Increased retention of calcium in the dendrites of long-term potentiated CA1 neurons of the hippocampal slice. A combined electrophysiological and electron histochemical study

In view of the importance of calcium in the induction of long-term potentiation (LTP), experiments were carried out to localize calcium at the electron microscopic level in the CA1 region of guinea pig hippocampal slices, following high-frequency stimulation of the Schaffer collaterals. Apart from the ultrastructural localization, a semi-quantitative method was used to count the calcium-containing deposits in electron micrographs. Significantly more calcium-containing deposits were seen in the dendrites of the stratum radiatum in slices with LTP than in those without it. A moderate increase of the extradendritic deposits was observed, too. The calcium content of the deposits was determined by means of EGTA incubation and X-ray analysis. The presented results, together with the relevant literature data, underline the importance of calcium-activated processes in postsynaptic structures probably involved in the generation of LTP.     

Characterization of the mitochondrial Na+-H+ exchange. The effect of amiloride analogues

The kinetic properties and inhibitor sensitivity of the Na+-H+ exchange activity present in the inner membrane of rat heart and liver mitochondria were studied. (1) Na+-induced H+ efflux from mitochondria followed Michaelis-Menten kinetics. In heart mitochondria, the Km for Na+ was 24 +/- 4 mM and the Vmax was 4.5 +/- 1.4 nmol H+/mg protein per s (n = 6). Basically similar values were obtained in liver mitochondria (Km = 31 +/- 2 mM, Vmax = 5.3 +/- 0.2 nmol H+/mg protein per s, n = 4). (2) Li+ proved to be a substrate (Km = 5.9 mM, Vmax = 2.3 nmol H+/mg protein per s) and a potent competitive inhibitor with respect to Na+ (Ki approximately 0.7 mM). (3) External H+ inhibited the mitochondrial Na+-H+ exchange competitively. (4) Two benzamil derivatives of amiloride, 5-(N-4-chlorobenzyl)-N-(2',4'-dimethyl)benzamil and 3',5'-bis(trifluoromethyl)benzamil were effective inhibitors of the mitochondrial Na+-H+ exchange (50% inhibition was attained by approx. 60 microM in the presence of 15 mM Na+). (5) Three 5-amino analogues of amiloride, which are very strong Na+-H+ exchange blockers on the plasma membrane, exerted only weak inhibitory activity on the mitochondrial Na+-H+ exchange. (6) The results indicate that the mitochondrial and the plasma membrane antiporters represent distinct molecular entities.     

The effect of various types of portocaval anastomoses and hepatic artery ligation on the metabolism of hepatic mitochondria in rats

The results of investigations are presented concerning the disorders of metabolism of mitochondria isolated from the liver of rats after various operations on the portal vein and hepatic artery. The mitochondria were studied after end-to-side portocaval anastomosis (PCA), end-to-side anastomosis of the mesenteric vein to the inferior caval vein (M-PCA) and after hepatic artery ligation. The investigations were carried out 3.5 months after these operations. The obtained results showed that the greatest and most significant statistically dissociation of oxidative phosphorylation and reduction of oxygen uptake developed in the mitochondria isolated from rats after M-PCA anastomosis. Simultaneously conducted investigations of citrulline production by suspension of mitochondria failed to demonstrate any changes in the urea cycle.     

A microcomputer method for recording and analysing behavioural elements

The trend in ethology, psychopharmacology and behaviour genetics is to get increasingly higher resolution of the behaviour of animals, since it increases the sensitivity of the tests used. Consequently the higher resolution requires an increased data-logging efficiency, and a decreased time-investment for data handling. In this paper a method for inexpensive microcomputers is presented, which enables an individual experimenter to obtain frequency, relative duration and its variance from as many behavioural elements as desired.     

Pharmacogenetically hazardous drugs: a proposed new scoring method.

Similar doses of a drug given to different individuals can result in widely disparate plasma concentrations and hence effects. Beside intraindividual differences also inter-ethnic differences of drug response must be taken into consideration. Both inter-individual and inter-ethnic variations of drug response are mostly related to genetic factors (polymorphism) involved in drug metabolism and kinetics. The farmacogenetic disorders involved clinically result in pharmacogenetic side effects. In order to avoid pharmacogenetic side effects, beside phenotyping of the patients, selection of drugs subjected to different pharmacogenetic disorders may be of great clinical importance. Therefore, a scoring method was carried out for the selection of pharmacogenetically hazardous drugs. With regard to both genetic and environmental factors influencing the drug response, 140 suspicious drugs were studied and classified with the method. Eighteen was the maximum point value for genetic and 12 for contributing factors involved, so 30 was the maximum point number in each drug studied. Out of 140 substances 50 drugs (qualified with 20 points or more) proved to be hazardous in different pharmacogenetic disorders, among them several widely used agents, e.g. Diazepam, Isoniazid, Phenytoin, Warfarin, Quinidine, Tolbutamide, etc. The article sums up the findings in a Table and comments them. This scoring method may be useful in drug safety and preventive medicine.