A humanized version of Foxp2 does not affect ultrasonic vocalization in adult mice.

The transcription factor FOXP2 has been linked to severe speech and language impairments in humans. An analysis of the evolution of the FOXP2 gene has identified two amino acid substitutions that became fixed after the split of the human and chimpanzee lineages. Studying the functional consequences of these two substitutions in the endogenous Foxp2 gene of mice showed alterations in dopamine levels, striatal synaptic plasticity, neuronal morphology and cortico-striatal-dependent learning. In addition, ultrasonic vocalizations (USVs) of pups had a significantly lower average pitch than control littermates. To which degree adult USVs would be affected in mice carrying the 'humanized' Foxp2 variant remained unclear. In this study, we analyzed USVs of 68 adult male mice uttered during repeated courtship encounters with different females. Mice carrying the Foxp2(hum/hum) allele did not differ significantly in the number of call elements, their element structure or in their element composition from control littermates. We conclude that neither the structure nor the usage of USVs in adult mice is affected by the two amino acid substitutions that occurred in FOXP2 during human evolution. The reported effect for pup vocalization thus appears to be transient. These results are in line with accumulating evidence that mouse USVs are hardly influenced by vocal learning. Hence, the function and evolution of genes that are necessary, but not sufficient for vocal learning in humans, must be either studied at a different phenotypic level in mice or in other organisms.

[Anti-ischemia effects of gallopamil and esmolol in an intra-individual comparison in patients with coronary heart disease]. / Antiischämische Auswirkungen von Gallopamil und Esmolol im intraindividuellen Vergleich bei Patienten mit koronarer Herzkrankheit.

To compare the hemodynamic, antiischemic, metabolic, and neurohumoral effects of intravenous esmolol (beta 1 blocking agent) and gallopamil (verapamil-like calcium channel blocker), 14 patients with angiographically proven CAD and reproducible ST segment depression were studied at rest and during exercise under control conditions and after an intravenous bolus injection of esmolol (0.5 mg/kg/1 min, followed by an infusion with 0.2 mg/kg/min) or gallopamil (0.025 mg/kg/3 min). In contrast to gallopamil, esmolol significantly reduced systolic blood pressure (175.7 vs. 160 mm Hg) and heart rate (107.4 vs. 96.9 min-1) during exercise as well as cardiac output (11.57 vs. 9.38 l/min) and significantly enhanced systemic vascular resistance both at rest (1241 vs. 1479 dynes.s.cm-5) and during exercise (805 vs. 947 dynes.s.cm-5). On the other hand, exercise filling pressures and lactate levels (3.66 vs. 3.05 mmol/l) were significantly reduced by gallopamil only. Thus, the significant improvement of exercise tolerance by both esmolol and gallopamil is based on different mechanisms of action: esmolol improves myocardial ischemia by appreciably reducing myocardial oxygen consumption, whereas gallopamil primarily improves oxygen supply and ventricular performance. Plasma catecholamines, atrial natriuretic factor, and aldosterone levels as well as plasma renin activity were identically influenced by esmolol and gallopamil, respectively. A reflex activation of the sympathetic system did not occur.

Efficacy and tolerability of slow-release gallopamil in patients with stable exercise-inducible angina pectoris.

The anti-ischemic properties and tolerability of a slow-release formulation (SR) of gallopamil were investigated in 118 patients with exercise-inducible ST-segment depression and stable angina pectoris in this double-blind, randomized, placebo-controlled, multicenter study. After a placebo run-in period (A) of 2-7 days and a 7-day open therapy period (B) with gallopamil SR, the patients were randomized to a double-blind 7-day period (C) to receive placebo or gallopamil SR 100 mg twice a day. Each patient was submitted to gradual upright bicycle ergometry and electrocardiography (ECG) at rest on the last 2 days of each period at 6 and 12 h postadministration (p.a.) In period C, exercise time and exercise tolerance remained significantly prolonged at 6 and 12 h after gallopamil SR administration in comparison with the placebo values. Additionally the sum of ST-segment depression and maximal ST-segment depression were significantly reduced by gallopamil SR at 6 h p.a. as were the frequency of angina attacks and nitroglycerin consumption. Four patients were withdrawn from the study because of gallopamil-related adverse events, which, however, were not serious. Constipation was noted in 2.5% of the patients. These data suggest that gallopamil SR is effective in reducing exercise-inducible ST-segment depression and increasing exercise tolerance with no serious adverse effects in patients with stable angina pectoris.