RESUMO
BACKGROUND: Controversial findings regarding the association between pro-inflammatory cytokines and depression have been reported in pregnant subjects. Scarce data about anxiety and its relationships with cytokines are available in pregnant women. To understand the association between anxiety and cytokines during pregnancy, we conducted the present study in women with or without depression. METHODS: Women exhibiting severe depression (SD) and severe anxiety (SA) during the 3rd trimester of pregnancy (n = 139) and control subjects exhibiting neither depression nor anxiety (n = 40) were assessed through the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). Serum cytokines were measured by a multiplex bead-based assay. Correlation tests were used to analyze the data and comparisons between groups were performed. A general linear model of analysis of variance was constructed using the group as a dependent variable, interleukin concentrations as independent variables, and HDRS/HARS scores and gestational weeks as covariables. RESULTS: The highest levels of Th1- (IL-6, TNF-α, IL-2, IFN-γ), Th17- (IL-17A, IL-22), and Th2- (IL-9, IL-10, and IL-13) related cytokines were observed in women with SD + SA. The SA group showed higher concentrations of Th1- (IL-6, TNF-α, IL-2, IFN-γ) and Th2- (IL-4, and IL-10) related cytokines than the controls. Positive correlations were found between HDRS and IL-2, IL-6, and TNF-α in the SA group (p < 0.03), and between HDRS and Th1- (IL-2, IL-6, TNF-α), Th2- (IL-9, IL-10, IL-13) and Th17- (IL-17A) cytokines (p < 0.05) in the SD + SA group. After controlling the correlation analysis by gestational weeks, the correlations that remained significant were: HDRS and IL-2, IL-6, IL-9, and IL-17A in the SD + SA group (p < 0.03). HARS scores correlated with IL-17A in the SA group and with IL-17A, IL-17F, and IL-2 in the SD + SA group (p < 0.02). The linear model of analysis of variance showed that HDRS and HARS scores influenced cytokine concentrations; only IL-6 and TNF-α could be explained by the group. CONCLUSIONS: We found that the cytokine profiles differ when comparing pregnant subjects exhibiting SA with comorbid SD against those showing only SA without depression.
Assuntos
Ansiedade/imunologia , Depressão/imunologia , Complicações na Gravidez/imunologia , Adulto , Transtornos de Ansiedade , Estudos de Casos e Controles , Citocinas/sangue , Feminino , Humanos , Interleucina-10/sangue , Interleucina-17/sangue , Gravidez , Gestantes , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
Progesterone participates in the regulation of several functions in mammals, including brain differentiation and dopaminergic transmission, but the role of progesterone in dopaminergic cell differentiation is unknown. We investigated the effects of progesterone on dopaminergic differentiation of embryonic stem cells using a five-stage protocol. Cells were incubated with different progesterone concentrations during the proliferation (stage 4) or differentiation (stage 5) phases. Progesterone added at 1, 10 and 100 nm during stage 4 increased the number of dopamine neurones at stage 5 by 72%, 80% and 62%, respectively, compared to the control group. The administration of progesterone at stage 5 did not induce significant changes in the number of dopamine neurones. These actions were not mediated by the activation of intracellular progesterone receptors because RU 486 did not block the positive effects of progesterone on differentiation to dopaminergic neurones. The results obtained suggest that progesterone should prove useful with respect to producing higher proportions of dopamine neurones from embryonic stem cells in the treatment of Parkinson's disease.
Assuntos
Diferenciação Celular/fisiologia , Dopamina/metabolismo , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Embrionárias/fisiologia , Neurônios/efeitos dos fármacos , Progesterona/farmacologia , Animais , Células-Tronco Embrionárias/citologia , Antagonistas de Hormônios/farmacologia , Masculino , Camundongos , Mifepristona/farmacologia , Neurônios/fisiologiaRESUMO
We studied the effects of oestradiol and progesterone on progesterone receptor (PR) isoform content in the brain of ovariectomized rats and in intact rats during the oestrous cycle by Western blot analysis. In the hypothalamus and the preoptic area of ovariectomized rats, PR-A and PR-B content was increased by oestradiol, whereas progesterone significantly diminished the content of both PR isoforms after 3 h of treatment in the hypothalamus, but not in the preoptic area. In the hippocampus, only PR-A content was significantly increased by oestradiol while progesterone significantly diminished it after 12 h of treatment. In the frontal cortex, no treatment significantly modified PR isoform content. During the oestrous cycle, the lowest content of PR isoforms in the hypothalamus was observed on diestrus day and, by contrast, in the preoptic area, the highest content of both PR isoforms was observed on diestrus day. We observed no changes in PR isoform content in the hippocampus during the oestrous cycle. These results indicate that the expression of PR isoforms is differentially regulated by sex steroid hormones in a regionally specific manner.
