RESUMEN
Allele frequencies for 13 tetrameric short tandem repeat (STR) loci, CSF1PO, D18S51, D3S1358, D21S11, D5S818, FGA, D7S820, HUMTH01, D8S1179, TPOX, D13S317, VWA, and D16S539 were determined on 198 Turkish blood samples.
Asunto(s)
Frecuencia de los Genes , Secuencias Repetidas en Tándem/genética , Humanos , TurquíaRESUMEN
OBJECTIVE: Our objective was to evaluate the direct effect of tamoxifen citrate (TAM) on the endometrium, liver, breast tissue and the lipid profile in oophorectomized (OX) rats. STUDY DESIGN: An experimental animal study. MATERIAL AND METHODS: Forty-one mature rats (33 OX) were randomly divided into four groups and received either TAM (0.4 or 0.8 mg/kg p.o.) therapy or placebo over 60 days as follows: (1) sham; (2) OX + TAM (0.4 mg/kg); (3) OX + TAM (0.8 mg/kg); (4) OX. All histological changes in the endometrium, liver and breast tissue were evaluated under the light microscope by comparing the TAM-treated groups with the OX and sham-operated groups. Blood total cholesterol and low-density lipoprotein cholesterol levels were also analyzed. RESULTS: TAM-treated rats showed a significant reduction in body weight, blood cholesterol and low-density lipoprotein cholesterol levels, but the wet uterine weight was not affected. Estrogenic effects of TAM were not detected with either dosage on the endometrium. TAM-treated groups showed atrophic breast tissue. No histopathological changes were detected in the liver with TAM treatment. CONCLUSION: The data suggests that TAM may not act as an estrogen receptor agonist with the given dosage on the endometrium in OX rats. Two different doses of TAM do not cause histological changes in liver over 60 days of treatment.
Asunto(s)
Ovariectomía , Tamoxifeno/farmacología , Animales , Atrofia , Colesterol/sangre , LDL-Colesterol/sangre , Endometrio/efectos de los fármacos , Endometrio/patología , Femenino , Hígado/efectos de los fármacos , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/patología , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Wistar , Útero/anatomía & histología , Pérdida de PesoRESUMEN
The effects of chronic stress on the renin-angiotensin-aldosterone system were studied by analysis of plasma hormone levels, kidney renin mRNA levels, adrenal angiotensin II receptors, and steroidogenesis in rats subjected to repeated immobilization (2 h daily) or intraperitoneal injections of 1.5 M NaCI for 14 d. 24 after the last stress in both stress models, plasma aldosterone levels were reduced in spite of significant increases in plasma renin activity. Repeatedly intraperitoneal hypertonic saline-injected rats showed plasma renin activity responses to acute immobilization similar to controls, but markedly reduced plasma aldosterone responses. Concomitant with the increases in plasma renin activity, renin mRNA levels in the kidney were significantly increased in intraperitoneal hypertonic saline-injected rats, and these increases were prevented by beta-adrenergic receptor blockade with propranolol. In isolated adrenal glomerulosa cells from chronically stressed rats, maximum aldosterone responses to angiotensin II, ACTH, and 8-Br-cAMP were significantly decreased, whereas pregnenolone responses were increased. P450-aldosterone synthetase mRNA levels and binding of 125I-[Sar1,Ile8] angiotensin II were significantly reduced in the adrenal zona glomerulosa of stressed rats. These studies show that chronic repeated stress leads to renin stimulation due to sympathetic activation, and inhibition of aldosterone secretion due to inhibition of the late steroidogenic pathway. The data provide evidence for a role of chronic stress in the development of hyperreninemic hypoaldosteronism.
Asunto(s)
Glándulas Suprarrenales/enzimología , Hormona Adrenocorticotrópica/sangre , Aldosterona/metabolismo , Corticosterona/sangre , Renina/sangre , Estrés Fisiológico/metabolismo , Estrés Psicológico/metabolismo , Hormona Adrenocorticotrópica/farmacología , Aldosterona/sangre , Angiotensina II/farmacología , Animales , Citocromo P-450 CYP11B2 , Sistema Enzimático del Citocromo P-450/biosíntesis , Expresión Génica , Hibridación in Situ , Técnicas In Vitro , Masculino , Pregnenolona/biosíntesis , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Restricción Física , Solución Salina Hipertónica/análisis , Esteroide 11-beta-Hidroxilasa/biosíntesis , Estrés Fisiológico/sangre , Estrés Psicológico/sangre , Zona Glomerular/efectos de los fármacos , Zona Glomerular/metabolismoRESUMEN
The changes in angiotensin II receptor subtypes, type 1 (AT1) and type 2 (AT2) binding, and AT1 mRNA levels during development were studied in the rat kidney using autoradiographic and in situ hybridization techniques. Autoradiographic analysis of 125I-[Sar1,Ile8]Ang II binding to slide-mounted kidney sections from 2 and 5 day-old rats discerned AT2 binding sites associated with advancing tubules and ampullae of the ureteric bud, and in the metanephric mass in the nephrogenic zone of the cortex. AT1 binding was present in the metanephric mass and immature glomeruli on days 2, 5 and 7 after birth. Differentiating and mature kidneys of 14-day, 21-day and 14-week old adult rats had solely AT1 receptor binding over glomeruli in renal cortex and in the inner stripe of the outer medulla. AT1 mRNA was expressed discretely as early as 2 days of age in the immature glomeruli and in a diffuse radiating pattern in the renal cortex. In the medulla, AT1 receptor mRNA expression appeared discretely on day 7 and reached peak levels on day 21 in the inner stripe of the outer medulla. The data indicate that AT1 receptor mRNA is developmentally regulated in rat kidney and its expression in the cortex precedes that of AT1 receptor ligand binding. The temporal pattern of expression of binding for both receptor subtypes suggests that while AT2 receptors may be involved in cell proliferation and early differentiation of the nephron, AT1 receptors have a dual role, early in nephron differentiation and later in development in renal function.
