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Biomedical subjects

M Sokolowska

Publications and source records attributed to M Sokolowska.

At least 19 recordsLinked to original sources

Synthesis and properties of N-methyl and N-phenyl derivatives of 1,4-dioxo-1,2,3,4-tetrahydropyrido[3,4-d]pyridazines.

2-Methoxy- and 2-ethoxy-6-methyl-3,4-pyridinedicarboximides (XI, XII) reacted with N-methylhydrazine giving 2- and 3-methyl derivatives of the appropriate 1,4-dioxo-1,2,3,4-tetrahydropyrido[3,4-d]pyridazines (XV, XIII and XVI, XIV). In both cases 3-methyl isomer (XIII, XIV) was formed in higher yield than 2-methyl derivative (XV, XVI). Reaction of the imide XII with N-phenylhydrazine gave the salts of the suitable N-phenyldihydropyrido[3,4d]pyridazines with NH2-NHC6H5 (XXI and XXII) which transformed into N-phenylaminoimide (XXIII) during the boiling in 80% CH3COOH. Imide XXIII isomerized to the appropriate 2-phenyl and 3-phenylpyrido[3,4-d]pyridazines (XXIV - main reaction product and XXV) under the influence of heating in ethanolic solution of C2H5ONa. Some of N-phenylpiperazinylhydroxyalkyl(alkyl) derivatives of compound XXIV (XXVII, XXVIII) were pharmacologically active.

Analgesics, Non-Narcotic↗

Effect of acute administration of 1,2,3,4-tetrahydroisoquinoline on the levels of glutathione and reactive oxygen species, and on the enzymatic activity of gamma-glutamyl transpeptidase in dopaminergic structures of rat brain.

The effect of acute administration of 1,2,3,4-tetrahydroisoquinoline, an endogenous substance suspected of producing Parkinsonism in humans, on the levels of glutathione and reactive oxygen species and on the enzymatic activity of gamma-glutamyl transpeptidase was investigated in the substantia nigra, striatum and cortex of rat brain. Four hours after a single dose of 1,2,3,4-tetrahydroisoquinoline (100 mg/kg i.p.), a significant increase in tissue glutathione level was found in the dopaminergic structures studied. The most pronounced effect was observed in the substantia nigra and cortex, and the weakest in the striatum. At the same time, significant inhibition of gamma-glutamyl transpeptidase was observed in the substantia nigra, cortex and striatum whose extent strictly corresponded to the increase in glutathione levels in those structures. Moreover, in 1,2,3,4-tetrahydroisoquinoline-treated rats, the production of reactive oxygen species was significantly reduced in the substantia nigra, whereas it was markedly enhanced in the striatum.Our results suggest that the increase in tissue glutathione level in the dopaminergic structures studied results from inhibition of gamma-glutamyl transpeptidase and refers to the extracellular pool of this peptide. Moreover, it is likely that both the 1,2,3,4-tetrahydroisoquinoline-induced alterations in glutathione level and the enhanced production of reactive oxygen species in the striatum may have implications for the pathogenesis of Parkinson's disease.

Animals↗

Gonadotropin production and release in female goldfish (Carassius auratus) after administration of pimozide and an LHRH analogue as studied by electron microscopy and radioimmunoassay.

The effect of pimozide and an LHRH-analogue (LHRH-A) on gonadotropic cells of the goldfish pituitary gland were described qualitatively and quantitatively. A scale of four categories was devised to reflect various ultrastructural appearances of the cells. Experimental animals were divided into a control group, a group injected with LHRH-A alone, pimozide alone, and groups receiving these two substances in combination. Fish injected with the single substance were killed 12 h after injection while the groups receiving the combined treatments were killed at 4, 12 and 48 h. Serum levels of gonadotropin measured by radioimmunoassay were used to indicate whether an increase in hormone release had occurred. An immunocytochemical technique, the protein A-gold procedure, assured that the cells studied were gonadotropes. The control group showed variation in the profiles of gonadotropic cells. The single treatment groups showed some increase in secretory inclusions. At 4 h after injection the combined treatment caused a significant increase in hormone granules; at 12 and 48 h there was a gradual decrease in content of secretory products, and an increase in vacuolization. The results indicate that the combined pimozide and LHRH-A treatment stimulated gonadotropin production as well as release.

