Combined treatment with renin-angiotensin system blockers and polyunsaturated fatty acids in proteinuric IgA nephropathy: a randomized controlled trial

Background. Currently, several therapeutic protocols exist forIgA nephropathy (IgAN); results in slowing the progression toend-stage renal disease (ESRD) are variable, but 30–40%of patients require replacement therapy (dialysis or renal transplantation)by 20 years from the onset. The adverse effects brought by thechronic assumption of drugs can be a potential limit. Actually,the most used therapies for IgAN are renin–angiotensinsystem blockers (RASB), glucocorticoids and immunosuppressiveagents. Trials with polyunsaturated fatty acids (PUFA) in IgANhave been done since the first successful attempt by Hamazakiin 1984, resulting in alternate answers, but no trials haveever been done testing the efficacy of combined therapy withRASB and PUFA. Methods. We tested the effect of a 6-month course of PUFA (3grams/day) in a group of 30 patients with biopsy-proven IgANand proteinuria already treated with RASB randomized to receivePUFA supplementation or to continue their standard therapy.The primary end-point was the percent reduction of proteinuriafrom the baseline. Secondary end-points were modifications inglomerular filtration rate (GFR), blood pressure, serum triglyceridesand erythrocyturia. Results. At the end of the 6-month trial, the percent reductionof proteinuria was 72.9% in the PUFA group and 11.3% in theRASB group (P < 0.001). A reduction of 50% of baseline proteinuriawas achieved in 80.0% of PUFA patients and 20.0% of RASB patients(P = 0.002). Erythrocyturia was significantly lower in the PUFAgroup (P = 0.031). No significant changes in renal function,blood pressure and triglycerides were observed. Conclusions. PUFA associated with RASB reduced proteinuria inpatients with IgAN more than RASB alone.     

培哚普利联合厄贝沙坦治疗大鼠扩张型心肌病近期和远期疗效

目的:探讨培哚普利联合厄贝沙坦治疗扩张型心肌病(DCM)大鼠的近、远期疗效.方法:腹腔注射阿霉素建立大鼠DCM模型.实验大鼠分4组:A组(n=14)为正常大鼠,B组(n=26)为DCM大鼠,均无药物干预; C(n=24),D(n=24)组均为DCM大鼠,其中C组予以培哚普利2mg/(kg·d)灌胃,D组予以培哚普利1mg/(kg·d) 联合厄贝沙坦25mg/(kg·d)灌胃.酶联免疫吸附法检测血浆脑利钠肽(BNP)水平;检测血钾、血肌酐水平;心肌HE染色后进行病理评分;记录干预过程各只大鼠存活期.结果:药物干预3周后,D组BNP水平低于C组(P＜0.05);各组干预前后血钾、血肌酐水平差异无统计学意义(P＞0.05);与B组比较,C和D组心肌病理损害均减轻(P＜0.01),而C与D组间心肌病理损害的差异无统计学意义(P＞0.05).对数秩检验显示:C组存活期短于D组(P＜0.05);Cox回归分析显示:联合用药或单用培哚普利为延长生存期因素,联合用药作用更明显.结论:培哚普利联合厄贝沙坦治疗DCM大鼠,在改善心功能及远期预后方面优于单用培哚普利,2种方案均能减轻心肌病理损害且未见血钾、血肌酐升高不良反应.     

Immune-mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution

Targeted biologic therapies have revolutionised treatment of immune-mediated inflammatory diseases (IMIDs) due to their efficacy, speed of onset and tolerability. The discovery that clinically unrelated conditions, such as rheumatoid arthritis and Crohn's disease, share similar immune dysregulation has led to a shift in the management of IMIDs from one of organ-based symptom relief to mechanism-based treatment. The fact that anticytokine therapy has been effective in treating multiple orphan inflammatory conditions confirms the IMID paradigm. In this review we examine the biologic agents currently licensed for use in the US and Europe: infliximab, etanercept, adalimumab, rituximab, abatacept, anakinra, alefacept and efalizumab. We also discuss the rationale behind the management of IMIDs using rheumatoid arthritis, Crohn's disease, psoriasis and psoriatic arthritis as examples. For the medical profession, IMID represents a breakthrough in the way pathology is classified. In this burgeoning era of biologic therapy the prospect of complete disease remission is conceivable.     

