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Biomedical subjects

A N Smirnov

Publications and source records attributed to A N Smirnov.

At least 19 recordsLinked to original sources

Nuclear melatonin receptors.

Current opinions on the potential role of orphan nuclear retinoid receptors of the ROR/RZR subfamily in regulatory activities of the pineal gland hormone melatonin are reviewed. The mechanisms of receptor--DNA interactions and known coactivators, tissue peculiarities of the expression of different receptor isoforms, and its regulation are described. The spectrum of probable targets for regulation by the receptors, the most promoted of which in this aspect being the immune and central nervous systems, is traced. It is clear that for final "adoption" of the orphan ROR/RZR receptors, there is need for a full collaboration of endocrinologists for solution of the still debatable questions whether and under which situations melatonin does serve as a physiological modulator of the activities of these receptors.

Animals↗

16alpha,17alpha-cycloalkane derivatives of progesterone intensively bind to a rat serum protein.

The interaction of 6alpha-methyl-[1,2-3H]16alpha,17alpha-cyclohexanoprogesterone with rat serum proteins has been studied. Specific binding of this ligand characterized by Kd = 0.36 +/- 0.10 microM and concentration of binding sites (Bmax) of about 1 microM (27.8 +/- 12.5 pmol/mg total protein) was found. According to competitive analysis, the affinity of the studied progestins to a protein that differs from transcortin was to some extent correlated with their hydrophobicity. The dissociation kinetics of 3H-ligand-protein complexes were biphasic, the binding sites forming stable and labile complexes with 3H-ligand being eluted in the same region during ion-exchange chromatography. In overall properties, the serum protein differs from the progesterone receptor and the pregna-D'-pentarane-specific protein from rat uterus. It is suggested that the revealed protein may provide high progestagenic activity of 6alpha-methyl-16alpha,17alpha-cyclohexanoprogesterone by prolonging its retention in the bloodstream.

Animals↗

Bioactive 5-reduced 16 alpha,17 alpha-cyclohexanoprogesterone derivatives weakly interact with proteins of the soluble uterine fraction.

We studied competitive activities of 16 alpha,17 alpha-cyclohexano-5 alpha- and 5 beta-dihydroprogesterone in replacing(3)H-progesterone and(3)H-16 alpha,17 alpha-cyclohexano-6 alpha-methylprogesterone from protein complexes. Direct binding of(3)H-5-reduced derivatives with proteins of soluble fractions from rat and rabbit uteri was also assayed. C(d) values for 5-reduced derivatives were in the micro- or submicromolar range. The data suggest that biological effects of these analogues are not mediated via soluble uterine receptors.

Animals↗

Expression of prolactin receptors in rat reproductive tissues during periovulatory prolactin imbalance.

Indirect immunoperoxidase technique in combination with cytophotometry showed that prolactin imbalance in the periovulatory period is characterized by considerable changes in the expression of prolactin receptors in uterine glands and endometrial stroma (but not in the myometrium) and in the pituitary gland and hypothalamus, while receptor compartmentalization pattern remains unchanged.

Animals↗

The size and/or configuration of the cycloalkane D' ring in pentacyclic progesterone derivatives are crucial for their high-affinity binding to a protein in addition to progesterone receptor in rat uterine cytosol.

[(3)H]labeled progesterone and a number of its 16alpha, 17alpha-cycloalkano derivatives with an additional three to six-membered D' ring were investigated for mutual competition and equilibrium binding to proteins from rat uterine cytosol. The interaction of all studied [(3)H]ligands with proteins was characterized by comparable affinity (K(d) in nM region) and apparent homogeneity in terms of affinity. At the same time, the concentrations of binding sites for ligands bearing 16alpha,17alpha cyclopentano, cyclohexano, or cyclohexeno substituents were several-fold higher than those for progesterone or 16alpha, 17alpha-cyclopropanoprogesterone. In mutual competition experiments, when [(3)H]progesterone or [(3)H]16alpha, 17alpha-cyclopropanoprogesterone were used, the curves of 'bound radioactivity-log of competitor concentration' for all compounds studied were parallel and corresponded to a model of 'one protein-two ligands.' However, when [(3)H]ligands with bulky 16alpha, 17alpha-substituents (with the possible exception of cyclohexene derivative) were used, competitive curves for various ligands had different appearances and fell into two groups. Parallel curves for derivatives with 5 or 6 carbons in D' ring described by a model of 'one protein-two ligands' formed the 1st group. The 2nd group comprised curves for progesterone or 16alpha, 17alpha-cyclopropanoprogesterone that had lower slopes and could be described by a model of 'two proteins-two ligands.' Taken together, the results suggest the presence in rat uterine cytosol, of a protein in addition to progesterone receptor capable of discriminating between ligands with no or small 16alpha, 17alpha-cycloalkano substituents and ligands with more bulky substituents.

