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Ginkgo biloba Extract: A Novel Addition to Antipsoriasis Ammunition?
The aim of this study was to investigate the effect of biflavonoids in Ginkgo biloba leaves on tacrolimus metabolism. Firstly, the inhibitory effects of 5 main biflavonoids (amentoflavone, sciadopitysin, ginkgetin, isoginkgetin, bilobetin) in Ginkgo biloba leaves on tacrolimus metabolism were investigated in vitro in human liver microsomes (HLM), and the concentration-dependent inhibition was further calculated. Then the time-dependent inhibition activities of 5 biflavonoids were studied and the drug interaction was studied in SD rats. Finally, the molecular mechanism of inhibition was explored by molecular docking. The results of in vitro incubation in HLM showed tacrolimus metabolism was strongly inhibited by amentoflavone, ginkgetin and bilobetin, which IC50 value was 5.57, 3.16 and 5.03 μM, respectively. The time-dependent inhibition of the 3 above biflavonoids at 50 μM was 33.47%∼50.89%. In the in vivo study in rats, the AUC0-t and Cmax of tacrolimus increased 3.8 folds and 2.5 folds after oral pre-administration with amentoflavone. Molecular docking results showed that the inhibitory effect may be related to the formation of hydrogen bonds. The results showed that long-term combination of Ginkgo biloba leaves and tacrolimus may cause drug-drug interactions. This study provided theoretical and experimental basis for rational drug use in clinical practice. This article is protected by copyright. All rights reserved.
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.
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.
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.
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.
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.
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.
Psoriasis is a chronic immunologically-based inflammatory skin disease. B-chronic lymphocytic leukemia (B-CLL) is a form of leukemia characterized by the slow and progressive accumulation of monoclonal CD5+ B lymphocytes in peripheral blood, bone marrow, lymph nodes and other organs. A T-helper 1 cytokine-mediated pathway is involved in these disorders in which tumor necrosis factor-α (TNF-α) plays a central role. TNF-α is involved in physiological phenomena, such as host defense, inflammation and cell differentiation, and in many pathological conditions, such as fever and some malignant neoplasms. TNF-α involvement in psoriasis has been well validated by the clinical success of anti-TNF-α therapy. TNF-α has been well studied in the pathogenesis of B-CLL, suggesting it as a target in B-CLL therapy. We present the case of a patient suffering from plaque psoriasis and B-CLL. Since TNF-α is reported as a common link between psoriasis and B-CLL, the patient was treated with etanercept followed by infliximab, two anti-TNF-α drugs. During 3 years of therapy, the patient did not show significant modifications of lymphocyte levels, indicating no progression of B-CLL. We report this case to highlight the possibility to administer anti-TNF-α treatment in psoriatic patients affected by concomitant B-CLL.
The feasibility of conducting a large-scale Polypill clinical trial in developing countries remains unclear. More information is needed regarding the efficacy in reducing the risk factors of cardiovascular disease (CVD), side effects, improvement in adherence and physician/patient "acceptability" of the Polypill.
We conducted an open-label, parallel-group, randomized clinical trial involving three sites in Sri Lanka that enrolled a total of 216 patients without established CVD. The trial compared a Polypill (75 mg aspirin, 20 mg simvastatin, 10 mg lisinopril and 12.5 mg hydrochlorothiazide) to Standard Practice. After randomization, patients were followed monthly for three months. Pre-specified primary outcomes included reduction in systolic blood pressure, total cholesterol and estimated 10-year CVD risk. We also evaluated the recruitment process and acceptability of the Polypill by both physicians and patients.
Patients were recruited in a six-month period as planned. Two hundred three patients (94.0%) completed the treatment program and returned for their three-month follow-up visits. No safety concerns were reported. These findings suggest a high rate of patient acceptability, a finding that is bolstered by the majority of patients completing the trial (90%) indicating that they would take the Polypill "for life" if proven to be effective in reducing CVD risk. Approximately 86% of the physicians surveyed agreed with and supported use of the Polypill for primary prevention and 93% for secondary prevention of CVD. Both the Polypill and Standard Practice resulted in marked reductions in systolic blood pressure, total cholesterol and 10-year risk of CVD. However, the differences between the treatment groups were not statistically significant.
We successfully completed a Polypill feasibility trial in Sri Lanka. We were able to document high acceptability of the Polypill to patients and physicians. We were unable to estimate the risk factor reductions on the Polypill because the control group received similar treatment with individual drugs. The Polypill was however simpler and achieved comparable risk factor reductions, highlighting its potential usefulness in the prevention of CVD.
