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Ginkgo biloba Extract: A Novel Addition to Antipsoriasis Ammunition?

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Thesis
Le psoriasis est une maladie dans laquelle le pronostic vital n’est pas engagé. C’estpourquoi, la prise en charge de cette dermatose dépend de la qualité de vie dupatient. Nous abordons ici les différentes approches thérapeutiques : homéopathie,diététique, phytothérapie, aromathérapie mais également les produits cosmétiquesconseils. Cette thèse a pour but de présenter aux pharmaciens d’officine toutes lesoptions et les différents domaines auxquels ils ont accès afin de répondre au mieuxau besoin du patient psoriasique.
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Skin integrity is restored by a physiological process aimed at repairing the damaged tissues. The healing process proceeds in four phases: hemostasis, inflammation, proliferation and remodeling. Phytomedicine presents remedies, which possess significant pharmacological effects. It is popular amongst the general population in regions all over the world. Phytotherapeutic agents have been largely used for cutaneous wound healing. These include Aloe vera, mimosa, grape vine, Echinacea, chamomile, ginseng, green tea, jojoba, tea tree oil, rosemary, lemon, soybean, comfrey, papaya, oat, garlic, ginkgo, olive oil and ocimum. Phytotherapy may open new avenues for therapeutic intervention on cutaneous wounds. This article provides a review of the common beneficial medicinal plants in the management of skin wounds with an attempt to explain their mechanisms. © 2014 S. Karger AG, Basel.
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Macrophage migration inhibitory factor (MIF) is a critical immunoregulatory pluripotent cytokine. It has been re-evaluated as a proinflammatory cytokine, pituitary hormone and glucocorticoid-induced immunoregulatory protein. MIF exists in human epidermis, especially in the basal layer and also is expressed constitutively by monocytes/macrophages, T cells, B cells, endocrine, and epithelial cells. In the field of dermatology, MIF is believed to be a detrimental factor in inflammatory dermatological diseases including atopic dermatitis (AD), psoriasis, vitiligo, pemphigus vulgaris, bullous pemphigoid (BP), alopecia areata (AA) as well as other conditions such as photoaging, and photocarcinigenesis. The objective of this review is to gather and summarize MIF related disorders in dermatology and present valuable information for readers and researchers.
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Interleukin (IL)-1 is a pivotal proinflammatory cytokine consisting of two molecular species, IL-1α and IL-1β. Anakinra (Kineret), a recombinant human IL-1 receptor antagonist, is regarded as a biological agent which blocks the inflammatory effects of IL-1. The aim of this review was to search the literatures and summarizes in vivo, in vitro and human studies on anakinra uses in dermatological disorders. The results show that anakinra is currently used clinically for the treatment of a variety of skin conditions such as psoriasis, atopic dermatitis, photoagaing, melanoma, Schnitzler syndrome, pyoderma gangraenosum, PAPA syndrome, hidradenitis suppurativa, lamellar ichthyosis, Sweet's syndrome, panniculitis, Muckle-Wells syndrome, familial Mediterranean fever, SAPHO syndrome and other disorders. Notably, anakinra is expensive to produce and administer. Injection is the route of therapy and allergic reaction is most possible.
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Dyslipidemia is an independent risk factor of cardiovascular diseases. The statins are a milestone in the primary and second prevention of cardiovascular diseases and significantly improved its prognosis. Along with the long-term treatment with statins in combination with other hypolipidemic drugs or alone, its safety has attracted a particular attention in clinic, such as the elevation of transaminase and rhabdomyolysis, which have raised an idea of developing the other types of lipid-lowering agents from botanic materials. Traditional Chinese medicine (TCM) has been used in clinical practice for more than 2000 years in China and showed some beneficial effects for human health and many diseases. Recently, many studies demonstrated a favorable effect of TCM for treating dyslipidemia; however, its mechanism remains unclear or totally unknown. The progress and perspective of studies on dyslipidemia with single Chinese herb and its monomers or effective extracts during the past 10 years are discussed in the present review.
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Coronary heart disease (CHD) is the leading cause of death. As the main treatment of CHD, modern medicine has improved dramatically in recent years. Although researches of TCM and integrative medicine on CHD are witnessed encouraging progress in many respects, the role TCM playing in the prevention and treatment of CHD has been unprecedentedly challenged under such circumstance of the very fast development of modern medicine. In order to share mutual complementary advantages of TCM and western medicine, this review summarizes the relatively prominent researches of TCM and integrative medicine on CHD in recent years, and illuminates the issue of the orientation of the further research of integrative medicine on CHD, including (1) original innovation of TCM etiology and pathogenesis, (2) combination of disease and TCM syndrome, (3) biological basis of TCM syndrome of CHD, (4) clinical design and quality control of integrative medicine research, (5) herb-drug interaction, (6) difficulties and hot issues of modern medicine.
