory diseases [14,15]. ...
... COX-2 inhibition, exemplified by mefenamic acid, curbs prostaglandin production, alleviating symptoms. This is pivotal in anti-inflammatory drug developmen [23,24]. Apart from its antiinflammatory properties, licorice root extract also possesses antioxidant and antimicrobial attributes, enhancing its status as a versatile anti-inflammatory agent. ...
Background: Inflammation represents the body's natural response to injury, which can be induced by chemical, physical, or biological agents. Current approaches to managing inflammatory conditions involve addressing the primary etiological factors and administering anti-inflammatory medications like Nonsteroid Anti Inflammatory Drugs (NSAIDs) in inhibiting cyclooxygenase 2 (COX-2). However, data from 2021 reveals that 78.8% of patients experience gastritis as a side effect of such treatment. Licorice root extract (LRE)-an ayurvedic plants emerges as a promising alternative due to its potent anti-inflammatory properties attributed to the presence of glycyrrhizin, constituting between 2% to 25% of its dry weight. Objectives: To find out and determine the molecular inhibition of compound in LRE against COX-2 enzyme. Method: The process involves isolating the active constituents of LRE using pubchem and BioVia application, isolation active site of COX-2 by exploring RCSB PDB and isolate it using PyMol and engaging in molecular docking simulations using PyRx. Results and discussions: Cyclooxygenase-2 (COX-2) emerges as a pivotal enzymatic orchestrator intricately woven into the fabric of the inflammatory cascade. Licorice root extract stands at the forefront of prospective candidates in the realm of anti-inflammatory drug development, buoyed by its remarkable anti-inflammatory attributes. Regarding to ∆Gbind value, molecular docking tests show LRE compounds inhibit COX-2 better than arachidonic acid and mefenamic acid. Six LRE compounds outperform reference compounds, indicating potential anti-inflammatory capabilities. Other compounds show anti-inflammatory activity, and RMSD values affirm the accuracy of in silico predictions. Conclusion: LRE had potential as oral topical anti-inflammatory drugs through COX-2 inhibition with the best anti-inflammation ability is 18β‐glycyrrhetic acid.
... Inflammation is a rapid and essential immune response that is initiated in response to tissue damage and injury, whether that is due to infections or sterile insults [1,2]. Localized inflammation causes vasodilation, increased vascular permeability, which allows immune cells to infiltrate the injury site. ...
... This is accompanied by edema, heat and swelling. The end result is clearing the infection, removing dead tissues, and initiating tissue repair [2,3]. ...
While inflammation is an important immune response for protection from infections, excessive or prolonged inflammation can lead to a variety of debilitating diseases including skin disease, diabetes, heart disease, stroke, autoimmune diseases and cancer. Inflammation is a graded response that is typically initiated when resident macrophages sense the presence of pathogens or damage in the tissue and produce inflammatory cytokines and chemokines to kill the pathogen, clear debris and dead tissue, and initiate tissue repair. Here we show that copper-infused fabrics can prevent inflammation by blocking the production of inflammatory cytokines from macrophages after being exposed to LPS, a component of bacterial cell wall. Mechanistically, we show that copper-infused fabrics can significantly reduce the NF-κB and IRF3 activation in LPS-stimulated macrophages. Given the importance of excessive inflammation in diabetes, we show that copper can reduce insulin resistance mediated by inflammatory cytokines in muscle cells. Our data show that copper infused fabrics may be useful to reduce excessive inflammation in macrophages and improve insulin sensitivity in skeletal muscles.
... xy21 produced phomopsol A (91), a polyketide-derived alkaloid with a unique 3,4-dihydro-2H-indeno [1,2-b]pyridine 1-oxide motif, phomopsol B (92), which is a highly oxidized polyketide with a new 3,5-dihydro-2H-2,5-methanobenzo[e] [1,4]-dioxepine moiety, and 3-(2,6-dihydroxyphenyl)-4-hydroxy-6-methylisobenzofuran-1(3H)-one (93) [49]. Gao et al. [50] reported that Eucalactam B (94) was obtained from D. eucalyptorum KY-9 fungi found in the leaves of M. azedarach [50]. Citrinin (95) is a well-known mycotoxin produced mainly by Penicillium citrinum and several Aspergillus species. ...
... It can also be defined as a defense mechanism that aids in the elimination of potentially harmful factors and establishes homeostasis in the body. This causes increased blood flow to the site of inflammation due to the increased permeability of capillaries and white blood cells, resulting in symptoms such as redness, swelling, and pain [94,95]. Endophytic fungi are a valuable source of pharmacologically active metabolites, one of which is anti-inflammatory [96,97]. ...
Meliaceae plants are found worldwide in tropical or subtropical climates. They are important ethnobotanically as sources of traditional medicine, with 575 species and 51 genera. Previous research found that microorganisms are plant pioneers to produce secondary metabolites with diverse compound structures and bioactivities. Several plants of the Meliaceae family contain secondary metabolites isolated from endophytic fungi. Furthermore, related articles from 2002 to 2022 were collected from SciFinder, Google Scholar, and PubMed. About 276 compounds were isolated from endophytic fungi such as terpenoids, polyketides, lactones, pyrones, quinone, anthraquinones, xanthones, coumarines, isocoumarines, resorcylic acid lactones, cytochalasins, aromatics, ester, quinols, alkaloids, nitro compound, fatty acids, and sugars with bioactivities such as antioxidant, antibacterial, antifungal, anti-influenza, neuroprotective activities, anti-HIV, cytotoxic, allelopathic, anti-inflammatory, antifeedant effects, and BSLT toxicity. Meanwhile, secondary metabolites isolated from endophytic fungi were reported as one of the sources of active compounds for medicinal chemistry. This comprehensive review summarizes the ethnobotanical uses and secondary metabolites derived from Meliaceae endophytic fungi.
... Inflammation can be called the body's response to injury; it is a defense mechanism to various factors (bacterial, physical, and chemical) [51]. Acute and chronic inflammation are distinguished, depending on the duration and active mechanism. ...
Background: Malnutrition is a clinical condition that leads to unfavourable changes in health. It affects 35–55% of hospitalized patients, and in the case of cancer, this prevalence rises to 40–90% of patients. Screening nutritional status is essential for preventing undernutrition, which is crucial as its treatment. Undernutrition in patients after severe injuries significantly increases catabolic changes. Cytokines and hormones, such as epinephrine, glucagon, and cortisol, are released, which can increase energy expenditure by 50%. Properly conducted nutritional treatment aims to maintain or improve the nutritional status of patients whose nutrition with a natural diet is insufficient, moreover, in some cases, treatment of the underlying disease. Methods: This study is a narrative review focused on immunonutrition. The search for source articles, mainly from the last 10 years, was conducted in the PubMed and Google Schoolar databases, as well as in printed books. The key words used were “malnutrition”, “inflammation”, “clinical nutrition”, “immunomodulatory components”, “nutritional status assessment”, “enteral nutrition”, “parenteral nutrition”, and their combinations. Results: Providing substances such as omega-3 fatty acids, glutamine, arginine, nucleotides, antioxidants, and prebiotic fiber has a beneficial impact on immunological and anti-inflammatory pathways. The above-mentioned ingredients may inhibit the secretion of pro-inflammatory cytokines, activate anti-inflammatory cytokines, stimulate immune cells, and have a beneficial effect in allergic diseases, respiratory infections, or wound healing. Conslusion: Immunonutrition can be administrated via oral, enteral, and parenteral routes. It is crucial to highlight the importance of proper nutritional status in patients. The relationship between inflammation and malnutrition creates a vicious cycle, where one negatively affects the other due to increased metabolic demand, loss of appetite, weakened immune system, and gut dysbiosis.
... Inflammation is the result of the body's anti-inflammatory response to various stimuli [1] [2], which may be physical, chemical, biological or infectious [3] [4]. To treat these manifestations, a variety of anti-inflammatory drugs are used, including steroids and non-steroids [5]. ...
... It is a vital immunological reaction by the body's immune system that permits eliminating detrimental stimuli and restoring damaged tissue. [1] Any organism with a functioning innate immune system often experiences inflammation within minutes of being stimulated by an appropriate agent, such as a microbial infection, foreign invaders, or any exterior or interior irritation. The intended target tissues of inflammatory pathways differ greatly depending on the type of stimulants used. ...
... Freeing the host organism from the primary cause of inflammation protects it from the development of many diseases and illnesses. It is said that inflammation is a reaction necessary for survival [127]. ...
Anthocyanins, a class of flavonoid compounds responsible for the vibrant colors of many fruits and vegetables, have received considerable attention in recent years due to their potential health benefits. This review, focusing on evidence from both in vitro and in vivo studies, provides a comprehensive overview of the current state of knowledge regarding the health-promoting properties of anthocyanins. The chemical structure and diversity of anthocyanins, their bioavailability, and their mechanisms of action at the cellular and molecular level are examined. Research on the antioxidant, anti-inflammatory, anticancer, and neuroprotective effects of anthocyanins is critically reviewed. Special emphasis is placed on the role of anthocyanins in the prevention and treatment of chronic diseases such as cardiovascular diseases, diabetes, and neurodegenerative diseases. This review also discusses the challenges of translating in vitro findings to in vivo and highlights the importance of considering dose, bioavailability, and metabolism when assessing the therapeutic potential of anthocyanins. This review concludes with the identification of gaps in current research and suggestions for future directions for anthocyanin studies, including the need for more long-term clinical trials and investigations into potential synergistic effects with other phytochemicals. This comprehensive analysis highlights the promising role of anthocyanins in promoting human health and provides valuable insights for researchers, health professionals, and the nutraceutical industry. This study provides new insights, as it comprehensively investigates the dual anti-inflammatory and anticancer effects of anthocyanins in both in vitro and in vivo models. By uncovering the biological properties of anthocyanins from a variety of natural sources, this research not only expands our knowledge of the action of these compounds at the cellular level, but also enhances their clinical relevance through in vivo validation. Furthermore, the innovative use of anthocyanins may lead to important advances in their therapeutic application in the future.
... The inflammatory response is characterized at the tissue level by increased vascular permeability, protein denaturation, and alteration of cell membranes [24,25].Therefore, to assess the anti-inflammatory potential of substances extracted from plants, the simplest approaches would be to evaluate their red blood cell membranestabilizing activity in vitro and their ability in vivo to reduce paw diameter and exhibit immunomodulatory potential through TNFα, a chemical mediator of inflammation. Before conducting the sap membrane stabilization test, a toxicity test is necessary to determine the concentrations to be used. ...
Inflammatory diseases remain a significant public health issue, posing challenges in their management due to the adverse effects associated with conventional anti-inflammatory drugs. Exploring medicinal plants as a viable avenue for researching novel anti-inflammatory drugs offers a promising alternative. Jatropha multifida is a well-known traditional plant of the Euphorbiaceae family with undisputed medicinal properties, both haemostatic and antimicrobial. Very little data exists on its anti-inflammatory properties. This study aimed to assess the anti-inflammatory and immunomodulatory properties of Jatropha multifida stem sap The anti-inflammatory activity of the stem sap was evaluated in vitro by the anti-hemolytic activity assessment method, in vivo by the paw edema test in rats. The immunomodulatory potential was determined using a chemical mediator of inflammation, TNFα. Its antioxidant activity by the DPPH method was evaluated. The results of this study revealed that Jatropha multifida sap with an LC50 of 0.604 mg/mL, is non-toxic and showed a 66.21% higher anti-hemolytic effect than Diclofenac (25.94 %) and Ibuprofen (40 %). It also has a high DPPH inhibitory power (86.61 %) at 0.5 mg/mL similar to that of vitamin C. Sap at the concentration of 800 mg/Kg has overall the same effects on paw inflammation as Diclofenac and results in a greater decrease in TNFα (286.15) at values similar to those of normal control rats. The therapeutic use of this sap in a traditional setting is therefore once again justified due to its proven anti-inflammatory and immunomodulatory properties.
... n as non-specific immune responses. Inflammation/inflammation is also defined by the presence of five microscopic pathological phenomena, namely tumor (swelling of the tissue), heat (increase in tissue temperature), rubor (redness like the color of blood from vascular tissue in the area where inflammation occurs), dolor (organ function disorder)(V.Stankov, 2012). The enzymes that play a role in the synthesis of thromboxane, prostaglandins, and prostacyclines are the enzyme Cyclooxygenase (COX) which causes inflammation, platelet aggregation and pain Indawati DOI 10.62885/medisci.v2i1.400 | 18 ...
Introduction: Oxidative stress causes various diseases. Inflammation is the body's response to tissue infections and injuries. Mulberry is a multifunctional plant with bioactive components that have potent antioxidant and anti-inflammatory activities. This study aims to determine the activity of antioxidants, anti-inflations, extraction processes, active compounds, and methods used for antioxidant and anti-inflammatory testing. Methods: Narrative review using a literature search using Google Scholar and PubMed. Results: The results of Morus alba and Morus nigra have antioxidant activity, the plant parts used by leaves, fruits, and roots. Various methods were used to determine antioxidant activity, including DPPH, reducing power assay, β-carotene bleaching, and Hydroxyl radical scavenger capacity. Conclusion: Anti-inflammatory mechanism of mulberry bioactive compounds by inhibiting several cytokines and inflammatory mediators such as IL-1β, IL-6, IL-8, IL-9, IL-10, IL-23a, IFN-ɣ, TNF-ɑ, MMP-3, MMP-9, TLR, COX-2, NF-kB and iNOS. Testing of antioxidant activity by DPPH, ABTS, FRAP, reducing power assay, β-carotene bleaching, and Hydroxyl radical scavenger capacity
... It is characterized by redness, warmth, swelling, and pain. Nowadays, inflammation is considered to be a type of general immune response [70]. ...
