Treatment of advanced alcoholic liver disease

The poor prognosis of severe acute alcoholic hepatitis has stimulated interest in specific forms of treatment aimed at reducing the short term mortality as well as preventing progression to cirrhosis. Several controlled trials of steroid therapy have suggested an improvement in short-term survival, but the benefit seems to apply to highly selected cases only. Treatment with propylthiouracil and insulin and glucagon infusions has also shown promising results in controlled studies but there is still no general agreement on their value. Despite recent interest in the use of colchicine to prevent progression of cirrhosis in chronic liver disease of other aetiologies, its role in alcoholic liver disease is not yet clear. In end-stage alcoholic cirrhosis, excellent results are now being achieved with liver transplantation, although this is limited to patients who are not alcohol dependent and in whom there is no alcohol-induced extrahepatic disease.     

Molluscicides in schistosomiasis control

Although mollusciciding can be a cost-effective method of controlling schistosomiasis transmission, only one organic molluscicide, niclosamide, is now being produced commercially, and only a few compounds are at present being tested in the laboratory. In future, improved cost-effective use of molluscicides will require more precise knowledge of schistosomiasis transmission patterns in each endemic area and improved application techniques. In snail control studies using controlled-release formulations only the organotins, especially tributyltin oxide (TBTO), have given satisfactory long-term results. However, large-scale field trials of organotin formulations have not been implemented and their use cannot be recommended as their chronic toxicity in mammals has not yet been determined. The development of molluscicides of indigenous plant origin deserves support. Endod, derived from the berries of the climbing plant Phytolacca dodecandra, is the most extensively tested plant molluscicide, but data on its chronic toxicity to non-target organisms are lacking. The mode of action of molluscicides has not been extensively studied, though knowledge of the properties required of molluscicidal molecules has contributed to the discovery and development of niclosamide and nicotinanilide. In general, molluscicides probably cause stress on the water balance system, which in gastropods in thought to be under neurosecretory control.     

Phytochemicals as Therapeutic Interventions in Peripheral Artery Disease

Peripheral artery disease (PAD) affects over 200 million people worldwide, resulting in significant morbidity and mortality, yet treatment options remain limited. Among the manifestations of PAD is a severe functional disability and decline, which is thought to be the result of different pathophysiological mechanisms including oxidative stress, skeletal muscle pathology, and reduced nitric oxide bioavailability. Thus, compounds that target these mechanisms may have a therapeutic effect on walking performance in PAD patients. Phytochemicals produced by plants have been widely studied for their potential health effects and role in various diseases including cardiovascular disease and cancer. In this review, we focus on PAD and discuss the evidence related to the clinical utility of different phytochemicals. We discuss phytochemical research in preclinical models of PAD, and we highlight the results of the available clinical trials that have assessed the effects of these compounds on PAD patient functional outcomes.     

Zinc toxicity

Although consequences of zinc deficiency have been recognized for many years, it is only recently that attention has been directed to the potential consequences of excessive zinc intake. This is a review of the literature on manifestations of toxicity at several levels of zinc intake. Zinc is considered to be relatively nontoxic, particularly if taken orally. However, manifestations of overt toxicity symptoms (nausea, vomiting, epigastric pain, lethargy, and fatigue) will occur with extremely high zinc intakes. At low intakes, but at amounts well in excess of the Recommended Dietary Allowance (RDA) (100-300 mg Zn/d vs an RDA of 15 mg Zn/d), evidence of induced copper deficiency with attendant symptoms of anemia and neutropenia, as well as impaired immune function and adverse effects on the ratio of low-density-lipoprotein to high-density-lipoprotein (LDL/HDL) cholesterol have been reported. Even lower levels of zinc supplementation, closer in amount to the RDA, have been suggested to interfere with the utilization of copper and iron and to adversely affect HDL cholesterol concentrations. Individuals using zinc supplements should be aware of the possible complications attendant to their use.     

Clinical research on malaria: what for the future?

Malaria still remains one of the main public health problems in the world. In spite of early and numerous clinical trials, the situation seems to have been worsening in the last ten years. Malaria clinical research involves several levels: Several meta-analyses have been performed on this topic (in particular, the Cochrane Database Library has published studies on malaria prevention during pregnancy, management of clinical malaria attacks, vaccine trials or impregnated bed net trials). All these studies show the uneven quality of trials (only 10% to 50% can be kept in the analysis for methodological reasons), which seldom lead to similar conclusions. Besides, as resistances of both parasites and vectors to drugs or insecticides are regularly increasing, trials have to be repeated and new molecules have to be found and evaluated. Finally, practical application of such interventions may be difficult, due to the heterogeneity of epidemiological situations and the poverty of target populations. Various initiatives aiming to develop malaria clinical research have recently been launched. Donators are public or international (Global Fund, Roll Back Malaria Initiative, NIH, EDCTP programme), as well as private (Bill & Melinda Gates Foundation). These substantial funds should enhance the research of new antimalarial drugs and large-scale, adequately designed trials. However, to make sure these trials really benefit to populations exposed to the disease, ethical principles should be co-elaborated with developing countries, within collaborative networks between laboratories from industrialized and developing countries.     

Heart disease and single-vitamin supplementation

Heart disease is the number one cause of death in the United States and has long been recognized to be multifactorial. A growing body of evidence suggests that not only free radical-mediated reactions but also inflammatory responses play major roles in atherogenesis. Vitamin E has both antioxidant and antiinflammatory properties and is the most widely studied vitamin in clinical trials and thus will be the primary example used in this review. Clinical trials of vitamin E efficacy, in hindsight, have been overly optimistic in their expectation that a vitamin could reverse poor dietary habits and a sedentary lifestyle as well as provide benefit beyond that of pharmaceutical agents in treating heart disease. However, it is also apparent that most Americans do not consume dietary amounts adequate to meet established vitamin E requirements. In response to oxidative stressors, vitamin E can decrease biomarkers of lipid peroxidation, is itself killed, and requires optimal vitamin C status to function most effectively. Thus, adequate vitamin E intakes are clearly needed, but what is adequate for what function has yet to be defined. It is noteworthy that in most trials, biomarkers were not used nor were oxidative stress and lipid peroxidation markers used or plasma vitamin E concentrations measured.     

儿童2019冠状病毒病的研究进展

2019冠状病毒病(COVID-19)是由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的以呼吸系统症状为主要表现的疾病,其发病机制可能与血管紧张素转换酶2(ACE2)受体有关。儿童作为一个较特殊的群体有自己的独特性,大部分感染SARS-CoV-2的儿童表现为无症状或者轻度症状,严重的患儿可表现为多系统炎症综合征。目前针对该疾病的治疗方案仍以一般治疗为主,相关药物治疗仍处在临床试验阶段。该文从流行病学、临床表现、实验室检查、影像学表现、诊断及治疗方案方面对儿童感染SARS-CoV-2进行综述。