NCT00567307.
To investigate the long-term associations of magnesium intake with incidence of diabetes, systemic inflammation, and insulin resistance among young American adults.
A total of 4,497 Americans, aged 18-30 years, who had no diabetes at baseline, were prospectively examined for incident diabetes based on quintiles of magnesium intake. We also investigated the associations between magnesium intake and inflammatory markers, i.e., high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and fibrinogen, and the homeostasis model assessment of insulin resistance (HOMA-IR).
During the 20-year follow-up, 330 incident cases of diabetes were identified. Magnesium intake was inversely associated with incidence of diabetes after adjustment for potential confounders. The multivariable-adjusted hazard ratio of diabetes for participants in the highest quintile of magnesium intake was 0.53 (95% CI, 0.32-0.86; P(trend) < 0.01) compared with those in the lowest quintile. Consistently, magnesium intake was significantly inversely associated with hs-CRP, IL-6, fibrinogen, and HOMA-IR, and serum magnesium levels were inversely correlated with hs-CRP and HOMA-IR.
Magnesium intake was inversely longitudinally associated with incidence of diabetes in young American adults. This inverse association may be explained, at least in part, by the inverse correlations of magnesium intake with systemic inflammation and insulin resistance.
Non-alcoholic fatty liver disease (NAFLD) has been deeply associated with visceral adiposity, adipose tissue inflammation and a variety of adipocytokines. We reported previously that genistein inhibited NAFLD by enhancing fatty acid catabolism. However, this molecular approach focused on hepatic metabolism. Thus, we have attempted to determine whether this anti-steatotic effect of genistein is linked to visceral adipocyte metabolism. C57BL/6J mice were fed on normal-fat (NF) diet, high-fat (HF) diet and HF diet supplemented with genistein (1, 2 and 4 g/kg diet) for 12 weeks. Mice fed on the HF diet gained body weight, exhibited increased visceral fat mass and elevated levels of serum and liver lipids, and developed NAFLD, unlike what was observed in mice fed on the NF diet. However, genistein supplementation (2 and 4 g/kg diet) normalised these alternations. In the linear regression analysis, visceral fat (R 0·77) and TNFα (R 0·62) were strongly correlated with NAFLD among other NAFLD-related parameters. Genistein supplementation suppressed the hypertrophy of adipocytes via the up-regulation of genes involved in fatty acid β-oxidation, including PPARα, 5'-AMP-activated protein kinase and very long-chain acyl CoA dehydrogenase, as well as through the down-regulation of genes associated with adipogenesis or lipogenesis, including liver X receptor-α, sterol-regulatory element-binding protein-1c, PPARγ, retinoid X receptor-α and acetyl CoA carboxylase 2. Moreover, genistein supplementation augmented an anti-steatohepatitic adiponectin TNF and reduced a steatohepatitic TNFα. Collectively, these findings show that genistein may prevent NAFLD via the regulation of visceral adipocyte metabolism and adipocytokines.
Recent evidence supports the protective effects of n-3 (omega-3) fatty acids (n-3 FAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on vascular function.
We investigated the effects of EPA and DHA on postprandial vascular function in subjects with type 2 diabetes mellitus.
In a double-blind, placebo-controlled, randomized, crossover manner, 34 subjects with type 2 diabetes mellitus received daily either 2 g purified EPA/DHA (termed n-3 FAs) or olive oil (placebo) for 6 wk. At the end of this period, we measured macrovascular (brachial ultrasound of flow-mediated dilatation; FMD) and microvascular [laser-Doppler measurements of reactive hyperemia (RH) of the hand] function at fasting and 2, 4, and 6 h after a high-fat meal (600 kcal, 21 g protein, 41 g carbohydrates, 40 g fat).
Fasting vascular function remained unchanged after n-3 FAs and placebo. Postprandial FMD decreased from fasting after placebo, with a maximum decrease (38%) at 4 h-an effect that was significantly reduced (P = 0.03 for time x treatment interaction) by n-3 FA supplementation (maximum decrease in FMD was at 4 h: 13%). RH remained unchanged after placebo, whereas it improved significantly (P = 0.04 for time x treatment interaction) after n-3 FA supplementation (maximum increase was at 2 h: 27%). Conclusions: In subjects with type 2 diabetes mellitus, 6 wk of supplementation with n-3 FAs reduced the postprandial decrease in macrovascular function relative to placebo. Moreover, n-3 FA supplementation improved postprandial microvascular function. These observations suggest a protective vascular effect of n-3 FAs.