Commiphora mukul is one of the most important plants having a wide range of therapeutic values. It belongs to family Burseraceae which is an important plant family with plethora of medicinal plants. C. mukul is commonly known as guggul. Gum resin of guggul is the main constituent of this plant which is used as a medicine. The medicinal importance of guggul has been mentioned in ancient literatures of medicine. In Ayurveda, it has been mentioned as a cure for various diseases. It exhibits various pharmacological activities such as hypolipidemic, antiobesity, antiinflammatory, antioxidant, antiatherosclerotic, antiarthritic, cardioprotective, antidiabetic, cytotoxic, hepatoprotective, thyroid stimulatory activity, antimicrobial, neuroprotective, antiacne, antipsoriatic, antifertility, antihemmorhoid, and antiurolithic activities. Guggul is also used for various traditional, medicinal and religious purposes. This plant has a complex phytochemical profile having abundance of bioactive constituents. Guggulsterones are the important chemical constituents of guggul with several therapeutic uses. Other chemical components include terpenoids, steroids, flavonoids, guggulsterols, lignans, amino acids and sugars. Being a highly beneficial plant, it has a great demand in pharmaceutical industries. It has been overexploited, due to which it is becoming endangered. In this article, we have made efforts to describe about the phytochemical profile and various therapeutic uses of Commiphora mukul.
... Morinda citrifolia [25], [29] Esculetin Antioxidant, Anticoagulant Solanum melongena [25], [30] Benzenedio Antinflammatory Hylocereus polyrhizus [14], [31] Methyl Butanol Antimicrobial Centella asiatica [15], [31] Hydroxy Acid Antinflammatory Cinnamomum verum [16], [32] ...
This Inflammation is a defensive response to tissue damage that occurs locally. NSAID (Non Steroid Anti-Inflammatory Drugs) and AIS (Antiinflammatory Steroids) have been used in Indonesia to treat inflammation but have side effects on the body. Purple sweet potato leaf (Ipomoea batatas) is one of the herbal medicines used by the community to treat inflammation. This research is a literature review by collecting information from Google Scholar, PubMed, Scopus, and Garuda. The results showed that the active anti-inflammatory compounds in purple sweet potato leaves were flavonoids. Flavonoids can work as anti-inflammatory compounds by passing through several pathways such as inhibition of cyclooxygenase (COX) and lipoxygenase enzyme activities, inhibition of neutrophil degranulation, inhibition of histamine increase, and inhibition of leukocyte accumulation. Purple sweet potato (Ipomoea batatas) leaves are scientifically proven to have anti-inflammatory activity as evidenced by the presence of compounds that have anti-inflammatory effects and can be developed into products for inflammation.
... Fluid retention in tissues can indicate underlying inflammation [49]. In the present study, our analysis of optic nerve homogenates for content of cytokines, chemokines, and matrix-metalloproteases (MMPs) showed minor changes in the inflammation biomarker profiles of diabetic mice (Suppl. ...
Glymphatic transport is vital for the physiological homeostasis of the retina and optic nerve. Pathological alterations of ocular glymphatic fluid transport and enlarged perivascular spaces have been described in glaucomatous mice. It remains to be established how diabetic retinopathy, which impairs vision in about 50% of diabetes patients, impacts ocular glymphatic fluid transport. Here, we examined ocular glymphatic transport in chronic hyperglycemic diabetic mice as well as in healthy mice experiencing a daily transient increase in blood glucose. Mice suffering from severe diabetes for two and four months, induced by streptozotocin, exhibited no alterations in ocular glymphatic fluid transport in the optic nerve compared to age-matched, non-diabetic controls. In contrast, transient increases in blood glucose induced by repeated daily glucose injections in healthy, awake, non-diabetic mice accelerated antero- and retrograde ocular glymphatic transport. Structural analysis showed enlarged perivascular spaces in the optic nerves of glucose-treated mice, which were absent in diabetic mice. Thus, transient repeated hyperglycemic events, but not constant hyperglycemia, ultimately enlarge perivascular spaces in the murine optic nerve. These findings indicate that fluid transport in the mouse eye is vulnerable to fluctuating glycemic levels rather than constant hyperglycemia, suggesting that poor glycemic control drives glymphatic malfunction and perivascular enlargement in the optic nerve.
... Inflammation was once assumed to be a harmful response to the body, but it was subsequently determined as the body's protective response to the stimuli [1]. Inflammation manifests itself in five ways: pain, swelling, redness, loss of function, and temperature [2]. Some mediators, such as prostaglandins, are synthesized by the cyclooxygenase (COX) pathway and are responsible for inflammation and pain. ...
In the current studies two naproxen derivatives (NPD) were evaluated for analgesic and anti-inflammatory properties. The acetic acid and hot plate animal models were used to screen the compounds for analgesic potential. While the anti-inflammatory potential was evaluated through animal paw edema, induced by several inflammatory mediators (carrageenan, bradykinin, and prostaglandin E2), the xylene-induced ear edema was also used as an inflammatory model. Both NPDs showed significant (p < 0.001) antinociceptive effects in the acetic acid-induced writhing paradigm. In the case of the hot plate, the NPD 1 at the tested dose of 5 mg/kg enhanced the latency time after 60 min of injection, which remained significant (p < 0.001) up to the end of the experiment duration. The maximum percent inhibition of NPD 1 was 87.53. The naloxone injection significantly lowered the latency time of NPD 1 as compared to NPD 2. Regarding the anti-inflammatory effect, both of the tested NPDs demonstrated a significant reduction in paw edema against various inflammatory mediators, as mentioned above; however, the anti-inflammatory effect of NPD 1 was better. The maximal percent inhibition by NPD 1 and 2 was 43.24 (after 60 min) and 45.93 (after 90 min). A considerable effect also resulted from xylene-induced ere edema. Further, a molecular docking study was carried out to investigate the binding modes of the NPD. The docking analysis revealed that the NPD significantly interacted with the COX2 enzyme. Furthermore, molecular dynamics simulation was carried out for the docked complexes. The MD simulation analysis revealed the high stability of the two naproxen derivatives.
... Istilah inflamasi berasal dari kata Bahasa Latin inflammare yang berarti terbakar (Ravikiran et al., 2012). Inflamasi ditandai dengan perubahan klinis berupa tumor, dolor, calor, rubor dan fuction laesa (Stankov, 2012). Menurut Medzhitov (2010), Ferrero-Miliani et al., (2007), dan Chen et al., (2018), inflamasi adalah respon sistem imun terhadap stimulus yang bersifat merusak (seperti agen penyakit, sel yang mati, senyawa toksik dan radiasi), dan beraksi dengan cara membersihkan penyebab kerusakkan dan menginisiasi proses kesembuhan. ...
Penelitian ini bertujuan untuk membuat model inflamasi kulit pada punggung mencit betina galur Swiss dengan menggunakan karagenin dengan berbagai konsentrasi. Pada penelitian ini akan digunakan 45 ekor mencit betina galur Swiss umur 2 bulan yang dibagi dalam tiga kelompok secara acak. Kelompok I diberi karagenin 1%. Kelompok II diberi karagenin 2%, dan kelompok III diberi karagenin 4%. Induksi inflamasi dengan karagenin dilakukan melalui injeksi sub kutan karagenin dengan volume 0,1 mL pada kulit punggung mencit. Sebelum dilakukan injeksi karagenin tebal lipat kulit (skin-fold thickness) diukur dengan menggunakan jangka sorong digital. Selanjutnya setiap jam setelah injeksi sampai dengan jam ke- 6 pasca injeksi. Hewan coba selanjutnya dietanasi dengan cara dislokasi servikalis pada akhir jam ke-6. Organ kulit diambil dengan memotong kulit pada area dimana injeksi karagenin dilakukan dan selanjutnya diawetkan dengan formalin 10% untuk pemeriksaan histopatologis dengan pewarnaan hematoxylin eosin. Analisis data tebal lipat kulit dianalisis dengan Two Ways Anova dan diikuti dengan post hoc test Tukey test. Hasil penelitian memperlihatkan ada perbedaan bermakna pada tebal lipat kulit antar kelompok perlakuan (p<0,05). Injeksi subkutaneuos karagenin 1%, 2% dan 4% meningkatkan tebal lipat kulit sebesar 35%, 50% dan 60% pada jam pertama pasca injeksi (p<0,05). Inflamasi mild dan moderate pada bagian dermis ditemukan pasca injeksi karagenin 1% dan 2%. Infamasi severe pada bagian dermis dan panikulus ditemukan pasca injeksi karagenin 4%. Karagenin dapat dipakai sebagai model inflamasi akut pada kulit punggung mencit.
... . Hal ini terjadi karena akumulasi lemak pada obesitas bersifat "proinflamasi" dan terjadi resistensi hormon insulin sehingga menyebabkan gangguan metabolisme (6,7,8). Akumulasi lemak juga dapat menyebabkan peningkatan pelepasan asam lemak bebas (ALB) sehingga terjadi peningkatan hidrolisis trigliserida (9). ...
Akumulasi trigliserida di hepar dapat terjadi akibat diet tinggi lemak yang berlebihan, sehingga dapat menginduksi terjadi inflamasi dan stres oksidatif di hepar. Perlemakan hepar secara histopatologis ditandai oleh adanya steatosis. Tanaman Limau Kuit (Citrus amblycarpa Hassk) sebagai tanaman lokal Kalimantan Selatan memiliki manfaat dalam menghambat pembentukan akumulasi lemak berlebihan karena kulit jeruk Limau Kuit mengandung alkaloid, saponin, triterpenoid, tanin, dan flavonoid. Penelitian ini bertujuan untuk menganalisis pengaruh pemberian ekstrak kulit Limau Kuit (Citrus amblycarpa Hassk) terhadap perlemakan hepar tikus (Rattus norvegicus) yang diberi diet tinggi lemak. Metode penelitian adalah true experimental design dengan posttest with control group design dengan 6 kelompok, yaitu KI (diet standar + akuades, KII (diet tinggi lemak + akuades), KIII (diet tinggi lemak + orlistat), KIV (diet tinggi lemak + ekstrak kulit Limau Kuit 200 mg/KgBB), KV (diet tinggi lemak + ekstrak kulit Limau Kuit 300 mg/KgBB), dan KVI (diet tinggi lemak + ekstrak kulit Limau Kuit 400 mg/KgBB). Perlakuan diberikan selama 6 minggu. Perlemakan hepar dinilai dari jumlah sel hepar yang mengalami perlemakan pada 5 lapangan pandang dari sediaan histologis hepar yang diwarnai HE dan perbesaran 400 x. Uji statistik menggunakan Kruskal-Wallis test. Hasil penelitian menunjukkan rerata perlemakan hepar KI 38,83 + 35,63, KII 24,00 + 21,46, KIII 20,40 + 13,90, KIV 42,40 + 11,93, KV 19,60 + 12,50, KVI 30,50 + 14,80, dengan p = 0,447. Kesimpulan penelitian ini adalah tidak ada perbedaan yang bermakna dari pemberian ekstrak kulit Limau Kuit terhadap perlemakan tikus (Rattus norvegicus) yang diberi pakan tinggi lemak (p > 0,05).Keywords: Diet tinggi lemak; Kulit jeruk Limau Kuit; Perlemakan hepar; Rattus norvegicus; Steatosis.
... Most of the clinically employed non-steroidal anti-inflammatory drugs (NSAIDs) are known to inhibit the two isoforms of cyclooxygenase (COX) enzyme: COX-1 (constitutive form) and COX-2 (inducible form) [34][35][36][37][38] . Concomitant use of non-selective NSAIDs such as indomethacin (8) which act on both COX isoforms results in an increased risk of gastrointestinal complications [39][40][41] . ...
A new series of bis-triazole 19a-l was synthesised for the purpose of being hybrid molecules with both anti-inflammatory and anti-cancer activities and assessed for cell cycle arrest, NO release. Compounds 19c, 19f, 19h, 19 l exhibited COX-2 selectivity indexes in the range of 18.48 to 49.38 compared to celecoxib S.I. = 21.10), inhibit MCF-7 with IC50 = 9–16 μM compared to tamoxifen (IC50 = 27.9 μM). and showed good inhibitory activity against HEP-3B with IC50 = 4.5–14 μM compared to sorafenib (IC50 = 3.5 μM) (HEP-3B). Moreover, derivatives 19e, 19j, 19k, 19 l inhibit HCT-116 with IC50 = 5.3–13.7 μM compared to 5-FU with IC50 = 4.8 μM (HCT-116). Compounds 19c, 19f, 19h, 19 l showed excellent inhibitory activity against A549 with IC50 = 3–4.5 μM compared to 5-FU with IC50 = 6 μM (A549). Compounds 19c, 19f, 19h, 19 l inhibit aromatase (IC50 of 22.40, 23.20, 22.70, 30.30 μM), EGFR (IC50 of 0.112, 0.205, 0.169 and 0.066 μM) and B-RAFV600E (IC50 of 0.09, 0.06, 0.07 and 0.05 μM).