Assuntos
Química Encefálica/fisiologia , Estradiol/farmacologia , Ciclo Estral/fisiologia , Progesterona/farmacologia , Receptores de Progesterona/metabolismo , Animais , Western Blotting , Química Encefálica/efeitos dos fármacos , Estradiol/metabolismo , Estrogênios/metabolismo , Feminino , Isomerismo , Proteínas do Tecido Nervoso/metabolismo , Ovariectomia , Progesterona/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Progesterona/efeitos dos fármacosRESUMO
The synthesis of dihydrotestosterone (DHT) is catalyzed by steroid 5alpha-reductase isozymes 1 and 2, and this function determines the development of the male phenotype during embriogenesis and the growth of androgen sensitive tissues during puberty. The aim of this study was to determine the cytosine methylation status of 5alpha-reductase isozymes types 1 and 2 genes in normal and in 5alpha-reductase deficient men. Genomic DNA was obtained from lymphocytes of both normal subjects and patients with primary 5alpha-reductase deficiency due to point mutations in 5alpha-reductase 2 gene. Southern blot analysis of 5alpha-reductase types 1 and 2 genes from DNA samples digested with HpaII presented a different cytosine methylation pattern compared to that observed with its isoschizomer MspI, indicating that both genes are methylated in CCGG sequences. The analysis of 5alpha-reductase 1 gene from DNA samples digested with Sau3AI and its isoschizomer MboI which recognize methylation in GATC sequences showed an identical methylation pattern. In contrast, 5alpha-reductase 2 gene digested with Sau3AI presented a different methylation pattern to that of the samples digested with MboI, indicating that steroid 5alpha-reductase 2 gene possess methylated cytosines in GATC sequences. Analysis of exon 4 of 5alpha-reductase 2 gene after metabisulfite PCR showed that normal and deficient subjects present a different methylation pattern, being more methylated in patients with 5alpha-reductase 2 mutated gene. The overall results suggest that 5alpha-reductase genes 1 and 2 are differentially methylated in lymphocytes from normal and 5alpha-reductase deficient patients. Moreover, the extensive cytosine methylation pattern observed in exon 4 of 5alpha-reductase 2 gene in deficient patients, points out to an increased rate of mutations in this gene.
Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Metilação de DNA , Isoenzimas/genética , Linfócitos/enzimologia , Sequência de Bases , Estudos de Casos e Controles , Primers do DNA , Humanos , Masculino , Reação em Cadeia da PolimeraseRESUMO
Progesterone receptor (PR) isoforms expression was determined in several regions of the prepuberal and adult male rat brain by using reverse transcription coupled to polymerase chain reaction. Rats under a 14:10-h light-dark cycle, with lights on at 0600 h were used. We found that in the hypothalamus of prepuberal animals the expression of both PR isoforms was similar, whereas PR-A expression was higher than that of PR-B in adults. In the cerebellum PR-B expression was predominant in both prepuberal and adult rats. In both ages PR-A and PR-B exhibited a non-significant tendency to be predominant in the hippocampus and the preoptic area respectively. In the frontal cortex and the olfactory bulb PR isoforms were expressed at a similar level. These results indicate a differential expression pattern of PR isoforms in the male rat brain and suggest that the tissue-specific expression of PR-A and PR-B is important for the appropriate response of each cerebral region to progesterone.
Assuntos
Química Encefálica/genética , Encéfalo/crescimento & desenvolvimento , Receptores de Progesterona/genética , Maturidade Sexual/fisiologia , Fatores Etários , Animais , Regulação da Expressão Gênica no Desenvolvimento , Hipocampo/química , Hipocampo/crescimento & desenvolvimento , Hipocampo/fisiologia , Hipotálamo/química , Hipotálamo/crescimento & desenvolvimento , Hipotálamo/fisiologia , Isomerismo , Masculino , Bulbo Olfatório/química , Bulbo Olfatório/crescimento & desenvolvimento , Bulbo Olfatório/fisiologia , Área Pré-Óptica/química , Área Pré-Óptica/crescimento & desenvolvimento , Área Pré-Óptica/fisiologia , Ratos , Ratos Wistar , Receptores de Progesterona/química , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Steroid hormone receptors are involved in the regulation of tumor growth. Two progesterone receptor (PR) isoforms have been identified in humans: a larger form (PR-B) and the N-terminally truncated one (PR-A). PR isoforms can exert opposite functions and are differentially regulated by estrogens. PR have been detected in several brain tumors including chordomas, however, it is unknown which PR isoform is expressed in brain tumors. The aim of this study was to determine by reverse transcription-polymerase chain reaction (RT-PCR) and by immunohistochemistry the expression pattern of PR isoforms in chordomas as well as its correlation with the expression of estrogen receptor a (ER-alpha). All studied chordomas expressed both PR and ER-alpha. PR-B was the predominant isoform in chordomas both at the mRNA and at the protein level. These data suggest that PR-B should be the predominant PR isoform expressed in human chordomas.
