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.     

Excitable membranes--object for evaluating the effect of heavy metal pollution

In acute experiments the interaction of heavy metals (CdCl2 and HgCl2) with neurotransmitters (ACh and 5HT) was studied on the excitable membrane of the identified neurons in the central nervous system of Helix pomatia L. (Gastropoda, Mollusca). It was shown that cadmium and mercury ions exert different influence on both resting and action potentials as well as on the responsiveness of the neural membranes to ACh and 5HT. The selective blocking effect of cadmium and mercury ions can be interpreted on the basis of specificity of postsynaptic receptor structures responsible for the transmitter action and of ion-channels involved in the excitatory processes. The heavy metal effect was not uniform for the different types of neurons, suggesting that pollutants can modify various functions to a different degree. The results show that testing on nerve cell membranes can serve as a useful method and model in investigating the effect of sublethal environmental contamination, as they may cause a profound modulation on the elements of the neural circuitry responsible for the regulation of the animal's behavior.     

The effect of dopamine on the release of prolactin in sheep with lesions of the hypothetical centre producing prolactin inhibiting factor (PIF)

It has been demonstrated in our previous papers that in the anterior part of medial basal hypothalamus (AM BH) in sheep a stimulating, while in the caudal part of MBH (CMBH) an inhibiting centre of prolactin release are situated. These results suggested that CMBH might be the site of PIF production and prompted us to investigate the effect of dopamine (DA) on the concentration of prolactin in the peripheral blood (p.bl.) in animals in which CMBH had been previously lesioned and this concentration was very high. Microinfusion of L-dopamine into the third cerebral ventricle (c.v.) or into the internal maxillary artery in intact as well as in lesioned lactating ewes depressed distinctly the prolactin level in the p.bl. This action of DA suggests that in the CMBH exists dopaminergic system which itself plays an inhibitory role in the control of prolactin release without involvement of PIF.     

Alpha 1-adrenoceptor blocking properties of spiroxatrine in rat aorta.

This preliminary study has analyzed the potential ability of the 5-HT1A ligand spiroxatrine to interact with vascular alpha 1-adrenoceptors. Norepinephrine and the selective alpha 1-adrenoceptor agonist, methoxamine, elicited concentration-dependent contractions of rat aortic rings. In contrast, (+/-)-spiroxatrine (from 10(-8) to 3.1X10(-7) M) was devoid of any effect on vascular tone per se, but shifted the concentration-response curves of norepinephrine and methoxamine to the right in a concentration-dependent manner with pA2 values of 8.48 +/- 0.22 and 8.93 +/- 0.33, respectively. Endothelium removal did not significantly affect the above pA2 values of (+/-)-spiroxatrine. These data, taken in concert, support the contention that (+/-)-spiroxatrine displays alpha 1-adrenoceptor blocking properties in rat aortic rings.     

Drought tolerance increases with seed size in a semiarid grassland from southern Mexico

Plant Ecology - Due to increased reserves available to face adverse conditions, drought tolerance should increase with seed size. This has been confirmed in the laboratory, but under field...     

Synergistic effects of kinship, sex and rank in the behavioural interactions of captive stump-tailed macaques

In almost all non-human primate species kinship, sex and rank bias the patterning of interactions among subjects, seemingly in a way that favours the individual's fitness. A number of studies have been done in order to study separately the effects of these variables, concluding that an adequate model of interactions cannot be developed assuming preponderance of a single variable. The 'willingness' of one animal to interact with another can be explained as the result of assessing the possible outcomes (proximate and/or ultimate) of the interaction. The interrelationship of variables such as kinship, sex and rank, among others, provides the actors with a basis for deciding their rates of social interactions. The following study was done to assess whether kinship, rank and sex exerted independent, additive effects in the within-group distributions of eight social behaviour categories of captive groups of stump-tailed macaques. We found that the three variables synergistically affected the patterning of all behavioural categories. This suggests that the pay-offs of social interactions do not vary linearly, being intrinsically correlated with the actors' attributes so that uncertainty in the choice of a potential partner is minimized.