... Inflammation plays an important role in the host's immune defense against injury and infectious agents. Chronic inflammation contributes to the pathophysiology of many chronic diseases, such as atherosclerosis, diabetes, inflammatory bowel diseases, and neurodegenerative diseases, and is also related to an increased risk of cancer [17]. An active lifestyle combined with a diet rich in fruits and vegetables can help prevent pathologically prolonged inflammatory processes [18][19][20]. ...
Inflammation plays an important role in the immune defense against injury and infection agents. However, the inflammatory chronic process may lead to neurodegenerative diseases, atherosclerosis, inflammatory bowel diseases, or cancer. Flavanones present in citrus fruits exhibit biological activities, including anti-oxidative and anti-inflammatory properties. The beneficial effects of flavanones have been found based on in vitro cell cultures and animal studies. A suitable in vitro model for studying the inflammatory process are macrophages (RAW264.7 cell line) because, after stimulation using lipopolysaccharide (LPS), they release inflammatory cytokines involved in the immune response. We determined the nitrite concentration in the macrophage cell culture and detected ROS using chemiluminescence. Additionally, we measured the production of selected cytokines using the Bio-Plex Magnetic Luminex Assay and the Bio-PlexTM 200 System. For the first time, we have shown that methyl derivatives of flavanone inhibit NO and chemiluminescence generated via LPS-stimulated macrophages. Moreover, the tested compounds at 1–20 µM dose-dependently modulate proinflammatory cytokine production (IL-1β, IL-6, IL-12p40, IL-12p70, and TNF-α) in stimulated RAW264.7 cells. The 2′-methylflavanone (5B) and the 3′-methylflavanone (6B) possess the strongest anti-inflammatory activity among all the tested flavanone derivatives. These compounds reduce the concentration of IL-6, IL-12p40, and IL12p70 compared to the core flavanone structure. Moreover, 2′-methylflavanone reduces TNF-α, and 3′-methylflavanone reduces IL-1β secreted by RAW264.7 cells.
... Common causes of inflammation includes Bacteria, fungi, or viruses Blunt or penetrating trauma (scrapes, wounds, bruises, etc.), Radiation or chemical exposure, Persistent and consistent use of a body part, Autoimmune diseases (recognizing a normal part of the body as a foreign invader). 4 Typical symptoms of inflammation include Redness, Swelling, Pain, Warmness and Stiffness. ...
Higher organisms developed the inflammation as a defence mechanism against infection and injuries. Chronic Inflammation is a progressive reaction which end at damage of living tissues. Several synthetic compounds had been used for fighting against uncontrolled inflammation. However, some of these compounds had significant adverse along with their anti-inflammatory properties. So, there is still need of some new anti-inflammatory compounds with least or no adverse effects. Numerous herbs including Ashwagandha, Calendula, Cat’s claw; Chamomile, Cilantro, Licorice root, Parsley, Curcuma longa, Zingiber officinale, Rosmarinus officinale, Borago officinale, Rosemary, Evening primrose, Devil’s claw had been evaluated for their anti-inflammation potentials and potent results was obtained with non-significant adverse effects. Plant named as Artemisia princeps. Family-Asteraceae has been evaluated for its pharmacological abilities and proved as significant herb for treatment of various pathological conditions. This review comprises the pharmacological abilities of Artemisia princeps. Linn and its Phytoconstituents with special emphasis on its anti-inflammatory potential. In the current literature survey, Selected plant was found to contain substantial number of phytoconstituent with pharmacological abilities Including Apigenin, Diosmetin, Eriodicytol, Eupafolin, Kaempferol, Vitex, Jaceosidine and Querecetine. Further literature survey also provides the anti-inflammatory potentials of phytoconstituents present in Artemisia princeps.
... Saline solution (SS), Dimethyl sulfoxide (DMSO), Indomethacin, HELBg, and HESBg were used as a treatment protocol, administered orally 60 minutes before the acute inflammatory induction by carrageenan [4]. Consequently, abdominal edema was formed, characterized by inflammatory swelling due to the local accumulation of low molecular weight catabolic products and extra fluid due to increased tissue osmotic pressure [31]. ...
The leaves and stems of Bauhinia guianensis Aubl. are used in traditional Amazonian phytotherapy for the treatment of pain and inflammation. This study investigates the anti-inflammatory and antinociceptive effects of hydroethanolic extracts from B. guianensis Aubl. leaves and stems (HELBg and HESBg, respectively) in in vivo models of inflammation and hyperalgesia. Danio rerio experimental animals were submitted to the acute inflammation test, induced by intraperitoneal (ip.) administration of carrageenan 20 μg / animal (abdominal edema), the groups were previously treated orally with saline solution 2 μl / animal (SS), Dimethyl sulfoxide 2 μl / animal (DMSO), Indomethacin 10 mg/kg, HELBg 100 mg/kg and HESBg 100 mg/kg, n = 12 per experimental group, to evaluate inhibition of edema and alterations histopathology of the liver, intestine and kidney of these animals. The antinociceptive effect was observed from the body curvature index and the behavioral responses of Danio rerio, after an experimental protocol for the induction of hyperalgesia, by ip. administration of 10 μl / animal of 2.5% acetic acid, the animals were previously orally treated with saline solution 2 μl/animal (SS), dimethyl sulfoxide 2 μl/animal (DMSO), morphine 2.5 mg/kg, HELBg 100 mg/kg and HESBg 100 mg/kg, n = 5 per experimental group. In carrageenan-induced edema, the group treated with HESBg inhibited edema formation over the 3 hours of the experiment. Maximum edema was inhibited by 54% (p < 0.05) when compared to the control group. Both HELBg and HESBg prevented body curvature index changes (t (df = 3 8) =, 6.96 and t (df = 3, 8) = 6.61, respectively, both p < 0.0001). In the behavioral parameters sensitive to antinociceptive pharmacological modulation, due to the abdominal constriction induced by acetic acid, the administration of HELBg and HESBg resulted in an improvement in swimming activity, by increasing the distance covered (F (df = 3, 16) = 6.50 and F (df = 3, 16) = 7.72, respectively, both p < 0.0001), decrease in freezing time (F (df = 3, 16) = 2.04 and F (df = 3, 16) = 1.28, respectively, both p < 0.0059), increase in the number of ascents to the upper area of the tank (F (df = 3, 16) = 33.02 and F (df = 3, 16) = 35.62, respectively, both p < 0.0009 ) and decreased time spent in that area (F (df = 3, 16) = 101.19 and F (df = 3, 16) = 103.59, respectively, both p < 0.0038). It is reasonable to suppose that both extracts modulated the variations induced by carrageenan and acetic acid through the inhibition of prostaglandin biosynthesis, decreasing the release of inflammatory mediators and the sensitization of peripheral nociceptors and, consequently, the perception of pain. These results suggest that HELBg and HESBg have anti-inflammatory and antinociceptive activities, probably of peripheral origin and linked to the inhibition of prostaglandin biosynthesis.
... Inflammation is a local protective response caused by tissue damage due to physical trauma, destructive chemical or microbiological substances that involve various physiological processes in the body. 1,22 Inflammation treatments that are easily found and have a fast effect are chemical anti-inflammatory drugs. Traditional medicine using herbal plant has also been carried out by Indonesian population, one of them is Tamarillo. ...
Background Inflammation is a local protective response by tissue damage. Tamarillo fruit peel ethanol extract has flavonoid as anti-inflammatory, anti-oxidant, inhibit cyclooxygenase and lipoxygenase as well as leukocyte accumulation. This study aims to determine anti-inflammatory effect of Tamarillo fruit peel ethanol extract on carrageenan-induced buccal mucosa of rats. Methods Extraction was done by maceration with 70% ethanol. The 30 rats divided into five groups, namely positive control (diclofenac sodium), negative control (NaCl), and extract doses of 70, 140 and 280 mg/kgBW. Carrageenan was injected as inflammation inducer in the right buccal mucosa. Macroscopic and microscopic observations were performed at three times, 24, 48, and 72 hours after carrageenan injection. Results At 24 hours, inflammatory cells of 70 mg/kg extract were 37, at 140 and 280 mg/kgBW were 18; positive and negative control as 35 and 405. At 48 hours, inflammatory cells of positive control were 22; extract of 70, 140, and 280 mg/kgBW were 21, 17, and 16 while negative control was 26. At 72 hours, positive and negative controls were 18 and 27. Extract of 70, 140, and 280 mg/kgBW had 20, 12 and 9 cells. Extract groups had no significant differences with the positive control (p>0.05) except for the 48th hours of 70 mg/kgBW however the extract groups showed significance with negative control (p<0.05). The lowest number cells (6) was at 280 mg/kgBW on 72 hours. Conclusion Tamarillo fruit peel ethanol extract is effective anti-inflammatory agent especially dose of 280 mg/kgBW on 72 hours.
... A localised manifestation of the physiological reactions that occur throughout the body, inflammation is characterised by the affected part of the body generating redness and swelling in addition to pain. 76 Inflammation is a localised manifestation of the physiological reactions that occur throughout the body. Inflammation could be caused by a large variety of underlying variables, any one of which could be accountable for it. ...
... Inflammation is the basic process by which body tissues respond or react to infection, irritation, or other injuries. Inflammation is defined by the presence of 5 macroscopic pathological phenomena, namely tumor (swelling of tissue), calor (increased tissue temperature), rubor (redness of the vascular tissue), dolor (painful stimulation of the tissue), and functio laesa (impaired function of the affected organ) [1]. ...
... Saline solution (SS), Dimethyl sulfoxide (DMSO), Indomethacin, HELBg and HESBg were used as treatment protocol, administered orally 60 minutes before the acute inflammatory induction by carrageenan [4]. Consequently, there was the formation of abdominal edema, a response characterized by inflammatory swelling, due to the local accumulation of catabolic products of low molecular weight and extra fluid, due to the increase in tissue osmotic pressure [31]. ...
The leaves and stems of Bauhinia guianensis Aubl. are used in traditional Amazonian phytotherapy for the treatment of pain and inflammation. This study investigates the anti-inflammatory and antinociceptive effects of hydroethanolic extracts from B. guianensis Aubl. leaves and stems (HELBg and HESBg, respectively) in in vivo models of inflammation and hyperalgesia. Danio rerio experimental animals were submitted to the acute inflammation test, induced by intraperitoneal (ip.) administration of carrageenan 20 μg / animal (abdominal edema), the groups were previously treated orally with saline solution 2 μl / animal (SS), Dimethyl sulfoxide 2 μl / animal (DMSO), Indomethacin 10 mg/Kg, HELBg 100 mg/Kg and HESBg 100 mg/Kg, n = 12 per experimental group, to evaluate inhibition of edema and alterations histopathology of the liver, intestine and kidney of these animals. The antinociceptive effect was observed from the body curvature index and the behavioral responses of Danio rerio, after an experimental protocol for the induction of hyperalgesia, by ip administration. of 10 μl / animal of 2.5% acetic acid, the animals were previously orally treated with saline solution 2 μl/animal (SS), dimethyl sulfoxide 2 μl/animal (DMSO), morphine 2.5 mg/Kg, HELBg 100 mg/Kg and HESBg 100 mg/Kg, n = 5 per experimental group. In carrageenan-induced edema, the group treated with HESBg inhibited edema formation over the 3 hours of the experiment. Maximum edema was inhibited by 54% (p < 0.05) when compared to the control group. Both HELBg and HESBg prevented body curvature index changes (t (df = 3 8) =, 6.96 and t (df = 3, 8) = 6.61, respectively, both p < 0.0001). In the behavioral parameters sensitive to antinociceptive pharmacological modulation, due to the abdominal constriction induced by acetic acid, the administration of HELBg and HESBg resulted in an improvement in swimming activity, by increasing the distance covered (F (df = 3, 16) = 6.50 and F (df = 3, 16) = 7.72, respectively, both p < 0.0001), decrease in freezing time (F (df = 3, 16) = 2.04 and F (df = 3, 16) = 1.28, respectively, both p < 0.0059), increase in the number of ascents to the upper area of the tank (F (df = 3, 16) = 33.02 and F (df = 3, 16) = 35.62, respectively, both p < 0.0009 ) and decreased time spent in that area (F (df = 3, 16) = 101.19 and F (df = 3, 16) = 103.59, respectively, both p < 0.0038). It is reasonable to suppose that both extracts modulated the variations induced by carrageenan and acetic acid through the inhibition of prostaglandin biosynthesis, decreasing the release of inflammatory mediators and the sensitization of peripheral nociceptors and, consequently, the perception of pain. These results suggest that HELBg and HESBg have anti-inflammatory and antinociceptive activities, probably of peripheral origin and linked to the inhibition of prosta-glandin biosynthesis
... "In a similar way, inflammation, which is employed by both the innate and adaptive immune systems, is a protective response of the body to various obnoxious stimuli such as infections and tissue injury. Inflammation is a characteristic of non-specific immune response that occurs as a result of pathogen entry, injury, allergic reaction or chemical irritation" [4]. ...