Polyunsaturated fatty acids can have beneficial effects on human immune cells, such as peripheral blood mononuclear cells (PBMCs). However, the mechanisms of action of polyunsaturated fatty acids on immune cells are still largely unknown.
The objective was to examine the effects of supplementation with the polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on whole-genome PBMC gene expression profiles, in healthy Dutch elderly subjects participating in a double-blind trial, by using whole-genome transcriptomics analysis.
The subjects were randomly allocated to 1 of 3 groups: 1) consumption of 1.8 g EPA+DHA/d (n = 36), 2) consumption of 0.4 g EPA+DHA/d (n = 37), or 3) consumption of 4.0 g high-oleic acid sunflower oil (HOSF)/d (n = 38). All supplements were given in capsules. Before and after 26 wk of intervention, blood samples were collected. Microarray analysis was performed on PBMC RNA from 23 subjects who received 1.8 g EPA+DHA/d and 25 subjects who received HOSF capsules. Quantitative real-time polymerase chain reaction was performed in all 111 subjects.
A high EPA+DHA intake changed the expression of 1040 genes, whereas HOSF intake changed the expression of only 298 genes. EPA+DHA intake resulted in a decreased expression of genes involved in inflammatory- and atherogenic-related pathways, such as nuclear transcription factor kappaB signaling, eicosanoid synthesis, scavenger receptor activity, adipogenesis, and hypoxia signaling.
These results are the first to show that intake of EPA+DHA for 26 wk can alter the gene expression profiles of PBMCs to a more antiinflammatory and antiatherogenic status. This trial was registered at clinicaltrials.gov as NCT00124852.
Recent evidence suggests that the angiotensin converting enzyme (ACE) is present in skin. The real value of the determination of ACE activity as a clinical-biochemistry test for the diagnosis of psoriasis has not been attained. Serum and tissue ACE were measured in 60 patients with psoriasis, 20 patients with lichen planus, 20 patients with seborrhoic dermatitis and in 20 healthy individuals. The serum and tissue ACE activity was determined before and after therapy, using the spectrophotometric method and hippuryl-l-histidyl-l-leucine as a substrate. The results showed that serum ACE activity before therapy was significantly increased in both groups--patients with psoriasis (p < 0.001) and patients with lichen planus (p < 0.001) in comparison to healthy individuals. However, there were no significant differences in serum ACE activity among patients with seborrhoic dermatitis and healthy individuals. After therapy, serum ACE activity significantly decreased in both groups of patients with psoriasis and patients with lichen planus comparing it to the level found in the control group. The values in both were similar. The tissue ACE activity in altered skin was significantly increased only in the patients with psoriasis in comparison to uninvolved skin of these patients, as well as the skin of healthy individuals. After therapy, there were no significant differences in tissue ACE activity between the treated skin and the healthy skin. In conclusion, determination of tissue angiotensin converting enzyme activity can be used in the differential diagnostic of indistinct clinical forms of psoriasis.
Data on the relations of different types of fish meals and long-chain n-3 polyunsaturated fatty acids (PUFAs) to measures of atherosclerosis are sparse.
We examined intakes of long-chain n-3 PUFAs and fish in relation to clinical measures of subclinical atherosclerosis.
A cross-sectional study was conducted in a multiethnic group of 5,488 adults aged 45-84 y and free of clinical cardiovascular disease. Diet was assessed by using self-administered food-frequency questionnaires. Subclinical atherosclerosis was determined by measurements of common carotid intima-media thickness (cCIMT, >80th percentile), internal CIMT (iCIMT, >80th percentile), coronary artery calcium score (CAC score, >0), or ankle-brachial index (ABI, <0.90).
After adjustment for potential confounders, intakes of long-chain n-3 PUFAs and nonfried (broiled, steamed, baked, or raw) fish were inversely related to subclinical atherosclerosis determined by cCIMT but not by iCIMT, CAC score, or ABI. The multivariate odds ratio comparing the highest to the lowest quartile of dietary exposures in relation to subclinical atherosclerosis determined by cCIMT was 0.69 (95% CI: 0.55, 0.86; P for trend < 0.01) for n-3 PUFA intake; 0.80 (95% CI: 0.64, 1.01; P = 0.054) for nonfried fish consumption; and 0.90 (95% CI: 0.73, 1.11; P = 0.38) for fried fish consumption.
This study indicates that the dietary intake of long-chain n-3 PUFAs or nonfried fish is associated with a lower prevalence of subclinical atherosclerosis classified by cCIMT, although significant changes in iCIMT, CAC score, and ABI were not observed. Our findings also suggest that the association of fish and atherosclerosis may vary depending on the type of fish meal consumed and the measures of atherosclerosis.
