AFS, treated with azithromycin, was associated with a higher risk of prematurity, but not independently after adjustment for cervical length and second trimester vaginal bleeding. Further studies need to evaluate the effect of antibiotics in pregnancies with AFS.

Whole-blood viscosity is increasingly being recognized as a factor implicated in the vascular disease progression in high-risk chronic kidney disease patients. Intermittent hemodialysis and hemodiafiltration sessions, characterized by rapid volume changes and anemia correction by erythropoietin stimulating agents, are favorable conditions for enhancing whole-blood viscosity changes and consequently triggering cardiovascular events. To evaluate whole-blood viscosity changes induced by hemodiafiltration, a cross-sectional study has been performed in a group of 28 stable patients. In order to assess the impact of vessel size on whole-blood viscosity changes, we performed a dynamic whole viscosity analysis on a wide spectrum of shear rates reproducing vasculature hemorheologic conditions. Blood viscosity changes are dependent on patient characteristics, hemoglobin, and total plasma protein concentrations. Whole blood viscosity increases significantly during hemodiafiltration over the complete spectrum of shear rates. Dynamic whole-blood viscosity (WBV) increases up to 60%, predominantly at low shear rates in small arterioles and capillary beds. This observation underlines the potential pathogenic contribution of WBV increase in capillaries triggering cardiovascular events in the postdialysis period. Eight patients died from cardiovascular events. Higher WBV increase was noted in this group but did not reach statistical significance due to the insufficient power of the study. Hemorheological changes associated with WBV increase in capillary beds may contribute to aggravate silent tissue hypoxemia and precipitate cardiovascular events in chronic kidney disease patients. Prospective studies specifically designed and powered to evaluate the impact of WBV changes on cardiovascular events in dialysis patients are required.

Irbesartan (SR 47436, BMS 186295) is an imidazole derivative that specifically binds to the angiotensin type 1 receptor. The purpose of this study was to assess the inhibitory effect of irbesartan on the pressor action of exogenous angiotensin II in healthy subjects, to evaluate the dose dependency and duration of this inhibition, and to determine the effect of irbesartan on plasma components of the renin-angiotensin system. Forty-two healthy male volunteers maintained on ad libitum sodium intake were enrolled in a randomized, double-blind, placebo-controlled, parallel-design, dose-ranging study. On 2 study days 1 week apart, volunteers were given either a placebo or the active drug at one of the chosen doses (5, 25, 50, 75, 100, 150, or 300 mg). The pressor effects of an individually titrated test dose of exogenous angiotensin II as well as plasma levels of angiotensin II, active renin, aldosterone, and treatment drug were determined before and throughout the 24 h after drug administration. The inhibitory effect of irbesartan on the pressor response to angiotensin II was observed within 1 h after dosing, peaked between 2 and 4 h, and lasted more than 24 h for doses of 25 mg and more. The effect was clearly dose related. Two and 24 h after administration of irbesartan, 300 mg, the response of arterial blood pressure (systolic and diastolic) to a given dose of angiotensin II was reduced by approximately 100% and 60%, respectively. Plasma concentrations of angiotensin II and active renin increased markedly after irbesartan administration, whereas plasma concentrations of aldosterone decreased. No evidence was found that the high levels of circulating angiotensin II observed after irbesartan administration could override the inhibitory effect of irbesartan on any of the measured parameters up to 24 h after dose. In conclusion, irbesartan appears to be a well-tolerated, orally active, potent antagonist of the renin-angiotensin system in men.

A mild and general method for the synthesis of α,α-disubstituted benzocyclobutane amino acids through a [2+2] annulation of benzyne with dehydroalanine is described. Yields up to 88% of the constrained quaternary amino acids can be obtained and its application in peptidomimetic synthesis is demonstrated.