Search

We investigated the biophysical mechanism of inhibition of recombinant T-type calcium channels Ca(V)3.1 and Ca(V)3.2 by nitrous oxide (N(2)O). To identify functionally important channel structures, chimeras with reciprocal exchange of the N-terminal domains I and II and C-terminal domains III and IV were examined. In whole-cell recordings N(2)O significantly inhibited Ca(V)3.2, and - less pronounced - Ca(V)3.1. A Ca(V)3.2-prevalent inhibition of peak currents was also detected in cell-attached multi-channel patches. In cell-attached patches containing < or = 3 channels N(2)O reduced average peak current of Ca(V)3.2 by decreasing open probability and open time duration. Effects on Ca(V)3.1 were smaller and mediated by a reduced fraction of sweeps containing channel activity. Without drug, single Ca(V)3.1 channels were significantly less active than Ca(V)3.2. Chimeras revealed that domains III and IV control basal gating properties. Domains I and II, in particular a histidine residue within Ca(V)3.2 (H191), are responsible for the subtype-prevalent N(2)O inhibition. Our study demonstrates the biophysical (open times, open probability) and structural (domains I and II) basis of action of N(2)O on Ca(V)3.2. Such a fingerprint of single channels can help identifying the molecular nature of native channels. This is exemplified by a characterization of single channels expressed in human hMTC cells as functional homologues of recombinant Ca(V)3.1.

Diclofenac, as one of the most popular antiphlogistics, is produced in great quantities. Nowadays this drug is ubiquitously present in the aquatic environment due to its resistance to biodegradation. Degradation by ultrasonic irradiation is a possibility to eliminate diclofenac from water without the addition of chemicals. The sonolysis of diclofenac in water was investigated at ultrasound frequencies of 24 kHz, 216 kHz, 617 kHz, and 850 kHz and in the presence of various catalysts (TiO 2 , SiO 2 , SnO 2 , and titanosilicate). The degradation of diclofenac by sonolysis of an aqueous solution at 617 kHz followed first-order kinetics. Catalysts, especially TiO 2 increased the rate of degradation. Within 30 min of irradiation, the relative concentration of diclofenac decreased from 100% to 16%. By HPLC and GC-MS methods, chlorinated anilines, phenols and carboxylic acid derivatives were detected as a result of the sonolysis. About 35% of organic chlorine was transformed into inorganic chloride. Most of the identified degradation products in the sonolysis of diclofenac were the same compounds that were detected during photo-oxidation experiments with this anti-inflammatory drug.

Objectives: Cardiac troponins T (cTnT) and I (cTnI) are the most sensitive biochemical parameters in the detection of myocardial damage. In neonates, in utero exposure to tocolytic therapy results in detectable values of cardiac troponins after delivery. Additionally, some preliminary results suggest that the upper reference limits for healthy newborns are higher than those for adults but definitive reference limits for newborns are not available. Our objective was to determine those limits. Design and methods: In this study we investigated the distribution of cTnT and cTnI in cord blood of 869 healthy newborns. cTnT was determined with the 3rd generation assay and cTnI with the Dade Behring assay on a Dimension RxL. For data analysis Student's t test and the Mann–Whitney U test were used. Results: Using the 99th percentile, the upper reference limit in healthy termed newborns was 0.097 μg/l for cTnT and 0.183 μg/l for cTnI. Compared to the adult values, the newborn upper limit was tripled for cTnT and doubled for cTnI. Statistically significant differences were found between males and females for cTnT and between natural childbirth and caesarean section for cTnI. Conclusion: Healthy-termed newborns have a higher upper reference limit for both cTnT and cTnI compared to adults. This circumstance must be taken into account when interpreting slightly “elevated” cTnT and cTnI values in newborns.