Pain is an unpleasant sensation induced on the body in response to inflammation of tissues. To reduce or stop a painful sensation, a group of drugs broadly classified as pain relievers are administered. The current study aimed at assessing the analgesic and anti-inflammatory effects of the methanol extract of Anthocleista grandiflora wood bark crude extract using albino rats as the animal models. Samples of the wood bark were collected from a forest in Keana LGA of Nasarawa State, Nigeria, processed and extracted in methanol to obtain the crude extract. The phytochemical composition of the extract as well as the analgesic and anti-inflammatory properties were analyzed following standard procedures. A total of 25 adult albino rats were randomly grouped into five groups of 5 rats each for both the analgesic and anti-inflammatory studies. Results of the phytochemical analysis showed the presence of tannins, flavonoids, phenols, terpenoids and 94 cardiac glycosides in large amounts. While saponins and steroids in small amounts and alkaloids, glycosides, anthraquinones, phlobatamins and anthracyanine were absent. The results showed a significantly (p<0.05) high analgesic potential of different doses of the extract (50mg/kg body weight) and 100mg/kg bw at 0, 1, 2, 3, 4 and 5 hours compared to the control group. Analysis of anti-inflammatory potential showed a significantly (p<0.05) higher anti-inflammatory properties by the extracts (50mg/kg and 100mg/kg bw) compared to the control. The outcomes revealed that the plant extract may possess good analgesic and anti-inflammatory properties, which may be attributed to the phytochemical compounds present in the extract.
... All signs were considered secondary to a primary pathophysiological event, the increase in vascular permeability as a direct consequence of the tissue injury. 1,2 The drugs used against inflammatory phenomena are non-steroidal and steroidal anti-inflammatory drugs. Although these drugs are effective, they are associated with iatrogenic effects such as digestive bleeding after menstruation and wound healing as indications of Ximenia Americana. ...
Inflammation is the reaction of the immune system to an external or internal aggression of the organism. The symptoms (redness, edema, heat and pain) are secondary to the increase in vascular permeability. The hydroethanolic extract of and has anti-inflammatory properties in vitro. The aim was to examine the anti-inflammatory and analgesic activities of extracts alone and in combination. The anti-inflammatory activity was studied using the carragenan-induced paw edema and the type of interactions between the two extracts was determined by the combination index and on the isobologram. Acetic acid-induced torsion and Haffner's tail clamp test were performed to evaluate the analgesic activity. At a dose of 500 mg/kg, a and extracts showed a percentage of inhibition of 57.02% and 56.53% respectively. The Median-Effective Dose of combination 2 (174.02 mg/kg) was better than that of combination 1 (186.03 mg/kg). The combination index and isobologram indicated a synergistic interaction between the constituents of the two combinations. The extract of , and the combination at the dose of 500 mg/kg reduced the number of twists by 46.42; 50.17 and 65.53% respectively. The central analgesic response of the combination was maximal (37.36 ± 8.15 seconds) 60 min after administration. The extracts alone showed anti-inflammatory activity and the combinations showed a synergy of effects. The combination showed peripheral and central analgesic effects.
... There are varies kind of signs that show the present of inflammation like swelling, loss of function, redness, heat and pain (V. Stankov, 2012). Based on WebMD "What does anti-inflammatory mean?," ...
Introduction: Anticoagulant is the process of preventing the blood clot while the thrombolytic is the process of dissolving the blood clot. Both of this activity involve significantly with the clotting factor in our body. Ficus deltoidea plant is one of the medical plant that can be found in Peninsular Malaysia and yet it been use a lot in treating various diseases but not yet on this study. Objective: The present study aims to evaluate the ability of the methanolic extract of Ficus deltoidea to act as anticoagulant and thrombolytic agent. Methods: The extraction of Ficus deltoidea had been diluted into 3 different concentrations in order to observe their effect on anticoagulant test while in the thrombolytic test, only 10mg/mL of concentration of plant extract that will be measure during the experimental procedure. Results: The raw data will be run using the ANOVA and Post Hoc test in order to see it significances. The significant result can be seen on the anticoagulant test while for the thrombolytic test, the result is not significant but the expected outcome still can be seen. Conclusion: F. deltoidea can be one of new alternative as anticoagulant agent as this plant carry the chemical properties of flavonoid.
... These stressors can go unnoticed if they are not resolved by an efficient anti-inflammatory response, which can reverse the damage and restore homeostasis, known as acute inflammation. However, if inflammation is excessive, it can encourage homeostatic changes and be harmful, progressing to chronic inflammation [66,67]. ...
Human aging is a gradual and adaptive process characterized by a decrease in the homeostatic response, leading to biochemical and molecular changes that are driven by hallmarks of aging, such as oxidative stress (OxS), chronic inflammation , and telomere shortening. One of the diseases associated with the hallmarks of aging, which has a great impact on functionality and quality of life, is sarcopenia. However, the relationship between telomere length, sarcopenia, and age-related mortality has not been extensively studied. Moderate physical exercise has been shown to have a positive effect on sarcopenia, decreasing OxS and inflammation, and inducing protective effects on telomeric DNA. This results in decreased DNA strand breaks, reduced OxS and IA, and activation of repair pathways. Higher levels of physical activity are associated with an apparent increase in telomere length. This review aims to present the current state of the art of knowledge on the effect of physical exercise on telomeric maintenance and activation of repair mechanisms in sarcopenia.
... Inflammation is a degenerative process that elevates the osmotic pressure of the injured tissues through local accumulations. It is a pathological condition which results in swelling, stiffness, redness, and/ or pain [1]. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used and known to work against inflammatory disorders through the inhibition of cyclooxygenases (COX-1 and COX-2 subtypes), which convert arachidonic acid to prostaglandins [2]. ...
In the current medical era, the single target inhibition paradigm of drug discovery has given way to the multi-target design concept. As the most intricate pathological process, inflammation gives rise to a variety of diseases. There are several drawbacks to the single target anti-inflammatory drugs currently available. Herein, we present the design and synthesis of a novel series of 4-(5-amino-pyrazol-1-yl)benzenesulfonamide derivatives (7a-j) with COX-2, 5-LOX and carbonic anhydrase (CA) inhibitory activities as potential multi-target anti-inflammatory agents. The pharmacophoric 4-(pyrazol-1-yl)benzenesulfonamide moiety in Celecoxib was used as the core scaffold and different substituted phenyl and 2-thienyl tails were grafted via a hydrazone linker to enhance inhibitory activity against hCA IX and XII isoforms, yielding target pyrazoles 7a-j. All reported pyrazoles were evaluated for their inhibitory activity against COX-1, COX-2, and 5-LOX. Pyrazoles 7a, 7b, and 7j showed the best inhibitory activities against the COX-2 isozyme (IC50 = 49, 60 and 60 nM, respectively) and against 5-LOX (IC50 = 2.4, 1.9, and 2.5 μM, respectively) with excellent SI indices (COX-1/COX-2) of 212.24, 208.33, and 158.33, respectively. In addition, the inhibitory activities of pyrazoles 7a-j were evaluated against four different hCA isoforms I, II, IX, and XII. Both transmembrane hCA IX and XII isoforms were potently inhibited by pyrazoles 7a-j with KI values in the nanomolar range; 13.0–82.1 nM and 5.8–62.0 nM, respectively. Furthermore, pyrazoles 7a and 7b with the highest COX-2 activity and selectivity indices were evaluated in vivo for their analgesic, anti-inflammatory, and ulcerogenic activities. The serum level of the inflammatory mediators was then measured in order to confirm the anti-inflammatory activities of pyrazoles 7a and 7b.
... Reaksi inflamasi dikenal sebagai respon imun non spesifik. Inflamasi/peradangan juga didefinisikan dengan adanya lima fenomena patologis mikroskopis yaitu tumor (pembengkakan pada jaringan), kalor (peningkatan suhu jaringan), rubor (kemerahan seperti warna darah dari jaringan vaskularisasi pada daerah yang terjadi peradangan), dolor (gangguan fungsi organ) 1 . Penyebab utama terjadi inflamasi adalah adanya tekanan yang diakibatkan oleh trauma benda tumpul, benda asing, getaran, dan tekanan kronis dengan intensitas rendah 1 . ...
Inflamasi merupakan suatu kondisi dimana tubuh memberikan reaksi terhadap adanya infeksi, iritasi ataupun cedera yang ditandai dengan adanya kemerahan, panas, bengkak, dan juga nyeri. Reaksi inflamasi dikenal sebagai respon imun non spesifik. Tujuan dari review ini adalah untuk memberikan informasi mengenai tanaman herbal Indonesia, bagian tanaman maupun ekstrak dari herbal tersebut yang memiliki aktivitas sebagai anti-inflamasi. Dalam penelitian ini difokuskan pada review artikel-artikel pada studi eksperimental yang dilakukan secara in vivo dan komponen bioaktifnya. Penjelasan singkat mengenai pemberian, mekanisme anti inflamasi dari tanaman herbal tersebut dapat dimanfaatkan lebih lanjut untuk arah penelitian selanjutnya. Secara keseluruhan, artikel ini menyajikan profil tanaman herbal Indonesia sebagai anti inflamasi.
... 1,2 Edema is characterized by the presence of plasma fluid that moves from the bloodstream to the interstitial tissue at the trauma site. 3 The therapy widely used to treat skin inflammation is topical corticosteroids. Currently, topical corticosteroids are widely abused so that it often causes side effects. ...
Introduction: Inflammation is the body's response to body tissue injury characterized by swelling or edema. Moringa oleifera is known to have many benefits as herbal medicine. Moringa oleifera leaves have been shown to have anti-inflammatory activity. The polyphenol content in Moringa leaves, such as flavonoids and tannins, has been observed as a potential anti-inflammatory.Methods: Thirty white male Wistar rats were randomly divided into five groups. Group 0 (negative control group) was given base cream, group 1 (positive control) was given 2.5% hydrocortisone cream, group 2 was given 10% moringa leaves extract cream, group 3 was given 12% moringa leaves extract cream, and group 4 was given 14% moringa leaves extract cream. One hour after treatment was applied in the plantar area, all mice were induced with 0.1 ml of 1% carrageenan. The thickness of the rat paw edema was measured every 1 hour for 6 hours using a caliper.Results: This study showed a significant difference in rat paw edema between the base cream and the entire treatment groups (p<0.05). There was no significant difference between the 2.5% hydrocortisone cream group and the 10%, 12%, and 14% moringa leaves extract cream group (p>0.05). The 14% cream extract had the largest paw edema inhibition among other moringa leaves extract creams which were 27.4%.Conclusion: This study concludes that 10%, 12%, and 14% of moringa leaves extract cream have anti-inflammatory effects with higher concentrations resulting in better efficacy.
... Inflamasi adalah reaksi biologis yang terjadi sebagai akibat dari pertahanan tubuh terhadap serangan mikroorganisme asing dari luar [3]. Respon inflamasi menjdi aspek penting dari respons jaringan terhadap inflammogen yang merusak. ...
Inflammation is a normal process designed to protect oneself and promote healing of body tissues. The mechanism of action of flavonoids as antiinflammatory is through the inhibition of arachidonic acid and the secretion of lysosomal enzymes. The ethanol extract of Mangifera indica L. leaves (EEML) contains flavonoids and is widely used as a medicine empirically. This study was conducted to evaluate the antiinflammatory effect of EEML in vitro and in vivo. In vitro study of the antiinflammatory activity of EEML based on its effect on the stability of blood membranes using UV-Vis spectrophotometry method. While the in vivo activity was tested using the carrageenan induction method on white rats of the Wistar strain. In vitro activity was expressed as EC50 and in vivo activity was expressed as % edema reduction. The results showed that ethanol extract was able to increase membrane stability with an EC50 value of 8.56 ?g/ml better than positive control aspirin with EC50 21.57 ?g/ml. In vivo test results showed that the administration of EEML doses of 200 mg/kg.bw, 400 mg/kg.bw, and 800 mg/kg.bw was not significantly different from the positive control in reducing edema. EEML has shown antiinflammatory effects in vitro and in vivo, so it has the potential to be developed as an antiinflammatory agent.
Inflammation, characterized by uncontrolled cell proliferation and the ability to invade other tissues, remains a leading cause of morbidity and mortality worldwide. The multifactorial nature of inflammation involves genetic mutations, hormonal influences, and complex cellular signaling pathways. This study explores the design, synthesis, and biological evaluation of 2-amino-6-methylpyridine 4-thiazolidinone hybrid molecules as potential inhibitor of inflammation, aiming to contribute to the development of novel anti-inflammation agents. Firstly, 22 compounds were designed based on literature survey out of these compounds ten compounds were found to be most potent based on the docking studies and these ten new derivatives (DSB001-010) were synthesized and subjected to in silico, in vitro, and ADMET profiling to identify the most potent compound. Compound DSB-009 emerged as the most potent, with an IC 50 value of µM, confirmed by docking studies. These compounds were further characterized using IR, NMR, and mass spectrometry.
One of the prevalent illnesses is joint pain, which can be caused by several factors including aging, nutrient and vitamin deficiency, general health issues, physical weakness, and disease. The transdermal patches are different-sized pharmacological preparations that deliver one or more active ingredients into the bloodstream. Therefore, the investigation was carried out by fabricating of transdermal joint relief patch which is a medicated adhesive patch to find a painless, effective way to transmit blood stream. To administer a specific dose of drug through the skin and into the bloodstream, it is applied to the skin. One of the revolutionary drug delivery systems that replaces the traditional dosage form is the transdermal drug delivery system for the preparation of patches natural ingredients were taken like the material was used main API (thymol camphor, menthol camphor, natural camphor, mustard oil, clove oil). The polymer was used (Ethyl cellulose, Polyethylene Glycol, HydroxyPropylMethyl Cellulose, Tween -80). Propylene glycol was utilized as a plasticizer along with a variety of polymers in the formulation of the patches. Pig skin was employed as the permeating membrane in Franz diffusion cells for the in vitro permeation investigations, to evaluate the patches' physicochemical properties. The outcome revealed that maximum release yields demonstrated excellent results. Therefore, it may be inferred that such medicated adhesive type patches made of herbal ingredients could be effective for both topical and transdermal medication administration. Patch was prepared with ethyl cellulose, PEG & tween 80. Prepared patch was evaluated for physicochemical evaluation, thickness of patch, moisture content, moisture uptake, folding endurance, weight uniformity, drug content determination, invitro permeation studies, pH of patch. From the evaluation it was concluded that pain will be reduce by using natural ingredients in the transdermal patch.
