Effect of intramolecular interactions on circular dichroism of ortho-substituted 1-phenethylamines.

The synthesis of ortho-substituted (S)-1-phenethylamines via ortho-lithiation of its N,N-dimethyl derivative followed by reactions with different reagents is described. Circular dichroism spectra of synthesized compounds were measured. It is shown that the observed short-wave Cotton effects greatly depend on the existence of cyclic structure due to possible interactions such as hydrogen bond or electrostatic interaction.

Influence of serotonin on the development and migration of gonadotropin-releasing hormone neurones in rat foetuses.

This study used a pharmacological approach to evaluate the consequences of the metabolic perturbations of neurotransmitters on brain development. Pregnant rats received p-chlorophenylalanine (pCPA), an inhibitor of serotonin (5-hydroxytryptamine, 5-HT) synthesis, or saline (control) from the 11th day of gestation once or daily up to the 15th, 17th and 20th day, followed by processing of the forebrain and/or nasal cranium of foetal males and females for high-performance liquid chromatography of monoamines, radioimmunoassay of gonadotropin-releasing hormone (GnRH) and quantitative and semiquantitative immunocytochemistry for GnRH. The pCPA treatment resulted in a 50-70% depletion of 5-HT in the nasal crania and forebrains at any studied age. Radioimmunoassay showed no change in GnRH content in 5-HT deficient foetuses at E16 compared to controls, being higher in both cases in the rostral forebrain than in the hypothalamus. In controls at E21, the GnRH content in the hypothalamus exceeded that in the rostral forebrain, whereas in the 5-HT deficient group the opposite was found. These data suggest that 5-HT provided a stimulating effect on GnRH neurone migration, and this was confirmed by quantification of GnRH-immunoreactive neurones in the forebrain along the trajectory of their migration. At E18 and E21, the fractions of GnRH neurones in the rostral part of the trajectory in pCPA-treated foetuses were greater than those in control foetuses but the opposite was true for the caudal part of the trajectory. Moreover, 5-HT appeared to control the proliferation of the precursor cells of GnRH neurones and their differentiation, as derived from the observations of the increased number of GnRH neurones in the forebrain of foetuses of both sexes, as well as the region-specific decreased neuronal size and content of GnRH in 5-HT-deficient females. Thus, 5-HT appears to contribute to the regulation of the origin, differentiation and migration of GnRH neurones.

Minor groove binder-conjugated DNA probes for quantitative DNA detection by hybridization-triggered fluorescence.

Here we describe the properties of a novel class of oligonucleotide probes capable of sensitive hybridization-triggered fluorescence. These fluorogenic probes, known commercially as MGB Eclipse probes, are characterized by having a conjugated minor groove binder (MGB) ligand at the 5'-end and a fluorophore at the 3'-end. Additionally, they have an efficient quencher moiety at the 5'-end that is useful with a wide variety of fluorescent dyes. Fluorescence of the single-stranded MGB Eclipse probe is efficiently quenched by the interaction of the terminal dye and quencher groups when not hybridized. Upon hybridization to a complementary target, the MGB molecule folds into duplex and hyper-stabilizes it, allowing the use of shorter, more specific probe sequences. The 5'-MGB-quencher group also prevents nuclease digestion by Taq DNA polymerase during PCR. Because of the hybridization-triggered fluorescence and the excellent specificity imparted by the MGB, these 5'-MGB Eclipse probes have great versatility for real-time PCR applications. The high sensitivity and specificity are illustrated using single nucleotide polymorphism detection, viral load determination, and gene expression analysis.

Role of sex hormones in development of pituitary adenoma.

Role of sex hormones in the development of pituitary adenomas was investigated by analyzing the content of nuclear estradiol and testosterone receptors in different tumors of the anterior pituitary: prolactinomas, meningiomas, growth hormone-producing adenomas, astrocytomas, neurinomas, and ependymomas. The concentration of nuclear estrogen and androgen receptors in prolactin-secreting pituitary adenomas was much higher than in growth hormone-producing adenomas and other pituitary tumors.

Catalyzed asymmetric dialkylzinc addition to benzaldehyde in the presence of new chiral ligands--delta-(1-phenethyl)aminoalcohols.