类风湿关节炎常用药物治疗方案及进展

类风湿性关节炎(RA)是一种以非化脓性增生性滑膜炎为主的对称性自身免疫性疾病,最初会影响小关节,逐渐发展为大关节,最后影响皮肤、眼睛、心脏、肾脏和肺部.RA发病机制特殊,目前虽诊疗手段繁多,却暂无完美诊疗手段.现有的用于治疗RA的药物诸如甲氨蝶呤类慢性抗风湿类药物(DMARDs)、类固醇(GC)、非类固醇消炎药(NSA...     

丹参对非酒精性脂肪肝大鼠血清MDA、SOD、TNF、Leptin的影响

[目的]观察丹参对非酒精性脂肪肝大鼠血中丙二醛(MDA)、过氧化物歧化酶(SOD)、肿瘤坏死因子α(TNF-α)、瘦素(Leptin)的调节作用.[方法]59只大鼠随机分为5组,第1组为正常饮食对照组(正常组),11只,喂饲普通饲料;第2～5组为实验组,喂高脂饲料.其中第2组为高脂饮食组(模型组),16只;第3、4组为丹参注射液大、小剂量治疗组(治疗组),各11只;第5组为为还原型谷胱甘肽对照组(对照组),10只.治疗组大鼠每天丹参注射液3.3ml/kg、1.65ml/kg;对照组每天还原型谷胱甘肽溶液10ml/kg;正常组和模型组腹腔注射等量生理盐水,连续8W,观察肝组织的病理改变,比色法测定血清MDA、SOD,放免法测定血清中TNF-α、Leptin含量.[结果]模型组大鼠肝脏脂肪沉着面积,沉着程度及纤维化程度积分均较正常组明显增多,血清中MDA、TNF-α含量均较正常组明显升高(P＜0.01,P＜0.05),而SOD、Leptin含量较正常组明显减低(P＜0.05).丹参大剂量治疗组大鼠肝脏脂肪沉着面积积分较模型组明显减少(P＜0.05),血清中MDA含量较模型组明显降低(P＜0.05),Leptin含量较模型组明显升高(P＜0.05),而SOD、TNF-α的变化不明显(与模型组比P＞0.05).[结论]大剂量丹参可改善非酒精性脂肪肝大鼠肝脏脂肪变性情况,并能减少脂肪肝大鼠血中MDA含量,提高Leptin的表达.     

Physical activity as a proxy to ameliorate inflammation in patients with type 2 diabetes and periodontal disease at high cardiovascular risk

While the beneficial impact of physical activity has been ascertained in a variety of pathological scenarios, including diabetes and low-grade systemic inflammation, its potential remains still putative for periodontal health. Periodontal disease has been associated with inflammatory systemic alterations, which share a common denominator with type 2 diabetes mellitus and cardiovascular disease. Physical exercise, along with nutritional counseling, is a cornerstone in the treatment and prevention of type 2 diabetes, also able to reduce the prevalence of periodontal disease and cardiovascular risk. In addition, considering the higher incidence of periodontitis in patients with type 2 diabetes compared to healthy controls, the fascinating research question would be whether physical activity could relieve the inflammatory pressure exerted by the combination of these two diseases. This multi-disciplinary viewpoint discusses available literature in order to argument the hypothesis of a “three–way relationship” linking diabetes, periodontitis, and physical activity.     