Introduction
Inflammation is a biological response of the immune system to noxious stimuli. Typically, non-steroidal anti-inflammatory drugs are used to treat inflammatory diseases but have several adverse effects. Therefore, it is important to search for natural plant-based remedies to treat inflammatory conditions. Hibiscus rosa-sinensis is a flowering plant belonging to the genus Hibiscus, which is widely used as a home remedy in Sri Lanka.
Methods
The information was collected via major scientific databases including PubMed, ScienceDirect, Google Scholar, and Springer related to the H rosa-sinensis species, polyphenols, chemical composition, and how the flower extract shows anti-inflammatory potential. Collected data were then analysed and interpreted.
Results
The flower H rosa-sinensis is a rich source of polyphenolic compounds including flavonoids and non-flavonoids, tannins, alkaloids, glycosides, saponins, terpenoids, vitamins, and other organic acids, which are reported to exhibit antioxidant and anti-inflammatory potential. The anti-inflammatory activity of H rosa-sinensis flower is expressed via several mechanisms including the reduction of oxidative stress, inhibition of nuclear factor kappa-B and mitogen-activated protein kinase pathways, and the alterations of the arachidonic acid pathway. In addition, the inhibition of inducible nitric oxide synthase enzyme and caspase activity and reduction of polymorphonuclear leucocyte infiltration can be given as other mechanisms.
Conclusions
H rosa-sinensis flower is a rich source of bioactive compounds that exhibit potent antioxidant and anti-inflammatory activities.
Schisandra chinensis (Schisandraceae) is a medicinal plant widely used in traditional Chinese medicine. Under the name Wu Wei Zi, it is used to treat many diseases, especially as a stimulant, adaptogen, and hepatoprotective. Dibenzocyclooctadiene lignans are the main compounds responsible for the effect of S. chinensis. As a part of ongoing studies to identify and evaluate anti-inflammatory natural compounds, we isolated a series of dibenzocyclooctadiene lignans and evaluated their biological activity. Furthermore, we isolated new sesquiterpene 7,7-dimethyl-11-methylidenespiro[5.5]undec-2-ene-3-carboxylic acid. Selected dibenzocyclooctadiene lignans were tested to assess their anti-inflammatory potential in LPS-stimulated monocytes by monitoring their anti-NF-κB activity, antioxidant activity in CAA assay, and their effect on gap junction intercellular communication in WB-ras cells. Some S. chinensis lignans showed antioxidant activity in CAA mode and affected the gap junction intercellular communication. The anti-inflammatory activity was proven for (−)-gomisin N, (+)-γ-schisandrin, rubrisandrin A, and (−)-gomisin J.
The influence of modern lifestyle, diet, exposure to chemicals such as phytosanitary substances, together with sedentary lifestyles and lack of exercise play an important role in inducing reactive stress (RS) and disease. The imbalance in the production and scavenging of free radicals and the induction of RS (oxidative, nitrosative, and halogenative) plays an essential role in the etiology of various chronic pathologies, such as cardiovascular diseases, diabetes, neurodegenerative diseases, and cancer. The implication of free radicals and reactive species injury in metabolic disturbances and the onset of many diseases have been accumulating for several decades, and are now accepted as a major cause of many chronic diseases. Exposure to elevated levels of free radicals can cause molecular structural impact on proteins, lipids, and DNA, as well as functional alteration of enzyme homeostasis, leading to aberrations in gene expression. Endogenous depletion of antioxidant enzymes can be mitigated using exogenous antioxidants. The current interest in the use of exogenous antioxidants as adjunctive agents for the treatment of human diseases allows a better understanding of these diseases, facilitating the development of new therapeutic agents with antioxidant activity to improve the treatment of various diseases. Here we examine the role that RS play in the initiation of disease and in the reactivity of free radicals and RS in organic and inorganic cellular components.
Introduction: This research was conducted to validate the folkloric use of Quercus leucotrichophora (QL) leaf extracts against inflammation and arthritis and to determine the chemical composition using HPLC.
Method: The aqueous and methanolic extracts of QL were evaluated by in vitro anti-oxidant, anti-inflammatory (inhibition of protein denaturation and membrane stabilization) assays, and in vivo anti-inflammatory (carrageenan and xylene-induced edema) and anti-arthritic models. For anti-arthritic potential, 0.1 mL Complete Freund’s Adjuvant (CFA) was inoculated into the left hind paw of a Wistar rat on day 1, and oral dosing with QL methanolic extract (QLME) at 150, 300, and 600 mg/kg was begun at day 8 till the 28th day in all groups, except disease control that was given distilled water, while methotrexate was given as standard treatment.
Results and discussion: There was a noteworthy (p < 0.05–0.0001) restoration in body weight, paw edema, arthritic index, altered blood parameters, and oxidative stress biomarkers in treated rats as compared to the diseased group. Moreover, QLME treatment significantly (p < 0.0001) downregulated TNF-α, IL-6, IL-1β, COX-2, and NF-κB, while significantly (p < 0.0001) upregulating IL-10, I-κB, and IL-4 in contrast to the diseased group. The QLME exhibited no mortality in the acute toxicity study. It was concluded that QLME possessed substantial anti-oxidant, anti-inflammatory, and anti-arthritic potential at all dosage levels prominently at 600 mg/kg might be due to the presence of quercetin, gallic, sinapic, and ferulic acids.
The mechanism, whereby histamine and serotonin increase the permeability of blood vessels, was studied in the rat by means of the electron microscope. The drugs were injected subcutaneously into the scrotum, whence they diffused into the underlying (striated) cremaster muscle. An intravenous injection of colloidal HgS was also given, in order to facilitate the identification of leaks by means of visible tracer particles. After intervals varying from 1 minute to 57 days the animals were killed; the cremaster was fixed, embedded in methacrylate, and examined with the electron microscope.
One to 12 minutes after the injection, the blood vessels of the smallest caliber (3 to 5 micra as measured on electron micrographs) appeared intact. Numerous endothelial openings were present in blood vessels with a diameter of 7 to 8 micra or more. These gaps were 0.1 to 0.8 micra in width; portions of intercellular junctions were often present in one or both of the margins. The underlying basement membrane was morphologically intact. An accumulation of tracer particles and chylomicra against the basement membrane indicated that the latter behaved as a filter, allowing fluid to escape but retaining and concentrating suspended particulate matter of the size used.
Uptake of tracer particles by endothelial vesicles was minimal. Phagocytosis by endothelial cells became more prominent at 3 hours, but as a secondary occurrence; the pericytes were actively phagocytic at all stages. At the 3-hour stage no leaks were found.
The changes induced by histamine and serotonin were indistinguishable, except that the latter was more potent on a mole-to-mole basis. In control animals only small accumulations of tracer particles were found in the wall of a number of blood vessels.
With regard to the pathogenesis of the endothelial leaks, the electron microscopic findings suggested that the endothelial cells become partially disconnected along the intercellular junctions. Supporting evidence was provided at the level of the light microscope, by demonstrating—in the same preparation—the leaks with appropriate tracer particles¹, and the intercellular junctions by the silver nitrate method. The lipid nature of the chylomicron deposits observed in electron micrographs was also confirmed at the level of the light microscope, using cremasters fixed in formalin and stained in toto with sudan red.
Peroxisome proliferator-activated receptors (PPARα, -β and -γ) are nuclear receptors involved in transcriptional regulation of lipid and energy metabolism. Since the energy demand increases when cardiac progenitor cells are developing rhythmic contractile activity, PPAR activation may play a critical role during cardiomyogenesis of embryonic stem (ES) cells. It is shown that ES cells express PPARα, -β, and -γ mRNA during differentiation of ES cells towards cardiac cells. Treatment with PPARα agonists (WY14643, GW7647, and ciprofibrate) significantly increased cardiomyogenesis and expression of the cardiac genes MLC2a, ANP, MHC-β, MLC2v, and cardiac α-actin. Furthermore, WY14643 increased PPARα gene expression and the expression of the cardiogenic transcription factors GATA-4, Nkx2.5, DTEF-1, and MEF 2C. In contrast, the PPARα antagonist MK886 decreased cardiomyogenesis, whereas the PPARβ agonist L-165,041 as well as the PPARγ agonist GW1929 were without effects. Treatment with PPARα, but not PPARβ, and PPARγ agonists and MK886, resulted in generation of reactive oxygen species (ROS), which was inhibited in the presence of the NADPH oxidase inhibitors diphenylen iodonium (DPI) and apocynin and the free radical scavengers vitamin E and N-(2-mercapto-propionyl)-glycine (NMPG), whereas the mitochondrial complex I inhibitor rotenone was without effects. The effect of PPARα agonists on cardiomyogenesis of ES cells was abolished upon preincubation with free radical scavengers and NADPH oxidase inhibitors, indicating involvement of ROS in PPARα, mediated cardiac differentiation. In summary, our data indicate that stimulation of PPARα but not PPARβ and -γ enhances cardiomyogenesis in ES cells using a pathway that involves ROS and NADPH oxidase activity.
Disclosure of potential conflicts of interest is found at the end of this article.
Main contributors to adverse outcomes in severely burned pediatric patients are profound and complex metabolic changes in response to the initial injury. It is currently unknown how long these conditions persist beyond the acute phase post-injury. The aim of the present study was to examine the persistence of abnormalities of various clinical parameters commonly utilized to assess the degree hypermetabolic and inflammatory alterations in severely burned children for up to three years post-burn to identify patient specific therapeutic needs and interventions.
Nine-hundred seventy-seven severely burned pediatric patients with burns over 30% of the total body surface admitted to our institution between 1998 and 2008 were enrolled in this study and compared to a cohort non-burned, non-injured children. Demographics and clinical outcomes, hypermetabolism, body composition, organ function, inflammatory and acute phase responses were determined at admission and subsequent regular intervals for up to 36 months post-burn. Statistical analysis was performed using One-way ANOVA, Student's t-test with Bonferroni correction where appropriate with significance accepted at p<0.05. Resting energy expenditure, body composition, metabolic markers, cardiac and organ function clearly demonstrated that burn caused profound alterations for up to three years post-burn demonstrating marked and prolonged hypermetabolism, p<0.05. Along with increased hypermetabolism, significant elevation of cortisol, catecholamines, cytokines, and acute phase proteins indicate that burn patients are in a hyperinflammatory state for up to three years post-burn p<0.05.
Severe burn injury leads to a much more profound and prolonged hypermetabolic and hyperinflammatory response than previously shown. Given the tremendous adverse events associated with the hypermetabolic and hyperinflamamtory responses, we now identified treatment needs for severely burned patients for a much more prolonged time.
Hypoxia represents one of the strongest transcriptional stimuli known to us. In most cases, hypoxia-induced changes in gene expression are directed towards adapting tissues to conditions of limited oxygen availability.
As a well known example, physical exercise at high altitude results in the transcriptional induction of erythropoietin that functions to increase oxygen carrying capacity and red cell volume. Studies of the transcriptional pathway responsible for the induction of erythropoietin during conditions of hypoxia led to the discovery of the transcription factor hypoxia-inducible factor (HIF) that is known today as the key transcription factor for hypoxia adaptation. Surgical patients are frequently at risk for experiencing detrimental effects of hypoxia or ischemia, for example, in the context of acute kidney injury, myocardial, intestinal or hepatic ischemia, acute lung injury, or during organ transplantation.
In the present review, we discuss the mechanisms of transcriptional adaptation to hypoxia and provide evidence supporting the hypothesis that targeting hypoxia-induced inflammation can represent novel pharmacologic strategies to improve perioperative outcomes. Currently, such strategies are being explored at an experimental level, but we hope that some of these targets can be translated into perioperative patient care within the next decade.
Hydrofluoric acid (HF) is particularly dangerous due to the potential for systemic effects and induction of severe skin necrosis through two mechanisms: corrosiveness and local tissue toxicity. In addition, because it is only partially dissociated (pK(a) 3.2), it is capable of penetrating deeply into tissues. There is a lack of experimental studies that objectively characterize the behavior of HF diffusion into human skin, specifically the kinetics of tissue penetration resulting in severe cellular lesions.
We describe the cutaneous effects of HF using an established ex vivo human skin model. The diffusion of 70% HF starts within the first minute of contact at the epidermal surface and after 2 min reaches the basal layer. In the subsequent minute, the epidermis is destroyed and lesions appear in the papillary dermis after 4 min. Soon after, damage appears in the upper reticular dermis. Thus, 70% HF needs only 5 min of contact to completely penetrate human skin explants. This experiment is reproducible and corroborates previous studies and clinical effects reported in accidental HF exposures.
This study shows that the management of HF chemical skin exposure is a question of minutes, especially for initial decontamination. These experimental observations could be useful for objectively comparing skin decontamination methods. Further studies should help to confirm these preliminary results.