Dietary flavonoids may improve endothelial function and ultimately lead to beneficial cardiovascular effects.
The objective was to assess whether pure dietary flavonoids can modulate nitric oxide and endothelin-1 production and thereby improve endothelial function.
A randomized, placebo-controlled, crossover trial in 12 healthy men was conducted to compare the acute effects of the oral administration of 200 mg quercetin, (-)-epicatechin, or epigallocatechin gallate on nitric oxide, endothelin-1, and oxidative stress after nitric oxide production was assessed via the measurement of plasma S-nitrosothiols and plasma and urinary nitrite and nitrate concentrations. The effects on oxidative stress were assessed by measuring plasma and urinary F(2)-isoprostanes. Plasma and urinary concentrations of quercetin, (-)-epicatechin, and epigallocatechin gallate were measured to establish the absorption of these flavonoids.
Relative to water (control), quercetin and (-)-epicatechin resulted in a significant increase in plasma S-nitrosothiols, plasma nitrite, and urinary nitrate concentrations (P < 0.05), but not in plasma nitrate or urinary nitrite. Epigallocatechin gallate did not alter any of the measures of nitric oxide production. Quercetin and (-)-epicatechin resulted in a significant reduction in plasma endothelin-1 concentration (P < 0.05), but only quercetin significantly decreased the urinary endothelin-1 concentration. None of the 3 treatments significantly changed plasma or urinary F(2)-isoprostane concentrations. Significant increases in the circulating concentrations of the 3 flavonoids were observed (P < 0.05) after the corresponding treatment.
Dietary flavonoids, such as quercetin and (-)-epicatechin, can augment nitric oxide status and reduce endothelin-1 concentrations and may thereby improve endothelial function.
Genistein aglycone improves bone metabolism in women. However, questions about the long-term safety of genistein on breast as well as its continued efficacy still remain.
We assessed the continued safety profile of genistein aglycone on breast and endometrium and its effects on bone after 3 yr of therapy.
The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24-months. Subsequently, a subcohort (138 patients) continued therapy for an additional year. Patients and Interventions: Participants received 54 mg of genistein aglycone daily (n = 71) or placebo (n = 67). Both treatment arms received calcium and vitamin D(3) in therapeutic doses.
Mammographic density was assessed at baseline, 24 and 36 months by visual classification scale and digitized quantification. BRCA1 and BRCA2, sister chromatid exchange, and endometrial thickness were also evaluated. Lumbar spine and femoral neck bone mineral density were also assessed. Secondary outcomes were biochemical levels of bone markers.
After 36 months, genistein did not significantly change mammographic breast density or endometrial thickness, BRCA1 and BRCA2 expression was preserved, whereas sister chromatid exchange was reduced compared with placebo. Bone mineral density increases were greater with genistein for both femoral neck and lumbar spine compared to placebo. Genistein also significantly reduced pyridinoline, as well as serum carboxy-terminal cross-linking telopeptide and soluble receptor activator of NF-kappaB ligand while increasing bone-specific alkaline phosphatase, IGF-I, and osteoprotegerin levels. There were no differences in discomfort or adverse events between groups.
After 3 yr of treatment, genistein exhibited a promising safety profile with positive effects on bone formation in a cohort of osteopenic, postmenopausal women.
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.
Interest is increasing regarding the potential health effects of red yeast rice (RYR) consumption, which is described as a "natural statin" in China. This review aims to evaluate the efficacy of RYR on blood pressure (BP), lipid profile, and C-reactive protein (CRP) in treating hypertension. Seven electronic databases including the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (VIP), the Chinese Biomedical Literature Database (CBM), and the Wanfang database were searched. To investigate the role of RYR for hypertension, randomized controlled trials for the use of RYR either as monotherapy or in combination with conventional medicine versus placebo, no intervention, or conventional medicine for hypertension were identified. A total of 21 trials containing 4558 patients were analyzed, the majority of which had low methodological quality. "RYR plus conventional therapy" exhibited significant lowering effects on serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and CRP but exhibited no significant effect on systolic BP, diastolic BP, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) compared with "placebo plus conventional therapy". "RYR plus conventional therapy" showed significant lowering effects on systolic BP, TC, LDL-C, and CRP but no effect on diastolic BP, TG, and HDL-C compared with "placebo plus conventional therapy". No significant difference in BP and lipid profile between "RYR plus conventional therapy" and "statins plus conventional therapy" was observed. "RYR plus statins" appeared to be more effective in lowering BP, TC, TG, and LDL-C but without a significant difference in HDL-C compared to statins. No serious adverse events were reported. The results of this meta-analysis suggested some supportive but limited evidence regarding RYR for hypertension. Further rigorously designed trials are warranted before RYR could be recommended to hypertensive patients.