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Psoriasis is a common papulosquamous skin disease. The histopathology is characterized by epidermal hyperplasia and inflammation. Recent studies suggest that keratinocyte proliferation and inflammation in psoriasis are manifestations of the same underlying pathological process. Interleukin 6 (IL-6), a cytokine that is a major mediator of the host response to tissue injury and infection, is produced by both keratinocytes and leukocytes in culture. IL-6 expression was studied in psoriatic plaques by immunoperoxidase staining with two different polyclonal anti-recombinant IL-6 antisera and by in situ nucleic acid hybridization with IL-6 cRNA probes. Epidermal and dermal cells in active psoriatic plaques from 35 psoriasis patients stained heavily for IL-6 as compared with nonlesional skin and with plaques after treatment with antimetabolic and antiinflammatory agents. Absorption of the anti-recombinant IL-6 antisera with purified fibroblast-derived IL-6 or with recombinant IL-6, but not bovine serum albumin, removed the immunostaining. Increased levels of IL-6 were detected in the plasma of patients with active psoriasis (mean 3 ng/ml) by using two different bioassays. IL-6 production by proliferating keratinocytes was suggested by IL-6-specific immunostaining in cultured normal and psoriatic keratinocytes and by the detection of mRNA specific for IL-6 in psoriatic epidermis by in situ hybridization. IL-6 stimulated the proliferation of cultured, normal human keratinocytes as assessed by two different assays. Thus, IL-6 could directly contribute to the epidermal hyperplasia seen in psoriatic epithelium as well as affect the function of dermal inflammatory cells.
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Psoriasis is a chronic, inflammatory skin disorder, histologically characterized by epidermal hyperplasia, anomalous keratinocyte differentiation, angiogenesis, and by inflammatory cell infiltrate. Psoriasis has a significant impact on quality of life and is often associated with serious psychological effects. The use of biological agents is expanding worldwide as alternative treatment for chronic inflammatory diseases including psoriasis. The European Medicines Agency (EMEA) approved the use of Efalizumab, Etanercept, Infliximab and Adalimumab in the treatment of psoriasis on the basis of the positive findings obtained from well-designed clinical trials. The ongoing monitoring of tolerability and possible side-effects of these drugs has, however, recently lead to the EMEA suspending Efalizumab on the grounds that the possible risks of its use outweighed the benefits. Fifty-four patients treated with the two classes of biological drug (Efalizumab and anti-TNF-α) were studied. The choice of biological drug therapy was conditioned by the extent and seriousness of the disease and by the presence of concomitant pathologies. Nineteen patients presented adverse reactions, of which 9 necessitated interruption in treatment (6 Efalizumab and 3 anti-TNF-α). This work reports the adverse reactions to these biological therapies found in our patients along with a review of the literature concerning adverse reactions in psoriasis treatment. From our experience and basing ourselves on the literature reporting studies conducted in large centres, we feel that it is indispensable to continue monitoring any reactions during biological drug treatment. In this way, there is more likelihood of preventing, where possible, or better managing any reactions linked to the use of these drugs.
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Oxidized low-density lipoprotein (ox-LDL) causes endothelial dysfunction in part by decreasing the availability of endothelial nitric oxide (NO). Although HMG CoA reductase inhibitors restore endothelial function by reducing serum cholesterol levels, it is not known whether they can also directly upregulate endothelial NO synthase (ecNOS) activity. Human saphenous vein endothelial cells were treated with ox-LDL (50 microg/mL thiobarbituric acid reactive substances 12 to 16 nmol/mg) in the presence of HMG CoA reductase inhibitors simvastatin and lovastatin. In a time-dependent manner, ox-LDL decreased ecNOS mRNA and protein levels (91+/-4% and 67+/-8% reduction after 72 hours, respectively). Both simvastatin (1 micromol/L) and lovastatin (10 micromol/L) upregulated ecNOS expression by 3.8-fold and 3.6-fold, respectively, and completely prevented its downregulation by ox-LDL. These effects of simvastatin on ecNOS expression correlated with changes in ecNOS activity. Although L-mevalonate alone did not affect ecNOS expression, cotreatment with L-mevalonate completely reversed ecNOS upregulation by simvastatin. Actinomycin D studies revealed that simvastatin stabilized ecNOS mRNA (tau1/2, 43 versus 35 hours). Nuclear run-on assays and transient transfection studies with a -1.6 kb ecNOS promoter construct showed that simvastatin did not affect ecNOS gene transcription. Inhibition of endothelial HMG CoA reductase upregulates ecNOS expression predominantly by posttranscriptional mechanisms. These findings suggest that HMG CoA reductase inhibitors may have beneficial effects in atherosclerosis beyond that attributed to the lowering of serum cholesterol by increasing ecNOS activity.
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Tight junctions (TJ) are the topical most structure in epithelial and endothelial cells and play a key role in the control of permeability and prevention of tumour cell invasion of endothelium. In this study we examined the effects of a range of polyunsaturated fatty acids on the function of TJs and the expression of occludin, a key molecule in the TJs of the human vascular endothelial cell line, ECV304. Treatment of the endothelial cells with gamma linolenic acid, an anti-cancer PUFA, increased the transendothelial cell resistance (TER) and reduced the paracellular permeability to large molecules. The effects were seen without any changes in the viability of the endothelial cells. Occludin, a recently identified molecule, which plays a major role in tight junctions was up-regulated by this fatty acid as revealed by both Western blotting and immunofluorescence. Other fatty acids were also tested. Eicosapentaenoic acid (EPA) also exerted an up-regulatory effect, but LA and AA down-regulated the expression. We conclude that GLA and EPA which also have other anti-cancer effects, regulate the expression of occludin in endothelial cells and thus contribute to the modification of the TER of these cells.
