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Examining the effect of embryonic Oligopeptid mixture (Humanofort®) on chronic inflammatory musculo-skeletal disorders associated with pain in dogs
Abstract
The authors examined the clinical impact of the oligopeptide complex Humanofort®. Humanofort® is a standardized chicken embryo extract containing natural growth factors (such as IGF-1, IGF-2, FGF, NGF, EGF, and CTGF). In the experiment the authors examined clinically the anti-inflammatory and analgesic effects of Humanofort® veterinary pharmaceutical product in dogs having chronic pain associated with musculo-sceletal disorders. The experimental design was a multicenter, randomized, double-blinded, placebo-controlled arrangement carried out in accordance with the Good Clinical Practice regulations. The trials proved that the kinetic willingness of dogs suffering from chronic musculoskeletal disorders and treated with a compound containing the active substance Humanofort® has significantly improved compared to the placebo control group (n=49, p=0.0006).
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Metabolic Syndrome (MS) is a polymorph disease with a high frequency especially in older age. Any randomized study with nonhospitalized subjects might include those bearing MS, that greatly influenced the final results. Eighty subjects aged 50-75 years (38 men and 42 women) had consumed daily 4 caps of purified Embryonary Peptides (EP) for 60 days. The samples of blood from each subject were obtained before and after administration. Therefore, each subject was his own control. In all subjects, after administration, regardless of the MS presence, total cholesterol and LDL-cholesterol had decreased approximately 30% as compared with the initial values. Significant decreases of insulin and cortisol were also observed, but associated with modifications of PSA, CEA and IGF-1. The magnitude of these changes was lower in subjects with MS. The long-lasting modifications induced by EP seem to have an adaptive-regulatory character, affecting the lipid metabolism (already modified in MS), as well as some pathways from steroid biosynthesis. Thus, EP might act similarly to some stimulatory factors, such as IGF-1, in a reversible stage of MS.
This study aimed to establish the effect of a diet enriched with green-lipped mussel (GLM) on pain and functional outcomes in osteoarthritic dogs. Twenty-three client-owned dogs with osteoarthritis (OA) were fed a balanced control diet for 30 d and then a GLM-enriched balanced diet for the next 60 d. We assessed peak vertical force (PVF), which is considered to be the gold standard method, at Day (D)0 (start), D30 (end of control diet), and D90 (end of GLM-enriched diet). The owners completed a client-specific outcome measure (CSOM), which is a pain questionnaire, once a week. Motor activity (MA) was continuously recorded in 7 dogs for 12 wk. Concentrations of plasma omega-3 fatty acids were quantified as indicative of diet change. Statistical analyses were linear-mixed models and multinomial logistic regression for repeated measures. The GLM diet (from D30 to D90) resulted in an increase in concentrations of plasma omega-3 fatty acids (P < 0.016) and improvement of PVF (P = 0.003). From D0 to D30, PVF did not significantly change (P = 0.06), which suggests that the GLM diet had a beneficial effect on gait function. Moreover, PVF (P = 0.0004), CSOM (P = 0.006), and MA (P = 0.02) improved significantly from D0 to D90. In general, the balanced control diet could have contributed to reduced OA symptoms, an effect that was subsequently amplified by the GLM diet.
Objective —To determine whether oxidative stress could be induced in canine chondrocytes in vitro.
Sample —Chondrocytes obtained from healthy adult mixed-breed dogs.
Procedures —Harvested chondrocytes were maintained at 37°C with 5% CO 2 for 24 hours. To assess induction of oxidative stress, 2 stimuli were used: hydrogen peroxide and a combination of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). To determine the effect of hydrogen peroxide, a set of chondrocyte-seeded plates was incubated with control medium alone or hydrogen peroxide (100, 200, or 300μM) for 24 hours. For inhibition of oxidative stress, cells were incubated for 24 hours with N-acetylcysteine (NAC; 10mM) before exposure to hydrogen peroxide. Another set of chondrocyte-seeded plates was incubated with control medium alone or with IL-1β (10 ng/mL) and TNF-α (1 ng/mL) for 24 hours. Supernatants were obtained for measurement of prostaglandin E 2 production, and cell lysates were used for measurement of superoxide dismutase (SOD) activity and reduced-glutathione (GSH) concentration.
Results —Chondrocytes responded to the oxidative stressor hydrogen peroxide with a decrease in SOD activity and GSH concentration. Exposure to the antioxidant NAC caused an increase in SOD activity in hydrogen peroxide–stressed chondrocytes to a degree comparable with that in chondrocytes not exposed to hydrogen peroxide. Similarly, NAC exposure induced significant increases in GSH concentration. Activation with IL-1β and TNF-α also led to a decrease in SOD activity and increase in prostaglandin E 2 production.