Effects of arotinolol on exercise capacity and humoral factors during exercise in normal subjects

Summary A placebo-controlled, double-blind crossover study was undertaken in 10 normal subjects to examine the effects of arotinolol (10 mg bid), a nonselective beta blocker with alpha-blocking activity, on exercise capacity and hormone levels during exercise after a 2-week treatment period. Maximal oxygen uptake (VO₂ max) and blood lactic acid concentration (LA) were measured during progressive exercise testing. An exercise intensity equivalent to 4 mmol/l of LA was used for the constant workload exercise test. Humoral factors were measured after 20 minutes of constant workload exercise. The administration of arotinolol significantly decreased systolic blood pressure and heart rate at rest and during exercise, but diastolic blood pressure did not change. No significant difference was found between arotinolol and placebo with regard to VO₂ max and maximal workload. Plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (NE) levels at rest and during exercise did not differ between the two treatments. In contrast, plasma epinephrine (EN) levels at rest and during exercise were significantly greater with arotinolol. Atrial natriuretic peptide (ANP) at rest did not differ between the two treatments. However, exercise caused a significant increase in ANP after arotinolol treatment. These findings suggest that arotinolol decreases blood pressure and heart rate without affecting exercise capacity.     

The safety and tolerability of beta blockers in heart failure with reduced ejection fraction: is the current underutilization of this evidence-based therapy justified?

Introduction: Beta blockers are one of the cornerstones for treatment of Heart Failure with Reduced Ejection fraction (HFRef), yet their use is often limited by adverse effects, either perceived or real. We performed a review of available data using PubMed.gov utilizing beta blocker, heart failure, reduced ejection fraction and safety as key words.

Areas covered: Several well designed, large scale randomized clinical trials including CIBS-II (bisoprolol), MERIT-HF (metoprolol succinate), and Copernicus (carvedilol) among others, have been conducted in patients with HFRef and demonstrated an improvement in cardiac mortality and morbidity. Despite the preponderance of data supporting the use of beta blockers for patients HFRef, these medications remain underutilized and/or are often prescribed at lower than recommended dosages. Some of the reluctance to embrace beta blockade may be attributed to concern on the part of both the patient and prescriber about the non-cardiac adverse effects of this class of drugs. We have reviewed several recent reviews and meta-analyses of trials of beta blocker in heart failure which have conclusively demonstrated their tolerability in the populations studied.

Expert opinion: In the final section of this paper we provide our opinions regarding initiating and optimizing beta blocker therapy for patients with HFRef.     

Toxic trace elements at gastrointestinal level

Many trace elements are considered essential [iron (Fe), zinc (Zn), copper (Cu)], whereas others may be harmful [lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As)], depending on their concentration and chemical form. In most cases, the diet is the main pathway by which they enter our organism. The presence of toxic trace elements in food has been known for a long time, and many of the food matrices that carry them have been identified. This has led to the appearance of legislation and recommendations concerning consumption. Given that the main route of exposure is oral, passage through the gastrointestinal tract plays a fundamental role in their entry into the organism, where they exert their toxic effect. Although the digestive system can be considered to be of crucial importance in their toxicity, in most cases we do not know the events that occur during the passage of these elements through the gastrointestinal tract and of ascertaining whether they may have some kind of toxic effect on it. The aim of this review is to summarize available information on this subject, concentrating on the toxic trace elements that are of greatest interest for organizations concerned with food safety and health: Pb, Cd, Hg and As.     

Sphingolipid signalling and liver diseases.

Sphingolipids (SLs) comprise a class of lipids with important structural functions and increasing relevance in cellular signalling. In particular, ceramide has attracted considerable attention owing to its role as a second messenger modulating several cell functions such as proliferation, gene expression, differentiation, cell cycle arrest and cell death. Increasing evidence documents the role of SLs in stress and death ligand-induced hepatocellular death, which contributes to the progression of several liver diseases including steatohepatitis, ischaemia-reperfusion liver injury or hepatocarcinogenesis. Furthermore, recent data indicate that the accumulation of SLs in specific cell subcompartments, characteristic of many sphingolipidoses, contributes to the hepatic dysfunctions that accompany these inherited diseases. Hence, the regulation of the cell biology and metabolism of SLs may open up a novel therapeutic avenue in the treatment of liver diseases.