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The 2 kidney, 1-clip (2K, 1C) model of hypertension was used to investigate the potential antihypertensive effect of a standardized leaf extract of Ginkgo biloba (EGb 761). Clipping of the renal artery resulted in gradual elevation of the systolic blood pressure (SBP) reaching a plateau after 4 weeks of surgery. Treatment of hypertensive rats with EGb 761 (60, 90, 180 mg/kg/day orally) was therefore started 4 weeks after surgery and continued for 3 weeks. This led to a dose-dependent reduction in SBP with no significant change in heart rate. Control hypertensive rats showed a significant elevation of total protein thiols (Pr-SHs level) in both clipped and non-clipped kidneys as well as in the serum. However, glutathione peroxidase (GSH-Px) activity was decreased in the clipped kidneys but elevated in the non-clipped ones and in the blood. The malondialdehyde (MDA) level was raised in clipped kidneys but not in non-clipped ones nor in the serum. Nitric oxide (NO level) and angiotensin converting enzyme (ACE) activity were increased in both clipped and non-clipped kidneys but not in the serum. Endothelium-dependent and -independent relaxation of aortic rings towards acetylcholine (Ach) and sodium nitroprusside (SNP) were impaired. Treatment with EGb 761 (180 mg/kg/day for 3 weeks) was associated with recovery of GSH-Px activity in clipped kidneys, inhibition of ACE activity in both kidneys and a reduction in the elevated NO level of the non-clipped kidneys, decreased responsiveness to the vasoconstrictor NE and improvement of endothelial function as evidenced by restoration of endothelium-dependent vasorelaxation induced by Ach. The observed beneficial effects of the EGb 761 may be attributed to different factors, including ACE inhibition and maintenance of cellular antioxidant capacity as well as preserving vascular reactivity towards endothelium-dependent and -independent vasodilators while inhibiting responses to vasoconstrictors.
Article
Gentamicin is an effective and powerful antibiotic. Extended use or excessive dosages of which can result in irreversible damage to the inner ear. The development of otoprotective strategies is a primary and urgent goal in research of gentamicin ototoxicity. Ginkgo biloba leaves and their extracts are among the most widely used herbal products and/or dietary supplements in the world. We investigated the protection of EGb 761 (a standardized preparation of EGb) on gentamicin ototoxicity and the involvement of reactive oxygen species (ROS) and nitric oxide (NO)-related mechanisms using in vitro organ cultures and an in vivo animal model. Gentamicin induced hair cell damage in cochlear cultures that could be prevented by EGb 761. EGb 761 also significantly reduced gentamicin-induced ROS and NO production. Furthermore, EGb 761 inhibited cellular apoptosis in cultured cochleae treated with gentamicin. In guinea pigs with gentamicin application onto the round window membrane, the mean auditory brain stem response threshold, ratio of cochlear hair cell damage and apoptosis were significantly elevated compared with those in the control group, and this could be prevented by oral administration of EGb 761. Individual EGb 761 components quercetin, bilobalide, ginkgolide A and ginkgolide B, but not kaempferol, significantly prevented gentamicin-induced hair cell damage. These results indicate that EGb 761 has a protective effect against gentamicin ototoxicity through a reduction in the formation of ROS and NO and subsequent inhibition of hair cell apoptosis in the cochlea.
Article
Psoriasis is a chronic inflammatory skin disease associated with abnormal vascular expansion in the papillary dermis. Tumour necrosis factor (TNF)-α is a proinflammatory cytokine that can induce antiapoptotic proteins and endothelial cell activation factors in psoriasis. The present study investigated the effect of the anti-TNF-α agent etanercept on the expression of endothelial nuclear factor-κB (NF-κB), angiogenic vascular endothelial growth factor (VEGF), endothelial cell marker CD31, antiangiogenic factor thrombospondin-1 (TSP-1), and antiapoptotic factors Bcl-2 and Bcl-xL in psoriasis. Sixteen patients with moderate-to-severe psoriasis were included in the study and treated with etanercept 50 mg twice weekly subcutaneously for 12 weeks. Biopsies of lesional skin (baseline, weeks 3, 6 and 10) were obtained and immunohistochemically stained with antibodies for CD31, VEGF, TSP-1, NF-κB, Bcl-2 and Bcl-xL. Double immunofluorescence staining for VEGF and CD31 was evaluated with confocal laser microscopy. The terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) assay was applied for apoptosis detection. Etanercept caused a statistically significant time-dependent reduction in the number of dermal blood vessels, the number of CD31+ cells and VEGF in psoriatic lesions, with induction of endothelial cell apoptosis and statistically significant upregulation of TSP-1 in psoriatic vessels. Immunohistochemical analysis showed significant reduction of NF-κB, Bcl-2 and Bcl-xL expression in endothelial cells during treatment. These changes were accompanied by a marked clinical response. The present findings suggest that treatment with etanercept induces apoptosis, reduces apoptosis-inhibiting factors in psoriatic endothelial cells, and decreases angiogenesis in psoriatic skin.
Article
To evaluate the effect of Xuezhikang Capsule on the serum levels of inflammatory factors such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in patients with nonalcoholic fatty liver disease (NAFLD) and hyperlipidemia, and to explore whether it has anti-inflammatory effect. A total of 84 patients were randomly assigned to two groups with stratified block randomization, the treatment group (42 cases) and the control group (42 cases). They were treated with Xuezhikang Capsule and polyene phosphatidylcholine capsule for twenty-four weeks, respectively. The changes in serum TNF-alpha and IL-6 were measured by enzyme linked immunosorbent assay before treatment and at the 12th and 24th week. Compared with those before treatment, the serum levels of TNF-alpha and IL-6 significantly decreased in both groups after treatment (P<0.01). There was no significant change between the two groups for the treatments at different time points (P>0.05) and between the two groups for treatments at the same time points (P>0.05). Xuezhikang Capsule can inhibit the serum inflammatory factor in patients with NAFLD and hyperlipidemia.