Conclusions and Clinical Relevance —Canine chondrocytes responded to the oxidative stress caused by exposure to hydrogen peroxide and cytokines. Exposure to oxidative stress inducers could result in perturbation of chondrocyte and cartilage homeostasis and could contribute to the pathophysiology of osteoarthritis. Use of antioxidants, on the other hand, may be helpful in the treatment of arthritic dogs.
Background
The conceptual validity of kinetic gait analysis and disability outcome assessment methods has guided their use in the assessment of pain caused by osteoarthritis (OA). No consensus on the best clinical methods for pain evaluation in canine OA exists, particularly, when evaluating treatments where a smaller treatment effect is anticipated than with pharmacological pain killers. This study thus aimed at determining the technical validity of some clinical endpoints on OA pain in dogs using the green-lipped mussel (GLM)-enriched diet.
Twenty-three adult dogs with clinical OA completed the prospective controlled study. All the dogs were fed a balanced diet over a 30-day control period followed by a GLM-enriched diet over a 60-day period. The kinetic gait analysis parameter (PVFBW, peak vertical force adjusted for body weight change), electrodermal activity (EDA), and a standardized multifactorial pain questionnaire (MFQ) were performed on day (D) 0 (inclusion), D30 (start) and D90 (end). The owners completed a client-specific outcome measures (CSOM) instrument twice a week. Motor activity (MA) was continuously recorded in seven dogs using telemetered accelerometric counts. We hypothesized that these methods would produce convergent results related to diet changes. A Type I error of 0.05 was adjusted to correct for the multiplicity of the primary clinical endpoints.
Results
Neither the EDA nor the MFQ were found reliable or could be validated. Changes in the PVFBW (Padj = 0.0004), the CSOM (Padj = 0.006) and the MA intensity (Padj = 0.02) from D0 to D90 suggested an effect of diet(s). Only the PVFBW clearly increased after the GLM-diet (Padj = 0.003). The CSOM exhibited a negative relationship with the PVFBW (P = 0.02) and MA duration (P = 0.02).
Conclusions
The PVFBW exhibited the best technical validity for the characterization of the beneficial effect of a GLM-enriched diet. The CSOM and MA appeared less responsive following a GLM-diet, but these measures appeared complementary to gait analysis. Apparently, the CSOM provides the capacity to rely on pain OA assessment influenced by both lameness quantification (PVFBW) and physical functioning (MA).
Postnatal muscle stem cells, recognized as myogenic satellite cells, were isolated from sheep skeletal muscle and used in these experiments. Forty-one different metabolic compounds that are commonly found in commercially-available oral supplements were exposed to primary muscle stem cell cultures, in an effort to ascertain whether any one compound could alter satellite cell proliferation or differentiation (a first step towards elucidating the metabolomics or nutrigenomics of these stem cells). These compounds included energetic moieties, amino acid analogs, fatty acids and analogs including different forms of conjugated linoleic acid, minerals and mineral conjugates, insect hormones, caffeine, plant extracts, and extracts from over-the-counter supplements, and were obtained by key manufacturers in a form that would be commercially available. The compounds were sterilized and then exposed to myogenic satellite cell cultures at different levels (ranging from toxic to physiologic) to ascertain if there would be an effect. The results suggested that exposure of satellite cells to only a few compounds resulted in any measurable effect(s). Ten compounds elicited increases in proliferation, and four compounds promoted increases in differentiation. These results suggest avenues for the exploration of enhancing muscle stem cell activity of interest for muscle wasting disorders, sarcopenia of aging and physical performance.
Uncontrolled or sustained inflammation is the underlying cause of or actively contributes to the progression of many chronic pathologies such as atherosclerosis, arthritis, or neuroinflammatory diseases. Matricellular proteins of the CCN family (CYR61/CTGF/NOV) have emerged as localized multitasking signal integrators. These structurally conserved secreted proteins specifically interact with and signal through various extracellular partners, in particular integrins, which enable them to play crucial roles in various processes including development, angiogenesis, wound healing and diseases such as fibrosis, vascular disease and cancer. In this review, we discuss the possibility that the CCN family members could represent a putative new class of modulators of inflammation. In this context, we focused on their relationship with cytokines and chemokines. In vitro, CCN expression is finely regulated by diverse inflammatory mediators including cytokines (TNFα, IL1β, TGF-β), small factors such as prostaglandins, nitric oxide, histamine and serotonin, and extracellular matrix enzymes. In addition, CCN proteins acting alone or in concert with their specific partners appear to be potent regulators of the production of cytokines and chemokines in a context-dependent manner. Finally, emerging studies suggest a potential role for CCN proteins in chronic inflammatory diseases such as atherosclerosis, rheumatoid arthritis, inflammatory kidney diseases and neuroinflammatory pathologies such as Alzheimer's disease. CCN members could therefore represent new potential therapeutic targets for drug development against such diseases.
