The antiepileptic effects of sodium valproate and the calcium antagonist riodipine when used jointly in a model of generalized korazol-induced epileptic activity]

In experiments on male Wistar rats on the model of generalized pentylenetetrazol-induced epileptic activity the efficacy of the combination of the drugs influencing different mechanisms of epileptogenesis: sodium valproate enhancing GABA-ergic processes and calcium antagonist, ryodipine (1,4-dihydropyridine), have been studied. Sodium valproate and ryodipine when used in combination at relatively small doses (70 and 0.75 mg/kg, respectively) produced more marked antiepileptic effect than each of these drugs given alone. The results obtained suggest that complex pathogenetic therapy (CPT) as a combination of antiepileptic drugs acting on corresponding basic mechanisms of respective form of epilepsy is reasonable to be used. According to our previous results, CPT can reduce the risk of side effects of each drug due to decreased doses. CPT may be of great importance in case of long-term treatment.     

Effects of PN 200-110 on penicillin-induced epileptic activity in the cerebral cortex of rats]

In experiments on freely moving Wistar rats it was shown that an intraperitoneal administration of PN 200-110 in a dose of 2 mg/kg in the period of steady epileptic activity (EpA) with regular generation of ictal discharges in penicillin--induced focus resulted in suppression of EpA in most animals. Antiepileptic effect of the drug was manifested by decreasing frequency appearance of ictal discharges and shortening of the epileptic focus existence time. Intraperitoneal administration (5 mg/kg) and intraventricular injection (10 nmol) of PN 200-110 20 min before the epileptic focus formation resulted in an increased latency period of appearance interictal discharges and decreased number of ictal discharges, and shortening of the existence time of epileptic focus.     

Isolation and certain properties of human pituitary prolactin]

A simple method of isolation of highly purified prolactin from acetonated preparations of anterior hypophysial lobes is described. The new method permits to obtain higher (about 10-fold) yields of the hormone, as compared to those obtained using previously described methods. Prolactin was extracted by acid aqueous acetone and was subsequently purified of extract by fractionation with acetone and NaCl and by isoelectric precipitation. The final stage of the hormone purification involved gel-filtration through Sephadex G-200; prolactin yield was 400 microgram per 1 hypophysis. The lactogenic activity of the hormone is 14 MU/mg; the sequence of N-terminal amino acid residues of prolactin is as follows: NH2-Leu-Pro-Ile-x-Pro-Leu(?)-Gly-Ala-.     

New Hybrid Molecules Based on Sulfur-Containing Nicotinonitriles: Synthesis,Analgesic Activity in Acetic Acid-Induced Writhing Test,and Molecular Docking Studies

Russian Journal of Bioorganic Chemistry - New hybrid molecules bearing furyl and 1,4-dihydronicotinonitrile (or 1,4,5,6-tetrahydronicotinonitrile) fragments have been prepared. The analgesic...     

Involvement of proteolytic enzymes in the lipotropic effect of the pituitary polypeptide hormones

The influence of proteinase inhibitors on the lipolytic effect of the pituitary polypeptide hormones and epinephrine in an isolated adipose tissue of rabbits and rats has been studied. Neither of proteinase inhibitors changed the basal rate of lipolysis. Trasylol, a serine proteinase inhibitor, suppressed completely growth hormone (GH) effect and partially reduced the effect of adrenocorticotropin (ACTH) and beta-lipotropin (beta-LPH) but did not change the effect of epinephrine. Bacitracin proved ineffective with regard to the effect of polypeptide hormones. Pepstatin, an acid proteinase inhibitor, partially blocked the stimulation of lipolysis by ACTH without affecting the effect of GH and beta-LPH. The influence of proteinase inhibitors on the ACTH effect in rat adipose tissue was similar to that found in rabbit tissue. The Trasylol-induced inhibition of the hormone-stimulated lipolysis decreased to a considerable extent after GH or ACTH incubation with rabbit plasma or partial GH digestion with pepsin. This decrease was not observed when plasma serine proteinases were blocked during GH incubation with plasma. The results demonstrate an involvement of some proteolytic enzymes in the realization of the polypeptide hormone lipolytic effect and permit to suppose the requirement of preliminary activation of the hormones by means of proteolytic modification.     