Article
To observe the effect of combined therapy with Xuezhikang Capsule (XZK) and Valsartan on left ventricular hypertrophy (LVH) and heart rate turbulence (HRT) in hypertensive patients. Ninety primary hypertensive patients with LVH were randomly assigned to three groups. Basic treatment, including aspirin, beta-blockers, calcium antagonists, etc. were administered to all patients. Additionally, Valsartan (VS, 80 mg once a day) was given to the 30 patients in the VS group. Valsartan (in the same dosage) and XZK (600 mg, twice a day) were given to the 32 patients in the Chinese medicine (CM) group, while none was given to the 28 patients in the control group. The therapeutic course lasted for 24 months. Changes in left ventricular mass index (LVMI) measured by cardiac ultrasonic indices, HRT parameters, including the original heart rate (TO) and slope coeffificient (TS), systolic and diastolic blood pressures (SBP and DBP), as well as blood cholesterol level (TC) were measured before and after treatment. After treatment, TO and LVMI were lowered, while TS increased in both the VS group and the CM group (P<0.01), but changed insignificantly in the control group. Significant differences between the CM group and the control group were shown in terms of TO, LVMI, SBP, DBP and TS (P<0.01); and between the CM group and the VS group in terms of TO, LVMI and TS (P<0.01). Moreover, HRT parameters showed an evident correlation with LVMI (r=0.519-0.635, P<0.01). Combined therapy with XZK and Valsartan can improve hypertensive LVH and HRT parameters, and lessen the damage on the autonomous nervous system.
Article
“Polypill” describes a fixed dose combination pill containing several components designed to lower several cardiovascular risk factors simultaneously.1 For people who have had a cardiovascular disease event or related disorders such as angina pectoris, combination treatment has been practised for many years, although apart from the use of aspirin there has been a tendency to treat each risk factor rather than the overall risk of the disease. For example, until recently statins have been prescribed only if serum cholesterol is raised.2 3 4 Blood pressure lowering drugs are given only if a diagnosis of hypertension has been made.2 4 5 6 7 This is inappropriate and leads to many people not receiving preventive treatment who could benefit from receiving such treatment. The basis for preventing clinical cardiovascular disease with a combination of agents that reduce causal risk factors is that, within the range of values of these risk factors in the population, there is no threshold below which a reduction in risk factor ceases to confer a reduction in risk. Indeed, cohort (prospective observational) studies show that blood pressure and cholesterol exhibit a linear relation between the level of the risk factor and the risk of the disease when the risk of the disease is plotted on a proportional (that is, logarithmic) scale.8 9 10 11 12 This relation has great clinical significance, because it shows that for given changes in the risk factor there is a constant proportional change in the risk of disease. So, for example, a reduction of 1 mmol/l in low-density lipoprotein (LDL) cholesterol is associated with an approximate 40% reduction in the risk of having an ischaemic heart disease (IHD) event,13 and a 10 mm Hg decrease in diastolic blood pressure is associated with an approximate 60% decrease in risk of …
Article
The anti-inflammatory and antioxidant effects of epigallocatechin-3-gallate (EGCG) are considered important forces in attenuate liver injury and fibrosis. The aim of the study was to investigate the effect of EGCG on the expression of fibrogenic factors and whether EGCG attenuates the severity of oxidative stress and inflammatory response in chronic liver injury. Mice were administered with CCl(4) together with or without EGCG for 8 weeks (n=6-8 per group). Histopathological and biochemical analyses were carried out. The mRNA expression levels of TNF-alpha, COX-2, iNOS, alpha-smooth muscle actin (alpha-SMA), transforming growth factor (TGF-beta(1)), pro-collagen-I, matrix metalloproteinases (MMP-2, -9) and their inhibitors (TIMP-1, -2) were determined by RT-PCR. The collagen deposited in the liver was detected by Sirius Red staining. The formation of nitrotyrosine was measured as a marker of oxidative stress. The activity level of NF-kappaB and the expression level of C/EBP were also assessed. Chronic CCl(4) treatment caused liver injury, oxidative stress and nitrosative stress, and collagen accumulation in the liver. The expression levels of pro-inflammatory and pro-fibrotic mediators and the activity of NF-kappaB were increased. Treatment with EGCG significantly reduced liver injury, oxidative stress and the inflammatory response. EGCG also significantly reduced the formation of collagen in the liver, the expression of alpha-SMA and all of the assayed pro-fibrogenic markers except TIMP-2 and MMP-9. EGCG significantly attenuated the severity of CCl(4)-induced liver injury and the progression of liver fibrosis. The protective effect of EGCG may in part be a consequence of the reduction in oxidative stress and the pro-inflammatory response.