Obesity is an increasingly important health problem for both man and dog. Osteoarthritis (OA) is a significant cause of pain and disability in both species. A link between obesity and OA has been established in man, though the exact mechanism of the relationship remains to be fully elucidated - current research supports both biomechanical and biochemical theories. There is good evidence (class I*) to support weight loss as an effective treatment for human knee OA. In the dog, the relationship is just beginning to be investigated. The results of one study in dogs (class IV evidence*) suggest that preventing the development of overweightness and obesity reduces the prevalence of hip dysplasia and OA of the hip and other joints. Three other studies (class III and IV evidence*) support weight loss as an effective treatment for OA in affected overweight and obese dogs. Further research could yield greater understanding of the pathophysiology of this relationship, perhaps identifying novel therapeutic targets. Confirmation and better understanding of the positive effect of treating and preventing obesity on symptoms and prevalence of OA is likely to be valuable in the campaign against canine obesity.
Interleukin 8 (IL-8) is a recently described cytokine that functions as a potent neutrophil chemoattractant and activator. We sought to examine the link between the generation of reactive oxygen intermediates (ROI) and the regulation of IL-8 gene expression to specifically test the hypothesis that ROI would induce production of IL-8 mRNA and protein. In lipopolysaccharide-stimulated human whole blood, the OH radical scavenger dimethyl sulfoxide (Me2SO) dramatically inhibited (approximately 90%) IL-8 production, but had minimal effects on the production of tumor necrosis factor, interleukin 1 beta (IL-1), and IL-6. To determine whether NADPH-oxidase-generated free radicals were critical in the regulation of IL-8, studies were performed using blood from patients with chronic granulomatous disease. In both normal individuals and patients with chronic granulomatous disease, production of IL-8 could be initiated with lipopolysaccharide, phytohemagglutinin, or aggregated immune complexes, and this production could be inhibited by Me2SO (1% v/v). To examine if oxidant stress represents a ubiquitous mechanism for the induction of IL-8, experiments were performed in cultured cell lines. In the human hepatoma cell line Hep-G2, Me2SO dose-dependently inhibited tumor necrosis factor-stimulated IL-8 production, with a 74 +/- 1% reduction observed at a Me2SO concentration of 1%. Direct exposure to ROI demonstrated that H2O2 stimulated IL-8 production in a dose-dependent manner in Hep-G2 cells, A549 pulmonary type II epithelial cells, and human skin fibroblasts; this induction could be prevented by addition of catalase. The production of IL-8 appeared to be specific to an oxidant stress since exposure of the cells to heat shock or chemical stress did not induce expression of IL-8. These studies demonstrate that oxidant stress is an important regulator of IL-8 gene expression and support the hypothesis that low levels of ROI may serve to initiate IL-8 production which then serves to recruit neutrophils to sites of inflammation.
In this paper various aspects of animal pain and methods for its assessment are considered. The responses of lambs and calves to castration and of lambs to tail docking are used to illustrate quantitative approaches to the recognition and assessment of acute pain in farm animals. the validation of physiological and behavioral measurements for assessment of pain is examined by relating measurements made from young lambs, after a range of treatments, to an independent ranking of the order of severity of the treatments.
NSAIDs are the most widely used analgesics in veterinary medicine, and all have some toxic potential. The most common adverse class effects are gastrointestinal, renal, hepatic, and coagulation disorders. When treating chronic pain associated with osteoarthritis, the effectiveness of NSAIDs can be enhanced by physical therapy, use of chondroprotective agents, certain adjunctive drugs, and diet and exercise to control weight. To treat acute perioperative pain, NSAIDs are more effective when used preemptively, in the context of balanced (multimodal) analgesia, and in well-hydrated patients with normal blood pressure and renal function. Screening and monitoring to identify high-risk candidates for NSAID treatment should include a physical examination and patient history, identification of preexisting diseases or conditions, obtaining baseline and periodic hematologic and clinical chemistry values, and ensuring that other NSAIDs or contraindicated drugs are not used concurrently. When switching a patient from one NSAID to another (when no side effects have been seen), a washout period of 5 to 7 days minimizes chances for adverse drug interactions. Informing clients of the potential adverse effects of NSAID therapy and signs of NSAID toxicity greatly increases the likelihood of safe use of this class of drugs.