Alkanes↗

[Surgical treatment of fecal incontinence in children].

The experience of the faeces incontinence treatment in 295 children (age ranged from 1 to 15 years) is presented. Several original operations for surgical correction of the sphincter ani asthenia are proposed. The authors think that radical correction of faeces incontinence in children is necessary as early as at the age 6 to 7 years that is at the beginning of social activity. Efficient use of the above methods of the rectum closing apparatus creation allowed to achieve good results in 77.3-85.7% of the children.

Adolescent↗

[Pentacyclic steroid analogs: interaction of 16 alpha,17 alpha-cyclopentanoprogesterone with rat uterus proteins].

Using 3H-labeled derivatives, kinetic parameters of specific binding of progesterone (I) and 16 alpha, 17 alpha-cyclopentanoprogesterone (II) to proteins of the uterus soluble fraction in rats were measured. It was shown that their affinities to proteins are comparable (K 10.5 +/- 2.4 and 6.7 +/- 3.4 nM for (I) and (II), respectively, upon 22 h incubation). The unlabeled compound (II) can displace [3H]progesterone from complexes with the protein with a concentration-independent efficiency corresponding to the ratio of K values for compounds (I) and (II). At the same time, the efficiency of the unlabeled progesterone in the displacement of [3H]compound (II) from protein complexes fell with an increase in the progesterone concentration. The concentration of high-affinity sites of [3H]compound (II) exceeded by 1.5 to 2 times the concentration of sites for [3H]progesterone. Dynamics of dissociation of proteins complexes of [3H]progesterone and 3H]compound (II) had a two-phase character with a decrease in the dissociation rate constants for both phases as the times of exposition of [3H]ligands to proteins grew. The ratio of slow- and fast-dissociating ligand-receptor complexes was thereby unchanged. These data suggest the presence in the rat uterus soluble fraction of two types of proteins differing in the capacity to recognize the additional five-membered ring D' in the steroid molecule.

Animals↗

Laparoscopy in the treatment of intussusception in children.

PURPOSE: The technique and outcome of minimally invasive laparoscopic treatment of various forms of intussusception in children after ineffective attempt at conservative treatment are described. METHODS: Ninety-eight patients from 2 months to 11 years of age were analyzed. RESULTS: Suggested scheme of surgical treatment using laparoscopic technique was successful in 64 patients (65.3%), and conversion to open procedure occurred in 34 (34.7%). There was no mortality or intraoperative complications in our series. CONCLUSION: Practically every form of intussusception without bowel necrosis, including the most complex forms, can be reduced now using modern videolaparoscopic equipment and atraumatic instruments.

Cecal Diseases↗

Interactions of 16alpha,17alpha-cyclohexane derivatives of progesterone with the progesterone receptor from rat uterus.

Pregna-D'-pentaranes, 16alpha,17alpha-cyclohexanoprogesterone and 6alpha-methyl-16alpha,17alpha-cyclohexanoprogestero ne, were found to specifically interact with the progesterone receptor of soluble fraction from rat uterus. The formation of complexes between 3H-labeled derivatives of these steroids and the protein was complete within 1 to 3 h at 0-4 degreesC. The dissociation of these complexes was a two-phase process, the contribution of the fast dissociating complexes decreasing with increasing preincubation time. The dissociation constant (k-1) values for progesterone, 16alpha, 17alpha-cyclohexanoprogesterone, and 6alpha-methyl-16alpha, 17alpha-cyclohexanoprogesterone complexes with the protein after 1 h preincubation were 6.5 +/- 0.8, 8.8 +/- 5.5, and (16.6 +/- 5.6).10(-4) sec(-1) for the fast phase and 5.1 +/- 0.5, 3.5 +/- 0.8, and (2.8 +/- 0.6).10(-5) sec(-1) for slow phase, respectively. The equilibrium Kd values were 11.7 +/- 2.1, 19.0 +/- 2.0, and 66.1 +/- 14.6 nM for progesterone, 16alpha,17alpha-cyclohexanoprogesterone, and 6alpha-methyl-16alpha,17alpha-cyclohexanoprogestero ne, respectively. The steroids mutually inhibited the binding of their 3H-labeled derivatives to the protein, the inhibition being of competitive type. In the case of [3H]6alpha-methyl-16alpha, 17alpha-cyclohexanoprogesterone, the inhibitory efficacy of progesterone declined with an increase of its concentration; this points to possible heterogeneity of binding sites for the 3H-labeled ligand. The comparison of the results with those obtained by us earlier (Biochemistry (Moscow), 1996, 61, 1034-1041) suggests the existence of significant species differences in progesterone receptor structure within or near the region that interacts with the D-ring of a hormone molecule.

Animals↗