The present study is aimed to investigate the effect of Gualou Xiebai Decoction (GXD) ethanol extract on myocardial fibrosis and clarify the possible mechanism.
Rats with ligated left anterior descending coronary artery were treated with GXD ethanol extract (1.14 g/kg, 2.27 g/kg, 4.53 g/kg) daily via gavage for 4 weeks. Histopathological changes and collagen distribution were evaluated by haematoxylin and eosin and Masson staining. The mRNA levels of Collagen I and Collagen III were detected by real-time PCR. The expressions of TGF-β1, TGFβ receptor (TGFβR)I, TGFβRII, P-Smad2/3 and Smad7 were determined by Western blot.
GXD treatment was significantly reduced the heart weight/body weight ratio (P < 0.05) as well as the left ventricle weight/body weight ratio (P < 0.05). It also significantly alleviated the degree of inflammation, decreased myocardial collagen volume fraction (P < 0.05 ∼ 0.01), together with markedly prevented the upregulations of Collagen I and Collagen III (P < 0.05 ∼ 0.01). Moreover, GXD downregulated expressions of TGF-β1, TGFβRI, TGFβRII, Smad2/3 whereas improved Smad7 expression in the myocardial fibrosis rats.
GXD ameliorates myocardial fibrosis induced by cardiac infarction with ligated left anterior descending coronary artery, the mechanism maybe involve in inhibiting the TGF-β1 signalling pathway.
Psoriasis is a chronic inflammatory skin disease that affects approximately 2–4% of the population. We recently described
a novel non-coding RNA, psoriasis susceptibility related RNA gene induced by stress (PRINS), that was overexpressed in non-lesional
psoriatic epidermis, and its expression was induced by various stress factors such as serum starvation, contact inhibition,
ultraviolet (UV)-B irradiation, viral infection and translational inhibition in HaCaT cells. In the present work we set out
to compare the stress and microbial agent-induced PRINS expression in normal human keratinocytes (NHKs) and HaCaT cells. Since
nuclear factor-κB (NF-κB) is involved in the cellular stress response, we sought to explore whether there is a connection
between the NF-κB and PRINS-mediated signal transduction pathways in NHKs and HaCaT cells. We found that the PRINS expression
responded differentially to various stress signals and microbial agents in HaCaT cells and in NHKs: after translational inhibition
and UV-B treatment, similar induction of PRINS expression occurred with different time courses while after microbial agent
treatment, the PRINS expression was significantly induced in HaCaT cells, whereas we could not detect similar changes in NHKs.
To explore whether the known NF-κB abnormalities in HaCaT cells could be related to this differential PRINS expression, we
silenced the PRINS gene expression with small interfering RNA (siRNA) in both HaCaT cells and in NHKs and monitored NF-κB
signal transduction after lipopolysaccharide (LPS) treatment. Silencing of PRINS had no effect on LPS-induced NF-κB activity
either in HaCaT cells or in NHKs. Our results indicate that PRINS probably affects keratinocytes functions independently of
NF-κB signalling.
KeywordsNon-coding RNA–PRINS expression–NF-κB–HaCaT cells–Normal human keratinocytes–Psoriasis
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.
Bone mass declines progressively with age in both men and women from the age of approximately 30 y. Increased longevity will inevitability be associated with an increase in the incidence of osteoporosis, its associated complications, and incurred health care costs. Current pharmacologic approaches focus on inhibiting bone resorption in those with osteoporosis but do little to improve bone mass. Increased understanding of the cellular events responsible for normal bone formation has led to multiple pathways that can be targeted to positively influence bone mass. Bone morphogenetic proteins (BMPs) have been shown to stimulate bone formation, and the BMP2 gene was recently linked to osteoporosis. BMP-2 therefore represents one potential molecular target to identify new agents to simulate bone formation. Research is accumulating on the positive effects of dietary sources that stimulate the BMP2 promoter and their effects on bone formation. Flavonoids and statins occur naturally in food products and have been shown to promote bone formation. It may be possible to influence peak bone mass by dietary means and to decrease the risk of osteoporosis in later life. To ease the future burden of osteoporosis, focusing on prevention will be key, and this could include dietary interventions to stimulate bone formation.
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.
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.
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.
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.
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.
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.
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.
“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 …
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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)
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.
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.
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.