HUMANOFORT is a nutritive supplement extracted and purified from embryonated chicken eggs according to an original procedure under licence. Humanofort received the suitable consent from the Romanian Ministry of Health. The main components of Humanofort are two oligopeptides of 5,000 and 10,000 D molecular weight. 40 subjects aged 50-75 years (18 men and 22 women) consumed, daily, 4 caps of Humanofort for 60 days. The samples of blood from each subject were obtained before and after treatment. Therefore, each subject was his own control. In all subjects, after treatment, total cholesterol and LDL-cholesterol decreased approximately 30% as compared with the initial values. In 80% of patients, an increase of HDL cholesterol and a decrease of the insulin level in blood were also observed. After treatment, the cardiac risk factors (Aethna 2000 Program), such as total cholesterol/HDL and Apolipoproteins B/A were shifted towards lower range. These long-lasting modifications have an adaptative-regulatory character and seem to be produced by the growth factors contained in Humanofort.
Insulin-like growth factor II (IGF-II) plays a key role in mammalian growth, influencing foetal cell division and differentiation and possibly metabolic regulation. The mature 67 amino acid peptide shares sequence homology with both insulin and IGF-I. The liver is the main endocrine source of IGFs, but autocrine/paracrine activity is found in most tissues. The type 1 receptor mediates most of the biological effects of IGF-I and IGF-II; the type 2 receptor is involved with IGF-II degradation. Binding proteins may both localise IGFs to the receptors and regulate their activities. The IGF2 gene is maternally imprinted in mouse and human. Relaxation of IGF2 imprinting occurs in the Beckwith–Wiedemann syndrome of somatic overgrowth, sporadic Wilms' tumour and a number of other cancers. In the general adult population, the IGF2-INS gene cluster may also influence body weight, in which case IGF-II function could become a target for therapeutic intervention in obesity.
The aim of this systematic review was to identify, assess, and critically evaluate the quality of evidence of nonsteroidal anti-inflammatory drug (NSAID)-induced adverse effects in dogs. Original prospective studies published in peer-reviewed journals in English (1990-2012) that reported data on the safety of NSAIDs administration in dogs were searched. For each study, design type (I, II, III, or IV) and assessment of quality (+, Ø, -) were rated. For each drug, quantity and consistency rating (***, **, *) and strength of evidence (high, moderate, low, or extremely low) were identified and evaluated. The strength of evidence was defined in terms of how applicable and relevant the conclusions were to the target population. Sixty-four studies met the inclusion criteria. Thirty-five (55%) research studies and 29 (45%) clinical trials were identified. A high strength of evidence existed for carprofen, firocoxib, and meloxicam; moderate for deracoxib, ketoprofen, and robenacoxib; and low for etodolac. Quality and consistency rating were as follows: carprofen (***/***), deracoxib (**/***), etodolac (*/unable to rate), firocoxib (***/**), ketoprofen (**/***), meloxicam (***/***), and robenacoxib (**/**), respectively. Adverse effects were detected in 35 studies (55%) and commonly included vomiting, diarrhea, and anorexia. Three studies (5%) reported a power analysis related to adverse effects of ≥80%. In randomized, placebo-controlled, blinded studies (n = 25, 39%), the incidence of adverse effects was not statistically different between treated and control dogs. Finally, most studies were not appropriately designed to determine the safety of NSAIDs, and involved a healthy nongeriatric population of research dogs.
Objectives To discuss the clinical pharmacology of currently licensed veterinary NSAIDs and to review gastrointestinal and renal adverse effects as well as drug-drug interactions that have been reported with these drugs. To review the use of NSAIDs in the peri-operative setting and their use in patients with osteoarthritis. To further review the reported effects of NSAIDs on canine articular cartilage and liver as well as the clinical relevance of a washout period.
Databases used PubMed, CAB abstracts and Google Scholar using dog, dogs, nonsteroidal anti-inflammatory drugs and NSAID(s) as keywords.