To develop a sleep hypoxia (SH) in emphysema (SHE) rat model and to explore whether SHE results in more severe hepatic inflammation than emphysema alone and whether the inflammation changes levels of coagulant/anticoagulant factors synthesized in the liver.
Seventy-five rats were put into 5 groups: SH control (SHCtrl), treated with sham smoke exposure (16 weeks) and SH exposure (12.5% O(2), 3 h/d, latter 8 weeks); emphysema control (ECtrl), smoke exposure and sham SH exposure (21% O(2)); short SHE (SHEShort), smoke exposure and short SH exposure (1.5 h/d); mild SHE (SHEMild), smoke exposure and mild SH exposure (15% O(2)); standard SHE (SHEStand), smoke exposure and SH exposure. Therefore, ECtrl, SHEShort, SHEMild and SHEStand group were among emphysematous groups. Arterial blood gas (ABG) data was obtained during preliminary tests. After exposure, hepatic inflammation (interleukin -6 [IL-6] mRNA and protein, tumor necrosis factor α [TNFα] mRNA and protein) and liver coagulant/anticoagulant factors (antithrombin [AT], fibrinogen [FIB] and Factor VIII [F VIII]) were evaluated. SPSS 11.5 software was used for statistical analysis.
Characteristics of emphysema were obvious in emphysematous groups and ABGs reached SH criteria on hypoxia exposure. Hepatic inflammation parameters and coagulant factors are the lowest in SHCtrl and the highest in SHEStand while AT is the highest in SHCtrl and the lowest in SHEStand. Inflammatory cytokines of liver correlate well with coagulant factors positively and with AT negatively.
When SH is combined with emphysema, hepatic inflammation and coagulability enhance each other synergistically and produce a more significant liver-derivative inflammatory and prothrombotic status.
Caloric restriction (CR), in the absence of malnutrition, delays aging and prevents aging-related diseases through multiple mechanisms. A reduction in chronic inflammation is widely observed in experimental models of caloric restriction. The low inflammation status may contribute to the reduced incidence of osteoporosis, Alzheimer's disease, cardiovascular diseases and cancer in the aging subjects. The association of caloric restriction with low inflammation suggests a role of energy accumulation in the origin of the chronic inflammation. This point is enforced by recent advances in obesity research. Abundant literature on obesity suggests that chronic inflammation is a consequence of energy accumulation in the body. The emerging evidence strongly supports that the inflammatory response induces energy expenditure in a feedback manner to fight against energy surplus in obesity. If this feedback system is deficient (Inflammation Resistance), energy expenditure will be reduced and energy accumulation will lead to obesity. In this perspective, we propose that an increase in inflammation in obesity promotes energy expenditure with a goal to get rid of energy surplus. A decrease in inflammation under caloric restriction contributes to energy saving. Inflammation is a mechanism for energy balance in the body. Inflammation resistance will lead to obesity. We will review the recent literature in support of the viewpoints.
Recent advances in defining the molecular signaling pathways that regulate the phagocytosis of apoptotic cells have improved our understanding of this complex and evolutionarily conserved process. Studies in mice and humans suggest that the prompt removal of dying cells is crucial for immune tolerance and tissue homeostasis. Failed or defective clearance has emerged as an important contributing factor to a range of disease processes. This review addresses how specific molecular alterations of engulfment pathways are linked to pathogenic states. A better understanding of the apoptotic cell clearance process in healthy and diseased states could offer new therapeutic strategies.
One of the causes of sensorineural hearing loss is the loss of auditory hair cells following exposure to environmental stresses. Auditory hair cell death in response to cochlear trauma occurs via both necrosis and apoptosis. Apoptosis of hair cells involves the caspase and MAPK/JNK pathways which are activated by oxidative stress and secretion of inflammatory cytokines in response to trauma. Identification of the pathways that lead to apoptosis provides therapeutic targets for the conservation of hearing. Antioxidants reduce the level of reactive oxygen species and reactive nitrogen species generated by oxidative stress in response to acoustic trauma, aminoglycoside and platinum-based drugs. Caspase inhibitors affect both the extrinsic and intrinsic apoptotic pathways thereby reducing cisplatin, aminoglycoside, hydraulic trauma and ischemia-induced hearing losses. Corticosteroid therapy reduces inflammation and inhibits apoptosis while activating pro-survival pathways in the organ of Corti following exposure to noise, vibration, cisplatin, aminoglycoside, ischemia/reperfusion injury, bacterial meningitis and electrode insertion trauma. Inhibitors of JNK signaling pathway prevent apoptosis of auditory hair cells following electrode insertion trauma, acute labyrinthitis, acoustic trauma and aminoglycoside ototoxicity. This review provides an overview of the different pathways involved in auditory hair cell death following an environmental stress and both traditional and newly developed drugs that are currently being studied or used for the treatment of acute hearing loss. Recent patents related to otoprotective strategies to conserve hearing and auditory hair cells are also discussed in this review.
High mobility group box nuclear protein 1 (HMGB1) is a DNA nuclear binding protein that has recently been shown to be an early trigger of sterile inflammation in animal models of trauma-hemorrhage via the activation of the Toll-like-receptor 4 (TLR4) and the receptor for the advanced glycation endproducts (RAGE). However, whether HMGB1 is released early after trauma hemorrhage in humans and is associated with the development of an inflammatory response and coagulopathy is not known and therefore constitutes the aim of the present study.
One hundred sixty eight patients were studied as part of a prospective cohort study of severe trauma patients admitted to a single Level 1 Trauma center. Blood was drawn within 10 minutes of arrival to the emergency room before the administration of any fluid resuscitation. HMGB1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, von Willebrand Factor (vWF), angiopoietin-2 (Ang-2), Prothrombin time (PT), prothrombin fragments 1+2 (PF1+2), soluble thrombomodulin (sTM), protein C (PC), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and D-Dimers were measured using standard techniques. Base deficit was used as a measure of tissue hypoperfusion. Measurements were compared to outcome measures obtained from the electronic medical record and trauma registry.
Plasma levels of HMGB1 were increased within 30 minutes after severe trauma in humans and correlated with the severity of injury, tissue hypoperfusion, early posttraumatic coagulopathy and hyperfibrinolysis as well with a systemic inflammatory response and activation of complement. Non-survivors had significantly higher plasma levels of HMGB1 than survivors. Finally, patients who later developed organ injury, (acute lung injury and acute renal failure) had also significantly higher plasma levels of HMGB1 early after trauma.
The results of this study demonstrate for the first time that HMGB1 is released into the bloodstream early after severe trauma in humans. The release of HMGB1 requires severe injury and tissue hypoperfusion, and is associated with posttraumatic coagulation abnormalities, activation of complement and severe systemic inflammatory response.
Cells undergoing necrosis release endogenous danger signals that possess proinflammatory potential. In this study we show that mature IL-1beta and IL-18 are released by necrotic cells but not by apoptotic cells. We identify 7-bromoindirubin-3'-oxime, an indirubin oxime derivative that induces necrosis, as a potent inducer of caspase-1 activation and release of mature IL-1beta and IL-18. Inflammasome activation was triggered by other necrosis-inducing treatments but was not observed in response to apoptosis-inducing stimuli. Necrosis-induced inflammasome activation was mediated by the NLRP3 and ASC molecules. Release of IL-18 and IL-1beta in response to necrosis-inducing stimuli was observed in THP-1 macrophages and the MSTO-211H human mesothelioma cell line independently of LPS priming. Using the in vivo model of naphthalene-induced airway epithelial cell injury, we showed that necrosis activates the ASC inflammasome in vivo. Our study identifies a new mechanism through which necrosis generates proinflammatory molecules that contributes to the sterile inflammatory response.
There are several reports suggesting that hyperosmolarity induces inflammation. We recently showed that Dextran Sodium Sulfate causes inflammatory bowel disease due to hyperosmolarity. The aim of this study was to confirm the link between hyperosmolarity and inflammation by assessing osmolarity values in vivo during inflammation, compare the inflammatory potential of different osmotic agents and finally study the long-term consequences of hyperosmolarity on cell fate.
Osmotic pressures were measured in inflammatory liquids withdrawn from mice subjected to inflammation caused either by subcutaneous injection of Bacille Calmette-Guérin (BCG) or Freund adjuvant. Three epithelial cell lines (HT29, T24 and A549) were exposed up to 48 hours to increasing osmolarities (300, 600, 900 mOsm) of chemically inert molecules such as Mannitol, Propylene Glycol, and Glycerol and inflammatory response was assessed by Enzyme Linked ImmunoSorbent Assay (ELISA) and RNA Protection Assay (RPA). Finally, normal mouse macrophages were exposed to hyperosmotic conditions for long-term culture.
The inflammation caused either by BCG or Freund adjuvant is correlated to hyperosmolarity in inflammatory liquids. The exposure of cells to the different compounds, whatever their molecular weight, has no effect on the secretion of cytokines as long as the osmolarity is below a threshold of 300 mOsm. Higher osmolarities result in the secretion of proinflammatory cytokines (Interleukin-8, Interleukin-6, Interleukin-1beta and Tumor Necrosis factor-alpha). Long-term hyperosmotic culture extends normal macrophage half-life, from 44 days to 102 days, and alters the expression of p53, Bcl-2 and Bax.
The present study further suggests inflammation and hyperosmolarity are closely related phenomena if not synonymous.
Autoantibodies against double-stranded DNA (dsDNA) and nucleosomes represent a hallmark of systemic lupus erythematosus (SLE). However, the mechanisms involved in breaking the immunological tolerance against these poorly immunogenic nuclear components are not fully understood. Impaired phagocytosis of apoptotic cells with consecutive release of nuclear antigens may contribute to the immune pathogenesis. The architectural chromosomal protein and proinflammatory mediator high mobility group box protein 1 (HMGB1) is tightly attached to the chromatin of apoptotic cells. We demonstrate that HMGB1 remains bound to nucleosomes released from late apoptotic cells in vitro. HMGB1-nucleosome complexes were also detected in plasma from SLE patients. HMGB1-containing nucleosomes from apoptotic cells induced secretion of interleukin (IL) 1beta, IL-6, IL-10, and tumor necrosis factor (TNF) alpha and expression of costimulatory molecules in macrophages and dendritic cells (DC), respectively. Neither HMGB1-free nucleosomes from viable cells nor nucleosomes from apoptotic cells lacking HMGB1 induced cytokine production or DC activation. HMGB1-containing nucleosomes from apoptotic cells induced anti-dsDNA and antihistone IgG responses in a Toll-like receptor (TLR) 2-dependent manner, whereas nucleosomes from living cells did not. In conclusion, HMGB1-nucleosome complexes activate antigen presenting cells and, thereby, may crucially contribute to the pathogenesis of SLE via breaking the immunological tolerance against nucleosomes/dsDNA.
We recently observed that specific antibodies to type II collagen do not bind in appreciable amounts to the intact surface of articular cartilage, whereas antibodies to the minor collagen types V, VI, and IX do. These results suggest that the outermost cartilage surface layer prevented interaction of the antibodies with the major collagen type in articular cartilage. The present studies were designed to investigate the pathogenic mechanisms involved in the disruption of the cartilage surface layer in inflammatory arthritis. Articular cartilage obtained from rabbits undergoing acute antigen-induced arthritis of 72 h duration showed a significant increase in binding of anti-type II antibody to cartilage surfaces compared with normal control cartilage (P less than 0.01). Augmentation of anti-type II binding was also observed upon in vitro incubation of bovine articular slices or intact rabbit patellar cartilage for 1 h with human polymorphonuclear neutrophils (PMN), PMN lysates, or purified human PMN elastase. This increase was not inhibited by sodium azide, nor was it enhanced by incubation of cartilage with the strong oxidant hypochlorous acid. Chondrocyte-mediated matrix proteoglycan degradation in cartilage explants cultured in the presence of cytokines failed to increase antibody binding appreciably. The augmentation in antibody binding seen with PMN lysates was inhibited by the nonspecific serine-esterase inhibitor PMSF, but not by the divalent metal chelator EDTA. The elastase-specific inhibitor AAPVCMK also inhibited most of the PMN-induced increase in antibody binding, whereas the cathepsin G-specific inhibitor GLPCMK was much less effective. Incubation of intact cartilage with purified human PMN elastase indicated that this serine esterase could account for the increase in anti-type II collagen antibody binding to intact cartilage surfaces. These studies suggest that in an inflammatory response, PMN-derived elastase degrades the outer layer of articular cartilage, exposing epitopes on type II collagen. They also help clarify the pathogenic mechanisms involved in early articular cartilage damage in inflammatory joint diseases.
Ingestion of apoptotic cells in vitro by macrophages induces TGF-β1 secretion, resulting in an anti-inflammatory effect and suppression of proinflammatory mediators. Here, we show in vivo that direct instillation of apoptotic cells enhanced the resolution of acute inflammation. This enhancement appeared to require phosphatidylserine (PS) on the apoptotic cells and local induction of TGF-β1. Working with thioglycollate-stimulated peritonea or LPS-stimulated lungs, we examined the effect of apoptotic cell uptake on TGF-β1 induction. Viable or opsonized apoptotic human Jurkat T cells, or apoptotic PLB-985 cells, human monomyelocytes that do not express PS during apoptosis, failed to induce TGF-β1. PS liposomes, or PS directly transferred onto the PLB-985 surface membranes, restored the TGF-β1 induction. Apoptotic cell instillation into LPS-stimulated lungs reduced proinflammatory chemokine levels in the bronchoalveolar lavage fluid (BALF). Additionally, total inflammatory cell counts in the BALF were markedly reduced 1–5 days after apoptotic cell instillation, an effect that could be reversed by opsonization or coinstillation of TGF-β1 neutralizing antibody. This reduction resulted from early decrease in neutrophils and later decreases in lymphocytes and macrophages. In conclusion, apoptotic cell recognition and clearance, via exposure of PS and ligation of its receptor, induce TGF-β1 secretion, resulting in accelerated resolution of inflammation.