A series of delta-aminoalcohols prepared from (S)- and (R)-N,N-dimethyl-1-phenethylamines was found to catalyze the enantioselective addition of diethylzinc to benzaldehyde to yield optically active 1-phenylpropanol with enantiomeric excess 60-85%.

Luteinizing hormone-releasing hormone in thymus and hypothalamus of rat fetuses: suppressing effect of antagonist and of antibodies on concanavalin A-induced proliferation of thymocytes.

The effect of endogenous luteinizing hormone-releasing hormone (LHRH) on the proliferation induced by concanavalin A (Con A) in rat fetal thymocytes was studied. A selective antagonist (2 microg per fetus) or antibodies to LHRH (20 microl per fetus) were injected in utero into 20-day-old rat fetuses, and this resulted in a two- or fivefold decrease in the Con A-induced proliferation of thymocytes, respectively. In combined culture of the antagonist (10-5-10-6 M) with fetal thymocytes, the proliferative response was not decreased. The concentration of LHRH was determined by radioimmunoassay in tissues of immunocompetent organs and in blood serum of 18- and 21-day-old fetuses, and the hormone was found in the hypothalamus, thymus, and peripheral blood. The initially low level of LHRH in the thymus increased by 65 and 40%, respectively, on the first day after birth and became similar to the level in the hypothalamus. In the fetal blood serum, the LHRH level was significantly higher than in the thymus and hypothalamus of fetuses of the same age. The hormone concentration was greatest in the 18-day-old fetuses, and it decreased twofold by the 21st day. The findings indicate that LHRH is involved in regulation of T-cell immunity even during prenatal ontogenesis.

A new method for the postsynthetic generation of abasic sites in oligomeric DNA.

The abasic site is the most common lesion in DNA and is thought to play a critical role in mutagenesis. However, a general chemical method for the site-specific generation of true abasic sites in oligodeoxynucleotides has been lacking. We now describe a procedure which permits the postsynthetic generation of abasic sites in single- or double-stranded DNA oligomers without regard to their base composition. An appropriately protected 3-deoxyhexitol was synthesized and used as the monomer that was incorporated into DNA oligomers using the standard phosphoramidite method for automated DNA synthesis. The resulting stable diol-containing oligonucleotides were purified by HPLC and converted quantitatively into the corresponding abasic DNA sequences by mild periodate oxidation. The abasic site in DNA was found to be relatively stable at room temperature, but was completely cleaved when treated with putrescine at 95 degrees C. Identification of the major degradation products was accomplished by gel electrophoresis, HPLC isolation, and characterization by electrospray ionization mass spectrometry. The thermal stabilities of duplex oligonucleotides containing a natural abasic site were studied, and the results were compared with those from oligomers containing T/dA, F/dA, or the precursor diol opposite dA at the same site.

[Relationship between regulatory effects of serotonin and testosterone on the development of the LHRH producing system of the rat brain during the prenatal period of development]. / Vzaimosviaz' reguliatornykh vliianii serotonina i testosterona na razvitie liuliberinprodutsiruiushchei sistemy mozga u krys v prenatal'nom periode razvitiia.

We have performed radioimmunoassay of LHRH in rostral and septal-preoptic brain regions, as well as in mediobasal hypothalamus of male and female fetuses at day 21 of the prenatal period after the injection to pregnant females on days 11-20 of gestation of either p-chlorophenylalanine (PCPA) or of a combination of PCPA with ethane-1,2-dimethane sulfonate (EDS). Control animals received the injection of the same volume of physiological saline. In the control fetuses, both males and females, the level of LHRH in the rostral brain region was significantly lower than in the septal-preoptic region. The administration of PCPA increased the level of LHRH in the rostral brain region and decrease it in the septal-preoptic region, the effect being more prominent in males. When EDS was administered on the background of PCPA administration, sex-related differences in the level of LHRH in the studied brain regions were no longer present. It is proposed that serotonin stimulates migration of LHRH neurons in rostral-caudal direction, and this effect of serotonin is more significant in males, since it is potentiated by testosterone.

