Treatment of heart failure with sodium glucose co-transporter-2 inhibitors in people with type 2 diabetes mellitus: current evidence and future directions.

Diabetes is one the most common comorbidities among people with established heart failure. Interest in heart failure as an outcome among people with diabetes has emerged since it was shown that there was an association between increased risk of hospitalization for heart failure with use of thiazolidinediones and some dipeptidyl peptidase-4 inhibitors. Recently, sodium-glucose co-transporter-2 inhibitors were shown to lead to a reduction in the risk of cardiovascular death and hospitalization for heart failure in people with Type 2 diabetes mellitus and either cardiovascular risk factors or atherosclerotic cardiovascular disease. These findings appear to be consistent in people both with and without a baseline history of heart failure. Based on current evidence there are several clinical scenarios in which the use of sodium-glucose co-transporter-2 inhibitors would be justified for people with heart failure and atherosclerotic cardiovascular disease: (1) in people with a new diagnosis of Type 2 diabetes and for whom anti-hyperglycaemic management strategies are being considered; (2) in people with sub-optimal glycaemic control, regardless of baseline antihyperglycaemic therapy; and (3) in people with symptomatic heart failure (or other high-risk features such as recent hospitalization for heart failure), if glycaemic control is optimized and the individual is on a sulfonylurea or dipeptidyl peptidase-4 inhibitor; here, it may be reasonable to consider substituting one of those therapies for a sodium-glucose co-transporter-2 inhibitor. There are now a number of ongoing trials evaluating the role of sodium-glucose co-transporter-2 inhibitors as therapy for people with established heart failure (with preserved or with reduced ejection fraction) and regardless of the presence of diabetes. These trials will provide the evidence for the safety and efficacy of sodium-glucose co-transporter-2 inhibitors among people with established heart failure.

Assessment of middle cerebral artery diameter after aneurysmal subarachnoid hemorrhage by transcranial color-coded duplex sonography.

This study examined if vasospasm after aneurysmal subarachnoid hemorrhage could be visualized by middle cerebral artery (MCA) diameter changes in transcranial color-coded duplex sonography (TCCS). Comparative measurements between mean blood velocity (MBV) and MCA diameter were carried out in 17 patients in 76 instances. At two depth ranges (proximal, 60 55 mm: distal, 50-45 mm) two observers assessed the MCA diameter as indicated by the visualized blood flow column. At both points of measurement, the diameter differences between the two observers were within the ¿ 2 S.D. range of the mean difference indicating interobserver agreement. In 17 instances, MBV was > 120 cm/s indicating vasospasm but MBV did not correlate with absolute or relative diameter changes. MCA diameter assessment in TCCS seems reproducible. Because TCCS imaging is influenced by several factors comparative angiographic studies are necessary to clarify the TCCS findings.

In vitro postantibiotic effects following multiple exposures of cefotaxime, ciprofloxacin, and gentamicin against Escherichia coli in pooled human cerebrospinal fluid and Mueller-Hinton broth.

Multiple exposures with cefotaxime in either Mueller-Hinton broth or cerebrospinal fluid had no effect on killing or the duration of postantibiotic effect (PAE) in Escherichia coli strains tested. However, upon multiple exposures in Mueller-Hinton broth, ciprofloxacin and gentamicin PAEs significantly decreased with a concomitant reduction in bacterial killing. A reduction in bacterial killing following multiple ciprofloxacin and gentamicin exposures was also seen with cerebrospinal fluid; however, the PAE was maintained.

Carcinogen-induced diploid hepatocytes: sensitive target cells for transformation by mutated c-Ha-ras oncogene.

Sequential treatment of partially (two-thirds) hepatectomized rats with diethylnitrosamine and 2-acetylaminofluorene induces the emergence of diploid hepatocytes in rat liver. These carcinogen-induced diploid cell populations are thought to contain the progenitors of hepatocellular carcinoma (HCC), i.e., initiated, cells. In the study presented here, we addressed the question of whether putative mutations in carcinogen-induced diploid hepatocytes can cooperate with activated oncogenes in the process of transformation in vitro. Both carcinogenesis in vivo and transformation in vitro have been shown to be multistep processes requiring at least two independent transforming events. Diploid and polyploid rat hepatocytes were isolated by centrifugal elutriation. The purity of the elutriated fractions was 88 +/- 3% in the diploid fraction and 84 +/- 3% in the polyploid fraction. Hepatocytes from both the elutriated cell fractions and, for comparison, hepatocytes from untreated rats were transfected by electroporation with oncogene expression vectors containing the mutated human T24 c-Ha-ras gene and of the N-myc gene. Transient expression of transfected DNA was similar in both hepatocyte populations. No cell lines could be established by using the N-myc vector. In contrast, the carcinogen-induced diploid hepatocytes, but not polyploid hepatocytes, could be converted by transfection with the ras vector into permanent anchorage-independent growing cell lines with hepatocyte-like morphology and differentiation. These cell lines expressed the myc proto-oncogene and transforming growth factor-alpha constitutively. Thus, carcinogen-induced diploid hepatocytes are sensitive to transformation by the ras oncogene, suggesting cooperation between putative preexisting mutations in the diploid cells and the ras oncogene product in hepatocellular transformation.