Computer bank of amino acid sequences of protein hormones. Comparative analysis of the sequences in pro-opio-melanocortin, proenkephalin and prodynorphin: detection of phorphin--the 4th repeating peptide in prodynorphin

Using a BESM-6 computer, a computer system for accumulation and comparative analysis of amino acid sequences (AS) of protein-peptide hormones and their precursors (the so-called computer bank of protein hormone AS) was developed. A Fortran-based program designed for construction of correspondence schemes of AS and their local similarity profiles was elaborated. In combination with the previous programs this system allows a rapid inclusion of the newly deciphered sequences into the corresponding homologous groups, thus complementing the correspondence scheme and specifying the evolution profiles. A comparative analysis of AS in proopiomelanocortin (POMC), proenkephalin (PENK) and prodynorphin (PDIN) revealed evolutionary-conservative and variable sites. The conservative sites of AS are active centers of the hormones. The leu-enkephalin analog, phorphin, the fourth repeating peptide of this precursor, was detected in prodynorphin, which, similar to beta-neo-endorphin, dynorphin and rimorphin may possess a biological activity. The similarity of the effector sites of the melanotropin sequence from POMC to the met-enkephalin sequence from PENK and leu-enkephalin sequence from PDIN as well as to gastrin and cholecystokinin was established. This may suggest that the hormone-receptor complexes in target organs of these hormones are also similar.     

Luteinizing hormone of the sperm whale. Amino acid sequences of reduced and carboxymethylated beta-subunits

The amino acid sequence of reduced and carboxymethylated beta-subunit of the luteinizing hormone of the sperm-whale was established. The beta-subunit was found to consist of 118 amino acid residues, the N- and C-terminal amino acids being proline and leucine, respectively. The carbohydrate moiety is linked to the asparagine residue at position 13.     

Alterations in microsomal and plasma membranes during liver regeneration.

Investigations have been carried out on the alterations of membrane lipids and some enzyme activities during liver regeneration. The results indicated that 32 h after partial hepatectomy the membrane phospholipids per mg protein were augmented. The cholesterol esters were also increased in both microsomal and plasma membranes. The specific radioactivity of the separate phospholipid fractions, estimated by incorporation of 14C-palmitate into the phospholipid molecules, was higher in membranes from partially hepatectomized rats, compared to sham-operated ones, indicating an enhanced phospholipid synthesis. The content and specific radioactivity of diacylglycerols and triacylglycerols was enhanced in both types of membranes from regenerating liver. Moreover, we observed a fluidization of these membranes, which is illustrated by the decrease of the structural order parameter (SDPH) of the lipid bilayer as well as by the elevation of the excimer to monomer fluorescent ratio (IE/IM). 1,6-Diphenyl-1,3,5-hexatriene and pyrene were used as fluorescent probes for determination of the membranes physical state. Palmitoyl-CoA and oleoyl-CoA synthetase, acyl-CoA: lysophosphocholine and acyl-CoA:lysophosphoethanolamine acyltransferase as well as phospholipase C activities were augmented in membranes from partially hepatectomized rats. The biological significance of these alterations in the process of liver regeneration is discussed.     

Spectral studies of beta-melanocyte-stimulating hormone and beta-lipotropic hormone fragment]

Secondary structure of beta-melanocyte-stimulating hormone was studied by circular dichoism and infra-red spectroscopy. Left-helical conformation of poly-L-proline II type which was stabilized by temperature reduction was found in aqueous solution; in 60% ethanole the quota of this structure sharply decreased. The investigation of hormone films at different values of relative humidity (in the course of H--D metabolism) made it possible to discover a twisted beta-form and an elongated helix of poly-L-proline II type. Temperature induced changes of circular dichroism spectra specify the peculiarities of poly-L-proline II conformation in C-end fragment of beta-lipotropic hormone.