Conclusions A good understanding of the mechanisms by which NSAIDs elicit their analgesic effect is essential in order to minimize adverse effects and drug-drug interactions. Cyclooxygenase (COX) is present in at least two active isoforms in the body and is the primary pharmacologic target of NSAIDs. Inhibition of COX is associated with the analgesic effects of NSAIDs. COX is present in the gastrointestinal tract and kidneys, along with other areas of the body, and is also the likely reason for many adverse effects including gastrointestinal and renal adverse effects. The newer veterinary approved NSAIDs have a lower frequency of gastrointestinal adverse effects in dogs compared to drugs such as aspirin, ketoprofen and flunixin, which may be due to differential effects on the COX isoforms. There are currently no published reports demonstrating that the newer NSAIDs are associated with fewer renal or hepatic adverse effects in dogs. NSAIDs remain the cornerstone of oral therapy for osteoarthritis unless contraindicated by intolerance, concurrent therapies or underlying medical conditions. NSAIDs are also effective and frequently used for the management of post-operative pain.
To refine and test construct validity and reliability of a composite pain scale for use in assessing acute postoperative pain in cats undergoing ovariohysterectomy.
40 cats that underwent ovariohysterectomy in a previous study.
In a previous randomized, double-blind, placebo-controlled study, a composite pain scale was developed to assess postoperative pain in cats that received a placebo or an analgesic (tramadol, vedaprofen, or tramadol-vedaprofen combination). In the present study, the scale was refined via item analysis (distribution frequency and occurrence), a nonparametric ANOVA, and item-to-total score correlation. Construct validity was assessed via factor analysis and known-groups discrimination, and reliability was measured by assessing internal consistency.
Respiratory rate and respiratory pattern were rejected after item analysis. Factor analysis resulted in 5 dimensions (F1 [psychomotor change], posture, comfort, activity, mental status, and miscellaneous behaviors; F2 [protection of wound area], reaction to palpation of the surgical wound and palpation of the abdomen and flank; F3 [physiologic variables], systolic arterial blood pressure and appetite; F4 [vocal expression of pain], vocalization; and F5 [heart rate]). Internal consistency was excellent for the overall scale and for F1, F2, and F3; very good for F4; and unacceptable for F5. Except for heart rate, the identified factors and scale total score could be used to detect differences between the analgesic and placebo groups and differences among the analgesic treatments.
Results provided initial evidence of construct validity and reliability of a multidimensional composite tool for use in assessing acute postoperative pain in cats undergoing ovariohysterectomy.
Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently involved groups of medicines in hypersensitivity drug reactions. Two mechanisms can induce the reaction: immunological (sensitization) due to a specific IgE or T cell response and pharmacological (cyclooxygenase inhibition). The contribution of each of these mechanisms to the reactions is not well known.
To analyse a large group of subjects with confirmed hypersensitivity reactions to NSAIDs.
The drugs involved, the clinical entities induced and the time interval between drug intake and appearance of the reaction were studied. In cases where the diagnosis was not confirmed, a drug provocation test was carried out. Atopy status was also assessed with prick test and total IgE in serum.
A total of 659 patients were finally considered to have had hypersensitivity reactions to NSAIDs; 76% had cross-intolerance (CI) and 24% were selective responders (SR). The most important drugs involved in CI were propionic acid derivatives, in most cases ibuprofen, and in SR pyrazolones. In CI, the most frequent clinical entity was urticaria and angio-oedema and to a lesser extent airway involvement. The skin and airways were both involved in an important proportion of cases. The most frequent entities in SR were urticaria and/or angio-oedema followed by anaphylaxis. Atopy was significantly associated in the CI group (P<0.005).
Cutaneous hypersensitivity reactions by CI to NSAIDs are the most frequent entities induced by these compounds. In addition to aspirin, other NSAIDs are taking on a predominant role. Atopy can be a predisposing factor in patients with CI.
To describe the clinical entities, underlying mechanisms and diagnostic approach of hypersensitivity reactions to corticosteroids, emphasizing new data concerning hypersensitivity reactions to systemically administered corticosteroids.
Reactions after topical corticosteroid administration to the skin have been known for decades, appearing as an eczematous lesion and with diagnosis by patch testing. However, new data have appeared about cutaneous symptoms after inhaled and systemically administered corticosteroids. In fact, T-cell involvement in a generalized maculopapular exanthema induced by inhaled budesonide has recently been demonstrated by lymphocyte transformation tests. Moreover, T-cell involvement has also been shown in skin biopsies from a group of patients with urticaria and maculopapular exanthema after systemically administered corticosteroids, with detection of a significant increase in the expression of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), and a significant decrease in interleukin-4 and GATA-3 when samples obtained during the drug provocation test reaction were compared with samples from the resolution phase. In immediate allergic reactions to corticosteroids, an immunoglobulin E (IgE) response has recently been shown by skin testing, ImmunoCAP and basophil-activation tests.