Burn injury results in a rapid loss of intravascular volume as wound edema forms, which reduces the circulating blood volume and generates the need for fluid therapy to combat hypovolemia. Fluid resuscitation of a burn patient is usually carried out with isotonic, sodium- and chloride-containing fluids, such as lactated Ringer's solution. The initial 24 h resuscitation volume is based on the burn size and body weight of the patient. Following a successful resuscitation, the burn patient develops Stereotypic neurohormonal and metabolic responses that, depending on the extent of injury, last for several weeks or months. Breathing of incomplete products of combustion by the fire victim produces inhalation injury, the incidence of which rises with increasing burn size and the severity of which is proportional to the duration of exposure. Systemic hypoxia from carbon monoxide toxicity causes early death; chemical airway injury increases mortality and predisposes to subsequent pneumonia that further reduces survival. The diagnosis of inhalation injury is made by bronchoscopy and/or xenon scan and therapy involves support of ventilation. Thermal destruction of the cutaneous mechanical barrier and the presence of nonviable avascular burn eschar as well as impairment of other host defenses render the burn patient susceptible to local as well as systemic infections. Care following resuscitation is focused on topical antimicrobial therapy, burn wound excision, and wound closure by grafting. Nutritional support and the prevention and control of infection are constant themes in burn patient management. A progressive improvement in general care of the acutely injured patient, prevention of shock, effective means of maintaining organ function, prevention and control of burn wound and other infections, and physiologically based metabolic support have significantly increased burn patient survival in recent decades.
The effects of radiation at atomic and molecular levels have been discussed in the previous chapter: events that occur over
a time frame of nanoseconds to milliseconds. The present chapter relates to the effects of radiation on visible structures,
in other words cells and tissues: events that occur within a time range of seconds to months or even years. To begin with,
the theories relating to the infliction of radiation damage at the cellular level must be mentioned. It is considered that
this may occur in one of two main ways. There is the Direct Action theory, whereby the ionisation of and lesion to the target, most probably DNA, is the primary event. The Indirect Action theory refers to the formation of DNA lesions produced by free radicals, which have in this instance been the primary target
for ionisation by the radiation. Experimental work shows that the effect of oxygen on radiosensitivity is mediated by indirect
action, since the tissue pO2 affects the formation of the free radicals, which damage the DNA. Today, both modes of action are considered to be important
in producing cell death. It may be mentioned that while there is, as stated above, broad agreement that the most important
site of damage is the DNA of the cell nucleus, it may not be the only one. Some radiation effects, for example radiation oedema,
indicate that cell membranes may also be important targets. As stated in the previous chapter, the majority of cell deaths
are delayed and the result of mitotic catastrophe.
Patient outcome after traumatic brain injury (TBI) is highly variable. The underlying pathophysiology of this is poorly understood, but inflammation is potentially an important factor. Microglia orchestrate many aspects of this response. Their activation can be studied in vivo using the positron emission tomography (PET) ligand [11C](R)PK11195 (PK). In this study, we investigate whether an inflammatory response to TBI persists, and whether this response relates to structural brain abnormalities and cognitive function.
Ten patients, studied at least 11 months after moderate to severe TBI, underwent PK PET and structural magnetic resonance imaging (including diffusion tensor imaging). PK binding potentials were calculated in and around the site of focal brain damage, and in selected distant and subcortical brain regions. Standardized neuropsychological tests were administered.
PK binding was significantly raised in the thalami, putamen, occipital cortices, and posterior limb of the internal capsules after TBI. There was no increase in PK binding at the original site of focal brain injury. High PK binding in the thalamus was associated with more severe cognitive impairment, although binding was not correlated with either the time since the injury or the extent of structural brain damage.
We demonstrate that increased microglial activation can be present up to 17 years after TBI. This suggests that TBI triggers a chronic inflammatory response particularly in subcortical regions. This highlights the importance of considering the response to TBI as evolving over time and suggests interventions may be beneficial for longer intervals after trauma than previously assumed. ANN NEUROL 2011;
The role of the immune system in the pathogenesis of endometriosis remains elusive. It has been shown that patients have an altered peritoneal environment with increased levels of inflammatory cytokines, activated macrophages and reduced clearance of retrogradely transported endometrial fragments. However, it is not known if this unique inflammatory situation is cause or consequence of endometriosis. This study investigates the impact of a pre-existing peritoneal inflammation on endometriosis establishment in a mouse model.
Endometriosis was induced by intraperitoneal injection of enhanced green fluorescent protein (EGFP)-expressing endometrium in mice. In parallel, a peritonitis model was established via intraperitoneal injection of thioglycolate medium (TM). Finally, endometriosis was induced in the inflamed peritoneal cavity and lesion establishment as well as morphological and histological characteristics were analysed.
Induction of endometriosis in an inflamed peritoneal cavity resulted in fewer lesions and significantly lower sum of lesion surface area per mouse in the TM-treated group. Additionally, a higher amount of non-attached debris could be detected in the peritoneal cavity of TM-treated mice.
An intraperitoneal inflammation decreases endometriosis establishment in this mouse model. Thus, a pre-existing peritoneal inflammation might not be a factor favouring the development of endometriosis.
N-methyl-2,2'-dichlorodiethylamine (HN2)is a topical chemotherapeutic agent used as therapy for cutaneous T-cell lymphomas (CTCL). Di(2-chloroethyl)sulfide (SM), and less often HN2, have been used as chemical weapons, with the skin being a principle target. The mechanisms by which these chemicals produce their therapeutic and toxic effects in skin, however, are not clearly defined. We exposed human skin explants to two doses of HN2 and SM. At 18 hours after exposure, histopathologic features were compared. In addition, immunohistochemical markers to basement membrane proteins were used to evaluate the effects of both chemicals on the basement membrane zone. Gross vesication was not seen. Pyknotic nuclei with or without dyskeratotic changes within epidermal keratinocytes were present at both doses. These changes varied more between skin specimens than they did between doses. Ballooning degeneration was more marked after SM exposures. Diffuse dermal-epidermal separation was present only at high-dose exposures and did not appear to correlate with the degree of changes locally in the overlying epidermis. Antibodies to laminin-5 showed decreased immunoreactivity after exposure to HN2 and SM. Immunoreactivity for laminin- was decreased to a lesser extent, and immunoreactivity for collagen IV and VII was unchanged. HN2 and SM produce similar histopathologic and immunohistochemical features after cutaneous exposure. These features suggest that part of mechanism of action of HN2 and SM is a direct effect on the basement membrane zone. Understanding the effects of HN2 and SM separate from their effect on DNA may be important in designing therapies and in advancing our understanding of the pathophysiologic changes induced by these chemicals when delivered topically.
The aim of the study was to clarify the aging-associated changes in physical performance and energy metabolism in senescence-accelerated
prone mouse (SAMP1). The endurance of aged SAMP1 was significantly lower by 28% than the age-matched senescence-resistant
mouse (SAMR1). Oxygen consumption and fat oxidation in aged SAMP1 were lower by 19% and 22%, respectively. Peroxisome proliferator–activated
receptor-γ coactivator-1β and medium-chain acyl coenzyme A dehydrogenase messenger RNA expression was significantly lower
in aged SAMP1. Aged SAMP1 exhibited higher plasma glucose, insulin, leptin, and lower adiponectin concentrations. Aged SAMP1
also had higher malondialdehyde levels in plasma and tissues and lower peroxisome proliferator–activated receptor-γ messenger
RNA and protein levels in adipose tissue. These results indicate that physical performance and energy expenditure decrease
earlier with aging in SAMP1, accompanied by decreased fatty acid catabolism in muscle and liver and increased inflammation
and oxidative stress in adipose tissue. SAMP1 could thus be a useful accelerated functional depression model for studying
physical performance and energy metabolism.
Optical spectroscopy has been proposed to measure regional tissue hemodynamics in periodontal tissue. The objective of this study was to further evaluate the diagnostic potential of optical spectroscopy in peri-implant inflammation in vivo by assessing multiple inflammatory parameters (tissue oxygenation, total tissue hemoglobin, deoxyhemoglobin, oxygenated hemoglobin and tissue edema) simultaneously.
A cross-sectional study was performed in a total of 64 individuals who presented with dental implants in different stages of inflammation. In brief, visible-near-infrared spectra were obtained, processed and evaluated from healthy (n = 151), mucositis (n = 70) and peri-implantitis sites (n = 75) using a portable spectrometer. A modified Beer-Lambert unmixing model that incorporates a nonparametric scattering loss function was employed to determine the relative contribution of each inflammatory component to the overall spectrum.
Tissue oxygenation at peri-implantitis sites was significantly decreased (p < 0.05) when compared with that at healthy sites, which was largely due to an increase in deoxyhemoglobin and a decrease in oxyhemoglobin at the peri-implantitis sites compared with the mucositis and healthy sites. In addition, the tissue hydration index derived from the optical spectra in mucositis was significantly higher than that in other groups (p < 0.05).
In summary, the results of this study revealed that hemodynamic alterations can be detected around diseased peri-implant sites by optical spectroscopy, and this method may be considered an alternative and feasible approach for the monitoring and diagnosis of peri-implant diseases.
The inflammation which occurs around the silicone prosthesis is a complex process that can provoke the failure of the device and compromise the health of the implanted patient. Toll-like receptors (TLRs), which are transmembrane proteins, are now known to act in the innate immune response and in endogenous inflammation. The aim of our study was to assess the role of TLR4 in the foreign body reaction to a silicone shell prosthesis. Disks of shell silicone prosthesis were implanted in the subcutaneous tissue of C57BL6-TLR4-/- and C57BL6-WT mice. At day 14, inflammatory cell infiltrate and vessel sections around the prosthesis were less numerous in TLR4-/- than in WT mice. A histomorphometric analysis showed that the capsule around the implant was 1.96-fold less thick in depleted TLR4 than in wild-type mice. In addition, vascular endothelial growth factor and transforming growth factor 1 were underexpressed in the surrounding tissue of the prosthesis in TLR4-/- mice. Our study suggests, from this foreign body response model against silicone in mice, that TLR4 plays a key role in the reaction process around silicone implants.
Cardiac stress, mediated by increased catecholamines, is the hallmark of severe burn injury typified by marked tachycardia, increased myocardial oxygen consumption, and increased cardiac output (CO). It remains one of the main determinants of survival in large burns. Currently, it is unknown for how long cardiac stress persists after a severe injury. Therefore, the aim of this study was to determine the extent and duration of cardiac stress after a severe burn. To determine persistence of cardiac alteration, the authors determined cardiac parameters of all surviving patients with burns ≥ 40% TBSA from 1998 to 2008. One hundred ninety-four patients were included in this study. Heart rate, mean arterial pressure, CO, stroke volume, cardiac index, and ejection fractions were measured at regular intervals from admission up to 2 years after injury. Rate pressure product was calculated as a correlate of myocardial oxygen consumption. All values were compared with normal nonburned children to validate the findings. Statistical analysis was performed using log transformed analysis of variance with Bonferroni correction and Student's t-test, where applicable. Heart rate, CO, cardiac index, and rate pressure product remained significantly increased in burned children for up to 2 years when compared with normal ranges (P < .05), indicating vastly increased cardiac stress. Ejection fraction was within normal limits for 2 years. Cardiac stress persists for at least 2 years postburn, and the authors suggest that attenuation of these detrimental responses may improve long-term morbidity.
Mitochondria play critical roles in both the life and the death of cardiac myocytes. Various factors, such as the loss of ATP synthesis and increase of ATP hydrolysis, impairment in ionic homeostasis, formation of reactive oxygen species (ROS), and release of proapoptotic proteins are related to the generation of irreversible damage. It has been proposed that the release of cytochrome c is caused by a swelling of the mitochondrial matrix triggered by the apoptotic stimuli. However, there is a controversy about whether or not the mitochondria, indeed, swell during apoptosis. The major advantages of atomic force microscopy (AFM) over conventional optical and electron microscopes for bio-imaging include the fact that no special coating and vacuum are required and imaging can be done in all environments--air, vacuum or aqueous conditions. In addition, AFM force-distance curve measurements have become a fundamental tool in the fields of surface chemistry, biochemistry, and material science. In this study, we used AFM to observe the morphological and property changes in heart mitochondria that were isolated from a rat myocardial infarction model. From the shape parameters of the mitochondria in the AFM topographic image, it seemed that myocardial infarction caused the mitochondrial swelling. Also, the results of force-distance measurements showed that the adhesion force of heart mitochondria was significantly decreased by myocardial in infarction. Therefore, we suggested that myocardial infarction might be the cause of mitochondrial swelling and the changes in outer membrane of heart mitochondria.
Proceedings of a Symposium held at the University of Reading between 19 and 24 September, 1971 Incluye bibliografía e índice.