Animals↗

The temporal sequence of changes in oocyte maturation and ovarian steroid hormone production during induced ovulation in the common carp, Cyprinus carpio.

Oocytes taken from carp sacrificed 3-24 hr after injection with either carp hypophysial homogenate (chh) (primed) or saline (control) were incubated with or without chh for 24 hr at 20 degrees. In oocytes from the primed fish the percentage of peripheral germinal vesicles at sacrifice progressively increased with time from injection. No such change occurred in control fish. After incubation with chh, tissue from primed fish showed a progressive increase in oocyte maturity with increasing time between priming and sacrifice, with germinal vesicle breakdown (GVBD) in 50% of the oocytes in incubations begun 24 hr after priming. In contrast, incubated tissue from control fish showed no variation with time between saline injection and sacrifice, and oocyte maturity did not exceed 50% with peripheral germinal vesicles. GVBD was not significant in these fish. 17-Hydroxyprogesterone, testosterone, and testosterone glucuronide production in vitro showed no major changes with the interval between injection and sacrifice, nor between control and primed fish. In vitro production of 17,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta P), however, increased significantly between tissue taken from animals at 3 and at 6 hr after injection of chh, and thereafter remained unchanged. 17,20 beta P production preceded the increase in GVBD in primed fish but neither this hormone nor GVBD was found in incubations of control fish, supporting the suggestion that 17,20 beta P is the maturation-inducing hormone in carp. Steroid production was not detectable in the absence of chh in the incubation medium and oocyte maturation showed little advance on that at sacrifice.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗

Increased gonadotropin levels in goldfish do not result in alterations in circulating thyroid hormone levels.

To determine whether increases in gonadotropin levels are capable of altering thyroid function in goldfish, plasma thyroid hormone levels were measured following induced changes in endogenous gonadotropin secretion and injection of carp gonadotropin. Radio-frequency lesions placed in the nucleus preopticus periventricularis or monosodium-L-glutamate-induced lesions of the posterior nucleus lateralis tuberis (NLT) of the hypothalamus were capable of stimulating significant increases in plasma gonadotropin levels, but were without effect on plasma triiodothyronine (T3) or thyroxine (T4) at time intervals ranging from 5 hr to 10 days. Likewise, injections of a superactive analog of gonadotropin-releasing hormone resulted in profound increases in gonadotropin levels without associated changes in thyroid hormones. No changes in the circulating levels of T4 or T3 were observed in response to injection of purified carp gonadotropins whereas injection of bovine thyrotropin or carp pituitary extracts stimulated significant increases in T4. Radiofrequency lesions of the pituitary stalk or of the anterior NLT also resulted in significant increases in circulating levels of T4, but not of T3, at 10 and 30 hr postlesion. These results demonstrate that direct acute stimulation of circulating thyroid hormone levels is not an intrinsic action of endogenous goldfish gonadotropin and that activation of the reproductive system, leading to ovulation in some cases, is without effect on blood total thyroid hormone levels. Additionally, these results confirm that hypothalamic inhibition of the pituitary-thyroid axis exists in this teleost fish and demonstrate that interruption of this inhibition results in a time-dependent, high-magnitude increase in circulating thyroxine levels.

Animals↗

Health sector structures: the case of Poland.

A 'portrait' of the health system in Poland is presented in the context of Polish historical, political, cultural and socio-economical developments. As a sensitive indicator of overall societal functioning, the health system suffers from the grave systemic pathologies which are reflected in petrified, rigid structures, a continuous underfinancing and underinvestment, and a lack of adequate information. It is argued that: several problems of the Polish health system are characteristic of industrialized countries; the National Health Care in Poland bears more responsibilities than the National Health Care in Britain; the Polish health system deserves special appreciation for its desperate coping in the most difficult situation.