Neuroendocrine control of the gonadotropic function of the hypophysis in experimental diabetes.

The stability of the function of the reproductive system depends on a multitude of factors of the internal and external milieux. Serious disturbances in its function, with alterations in carbohydrate homeostasis, underlie such diseases as diabetes mellitus. Disturbances to the functional activity of the reproductive system in laboratory animals with diabetes are known to be associated not only with destructive changes in the gonads, but also with dysfunction of the hypothalamo-hypophyseal complex [9, 11]. Published data show that these lesions have different severities in male and female individuals [7, 8]. The question of the extent to which lesions due to the diabetic state depend on the level of sex steroids and insulin in the body thus far remains unanswered. Unlike the situation in males, females are characterized by cyclic changes in the activity of the reproductive system. Thus, it is possible that differences in the regulation of gonadotropic function in male and female rats, observed in normal animals, could explain their different sensitivities to diabetes. Thus, we elected to carry out various studies of the functional activity of the hypothalamo-hypophyseal-gonadal system in male and female rats with experimental diabetes induced by administration of streptozotocin (STZ).

[Phosphorus-containing inhibitors of penicillin acylase. 4. Irreversible inhibition of penicillin acylase from Escherichia coli by monoaryl esters of benzylphosphonic acid]. / Fosfor-soderzhashchie ingibitory penitsillinatsilazy. 4. Neobratimoe ingibirovanie penitsillinatsilazy iz Escherichia coli monoarilovymi éfirami benzilfosfonovoi kisloty.

Monoaryl of benzylphosphonic acid have been synthesized and studied as the inhibitors of penicillin acylase. These compounds were found to be effective and selective irreversible inhibitors of the enzyme. The kinetic parameters of enzyme inactivation are determined, and possible mechanism of the inhibition is discussed. These phosphonates should be useful as both penicillin acylase active site titrants and the tools for the enzyme function study. Benzylchloromethyl keton has been also prepared and it is an irreversible inhibitor of penicillin acylase.

[Development of the reproductive system in the progeny of rats with streptozotocin diabetes]. / Stanovlenie reproduktivnoi sistemy u potomstva krys, bol'nykh streptozototsinovym diabetom.

Specificities of functioning and development of the reproductive system and mechanism of its regulation with hypothalamic structures were studied in the progeny of rats with streptozotocin diabetes. For this purpose pituitary sensitivity was analyzed in mature animals, as was functional capacity of the feedback system mediating the hypothalamic regulation of gonadotropin secretion in rat males and females at the age when this system normally starts functioning in health. The hypothalamo-hypophyseo-gonadal system feedback mechanism was found to develop in the progeny of female rats with streptozotocin diabetes later than in health. Pituitary sensitivity to LH-RH was reduced and LH level reduced by 1.5 times in mature progeny of rats with streptozotocin diabetes as compared to that in the progeny of healthy rats. These results permit a conclusion that the progeny of rats with streptozotocin diabetes develop disorders in the mechanism regulating the reproductive system of the body, though not so grave as to make this system functioning impossible.

[Development of hypothalamic regulation of gonadotropic function of the pituitary in hypoinsulinemic rats]. / Formirovanie gipotalamicheskoi reguliatsii gonadotropnoi funktsii gipofiza v usloviiakh gipoinsulinemii u krys.

Effects of temporary hypoinsulinemia induced by streptozotocin in neonatal age on the development of the mechanism of hypothalamic regulation of hypophyseal gonadotropic function in rats were studied. With this aim the authors analyzed the status and functional capacity of feedback system mediating hypothalamic regulation of gonadotropin secretion in female and male rats at the age when this system starts functioning in health. Streptozotocin injection in the neonatal age induced a reduction of estradiol concentration and of estradiol and progesterone-stimulated preovulatory peak of luteinizing hormone (LH) in 28-day-old females and a reduction of LH concentration in 28-day-old castrated males. Reduced estradiol and LH peak were observed in adult females injected streptozotocin during the first week of life and reduced LH level in adult males. These results permit a hypothesis that streptozotocin administration to rats in the neonatal age disturbed the mechanism of hypophyseal gonadotropic function regulation in mature rats.