Assuntos
Cordoma/metabolismo , Receptores de Progesterona/metabolismo , Neoplasias Cranianas/metabolismo , Adolescente , Adulto , Cordoma/genética , Receptor alfa de Estrogênio , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Cranianas/genéticaRESUMO
Copulation in rabbits provokes behavioral and neuroendocrine changes in both sexes. To investigate if the activity of particular brain regions is modified accordingly we quantified, by the reverse transcription-polymerase chain reaction method, c-fos expression in the preoptic area, hypothalamus, hippocampus, and frontal cortex of male and female rabbits before mating, immediately afterwards, and 1 h later. Mating immediately increased c-fos expression in the hypothalamus of both sexes, the frontal cortex of females, and the preoptic area of males. c-fos expression did not change in the hippocampus after mating in either sex but decreased in the preoptic area of females following mating. Results show that mating provokes changes in brain activity, in a gender- and region-specific manner, which may underlie the behavioral and endocrine consequences of copulation in rabbits.
Assuntos
Encéfalo/citologia , Encéfalo/metabolismo , Regulação da Expressão Gênica/fisiologia , Proteínas Proto-Oncogênicas c-fos/genética , Comportamento Sexual Animal/fisiologia , Animais , Feminino , Masculino , RNA Mensageiro/metabolismo , CoelhosRESUMO
Progesterone participates in the regulation of several physiological processes in mammals. The biological response to progesterone is mediated by two forms of the progesterone receptor (PR) denominated PR-A and PR-B. The difference between them is that 164 amino acids of N-terminal of PR-B are absent in PR-A. Both PR isoforms are derived from a single gene but are generated from either alternative transcriptional or translational start sites, and are regulated by different estrogen-induced promoters. PR-B acts as a transcriptional activator in different cellular contexts whereas PR-A functions as a strong inhibitor of transcriptional activity. PR isoforms expression and function vary among target tissues such as the uterus, the mammary gland and the brain. The knowledge of the molecular mechanisms involved in the regulation of expression and function of PR isoforms will contribute to the understanding of fundamental biological processes such as sexual behavior and reproduction, and it will open the possibility of alternative therapies in fertility control as well as in the treatment of breast, endometrial and cerebral tumors.
Assuntos
Receptores de Progesterona/fisiologia , Sistema Nervoso Central/fisiologia , Humanos , Neoplasias/genética , Isoformas de Proteínas/fisiologia , Receptores de Progesterona/genéticaRESUMO
It has been suggested that some contraceptive derivatives of 19-nor-testosterone possess estrogenic activity that may facilitate the development of breast cancer. The aim of this work was to investigate the estrogenic properties of norethisterone (NET) and its A-ring-reduced derivatives by determining progesterone receptor (PR) and c-fos mRNA content of two estrogen-regulated genes in the uterus of ovariectomized rats. mRNA content was evaluated by Northern blot 1-6 h after 17 beta-estradiol administration. The highest PR and c-fos mRNA content was observed 3 h and 2 h after 17 beta-estradiol administration, respectively. NET did not modify either PR or c-fos mRNA content. In contrast, 5 alpha- and 3 beta, 5 alpha-NET significantly increased mRNA content of both genes. The increase in c-fos mRNA content induced by these reduced compounds was lower than that found with estradiol treatment. The overall results indicate that NET administration can indirectly induce estrogenic effects through the action of its 5 alpha-dihydro and 3 beta, 5 alpha-tetrahydro derivatives.