Article
In vitro and animal studies have suggested that soy protein and isoflavones have favorable effects on glucose and insulin regulation, but intervention studies in humans are limited, and the results are controversial. We investigated whether soy protein with isoflavones and soy isoflavone extracts could improve glycemic control and insulin sensitivity in postmenopausal women with early hyperglycemia. This was a randomized, double-blind, placebo-controlled trial that included 180 postmenopausal Hong Kong Chinese women with prediabetes or early untreated diabetes. After a 2-wk adaptation period, participants were randomly assigned to 1 of 3 arms to receive 15 g soy protein and 100 mg isoflavones, 15 g milk protein and 100 mg isoflavones, or 15 g milk protein on a daily basis for 6 mo. Three- or 6-mo treatments with soy protein with or without isoflavone supplementation did not result in favorable changes in the descriptors for glycemic control and insulin resistance, namely fasting and 2-h postload glucose, fasting and postload insulin, glycated serum protein, and homeostasis model assessment for insulin resistance and beta-cell function. This 6-mo randomized controlled trial did not support the hypothesis that soy protein with or without isoflavone supplementation had favorable effects on glycemic control and insulin sensitivity among postmenopausal Chinese women. The favorable change in postload glucose needs to be further confirmed.
Article
Atrial fibrillation (AF) is a common cardiac arrhythmia. Regular fish consumption has been shown to reduce the risk of AF in some but not all studies. Long-chain n-3 polyunsaturated fatty acids (PUFAs) from fish have been suggested to account for these beneficial effects. We tested this hypothesis by studying the association between the serum long-chain n-3 PUFAs eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid and risk of AF in men. A total of 2174 men from the prospective population-based Kuopio Ischemic Heart Disease Risk Factor Study, 42 to 60 years old and free of AF at baseline in 1984 to 1989, were studied. During the average follow-up time of 17.7 years, 240 AF events occurred. In the Cox proportional hazards model, the multivariable-adjusted hazard ratio in the highest (>5.33%) versus the lowest (<3.61%) quartile of eicosapentaenoic acid plus docosapentaenoic acid plus docosahexaenoic acid was 0.65 (95% confidence interval 0.44 to 0.96, P for trend=0.07). Evaluated individually, only serum docosahexaenoic acid was associated with the risk of AF (hazard ratio in the highest versus the lowest quartile 0.62, 95% confidence interval 0.42 to 0.92, P for trend=0.02). Exclusion of subjects (n=233) with myocardial infarction or congestive heart failure either at baseline or that preceded the AF event during follow-up slightly strengthened the associations. Serum intermediate chain-length n-3 PUFA, alpha-linolenic acid, or hair methylmercury concentration were not associated with the risk. An increased concentration of long-chain n-3 PUFAs in serum, a marker of fish or fish oil consumption, may protect against AF. Serum docosahexaenoic acid concentration had the greatest impact.
Article
To investigate the impacts of Xuezhikang (XZK) or pravastatin combined with antihypertensive drugs on circulating endothelial progenitor cells (CEPCs) in essential hypertensive (EH) patients. Eighty-eight EH patients were enrolled into the study and randomly assigned to the antihypertensive drug treatment group (ATH group, 29 cases), the pravastatin treatment group (PRA group, 29 cases) and the Xuezhikang treatment group (XZK group, 30 cases). Patients in the 3 groups were treated with routine antihypertensive drugs. In addition, pravastatin and Xuezhikang were given to the patients in the PRA group and XZK group, respectively. After an eight-week treatment, CEPCs were counted using a laser scanning confocal microscope, and their proliferation function was evaluated by the MTT colorimetric assay and the adherent cell number was counted to estimate the adhesion function. After the treatment, CEPCs in the PRA group (116.60+/-5.70) and XZK group (114.40+/-6.55) was significantly higher than that in the ATH group (88.00+/-6.32, P<0.01). CEPCs proliferation capability and the adhesion function in the PRA group (0.406+/-0.016, 33.60+/-4.26) and XZK group (0.415+/-0.018, 34.30+/-3.77) were obviously superior to those in the ATH group (0.333+/-0.021, P<0.01; 23.30+/-3.19, P<0.01). No significant difference was found between the pravastatin group and the XZK group. Combined use of XZK or pravastatin with the anti-hypertensive therapy could increase the CEPCs number and improve their function in EH patients with the blood pressure controlled by antihypertensive drugs, leading to benefits independent of pressure-lowering effects.
Article
Triglyceride (TG) levels can increase for numerous reasons, including a sedentary lifestyle, an unhealthy diet, especially one rich in refined carbohydrates, and comorbidities. According to the National Cholesterol Education Program (NCEP), the normal TG level is < 150 mg/dL. Patients with very high TG (VHTG) levels (> or = 500 mg/dL) should be promptly managed and treated to reach lipid treatment goals, as determined by the NCEP. Lowering TG levels is the primary management goal in these patients, while lowering low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol levels are secondary goals. Therapeutic lifestyle changes are often recommended initially for patients with elevated TGs; however, concomitant drug therapy is often required. Data show that intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can significantly decrease serum TGs, along with plasma concentrations of certain lipoproteins. Omega-3-acid ethyl esters are available by prescription or as dietary supplements. Clinical trials in adult patients with VHTGs show that four 1 g capsules of prescription omega-3 fatty acids, which contain 465 mg of EPA and 375 mg of DHA per capsule, can effectively decrease TG levels by up to 45%, and is generally well tolerated.
