Resolution of acute lower extremity deep vein thrombosis with rivaroxaban compared to warfarin

Journal of Thrombosis and Thrombolysis - Thrombosis resolution is an important component of treatment for deep vein thrombosis (DVT) and multiple anticoagulants are now available. It is unknown...     

Update of variants identified in the pancreatic β‐cell KATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes

The most common genetic cause of neonatal diabetes and hyperinsulinism is pathogenic variants in ABCC8 and KCNJ11. These genes encode the subunits of the β‐cell ATP‐sensitive potassium channel, a key component of the glucose‐stimulated insulin secretion pathway. Mutations in the two genes cause dysregulated insulin secretion; inactivating mutations cause an oversecretion of insulin, leading to congenital hyperinsulinism, whereas activating mutations cause the opposing phenotype, diabetes. This review focuses on variants identified in ABCC8 and KCNJ11, the phenotypic spectrum and the treatment implications for individuals with pathogenic variants.     

Haemodynamic, neurohumoral and exercise effects of losartan vs. captopril in chronic heart failure: results of an ELITE trial substudy. Evaluation of Losartan in the Elderly

BACKGROUND: The AT1 receptor antagonists differ from the angiotensin converting enzyme inhibitors by achieving a more complete blockade of angiotensin II's actions and by not affecting bradykinin metabolism. There is little information on whether this causes clinically significant differences in haemodynamics, neurohormones and exercise tolerance in heart failure. AIMS: To compare the effects of losartan and captopril upon central and regional haemodynamics, neurohormones and exercise capacity in heart failure. METHODS: In a double-blind, randomised trial 18 patients aged > or =65 years with symptomatic heart failure were allocated to treatment with losartan (10 patients) or captopril (eight patients). Patients underwent assessment at baseline, after the first dose, at 12 weeks and at 24 weeks. RESULTS: Systolic blood pressure fell by - 10.7% 1 h after captopril 6.25 mg (P = 0.007) and by - 4.8% 3 h after losartan 12.5 mg (P = 0.02). The blood pressure reduction was sustained with losartan at 12 and 24 weeks. Systemic vascular resistance fell acutely after captopril (-16.4%, P = 0.01). Captopril caused an acute and sustained rise in superior mesenteric artery blood flow (+ 22.9%, P = 0.04), and a slower rise in renal artery blood flow (+31.7%, P = 0.01). Losartan had no acute effects on regional haemodynamics but had increased superior mesenteric artery blood flow by 38.1% at 12 weeks (P = 0.02). There were no substantial differences between losartan and captopril, and no changes occurred in neurohormones or exercise capacity. CONCLUSION: No substantial differences were observed between losartan and captopril on central or regional haemodynamics, neurohormones or exercise capacity in elderly patients with stable symptomatic heart failure.     

鸟氨酸脱羧酶的生理病理特点及其药物研究概况

鸟氨酸脱羧酶(ornithinedecarboxylase,ODC)是多胺代谢中的关键酶,广泛存在于人体和动物各组织细胞内,其中对肠细胞的增生、移行和分化起重要作用.机体调节因素比较复杂.在黏膜损伤性疾病及某些癌前病变等细胞大量增生的病理情况下ODC的表达发生改变,可以作为这些疾病分期、预后及药物作用靶点或疗效的指标.寻找对ODC有作用的药物对于治疗其相关疾病是非常有意义的.     

R24 anti-GD3 ganglioside antibody can induce co-stimulation and prevent the induction of alloantigen-specific T cell clonal anergy

R24 is a monoclonal antibody directed against the cell surface ganglioside GD3. It can detect GD3 on the surface of a subset of T lymphocytes and can stimulate proliferation and secretion of cytokines in vitro. In the present report, we examined the effects of the R24 antibody upon antigen-specific T cell response, employing an HLA-DR7-specific T cell clonal model. As previously shown, primary stimulation of HLA-DR7-specific alloreactive T cell clones by transfectants expressing HLA-DR7 alone (t-DR7) in the absence of B7 co-stimulation resulted in anergy. Binding of cell surface GD3 on HLA-DR7-specific alloreactive T cell clones with R24 under these anergizing conditions resulted in interleukin-2 (IL-2) accumulation and prevented the induction of alloantigen-specific T cell clonal anergy. Binding of GD3 by R24 also prevented anergy under conditions where B7:CD28 interactions were blocked by CTLA4-Ig. The effect of R24 was abrogated in the presence of a combination of monoclonal antibodies for the α and β chains of the IL-2 receptor (IL-2R) or a neutralizing anti-IL-2 antibody. R24 does not appear to interact directly with the IL-2R since incubation of T cell clones with R24 did not induce early activation of IL-2R associated Jak kinases, Jak1 and Jak3, as was induced following incubation with IL-2. In contrast, incubation of HLA-DR7-specific clones with t-DR7 in the presence of R24 did result in phosphorylation of IL-2R related Jak kinases after 24 h. Our data indicate that the membrane ganglioside GD3 structure recognized by R24 may play an important role in antigen-specific T cell clonal response.     

A Sample of Female Adolescent Self-Identified Vegetarians in New Zealand Consume Less Protein and Saturated Fat,but More Fiber than Their Omnivorous Peers

This study aimed to describe the intake and food sources of macronutrients in vegetarian and non-vegetarian adolescent females. Cross-sectional data was collected between February and September 2019. Adolescent females, aged 15 to 18 years old, were recruited throughout New Zealand. Intakes were assessed via two 24-h diet recalls, adjusted to represent usual intake using the multiple source method. Of the 254 participants, 38 self-identified as vegetarian. Vegetarians had similar carbohydrate and fat intakes compared to non-vegetarians; however, their protein intakes were 2.1% kJ lower (95% confidence interval (CI) −3.0 to −1.1%). Vegetarians also consumed 1.1% kJ less saturated fat (95% CI –2.1 to −0.1%), 1.3% kJ (95% CI 0.7 to 1.9) more polyunsaturated fat, and 5 g/day (95% CI 1.8 to 8.0) more fiber than non-vegetarians. When consumed, bread-based dishes and discretionary foods were the highest sources of energy, fat, and carbohydrate in both vegetarians and non-vegetarians. This suggests that some adolescents, including vegetarians, were obtaining high amounts of fat and carbohydrate from food groups associated with poorer dietary quality. We recommend further research to assess how the changing food environment is influencing vegetarian eating patterns and their associations with health outcomes in the wider population.