In silico and in vitro drug screening identifies new therapeutic approaches for Ewing sarcoma.

The long-term overall survival of Ewing sarcoma (EWS) patients remains poor; less than 30% of patients with metastatic or recurrent disease survive despite aggressive combinations of chemotherapy, radiation and surgery. To identify new therapeutic options, we employed a multi-pronged approach using in silico predictions of drug activity via an integrated bioinformatics approach in parallel with an in vitro screen of FDA-approved drugs. Twenty-seven drugs and forty-six drugs were identified, respectively, to have anti-proliferative effects for EWS, including several classes of drugs in both screening approaches.

Influence of Insurance Status and Demographic Features on Recognition of Symptomatic and Asymptomatic Gonorrhea Cases.

A random sample of individuals diagnosed as having gonorrhea from 2009 to 2013 were interviewed. Demographic and clinical features for asymptomatic and symptomatic individuals were examined to elucidate trends in medical care. Age, race, and sexually transmitted disease history had no association with the absence of symptoms (e.

Chronic ingestion of H1-antihistamines increase progression of atherosclerosis in apolipoprotein E-/- mice.

Although increased serum histamine levels and H1R expression in the plaque are seen in atherosclerosis, it is not known whether H1R activation is a causative factor in the development of the disease, or is a host defense response to atherogenic signals. In order to elucidate how pharmacological inhibition of histamine receptor 1 (H1R) signaling affects atherogenesis, we administered either cetirizine (1 and 4 mg/kg. b.

Increased aldosterone: mechanism of hypertension in obesity.

The prevalence of both obesity and hypertension are increasing worldwide. Hypertension is a common consequence of obesity. Increased central adiposity is associated with increased aldosterone levels and blood pressure in human beings.

H1-antihistamines exacerbate high-fat diet-induced hepatic steatosis in wild-type but not in apolipoprotein E knockout mice.

We examined the effects of two over-the-counter H1-antihistamines on the progression of fatty liver disease in male C57Bl/6 wild-type and apolipoprotein E (ApoE)-/- mice. Mice were fed a high-fat diet (HFD) for 3 mo, together with administration of either cetirizine (4 mg/kg body wt) or fexofenadine (40 mg/kg body wt) in drinking water. Antihistamine treatments increased body weight gain, gonadal fat deposition, liver weight, and hepatic steatosis in wild-type mice but not in ApoE-/- mice.

Effects of nebivolol on aortic compliance in patients with diabetes and maximal renin angiotensin system blockade: the EFFORT study.

The beneficial effects of nebivolol on arterial stiffness and endothelial dysfunction are well documented in untreated hypertensive patients and differ from nonvasodilatory β-blockers. This study tests the hypothesis that the addition of nebivolol in predominantly African American patients with type 2 diabetes already receiving maximally tolerated doses of renin-angiotensin system (RAS) blockers will further improve large artery compliance. Patients with type 2 diabetes and hypertension on maximal RAS blockade (n=70) were randomized to nebivolol or metoprolol succinate daily.

Role of ambulatory blood pressure monitoring in hypertension and diabetes.

The prevalence of hypertension and diabetes are both rising in the USA and around the globe. The treatment of hypertension in the ambulatory setting begins with proper blood pressure measurement, and often the involvement of home blood pressure monitoring. If the diagnosis of hypertension is confirmed, then education on lifestyle modifications is the foundation to reaching blood pressure goals.

Noninsulin glucose-lowering agents for the treatment of patients on dialysis.

Chronic kidney disease (CKD) is a common complication of diabetes mellitus and the most common cause of end-stage renal disease (ESRD). As the worldwide prevalence of diabetes continues to increase, the number of patients with CKD will also increase. Therefore, it is essential that physicians know how to safely and effectively manage diabetes in the setting of CKD.

Interaction between Adiponectin and Aldosterone.

More than two thirds of the US population are considered overweight or obese. Adipocytes are now appreciated as important endocrine organs, secreting various factors with hormonal effects. Several different adipokines have been identified, including adiponectin, which is associated with improved insulin sensitivity, a better lipoprotein profile, and lower rates of vascular inflammation and cardiovascular disease.

Blood pressure targets for patients with diabetes or kidney disease.

The most recent scientific guideline statements from foundations and societies dealing with diabetes and kidney disease argue for blood pressure (BP) goals lower than 130/80 mm Hg, but whether the evidence from properly done clinical trials supports this BP level remains questionable. A review of all the evidence suggests that almost all of the data come from retrospective data analyses of randomized cardiovascular and chronic kidney disease (CKD) trials. Meta-analyses of all clinical trials to date demonstrate that reducing BP reduces risk for stroke and coronary heart disease, but none have achieved a mean BP goal of less than 130/80 mm Hg.

Quantification of the transporter substrate fexofenadine in cell lysates by liquid chromatography/tandem mass spectrometry.

Drug-drug interactions at transporters present a significant and under-investigated clinical problem. Investigations of specific transporter functions and screening for potential drug-drug interactions, both in vitro and especially in vivo, will require validated experimental probes. Fexofenadine, an approved, well-tolerated drug, is a promising probe for studies of membrane transporter function.