Disparate hemodynamic responses to mental challenge after antihypertensive therapy with beta blockers and calcium entry blockers

The hemodynamic response to mental challenge was studied in 40 male outpatients with mild essential hypertension. The patients were treated randomly either with a beta adrenoreceptor blocker (oxprenolol) or with a calcium entry blocker (nitrendipine). Cardiovascular reactivity was evaluated with two different mental arithmetic tasks before and six months after treatment by continuously measuring systolic and diastolic pressure (ultrasonic Doppler device), heart rate (electrocardiography), and stoke volume (impedance cardiography). Patients in both treatment groups had equal decreases in arterial pressure and the same pressures at rest. In patients receiving calcium entry blockers, mental challenge provoked an increase in stroke volume and a decrease in total peripheral resistance similar to results in the pretreatment phase. In contrast, beta adrenoreceptor blockade reversed the hemodynamic response pattern to a distinct decrease in stroke volume (p less than or equal to 0.05) and an increase in total peripheral resistance (p less than or equal to 0.05). In addition, an attenuated heart rate response (p less than or equal to 0.01) and a larger increase in diastolic pressure (p less than or equal to 0.01) were found in the beta blocker group compared with the calcium entry blocker group. Although beta blockers and calcium blockers produce equal decreases in arterial pressure, beta blockers evoke an abnormal hemodynamic response to mental challenge, whereas calcium entry blockers preserve the physiologic reactivity pattern of the untreated state.     

Neurulation and neurite extension require the zinc transporter ZIP12 (slc39a12)

Zn²⁺ is required for many aspects of neuronal structure and function. However, the regulation of Zn²⁺ in the nervous system remains poorly understood. Systematic analysis of tissue-profiling microarray data showed that the zinc transporter ZIP12 (slc39a12) is highly expressed in the human brain. In the work reported here, we confirmed that ZIP12 is a Zn²⁺ uptake transporter with a conserved pattern of high expression in the mouse and Xenopus nervous system. Mouse neurons and Neuro-2a cells produce fewer and shorter neurites after ZIP12 knockdown without affecting cell viability. Zn²⁺ chelation or loading in cells to alter Zn²⁺ availability respectively mimicked or reduced the effects of ZIP12 knockdown on neurite outgrowth. ZIP12 knockdown reduces cAMP response element-binding protein activation and phosphorylation at serine 133, which is a critical pathway for neuronal differentiation. Constitutive cAMP response element-binding protein activation restores impairments in neurite outgrowth caused by Zn²⁺ chelation or ZIP12 knockdown. ZIP12 knockdown also reduces tubulin polymerization and increases sensitivity to nocodazole following neurite outgrowth. We find that ZIP12 is expressed during neurulation and early nervous system development in Xenopus tropicalis, where ZIP12 antisense morpholino knockdown impairs neural tube closure and arrests development during neurulation with concomitant reduction in tubulin polymerization in the neural plate. This study identifies a Zn²⁺ transporter that is specifically required for nervous system development and provides tangible links between Zn²⁺, neurulation, and neuronal differentiation.     

Angiotensin-Converting Enzyme Inhibitors in Hypertension: To Use or Not to Use?

Most guidelines for the management of patients with cardiovascular disease recommend angiotensin-converting enzyme (ACE) inhibitors as first-choice therapy, whereas angiotensin receptor blockers (ARBs) are merely considered an alternative for ACE inhibitor–intolerant patients. The aim of this review was to compare outcomes and adverse events between ACE inhibitors and ARBs in patients. In patients with hypertension and hypertension with compelling indications, we found no difference in efficacy between ARBs and ACE inhibitors with regard to the surrogate endpoint of blood pressure and outcomes of all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. However, ACE inhibitors remain associated with cough and a very low risk of angioedema and fatalities. Overall withdrawal rates because of adverse events are lower with ARBs than with ACE inhibitors. Given the equal outcome efficacy but fewer adverse events with ARBs, risk-to-benefit analysis in aggregate indicates that at present there is little, if any, reason to use ACE inhibitors for the treatment of hypertension or its compelling indications.     

The association of the Friesinger score and pulse pressure in an urban South Asian patient population: pulse pressure,an independent predictor of coronary artery disease

Increase in pulse pressure has been shown to be predisposing factor for Coronary Artery Disease (CAD) in diverse patient populations but its relationship with the severity of CAD, particularly in the South Asians immigrant population of United States has not been demonstrated. We performed a single-center, cross-sectional study. Pulse pressure was calculated by the difference between the systolic and diastolic brachial blood pressures, and the Friesinger score (FS) was used to quantify the severity of CAD with the score of 5 used as a cutoff for extensive disease. We also sought to assess the correlation between the Friesinger score and the 10-year cardiovascular event (CVD) risk as calculated by the Framingham score. Odds ratios and 95% confidence intervals for the associations between explanatory variables and a high Friesinger score were estimated using multivariate logistic regression models. P values below .05 were considered to be statistically significant. Statistical analysis was performed using STATA version 10 software package (College Station, TX). The mean pulse pressure was significantly higher in participants with an FS of ≥5 compared with participants with an FS of <5 (63 vs. 46 mm Hg; P = .004). In univariate analysis, a pulse pressure ≥40 mm Hg was associated with a five-fold increased odds of a higher FS compared with a pulse pressure <40 mm Hg (P = .039), which was unchanged in multivariate analysis. In multivariate analysis, even after adjustment for presence of hypertension, a 10 mm Hg increase in pulse pressure was associated with a 1.97-fold increased odds of a higher FS (95% CI 1.22–3.71, P = .009). The mean Framingham score was higher in participants with a higher FS, but this difference was not significant (32.7 vs. 20.3; P = .1139). Our study demonstrates that pulse pressure, a well-established marker of vascular health, is a significant independent predictor of the severity of CAD as assessed by coronary angiography in South Asians.     

Zunehmende Augentrübung bei Trisomie 13

Ohne Zusammenfassung     

Diuretic therapy and the risk for renal cell carcinoma

Diuretics are important drugs in the treatment of arterial hypertension, congestive heart failure, the nephrotic syndrome, and other clinical conditions. With diuretic treatment, reduction of both morbidity and mortality has been clearly shown in those conditions. However, a recent meta-analysis showed an increased risk for renal cell carcinoma in patients treated with diuretics. We summarize and critically review data from studies examining the association between diuretic use and renal cell carcinoma. In general, in many clinical conditions, the reduction of mortality with diuretic therapy outweighs a potential risk of renal cell carcinoma. However, in certain conditions, alternative medical treatment should be considered.