The quest for a year round tan has led to an increase in the use of artificial tanning devices, namely sunbeds. There has been much debate in the press recently regarding the dangers of sunbed use and calls for tighter regulation of the industry, particularly the licensing of unmanned tanning salons. The dangers of sunbed use have long been recognised and the body of evidence linking sunbed use to skin malignancy is growing, in fact this month the Lancet published a review from the International Agency for Research on Cancer classifying UV emitting tanning devices as carcinogenic to humans. At the Welsh Centre for Burns and Plastic Surgery we noticed a rise in the number of patients presenting with burns related to sunbed use and present our data surrounding this injury over the last 6 years.
Unlabelled:
While occupational exposure to vibration is a common cause of acute and chronic musculoskeletal pain, eliminating exposure produces limited symptomatic improvement, and reexposure precipitates rapid recurrence or exacerbation. To evaluate mechanisms underlying these pain syndromes, we have developed a model in the rat, in which exposure to vibration (60-80Hz) induces, in skeletal muscle, both acute mechanical hyperalgesia as well as long-term changes characterized by enhanced hyperalgesia to a proinflammatory cytokine or reexposure to vibration. Exposure of a hind limb to vibration-produced mechanical hyperalgesia measured in the gastrocnemius muscle of the exposed hind limb, which persisted for approximately 2 weeks. When nociceptive thresholds had returned to baseline, exposure to a proinflammatory cytokine or reexposure to vibration produced markedly prolonged hyperalgesia. The chronic prolongation of vibration- and cytokine-hyperalgesia was prevented by spinal intrathecal injection of oligodeoxynucleotide (ODN) antisense to protein kinase Cepsilon, a second messenger in nociceptors implicated in the induction and maintenance of chronic pain. Vibration-induced hyperalgesia was inhibited by spinal intrathecal administration of ODN antisense to receptors for the type-1 tumor necrosis factor-alpha (TNFalpha) receptor. Finally, in TNFalpha-pretreated muscle, subsequent vibration-induced hyperalgesia was markedly prolonged.
Perspective:
These studies establish a model of vibration-induced acute and chronic musculoskeletal pain, and identify the proinflammatory cytokine TNFalpha and the second messenger protein kinase Cepsilon as targets against which therapies might be directed to prevent and/or treat this common and very debilitating chronic pain syndrome.
The experiments set forth here establish the fact that the heat of the inflamed part has its origin primarily in the local biochemical activity of the cellular elements which participate in the inflammatory process. The inflammatory hyperemia, instead of being the necessary and constant source of the inflammation must be considered a natural physiological compensation for the abnormal local calorification. The rapid circulation of the blood in the inflamed part tends to moderate the increase in local temperature and to equalize the temperature with that of other parts of the body.
Burns from seemingly innocuous substances are rare, probably underrecognized and typically present late. We describe a case of a child who sustained a full-thickness burn after an application of a coal ash poultice for ankle pain. This case report highlights a rare cause of a chemical burn that may become more common with increasing use of traditional remedies worldwide.
The transcription factor HIF-1 is one of the principal mediators of homeostasis in human tissues exposed to hypoxia. It is implicated in virtually every process of rapid gene expression in response to low oxygen levels. The most common causes of tissue hypoxia are inflammation and/or insufficient circulation or a combination of both. Inflamed tissues and the areas surrounding malignant tumors are characterized by hypoxia and low concentrations of glucose. Serious and generalized inflammation can lead to sepsis and circulatory collapse resulting in acute or chronic tissue hypoxia in various vital organs which induces a rapid homeostatic process in all nucleated cells of affected organs in the human body. Under hypoxic conditions the alpha and beta subunits of HIF-1 make an active heterodimer and drive the transcription of over 60 genes important for cell survival, adaptation, anaerobic metabolism, immune reaction, cytokine production, vascularization and general tissue homeostasis. In addition, HIF-1 plays a key role in the development of physiological systems in fetal and postnatal life. It is also a critical mediator of cancer, lung and cardiovascular diseases. The better understanding of the functions of HIF-1 and the pharmacological modulation of its activity could mean a successful therapeutic approach to these diseases.
We performed multiwavelength photoacoustic (PA) measurement for extensive deep dermal burns in rats to monitor the healing process of the wounds. The PA signal peak at 532 nm, an isosbestic point for oxyhemoglobin (HbO(2)) and deoxyhemoglobin (HHb), was found to shift to a shallower region of the injured skin tissue with the elapse of time. The results of histological analysis showed that the shift of the PA signal reflected angiogenesis in the wounds. Until 24 h postburn, PA signal amplitude generally increased at all wavelengths. We speculate that this increase in amplitude is associated with dilation of blood vessels within healthy tissue under the injured tissue layer and increased hematocrit value due to development of edema. From 24 to 48 h postburn, the PA signal showed wavelength-dependent behaviors; signal amplitudes at 532, 556, and 576 nm continued to increase, while amplitude at 600 nm, an HHb absorption-dominant wavelength, decreased. This seems to reflect change from shock phase to hyperdynamic state in the rat; in the hyperdynamic state, cardiac output and oxygen consumption increased considerably. These findings show that multiwavelength PA measurement would be useful for monitoring recovery of perfusion and change in local hemodynamics in the healing process of burns.
The pharmacokinetics and pharmacodynamics of drugs are significantly altered in the burn patient, and the burn patient population shows wide inter- and intraindividual variation in drug handling. Burn injury evolves in two phases. The first phase corresponds to the burn shock, which occurs during the first 48 hours after thermal injury. In this phase, hypovolaemia, oedema, hypoalbuminaemia and a low glomerular filtration rate are observed, which result in a slower rate of drug distribution and lower renal clearance. The second phase (beyond 48 hours after injury) is a hyperdynamic state with high blood flow in the kidneys and liver, an increased α1-acid-glycoprotein level and loss of the drug with exudate leakage. As a result, protein binding, drug distribution and clearance may be altered.
Because of the alteration in these variables, wide intraindividual variation of pharmacokinetic parameters occurs depending upon the time since thermal injury and fluid resuscitation. Interindividual variations may be correlated with the percentage of the body surface area that is burnt, creatinine clearance, albuminaemia or the α1-acid-glycoprotein level. A number of important variations in pharmacodynamic parameters have been described, but their mechanisms are poorly understood.
From a practical point of view, for the subpopulation of burn patients who eliminate drugs extremely rapidly, higher doses and/or shorter dosing intervals are required to avoid treatment inefficacy. Drug concentration measurements help to take into account interindividual variability. However, adaptation of doses based on Bayesian methods is frequently not possible because the distribution of pharmacokinetic parameters is poorly characterized in this population. Methods based only on individual data or on a surrogate marker for efficacy may be used to optimize the dosing regimen in this population.
The development of experimental disciform edema and necrotizing keratitis in the corneas or rabbits following intrastromal inoculation with the RE strain of herpes simplex virus is described. Following an initial episode of conjunctivitis and epithelial keratitis, a mild, centrally localized, stromal edema developed on the fifth day. Stromal edema, opcification, and neovascularization of the cornea reached maximum severity on the seventh to twenty-second day, and began to fade in most eyes thereafter. On the twenty-ninth day most corneas have attained a resolved state characterized by subepithelial granular opacities. Several eyes were observed which developed central necrotizing keratitis. Marked similarities between the animal model and human herpetic stromal keratitis were apparent. Histological observations show that early necrotizing keratitis in the rabbit is characterized by an infiltration of plasma cells and lymphocytes in the limbus, with polymorphonuclear leukocytes, lymphocytes, and macrophages in the central cornea.
Plasminogen, the inactive precursor of plasmin, a general trypsin-like proteinase, is present at high concentration in blood and in body fluids. Most cells can recruit this proteolytic potential by secreting plasminogen activator (PA) to generate localized proteolysis in the surrounding microenvironment. PA and plasmin are serine enzymes whose pH optima match extracellular pH; further, in view of the large amount of circulating proenzyme and the broad substrate range of plasmin, the possibility that this proteolytic system can initiate a variety of proteolytic reactions or sequences should be kept in mind. PA production is precisely regulated by hormones, temporal programming, or both; and enzyme synthesis is correlated with some physiological and pathological processes requiring proteolysis. Thus PA production is coordinately regulated with ovulation, trophoblast implantation, spermatogenesis, polypeptide hormone synthesis, and some developmental phenomena; and with inflammation, tumour promotion, and neoplasia. Tissue remodelling and cell migration are common to many of these processes. Macrophage (monocyte) and polymorphonuclear leucocyte PA production is modulated by many biologically active substances. Enzyme synthesis is induced and stimulated by stimuli that recruit these cells to sites of inflammation, and it is repressed by anti-inflammatory agents, notably by glucocorticoids.
The accumulation of 125I-labelled serum albumin and 51Cr-labelled erythrocytes was measured in mouse paw oedema induced by bradykinin or by heating the paw at 46.5 degrees. The extravasating fluid in bradykinin oedema consistently contained 50% of the albumin concentration of plasma, whereas the extravasating fluid induced by thermal injury initially had a low albumin content, but it progressively increased over a period of 30-40 min to equal albumin levels in plasma. Thermal injury also caused the extravascular accumulation of erythrocytes. Errors involved in attempting to measure the albumin content of the additional extravascular fluid in inflammation are discussed. Adrenaline suppressed bradykinin oedema, but potentiated thermal injury. These results do not support the view that bradykinin is the inflammatory mediator in thermally-induced oedema.
Ischemic brain damage can be partially ameliorated by barbiturate therapy applied postinsult. Catabolism-induced brain hyperosmolality during ischemia may contribute to the development of brain edema after restoration of circulation. To determine changes in brain osmolality during ischemia and the effect of barbiturate anesthetics in altering its course, we measured whole and regional (cerebral cortex, diencephalon-midbrain, and cerebellum) brain osmolality for up to 2 hours after decapitation ischemia in unanesthetized and pentobarbital anesthetized rats. Normal (nonischemic) brain osmolality in pentobarbital anesthetized rats was 319 +/- 2 mOsm/1 (mean +/- SEM) and higher than in unanesthetized rats (307 +/- 6 mOsm/1). The rate of increase in whole brain osmolality was 60% slower in pentobarbital anesthetized rats in the first 60 minutes of ischemia and regional brain osmolality increased by a maximum of 32 mOsm/1 compared to 45 mOsm/1 in unanesthetized rats. The potential for edema based on percent change in brain osmolality as well as the rapidity of the change was greater in unanesthetized rats. The significance of the increase in brain osmolality with barbiturate anesthesia and its attenuation of the rate and magnitude of increase during ischemia is discussed.
Respiratory failure after large body burns is a well recognized, but unexplained entity. The authors' objective was to define the pathophysiology and to characterize the time course of this injury on the pulmonary microcirculation. Microvascular integrity was continuously monitored using lung lymph flow (QL) and lymph to plasma protein ratio. These are sensitive and reliable indices of the fluid filtration rate and protein permeability characteristics across the microvascular membrane. Chronic lung lymph fistulas were created in 8 sheep. QL, protein content, and pulmonary and systemic vascular pressures were monitored continuously for 1 day prior to and 5 days after a 40% full-thickness burn. Animals were unanesthetized, except for a brief ketamine anesthetic for the burn itself. Resuscitation was with lactated Ringer's solution (3 cc/kg/% of body burn/24 hr). The authors' results can be divided into 3 phases after burn. From 0 to 18 hr, mean pulmonary arterial pressure increased, left atrial and central venous pressure decreased, and QL increased 50% to 200%. Between 18 and 48 hr, pulmonary arterial pressure remained elevated, left atrial and central venous pressure were baseline, and QL increased significantly in all animals for a variable time period (50% to 300%). As QL increased, lymph protein content decreased by 50%. From 48 to 120 hr, parameters gradually returned to baseline. The authors conclude that between 18 and 48 hr after burn, a large increase in QL occurs, due either to severe pulmonary venoconstriction raising microvascular hydrostatic pressure or to a selective increase in permeability to water and small solutes, as the membrane 'sieving' effect for protein remained intact.
Experimental pancreatitis was induced by cooling the splenetic part of rat pancreas with chlorethyl, and the cells of duodenal area of the pancreas were studied at different stages of pancreatitis using cytomorphometry, cytomorphology and autoradiography. Interlobular and interacinar oedemas were observed at the first hours after treatment. In 24 hours the intracellular oedema of exocrine pancreatic cells (EP) was detected. On day 14 after treatment typical acute edematous pancreatitis developed. The observed changes involve a pathological activation of EP of the duodenal area, a subsequent restoration of the structure of this area, and later a passage of pancreatitis into the chronic form. The usefulness of this model of pancreatitis for quantitative cytochemical studies of EP during pathogenesis and drug treatment is discussed.
Many physiological processes are based on the finely regulated interaction between cells and enzymatic reaction cascades. Mainly proteinases are involved in these processes, which are regulated by inhibitors, principally proteins. If this sensitive balance is disturbed, uncontrolled pathophysiological events can be induced, which are often associated with inflammatory reactions. Characteristic for inflammation are events like contact activation of hemostasis, increasing permeability of blood vessels caused by activation of the Kallikrein-Kinin- and the Complement-system and Plasmin-release induced by activation of fibrinolysis. The following uncontrolled proteolysis, leading to tissue destruction, is mainly associated with the degree of illness. Inflammatory cells excrete besides proteinases also mediators maintaining and increasing these processes. Only when the balance between proteinases and inhibitors is restored, inflammation subsides. Afterwards the controlled course of physiological reactions is possible again.