Female↗

Characterization of gonadotropin-releasing hormone (GnRH) binding to pituitary receptors in goldfish (Carassius auratus).

Goldfish pituitary gonadotropin-releasing hormone (GnRH) receptors were characterized by using a superagonist analog of teleost GnRH (tGnRH-A; [D-Arg6, Trp7, Leu8, Pro9-NHEt]-GnRH). Equilibrium binding of 125I-tGnRH-A to a goldfish pituitary membrane preparation was achieved after a 30-min incubation at 4 degrees C; binding was significantly reduced after increasing incubation temperature to 22 degrees C. Binding of the radioligand was a function of tissue concentration, with a linear correlation over the range of 0.5-2 pituitary per tube. Incubation of the pituitary membrane preparation with increasing concentrations of 125I-tGnRH-A indicated saturable binding at radioligand concentrations of 470 pM and above. The binding of 125I-tGnRH-A was found to be reversible after addition of the cold analog, and the dissociation curve could be resolved into two linear components; slower rates of dissociation of 125I-tGnRH-A were observed after the addition of excess unlabeled tGnRH than after the addition of tGnRH-A, indicating that the analog is more effective in displacing the label than the native peptide. Addition of the cold analog displaced bound 125I-GnRH-A, and Scatchard analysis suggested the presence of at least two classes of binding sites: a high-affinity/low-capacity site and a low-affinity/high-capacity site. Bound 125I-GnRH-A was displaced by tGnRH from both sites in parallel to that observed with tGnRH-A, indicating that both peptides bind to the same classes of binding sites; however, tGnRH-A had a greater affinity for the receptors than the native tGnRH. These results demonstrated the presence and provided characterization of GnRH receptors in goldfish pituitary.

Animals↗

Seasonal effects of pimozide and des Gly10 [D-Ala6] LH-RH ethylamide on gonadotrophin secretion in goldfish.

The seasonal changes in the gonadotrophin-release-inhibitory activity of dopamine and responsiveness to gonadotrophin-releasing hormone were investigated by determining the effects of injection of pimozide, a dopamine receptor antagonist, des-Gly10 [D-Ala6] LH-RH ethylamide (LRH-A), or the combination of pimozide plus LRH-A on serum gonadotrophin (GtH) levels of goldfish, held at 12 or 20 degrees C, at different stages of gonadal development. As in previous studies, pimozide greatly potentiated the GtH-release response to LRH-A. The highest concentrations of serum GtH induced by injection of pimozide or LRH-A alone, or the combination of pimozide plus LRH-A were in females in late stages of ovarian recrudescence; fish that were sexually regressed (males and females combined) were the least responsive, and fish that were in early stages of gonadal recrudescence, and mature females ( = prespawning, completed ovarian recrudescence) were intermediate. Fish held at 20 degrees C had a more rapid onset of GtH release and had higher serum GtH levels initially compared to fish at 12 degrees C at similar sexual stages; however, the fish held at 12 degrees C generally had a more prolonged increase in serum GtH levels, indicating that temperature influence the time course of the GtH-release response. The results indicate that there is a seasonal variation in responsiveness to injection of pimozide, LRH-A and the combination of pimozide plus LRH-A. These seasonal changes may be due to differences in the pituitary content of GtH, the ability of the pituitary to synthesize GtH, or changes in GtH cell receptors for GnRH and dopamine, or a combination of these and other unknown factors.

Animals↗

Structure-activity relationships of mammalian, chicken, and salmon gonadotropin releasing hormones in vivo in goldfish.