Article
Psoriasis is a chronic immune-mediated hyperproliferative inflammatory skin disease in which a cytokine network concept is well established. Skin is a major target of oxidative stress mainly due to reactive oxygen species (ROS) originating from the environment and skin metabolism itself. Although endogenous antioxidants attenuate the harmful effects of ROS, increased or prolonged presence of free radicals can override ROS defense mechanisms and mediate numerous cellular responses that contribute to the development of a variety of skin disorders, including psoriasis. Regarding psoriasis, antioxidant strategies have proven to be beneficial therapeutics. The cellular signaling pathways such as mitogen-activated protein kinase/activator protein 1, nuclear factor kappaB, and Janus kinase-signal transducers and activators of transcription are known to be redox sensitive and proven to be involved in the progress of psoriasis. This review summarizes the current knowledge of the role of the redox system in regulating these signaling pathways related to the pathogenesis of psoriasis.
Article
To investigate the benefits of long-term therapy with Xuezhikang, a cholestin extract, in combination with calcium channel blockers for improvement of left ventricular (LV) hypertrophy and function in patients with essential hypertension, as determined using echocardiography. Fifty-five (55) hypertensive patients with normal blood low-density lipoprotein cholesterol (LDL-C) levels were randomly assigned to the Xuezhikang group (n = 28, 1200 mg/d of Xuezhikang) or the placebo group (n = 27, matched placebo). All of the patients were treated with extended-release nifedipine (20 mg twice daily). Thirty (30) normotensive subjects, matched for age and gender, were selected as a control group. Conventional echocardiography and tissue Doppler imaging were used to measure the left ventricle (LV) wall thickness and LV diastolic function at weeks 0, 24, and 72 during the period of observation. The serum levels of lipids, carboxy-terminal propeptide of procollagen type I (PIP), and C-reactive protein (CRP) were determined as well. The hypertensive patients had significantly elevated PIP and CRP levels in serum, increased LV wall thickness, and impaired LV diastolic function compared with the normotensive subjects (0.01 < p < 0.05). Compared with the placebo group, the transmitral flow velocities (E/A ratio) (1.11 +/- 0.36 versus 0.85 +/- 0.24, p < 0.01) and the myocardial motion velocities (Em/Am ratio) at the septal mitral annulus (0.90 +/- 0.19 versus 0.70 +/- 0.18, p < 0.05) and the lateral mitral annulus (1.06 +/- 0.20 versus 0.86 +/- 0.14, p < 0.01) were significantly increased, while there was no significant change in the LV wall thickness after 72 weeks of therapy with Xuezhikang. The serum levels of PIP (0.43 +/- 0.13 ng/mL versus 0.51 +/- 0.20 ng/mL, p < 0.05) and CRP (0.32 +/- 0.13 mg/L versus 0.40 +/-0.17 mg/L, p < 0.05) were significantly reduced compared to placebo treatment. There was no significant correlation between changes in LV diastolic function and blood pressure or lipid profile with Xuezhikang therapy. Long-term therapy with Xuezhikang improved LV diastolic function, probably mediated through antifibrotic and anti-inflammatory effects and independent of blood pressure and lipid profiles in patients with essential hypertension.
Article
The cardioprotective effects of long-chain n-3 polyunsaturated fatty acids (PUFAs) and fish consumption have been observed. However, data on the specific associations of these dietary factors with inflammation and endothelial activation are sparse. A cross-sectional study was conducted of 5,677 men and women from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, including African Americans, Caucasians, Chinese, and Hispanics aged 45 to 84 years and free of clinical cardiovascular disease. Dietary information was collected using a self-administered food frequency questionnaire. Multivariate linear regression analyses were used to examine relations between the intake of long-chain n-3 PUFAs, nonfried fish, and fried fish and biomarkers of inflammation and endothelial activation. Long-chain n-3 PUFA intake was inversely associated with plasma concentrations of interleukin-6 (p = 0.01) and matrix metalloproteinase-3 (p = 0.03) independent of age, body mass index, physical activity, smoking, alcohol consumption, and dietary variables. Nonfried fish consumption was inversely related to C-reactive protein (p = 0.045) and interleukin-6 (p <0.01), and fried fish consumption was inversely related to soluble intercellular adhesion molecule-1 (p <0.01) but was not associated with other biomarkers after adjustment for potential confounders. In conclusion, the results of this study suggest that the dietary intake of long-chain n-3 PUFAs and fish is inversely associated with concentrations of some biomarkers, reflecting lower levels of inflammation and endothelial activation. These results may partially explain the cardioprotective effects of fish consumption.
Article
To investigate NF-kappaB and IkappaBalpha activities in HL-60 induced by TNF-alpha in order to understand the molecular mechanism of GbE in asthma treatment. The amount of IkappaBalpha in HL-60 cells stimulated by TNF-alpha and GbE was measured by western blotting. Plasmid pNF-kappaB-LuC was transfected and NF-kappaB activity was analyzed by measuring the expression level of luciferase. It showed in the luciferase assay that the activity of NF-kappaB could significantly be suppressed in HL-60 cells after the pretreatment with CGbE. However, the phosphorylation and subsequent degradation of IKBalpha induced by TNF-alpha can not be inhibited in HL-60 cells even we prolonged the treatment time or increased the concentration of GhE. GhE can suppress the NF-kappaB gene expression actively on independent of NIK/ IKK/ IkappaBalpha pathway in HL-60 cells.