Generalized cutaneous symptoms after corticosteroid administration occur with both IgE and T-cell involvement. Skin testing, in-vitro testing and drug provocation tests are useful diagnostic tools.
The study demonstrates the presence of oxidative stress (OS) in physiological conditions in sportsmen in competition and in elderly subjects over 65 years. The OS was estimated by measuring some biochemical parameters, such as peroxides, total antioxidants, uric acid and free SH groups in plasma and peroxides in urine. OS produces a significant increase of peroxides in plasma and urine and a decrease of plasma antioxidants and SH groups. The presence of OS suggests an increased formation of free radicals in young subjects in sporting competition, This increase is subsequently compensated by an increase of antioxidants. In old agers, this unbalance remains unchanged. The level of OS is higher in sportsmen during competition, but the subsequent compensation depends on the degree of training, individual adaptation, diet, etc. The administration of organic selenium partially compensates and decreases the intensity of OS. This study confirmed the hypothesis that in old agers the formation of free radicals increases in the ageing process and recommends the prevention of OS in young sportsmen by an adequate protection with antioxidants, such as organic selenium.
This study compared three methods of pain relief in dogs that had total ear canal ablation with lateral bulla osteotomy. The hypothesis was that systemic opioids with preoperative local nerve blocks would provide superior pain relief. Thirty-one dogs with chronic otitis externa were included in the study. Dogs were randomly assigned to one of three protocols: systemic opioids alone (10 dogs, group 1), systemic opioids with bupivacaine splash block (11 dogs, group 2), and systemic opioids with preoperative local bupivacaine nerve blocks (10 dogs, group 3). Twenty-one dogs had bilateral ear ablation and 10 had unilateral ablation. Pain was assessed preoperatively, at extubation, 2 hours postextubation, and 1 day postoperatively by a single observer blinded to the analgesic protocol used. Pain scores were not significantly different within or between groups, nor did unilateral versus bilateral ablation have a significant effect on the score. Mean scores were less than 3 (scale 1 to 5) for all groups at all observation times. Rough recoveries were noted in 30% of group 1 dogs, 0% of group 2, and 20% of group 3 dogs. Ninety-four percent of dogs were moderately to heavily sedated at extubation. Sixty percent of group 3 dogs remained moderately to heavily sedated 2 hours postextubation. Rectal temperature, pulse rate, respiratory rate, and postoperative change in serum cortisol levels were not significantly different between groups. Postoperative increase in blood glucose was significantly higher in groups 1 and 3 compared with preoperative levels. Twenty-three percent of the dogs required additional analgesia or tranquilization after surgery, as determined by the anesthetist; 1 dog in group 1, 2 in group 2, and 4 in group 3. Each of the three analgesic protocols provided similar pain relief in dogs undergoing total ear canal ablation.
To investigate the reliability of 3 scales used for assessment of pain in dogs.
Prospective study.
50 dogs that had surgery.
Dogs were allocated into 3 groups (group 1, 25 dogs assessed 1 hour after the end of surgery; group 2, 41 dogs assessed between 21 and 27 hours after the end of surgery; group 3, 16 dogs assessed on the day of surgery and on the subsequent day). Each dog was scored for pain 4 times by 3 (groups 1 and 3) or 4 (group 2) veterinarians, using all 3 scales (i.e. simple descriptive, numerical rating, and visual analogue) during each scoring period. Analysis of data was performed using ANOVA, log-linear modeling, calculation of reproducibility coefficients, and Cohen's kappa statistic.
Significant variability existed among observers for use of all 3 scales. Variability among observers and between observers and dogs accounted for 29 to 36% of the total variability (group 1, 36.1 and 32.3% and group 2, 35.1 and 29.7%, for visual analogue scale and numerical rating scale scores, respectively). Kappa statistic values calculated for data obtained by use of the simple descriptive scale indicated that agreement was fair for the observers (group 1, 0.244 to 0.299; group 2, 0.211 to 0.368; group 3, 0.233 to 0.321).
Analysis of pain score data in dogs must incorporate observer variability when more than 1 observer is used. Comparative analysis of data accrued from pain studies in various hospitals must account for this variability.