Asunto(s)
Riñón/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Angiotensina/genética , Receptores de Angiotensina/metabolismo , Animales , Animales Recién Nacidos , Autorradiografía , Regulación del Desarrollo de la Expresión Génica , Hibridación in Situ , Riñón/crecimiento & desarrollo , Corteza Renal/crecimiento & desarrollo , Corteza Renal/metabolismo , Médula Renal/crecimiento & desarrollo , Médula Renal/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Receptores de Angiotensina/clasificaciónRESUMEN
Fetal alcohol syndrome (FAS) is a set of signs and symptoms in offsprings born to mothers who abuse alcohol during pregnancy. We postulated that impairment in the placental endocrine function contribute to FAS. In this study, we examined in vitro effects of ethanol on the placental cells' (cytotrophoblast cells) capacity to synthesize progesterone. Cytotrophoblast cells were isolated from normal term placenta and were incubated (2 x 10(6)) with 20-, 30-, and 40-mM doses of ethanol for 6 h. Progesterone was measured in the incubate by RIA. The results showed that, at the 20-mM dose of ethanol, progesterone synthesis was significantly decreased (p less than 0.01), at the 30-mM dose level there was a further decrease of 20%. The differences between 30- and 40-mM ethanol dose levels were not significant. To determine the mechanism of ethanol effects on progesterone synthesis, cytotrophoblast cells were preincubated with 30 mM ethanol followed by 10 microliters of LDL (10 microliters LDL = 80 micrograms cholesterol) and vice versa. The results showed that ethanol effects on progesterone synthesis was dependent on whether ethanol was added prior to or following the addition of LDL in the medium. If ethanol was added in the medium prior to LDL, progesterone synthesis was decreased significantly (p greater than 0.01); however, when ethanol was added after the LDL, ethanol had no effect on progesterone synthesis. In the experiment where ethanol and LDL were added simultaneously in the medium, ethanol blunted the stimulatory effect of LDL on progesterone synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Etanol/toxicidad , Placenta/efectos de los fármacos , Progesterona/biosíntesis , Relación Dosis-Respuesta a Droga , Femenino , Trastornos del Espectro Alcohólico Fetal/etiología , Humanos , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacología , Placenta/metabolismo , Embarazo , Receptores de LDL/metabolismo , Trofoblastos/metabolismoRESUMEN
Recent developments in the field of oncogenes and growth stimulatory factors have provided limited but essential models in neuro-oncology. The observation in gliomas of platelet growth factor (PDGF)-like immunoreactivity fits with the autocrine secretion model, rising the possibility for the growth factor independence of the cancer cells. The discovery of the tumor suppressor genes, for which loss of function mutations are oncogenic as in the RB gene of the retinoblastoma and p53 gene, has introduced a new concept of oncogenesis which could be useful even in the cure of the neoplasms. Several oncogenes are amplified and/or expressed in brain tumors, some associated with polymorphism leading to abnormal protein products. Therefore, corresponding functions, such as production of deficient epidermal growth factor receptor (EGFR) encoded by erb-B, are impaired. Abnormal chromosomal patterns have been recognized in brain tumors and found mainly in chromosomes 7 and 22 on which oncogenes erb-B and sis are located, respectively. Location of proto-oncogenes, which are normally expressed in the brain, indicate that they share common distribution patterns mainly involving the cerebellum, hippocampus and olfactory bulbs. These proto-oncogenes may be regulated by physiological and pathological events. The concept of oncogene involvement in brain tumors must be extended to include the other factors such as G-proteins, growth factor receptors, membrane-associated and cytoplasmic protein kinases, which are all responsible for the control of the cell growth and their response to external signals including chemotherapeutic drigs.