β-阻滞剂塞利洛尔的合成

报道了β－阻滞剂塞利洛尔的简便制备方法，即以对乙氧基苯胺为原料，经酰胺化，傅克反应，以环氧氯丙烷取代，最后用叔丁胺直接与环氧基反应开环等４步反应制得。比文献五步反应缩短了一步，产物经元素分析、红外光谱、核磁共振谱、质谱等分析确定结构。     

Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis

Apoptosis, or programmed cell death, is a general mechanism for removal of unwanted cells from the immune system. It is characterized by chromatin condensation, a reduction in cell volume, and endonuclease cleavage of DNA into oligonucleosomal length fragments. Apoptosis is also accompanied by a loss of membrane phospholipid asymmetry, resulting in the exposure of phosphatidylserine at the surface of the cell. Expression of phosphatidylserine at the cell surface plays an important role in the recognition and removal of apoptotic cells by macrophages. Here we describe a new method for the detection of apoptotic cells by flow cytometry, using the binding of fluorescein isothiocyanate-labeled annexin V to phosphatidylserine. When Burkitt lymphoma cell lines and freshly isolated germinal center B cells are cultured under apoptosis inducing conditions, all cells showing chromatin condensation strongly stain with annexin V, whereas normal cells are annexin V negative. Moreover, DNA fragmentation is only found in the annexin V-positive cells. The nonvital dye ethidium bromide was found to stain a subpopulation of the annexin V-positive apoptotic cells, increasing with time. Our results indicate that the phase in apoptosis that is characterized by chromatin condensation coincides with phosphatidylserine exposure. Importantly, it precedes membrane damage that might lead to release from the cells of enzymes that are harmful to the surrounding tissues. Annexin V may prove important in further unravelling the regulation of apoptosis.     

Migration and species diversity in the tropics

If the young of a dominant species are subjected to disproportionately heavy predation, this, together with a limitation on food, can promote a high species diversity. This is seen among tropical birds, which are simultaneously exposed to both conditions to a far greater degree than are Temperate Zone species. Migration to the Temperate Zones during the spring provides a release from these restraints, while also precluding breeding in the Tropics.     

Linagliptin for the treatment of type 2 diabetes mellitus: a drug safety evaluation

Introduction: Established treatments for type 2 diabetes mellitus (T2DM) have side effects that limit their use in specific populations. New therapies with improved safety profiles are needed, especially because of the chronic and progressive nature of T2DM.

Areas covered: This review describes the overall safety and tolerability of linagliptin – a dipeptidyl peptidase-4 inhibitor that improves glycemic control without increasing risk for hypoglycemia and without weight gain. Specifically, the safety of linagliptin is evaluated in difficult-to-treat patients with T2DM, in relation to risk of cardiovascular (CV) events and acute pancreatitis, and in comparison with other antihyperglycemic drugs.

Expert opinion: Linagliptin is generally well tolerated in a broad range of patient populations. It can be used in patients with renal impairment without dose titration and may be a rational alternative treatment in this vulnerable population. Ongoing long-term trials are fully evaluating the CV and renal safety profile of linagliptin.     

X-linked chronic granulomatous disease: correction of NADPH oxidase defect by retrovirus-mediated expression of gp91-phox

Chronic granulomatous disease (CGD) is an inherited immunodeficiency resulting from the inability of an individual's phagocytes to produce superoxide anions because of defective NADPH oxidase. The disease may be treated by bone marrow transplantation and as such is a candidate for somatic gene therapy. Two thirds of patients have defects in an X- linked gene (X-CGD) encoding gp91-phox, the large subunit of the membrane cytochrome b-245 component of NADPH oxidase. Epstein-Barr virus-transformed B-cell lines from patients with CGD provide a model system for the disease. We have used retrovirus-mediated expression of gp91-phox to reconstitute functionally NADPH oxidase activity in B-cell lines from three unrelated patients with X-CGD. The protein is glycosylated and membrane associated, and the reconstituted oxidase is appropriately activated via protein kinase C. The kinetics of superoxide production by such reconstituted cells is similar to that of normal B-cell lines. These data show the potential of gene therapy for this disease.