The insulin-like growth factor-I receptor (IGF-IR) mediates the biological actions of IGF-I and IGF-II. The IGFs play a critical role in promoting development, stimulating growth and organogenesis via mitogenic, antiapoptotic and chemotactic activity. Recent research has focused on the events that occur intracellularly upon receptor activation. Several pathways have been shown to be important. The insulin-receptor substrate (IRS), SHC, GRB2, CRKII and CRKL adaptor proteins have all been implicated in transmitting signals to the nucleus of the cell. This review outlines some of the signalling pathways believed to be important in converting IGF-IR activation into changes in cell behavior and metabolism.
Hundreds of thousands of animals are presented to US veterinarians annually for surgery or for evaluation of painful disease. This large population offers the opportunity for clinical research of both acute and chronic pain syndromes. Although there is growing interest by veterinary clinical specialists to explore the nature of animal pain and how best to treat it, this resource is relatively unknown to the pain research community. Computer-assisted collection of behavioral data has created new opportunities for characterizing the pain experience in animal species for the benefit of both animals and humans. This review describes the current state of veterinary clinical pain studies in dogs and an application of computer-assisted behavioral analysis.
Oxidative stress, IL-1alpha, and IL-8 are known to contribute to mucosal inflammation of the gastrointestinal tract. We examined the IL-8 response after brief exposure to hydrogen peroxide induced oxidative stress in CaCo-2 cells (a human colon carcinoma cell line) and in human intestinal epithelial cells. In addition, we examined whether exposure to oxidative stress, followed by IL-1alpha, could modulate IL-8 production. A transient up-regulation of IL-8 mRNA expression was observed after hydrogen peroxide treatment. Hydrogen peroxide induced oxidative stress was also observed to promote IL-8 secretion. Exposure to hydrogen peroxide, followed by IL-1alpha, enhanced IL-8 production over that achieved with IL-1alpha alone. Thus, oxidative stress and IL-1alpha were observed to cooperatively enhance IL-8 production.
Veterinary Pharmacovigilance: Adverse Reactions to Veterinary Medicinal Products is an in-depth examination of veterinary pharmacovigilance, looking at the scientific methodologies involved, the role of regulatory agencies and legislation, and the underpinning science. Edited by a renowned expert, with over 20 years experience in the field, it draws together the expertise of authors from around the world. Adverse drug reactions may become apparent in treated animal patients, in exposed users or as adverse effects on the environment. They may also manifest as excess drug residues in food of animal origin. As a consequence, legislation and regulatory approaches have developed to address these issues and to ensure monitoring of continued product safety and, where necessary, the use of regulatory actions. All of these aspects are covered by the term "pharmacovigilance". Veterinary pharmacovigilance is a rapidly growing discipline in both regulatory and scientific terms, and its importance can only increase as regulatory agencies across the globe seek to improve their hazard and risk assessment of marketed veterinary medicines by applying the techniques of post-marketing surveillance. Its roots include veterinary medicine, medicine, pharmacology, toxicology, pathology and, increasingly, ecotoxicity and environmental safety. This book will be fundamentally important reading for all involved in the field of veterinary pharmacovigilance including veterinarians, physicians, environmental scientists, regulators and those involved in drug development and market maintenance.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to control acute and chronic pain as well as to manage oncologic and neurologic diseases in human and veterinary patients. Despite ongoing research and efforts to improve the safety and efficacy of existing drugs, adverse effects such as gastrointestinal irritation, renal and hepatic toxicity, interference with hemostasis, and reproductive problems persist. The true incidence of NSAID-induced adverse effects in animals is unknown, but is likely underestimated, because cats and dogs may be more sensitive than humans to NSAIDs due to alterations in drug metabolism, absorption, and enterohepatic recirculation. NSAIDs produce both analgesia and toxic adverse effects primarily by inhibiting cyclooxygenase (COX), thereby decreasing the production of prostaglandins that signal inflammation and pain as well as mediate physiologic functions such as platelet aggregation, gastric protection, and electrolyte balance in the kidney. The presence of at least 2 COX isoforms may account for variability in NSAID efficacy and toxicity both within and among species. This paper reviews and evaluates the published literature on the safety, pharmacology, uses, and complications of a subclass of COX-1-sparing drugs, the coxibs, in veterinary medicine. Coxibs and other COX-1-sparing drugs provide a clinically useful improvement over traditional NSAIDs, but data are incomplete and more in vivo species-specific, target-tissue, and clinical studies are needed.