Mammalian, chicken, and salmon gonadotropin releasing hormones (GnRHs), and anlogs of each peptide, were injected either alone or in combination with pimozide into goldfish, and the changes in serum gonadotropin (GtH) levels determined. The native peptides had similar potencies in terms of magnitude and duration of the GtH response. Analogs of LHRH that are superactive in mammals are also superactive in goldfish; although [(imBzl)-D-His6, Pro9-NEt]-LHRH is very highly superactive in mammals it has activity similar to [D-Ala6, Pro9-NEt]-LHRH in goldfish. D-Ala6 or (imBzl)-D-His6 substitutions of [Trp7, Leu8, Pro9-NEt]-LHRH are not superactive in goldfish, whereas the D-Arg6 substitution is highly superactive, indicating that there are differences in the factors that make salmon and mammalian GnRH superactive. These results also indicate that the structural modifications that determine superactivity of GnRHs in goldfish differ from what is known for mammals.

Animals↗

Effects of catecholaminergic agonists and antagonists on serum gonadotropin concentrations and ovulation in goldfish: evidence for specificity of dopamine inhibition of gonadotropin secretion.

The elevated serum gonadotropin (GtH) levels in goldfish receiving two injections of des Gly10, [D-Ala6] LH-RH ethylamide (LH-RH-A), given 12-hr apart, were reduced by apomorphine, a dopamine agonist, injected at either the first or the second LH-RH-A injection. Serum GtH concentrations in goldfish given two injections of LH-RH-A at a 3-hr interval were also depressed by bromocriptine, a specific D-2 dopamine receptor agonist, administered simultaneously with both LH-RH-A injections. Injections of dopamine antagonists, pimozide or metoclopramide (a specific D-2 antagonist) caused increased serum GtH concentrations in normal goldfish, but no changes were found following injections of the alpha-adrenergic antagonist phentolamine, the beta-adrenergic antagonist propranolol, or the sympathomimetic agent octopamine. Injection of pimozide or metoclopramide at the time of the second of two LH-RH-A injections given at an interval of 12 hr potentiated the LH-RH-A-induced increase in serum GtH concentrations; injections of phentolamine, propranolol, or octopamine did not alter the response to LH-RH-A. Injections of pimozide or metoclopramide also increased the frequency of ovulation in LH-RH-A-injected gravid female goldfish. These results suggest that stimulation of dopamine receptors can block the potentiating effect of multiple injections of GtH-releasing hormone, as well as ongoing LH-RH-A-stimulated release. The results also indicate that the dopamine inhibition of GtH secretion is specific and may be mediated by receptors resembling the D-2 type receptors in mammals.

Animals↗

Cognitive development and social policy.

The city of Warsaw was razed at the end of World War II and rebuilt under a socialist government whose policy was to allocate dwellings, schools, and health facilities without regard to social class. Of the 14,238 children born in 1963 and living in Warsaw, 96 percent were given the Raven's Progressive Matrices Test and an arithmetic and a vocabulary test in March to June of 1974. Information was collected on the families of the children, and on characteristics of schools and city districts. Parental occupation and education were used to form a family factor, and the district data were collapsed into two factors, one relating to social marginality, and the other to distance from city center. Analysis showed that the initial assumption of even distribution of family, school, and district attributes was reasonable. Mental performance was unrelated either to school or district factors; it was related to parental occupation and education in a strong and regular gradient. It is concluded that an egalitarian social policy executed over a generation failed to override the association of social and family factors with cognitive development that is characteristic of more traditional industrial societies.

Child↗

Women's emancipation and socialsm: the case of the People's Republic of Poland.

Determinants of occupational position in Poland, as elsewhere, include the socialization process, access to education, and the employment structure. The socialization process includes the domestic pattern of division of labor, occupational models encountered in person and in the various media, and parental and social pressures, including vocational counseling. Ecuational access is a critical determinant of the extent and type of participation in the labor force as well as attitudes toward work. Although Poland has made major attempts to improve the socialization process and acces by type of program, disparties are still encountered in pay received for similar work, and for work in positions that cannot be explained by differences in productivity or education. Employment policies being undertaken or considered include measures to improve working conditions and occupational position, to socialize a larger number of "domestic" tasks, and to provide more flexibility via part-time work and longer maternity leaves.

Attitude↗