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Biomedical subjects

I Belic

Publications and source records attributed to I Belic.

At least 19 recordsLinked to original sources

Predicting the anti-hypertensive effect of nitrendipine from plasma concentration profiles using artificial neural networks.

Nitrendipine is an effective and safe calcium-channel blocker for the treatment of mild to moderate hypertension. The aim of this study is to show that an artificial neural network (ANN) model of the relationship between nitrendipine plasma levels and pharmacodynamic effects can be built and used for pressure-drop prediction after oral administration of the drug in spite of the poor correlation between plasma concentrations and the effect. To achieve the goal, the following steps were taken: evaluation of the quality of the database for training the ANN, definition of the optimal input set for the ANN, and prediction of the diastolic pressure drop using the ANN. The possible consequences of successful ANN modelling are an optimisation of the drug administration regimen, to achieve the best possible effect, as well as optimal drug formulation for drugs with complicated pharmacokinetic/pharmacodynamic relationships.

Calcium Channel Blockers↗

Steroid hormone signalling system and fungi.

Three components of the steroid hormone signalling system, 17 beta-hydroxysteroid dehydrogenase, androgen binding proteins and steroid hormone signalling molecule testosterone were determined in the filamentous fungus Cochliobolus lunatus for the first time in a fungus. Their possible role in C. lunatus is discussed in comparison with their role in mammalian steroid hormone signalling system. The results are in accordance with the hypothesis, that the elements of primordial signal transduction system should exist in present day eukaryotic microorganisms.

17-Hydroxysteroid Dehydrogenases↗

Fungal 17 beta-hydroxysteroid dehydrogenase.

Two representatives of each of different fungal taxonomic classes were tested for constitutive 17 beta-hydroxysteroid dehydrogenase (HSDH) activity and the results were positive in all cases. The enzyme was found to be regioselective for C17 of the steroid ring and 20 beta-HSDH activity was only detected in Trichoderma viride. In most cases the oxidative pathway is favoured over the reductive pathway. The possible role of this enzyme in fungi is discussed.

17-Hydroxysteroid Dehydrogenases↗

Induction of steroidal 11 beta-hydroxylase of Cochliobolus lunatus.

The induction of steroidal 11 beta-hydroxylase of Cochliobolus lunatus was studied and the effect of the structure of steroid inducers and additives on the extent of enzyme induction determined. 21-Hydroxyprogesterone was found to be the best inducer and Torlak peptone 1 the best additive. A certain parallelism was found between the induction of 11 beta-hydroxylase of Cochliobolus lunatus and 11 alpha-hydroxylase of Rhizopus nigricans.

Detergents↗

11 beta-hydroxylation of steroids by Cochliobolus lunatus.

The substrate specificity of 11 beta-hydroxylase of Cochliobolus lunatus was studied and a close parallelism to the results obtained with 11 alpha-hydroxylase of Rhizopus nigricans was observed. It was found that the cell wall does not differentiate between the steroid substrates used and the absence of the cell wall increases the bioconversion.

Ascomycota↗

Hydroxylation of steroids with nonpolar side chains with 11 alpha-hydroxylase of Rhizopus nigricans.

Steroids with nonpolar side chains with 2, 4 and 8 C atoms were used as substrates for the 11 alpha-hydroxylase of Rhizopus nigricans. Their bioconversion was compared to that of progesterone, which was found to be far the best substrate giving the highest total bioconversion. 3-keto-4-ene steroids with nonpolar side chains were converted to their hydroxylated products in a small yield or not at all. The absence of an oxygen function in the side chain did not affect the regio-specificity of the hydroxylation, but resulted in a much lower total bioconversion. The strong effect of the oxygen function and of the length of the side chain on hydroxylation with the 11 alpha-hydroxylase of Rhizopus nigricans was demonstrated.

Hydroxylation↗

Hydroxylation of steroids with 11 alpha-hydroxylase of Rhizopus nigricans.

Three groups of 3-keto-4-ene steroids with different side chains were used as substrates for the induced 11 alpha-hydroxylase of Rhizopus nigricans. The highest total bioconversion as well as the highest yield of 11 alpha-hydroxylated product is found using progesterone as substrate. By changing the polarity of the side chain, much higher yields of 6 beta- and 7 beta-hydroxylated products relative to 11 alpha-hydroxylated product are obtained. Our results thus provide evidence for the importance of the side chain in steroid-enzyme interactions.

Bacterial Proteins↗

Bioconversion of steroid glycosides by Nocardia restricta.

The bioconversion of steroid alkaloid tomatine by Nocardia restricta yields the conjugate with lactic acid. We studied the bioconversion of some steroid glycosides without a nitrogen atom in the molecule to determine the effect of the nitrogen atom. The glycosides were of three different types: sterol glycosides, bufadienolide rhamnoside and steroid saponine. The results of bioconversions showed that Nocardia restricta converts steroid glycosides differently according to the sugar bound to the steroid aglycone. It can be concluded that in the absence of a nitrogen atom in the steroid molecule no conjugation with lactic acid by Nocardia restricta occurs.

Alkaloids↗