Article
Selenium is a central determinant of antioxidative glutathione peroxidase 1 (GPx-1) expression and activity. The relevance of selenium supplementation on GPx-1 in coronary artery disease (CAD) needs to be established. We assessed the effect of selenium supplementation on GPx-1 in cell culture and on endothelial function in a prospective clinical trial. Human coronary artery endothelial cells were incubated with 5.78 to 578 nmol/L sodium selenite, Se-methyl-selenocysteine hydrochloride, or seleno-l-methionine. Glutathione peroxidase 1 mRNA and protein expression and activity were measured. Coronary artery disease patients (n = 465) with impaired endothelial function (flow-mediated dilation [FMD] <8%) were randomly assigned to receive 200 or 500 microg sodium selenite daily or matching placebo during a 12-week period. We tested the effect on red blood cell GPx-1 activity and brachial artery FMD. Furthermore, differences in biomarkers of oxidative stress and inflammation were measured. Sodium selenite and Se-methyl-selenocysteine hydrochloride increased GPx-1 protein and activity in a dose-dependent manner (P < .0001). The intention-to-treat groups comprised 433 CAD patients. Glutathione peroxidase 1 activity increased from 37.0 U/gHb (31.3-41.7) to 41.1 U/gHb (35.2-48.4) (P < .0001) in the 200 microg and from 38.1 U/gHb (33.2-43.8) to 42.6 U/gHb (35.0-49.1) (P < .0001) in the 500 microg sodium selenite group treated for 12-weeks. No relevant changes were observed for FMD or biomarkers of oxidative stress and inflammation. Sodium selenite supplementation increases GPx-1 activity in endothelial cells and in CAD patients. Future studies have to demonstrate whether long-term CAD outcome can be improved.
Article
Combination therapy for the treatment of dyslipidemia and reduction of cardiovascular risk has been demonstrated to beneficially modify the lipid profile in multiple randomized clinical trials. As reported in the updated National Cholesterol Education Program Adult Treatment Panel III guidelines, low-density lipoprotein (LDL) cholesterol remains the primary treatment target, although the comprehensive management of dyslipidemia in high-risk patients includes the modification of secondary lipid parameters such as triglycerides, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol. Although statin therapy is the standard intervention for lowering LDL cholesterol, combination therapy has demonstrated added benefits on secondary lipid parameters and enhances statin-mediated reductions in LDL cholesterol. The benefits of modifying these secondary targets on all-cause or cardiovascular event-related mortality are currently under investigation in several clinical trials. Prescription omega-3 fatty acid (Lovaza) is a formulation of 2 highly purified omega-3-acid ethyl esters, eicosapentaenoic acid and docosahexaenoic acid. The recently completed Combination of Prescription Omega-3 With Simvastatin (COMBOS) study confirmed that prescription omega-3 fatty acid administered in combination with simvastatin achieves statistically significant improvements across a range of lipid indicators beyond the LDL primary target, including triglycerides, non-high-density lipoprotein cholesterol, and lipoprotein particle size. In conclusion, several classes of drugs, including omega-3 fatty acids, can be used in combination with statins to achieve more global improvements in lipid profiles.
Article
We studied the relation between diet, serum lipoproteins, and the progression of coronary lesions in 39 patients with stable angina pectoris in whom coronary arteriography had shown at least one vessel with 50 per cent obstruction before intervention. Intervention consisted of a two-year vegetarian diet that had a ratio of polyunsaturated to saturated fatty acids of at least 2 and that contained less than 100 mg of cholesterol per day. Dietary changes were associated with a significant increase in linoleic acid content of cholesteryl esters and a significant lowering of body weight, systolic blood pressure, serum total cholesterol, and the ratio of total to high-density lipoprotein (total/HDL) cholesterol. Angiographic examination was performed after 24 months; angiograms were assessed visually (with blinding) and by computer-assisted image analysis. Both types of assessment indicated progression of disease in 21 of 39 patients but no lesion growth in 18. Coronary lesion growth correlated with total/HDL cholesterol (r = 0.50, P = 0.001) but not with blood pressure, smoking status, alcohol intake, weight, or drug treatment. Disease progression was significant in patients who had values for total/HDL cholesterol that were higher than the median (greater than 6.9) throughout the trial period. No coronary-lesion growth was observed in patients who had lower values for total/HDL cholesterol (less than 6.9) throughout the trial or who initially had higher values (greater than 6.9) that were significantly lowered by dietary intervention.
Article
Dietary fish oils, which are rich in omega-3 fatty acids, have been reported to reduce plasma lipid levels in normolipidemic subjects. We examined the effects of fish oil in 20 hypertriglyceridemic patients: 10 with Type IIb hyperlipidemia and 10 with Type V. These patients were put on three diets differing primarily in fatty acid composition and fat content. The control diet contained a fatty acid mixture typical of a low-fat therapeutic diet (ratio of polyunsaturated to saturated fat, 1.4), the fish-oil diet contained omega-3 fatty acids, and the vegetable-oil diet was rich in the omega-6 fatty acid, linoleic acid. Each diet was followed for four weeks. In the Type IIb group, the fish-oil diet led to decreases in both plasma cholesterol (-27 per cent) and triglyceride (-64 per cent), as compared with the control diet. Very-low-density lipoproteins (VLDLs) were also reduced markedly. The vegetable-oil diet had much less effect. With fish oil, the Type V group had marked decreases in total cholesterol and triglyceride levels (-45 and -79 per cent, respectively). VLDL levels were dramatically lowered, as were apoprotein E levels. The vegetable-oil diet (unlike the fish-oil diet) produced a rapid and significant rise in plasma triglyceride levels. We conclude that fish oils and fish may be useful components of diets for the treatment of hypertriglyceridemia.