Osteoarthritis (OA) is a primarily non-inflammatory, degenerative joint disease characterized by progressive loss of articular cartilage, subchondral bone sclerosis, osteophyte formation, changes in the synovial membrane, and an increased volume of synovial fluid with reduced viscosity and hence changed lubrication properties. As OA is the most common type of arthritis and a leading cause of disability, there is a largely unmet medical need for disease-modifying and symptomatic treatment. Due to the localized nature of the disease, intraarticular (IA) drug injection is an attractive treatment approach for OA. The various glucocorticoid and hyaluronic acid (HA) formulations, which are currently available on the market for IA treatment, provide only short-term pain relief or/and often do not provide adequate pain relief. The available oral drugs for symptomatic treatment also have shortcomings, most notably side effects. Therefore, there is still a large unmet need for novel OA drugs, which provide effective long-term pain relief and/or have disease-modifying properties. To achieve long-term drug exposure, different established formulations such as suspensions and hydrogels, and also novel approaches such as lipid based formulations and nano- or microparticles are currently in development. The development of novel drugs in combination with new formulations for IA treatment of OA, represents a promising approach in this challenging area of research.
Ulcerative colitis is a chronic inflammatory disease of the gastrointestinal tract. Its etiology remains unclear, but it appears to result from a dysregulated immune response, with infiltration of phagocytic leukocytes into the mucosal interstitium. The production and release of reactive oxygen species by immune cells seems to play a crucial role in physiopathology of colitis. The aim of this work was to evaluate the effects of N-acetylcysteine (NAC) and deferoxamine (DFX) in the treatment of colitis induced by dextran sulfate sodium (DSS).
The effects of NAC and DRX on rats with DSS-induced colitis were determined by measuring intestinal parameters of oxidative stress and mitochondrial function, inflammatory response and bowel histopathological alterations.
DSS increased white blood cells count and NAC and DFX did not prevent this effect. However, DSS increased mitochondrial respiratory chain complex IV in colon of rats and NAC and DFX prevented this alteration. In addition, thiobarbituric acid reactive substances were increased in colon of DSS-treated rats. NAC and DFX, when taken together, prevented this effect. Complex II and succinate dehydrogenase were not affected by DSS, as protein carbonyl content.
It is speculated that NAC and DFX might be useful for treatment of colitis, but further research is necessary to clarify these effects.
Pain management in dogs and cats has undergone a dramatic evolution in the past decade. Current approaches focus on anticipation and prevention of pain, as well as both pharmacologic and non-pharmacologic management techniques. The veterinary team plays an essential role in educating pet owners about recognizing and managing pain in their pets.
Significant modifications of IGF-1 and cholesterol (total and LDL) were observed following the administration of an extract of embryonary peptides (EP) to old subjects for 60 days. For most of the subjects, due to the aging process, the initial values of the biochemical parameters were shifted towards pathological range. Following the administration of EP, the serum levels of IGF-1 and cholesterol (total and LDL) were shifted towards the physiological limits for their age. The most significant modifications towards physiological range were observed for subjects with high, initial levels of IGF-1, when the decrease was striking (1-2 orders of magnitude). For these subjects, significant modifications were observed simultaneously for cholesterol. The modifications induced following the administration of EP exhibit a regulatory feature, as they are dependent on the initial levels of these parameters. The action of EP on the levels of IGF-1 and cholesterol was significantly equal for both sexes, but the influence of EP was more clear-cut in men. In conclusion, our results support an implication of IGF-1 in the regulatory mechanisms of cholesterolemia in old subjects following the long-term administration of EP.
Clinical use of non-steroidal antiinfl ammatory agents (NSAIDs); the current position
- S Carmichael
CARMICHAEL, S.: Clinical use of non-steroidal antiinfl ammatory agents (NSAIDs); the current position.
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Lovak és kutyák orális kezelése glükózaminglikánnal
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HEITMANN, H. H.: Lovak és kutyák orális kezelése
glükózaminglikánnal. Magy. Állatorv. Lapja, 1995.
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Regulatory modifi cations of steroidogenesis following the administration of embryonary peptides
- G. -Olinescu Mihaescu
MIHAESCU, G. -OLINESCU, R. et al.: Regulatory
modifi cations of steroidogenesis following the
administration of embryonary peptides. Rom. J.
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Az IGF-1 és a rendszeres testedzés hatása az öregedés molekuláris folyamataira: a sirtuinek szerepe
- E Koltai
KOLTAI, E.: Az IGF-1 és a rendszeres testedzés
hatása az öregedés molekuláris folyamataira: a
sirtuinek szerepe. Doktori értekezés. http://tf.hu/
wp-content/uploads/2009/07/Dr.-Koltai-Erika-disszert%C3%A1ci%C3%B3.pdf.