Article
It is well established that plant sterols are absorbed to a certain extent by all animal species. Evidence is available to show that the absorption of C28 sterol (campesterol) is higher than that of C29 sterol (β-sitosterol). This finding suggests that great caution should be exercised in extrapolating absorption values for plant sterols by using mixtures of plant sterols. Tissue distribution of absorbed plant sterols closely parallels that of cholesterol and both sterols are subjected to similar metabolic reactions. The sitosterols are catabolized to the same steroid hormones as those formed from cholesterol. The plant sterols are converted into bile acids in the animal liver. The nature of bile acids depends mostly on the ability of the species to dealkylate the extra methyl or ethyl group present in the side chain. The fact that absorbed plant sterols are catabolized to a variety of products in animal tissues suggests that further work should be directed toward the effects of these products in cholesterol metabolism. These studies might explain the "extra absorptive" effect of sitosterols on serum cholesterol. Further studies should be carried out to determine whether the distribution of plant sterols in subcellular fractions and plasma lipoproteins is similar to that of cholesterol. The potential use of plant sterols as injectable hypocholesteremic agents depends on the available knowledge concerning the metabolic fate and the effects of plant sterols and their oxidation products in the animal body.
Article
Although elevated plasma cholesterol levels represent a well-established and significant risk for developing atherosclerosis, there is a wide spectrum of cholesterol levels in patients with coronary artery disease (CAD). Most secondary prevention studies have generated convincing evidence that cholesterol reduction in patients with high cholesterol levels is associated with improved clinical outcome by reducing risk of further cardiovascular events. However, other risk factors may play a prominent role in the pathogenesis of coronary disease in the majority of patients with near-normal cholesterol values. The Cholesterol and Recurrent Events (CARE) study was designed to address whether the pharmacologic reduction of cholesterol levels with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, pravastatin, would reduce the sum of fatal coronary artery disease (CAD) and nonfatal myocardial infarction (MI) in patients who have survived an MI yet have a total cholesterol value < 240 mg/dl (< 6.2 mmol/liter). The other inclusion criteria for this study were age 21-75 years, low density lipoprotein (LDL) cholesterol levels of 115-174 mg/dl (3.0-4.5 mmol/liter), and fasting serum triglyceride levels < 350 mg/dl (< 4.0 mmol/liter). A total of 4,159 eligible consenting patients without other study exclusions were then randomly assigned to receive either pravastatin 40 mg daily or matching placebo in addition to their individualized conventional therapy. The trial was designed to have a median follow-up of 5 years. Study endpoints will be evaluated with respect to predefined subgroups according to baseline lipid values, age, gender, prior cardiovascular risk factors, and history.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
IL-10 is a cytokine produced by B and T-cells, monocytes and keratinocytes with pleiotropic effects, some of which are directed towards suppressing monocyte activities (anti-inflammatory cytokine). No information at the protein level is available concerning IL-10 in suction blister fluids from psoriatic skin, even if contrasting data have been reported on IL-10 mRNA of psoriatic biopsies and on the cytokine patterns of the T-cell clones, isolated from psoriatic skin. The IL-10 blister fluid concentrations in psoriatic lesions were compared to those found in the non-lesional skin of 14 patients effected with plaque-type psoriasis, and to those found in the skin of healthy controls (9 subjects sharing sex ratio and age with psoriatic patients). No difference in the IL-10 levels was found between non-lesional and control skin. In contrast, lower IL-10 levels were observed in blister fluids obtained from lesional psoriatic skin (p < 0.0005). The possible meanings of these results have been evaluated in the context of the mechanisms activating or maintaining the chronic inflammatory components of psoriasis.
Article
Serum lipid levels in rats with hyperlipidemia induced by diet as well as by Triton were determined after oral administration of EtOAc extract of Pterocarpus marsupium heartwood and its flavonoid constituents, marsupsin [1], pterosupin [2], and liquiritigenin [3]. Administration of EtOAc extract for 14 consecutive days produced a significant reduction of serum triglyceride, total cholesterol, and LDL- and VLDL-cholesterol levels without any significant effect on the level of HDL-cholesterol. Liquiritigenin and pterosupin were able to effect a significant fall in serum cholesterol, LDL-cholesterol, and atherogenic index, pterosupin being additionally effective in lowering serum triglyceride.
Article
Clinical recovery after central nervous system (CNS) trauma or ischemia may be limited by a neural injury process that is triggered and perpetuated at the cellular level, rather than by a lesion amenable to surgical repair. It is widely thought that one such process, a fundamental pathological mechanism initiated by CNS injury, is a disruption of cellular Ca2+ homeostasis. Because of the critical role of Ca2+ ions in regulating innumerable cellular functions, this major homeostatic disturbance is thought to trigger neuronal and axonal degeneration and produce clinical disability. We review those aspects of normal and pathological Ca2+ homeostasis in neurons that relate to neurodegeneration and to the application of neuroprotective strategies for the treatment of CNS injury. In particular, we examine the contribution of Ca(2+)-permeable ionic channels, Ca2+ pumps, intracellular Ca2+ stores, intracellular Ca2+ buffering systems, and the roles of secondary, Ca(2+)-dependent processes in neurodegeneration. A number of hypotheses linking Ca2+ ions and Ca2+ permeable channels to neurotoxicity are discussed with an emphasis on strategies for lessening Ca(2+)-related damage. A number of these strategies may have a future role in the treatment of traumatic and ischemic CNS injury.