Assuntos
Anticoncepcionais Orais Sintéticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Genes fos/efeitos dos fármacos , Noretindrona/análogos & derivados , Noretindrona/farmacologia , Proteínas Proto-Oncogênicas c-fos/genética , Receptores de Progesterona/genética , Útero/metabolismo , Animais , Estradiol/farmacologia , Feminino , Ovariectomia , RNA Mensageiro/genética , Ratos , Ratos Long-Evans , Transcrição Gênica/efeitos dos fármacos , Útero/efeitos dos fármacosRESUMO
Rabbit submandibular glands produce secretions involved in olfactory communication. The histology of these glands and their secretory activity are: sexually dimorphic; vary across the female reproductive cycle; and are modified by gonadectomy. This suggests that gonadal steroids regulate the structure and function of such glands. To further support this idea we assessed by immunocytochemistry the presence of estrogen and progesterone receptors in male and female rabbit submandibular glands. Immunoreactivity was detected only in the nucleus of acini cells. The number of estrogen receptor-immunoreactive cells/field varied among estrus (26 +/- 6; mean +/- S.E.), ovariectomized (19 +/- 2), and ovariectomized-estrogen-treated animals (13 +/- 3). Intact males showed a significantly smaller number of estrogen receptor-immunoreactive cells/field (12 +/- 1) than estrous females. Interestingly, progesterone receptor-immunoreactive cells were more abundant in estrous (32 +/- 7) than in ovariectomized animals (7 +/- 1). Estradiol benzoate (5 micrograms daily for 5 days) increased the number of progesterone receptor-immunoreactive cells/field in ovariectomized females (17 +/- 1). Intact males showed fewer progesterone receptor-immunoreactive cells/field (16 +/- 2) than estrous females. Results show that the rabbit submandibular gland is a target for estrogen and progesterone and support the idea that these hormones participate in regulating the physiology of this gland.
Assuntos
Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Glândula Submandibular/metabolismo , Animais , Estradiol/farmacologia , Estro/fisiologia , Feminino , Imuno-Histoquímica , Masculino , Ovariectomia , Coelhos , Receptores de Estrogênio/efeitos dos fármacos , Receptores de Progesterona/efeitos dos fármacos , Caracteres Sexuais , Glândula Submandibular/citologia , Glândula Submandibular/efeitos dos fármacos , Distribuição Tecidual/fisiologiaRESUMO
Although the role of vitamins as prosthetic groups of enzymes is well known, their participation in the regulation of their genetic expression has been much less explored. We studied the effect of biotin on the genetic expression of rat liver mitochondrial carboxylases: pyruvate carboxylase (PC), propionyl-CoA carboxylase (PCC), and 3-methylcrotonyl-CoA carboxylase (MCC). Rats were made biotin-deficient and were sacrificed after 8 to 10 weeks, when deficiency manifestations began to appear. At this time, hepatic PCC activity was 20% of the control values or lower, and there was an abnormally high urinary excretion of 3-hydroxyisovaleric acid, a marker of biotin deficiency. Biotin was added to deficient primary cultured hepatocytes. It took at least 24 h after the addition of biotin for PCC to achieve control activity and biotinylation levels, whereas PC became active and fully biotinylated in the first hour. The enzyme's mass was assessed in liver homogenates from biotin-deficient rats and incubated with biotin to convert the apocarboxylases into holocarboylases, which were detected by streptavidin blots. The amount of PC was minimally affected by biotin deficiency, whereas that of the alpha subunits of PCC and of MCC decreased substantially in deficient livers, which likely explains the reactivation and rebiotinylation results. The expression of PC and alphaPCC was studied at the mRNA level by Northern blots and RT/PCR; no significant changes were observed in the deficient livers. These results suggest that biotin regulates the expression of the catabolic carboxylases (PCC and MCC), that this regulation occurs after the posttranscriptional level, and that pyruvate carboxylase, a key enzyme for gluconeogenesis, Krebs cycle anaplerosis, and fatty acid synthesis, is spared of this control.
Assuntos
Biotina/farmacologia , Carboxiliases/efeitos dos fármacos , Fígado/efeitos dos fármacos , Piruvato Carboxilase/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , Animais , Biotina/deficiência , Biotinilação , Carbono-Carbono Ligases/efeitos dos fármacos , Carbono-Carbono Ligases/metabolismo , Carboxiliases/genética , Carboxiliases/metabolismo , Eletroforese em Gel de Poliacrilamida , Fígado/citologia , Fígado/enzimologia , Masculino , Metilmalonil-CoA Descarboxilase , Piruvato Carboxilase/genética , Piruvato Carboxilase/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , EstreptavidinaRESUMO
In this work we determined progesterone receptor (PR) mRNA content in female rabbit lung during the first 5 days of pregnancy and in ovariectomized animals after subcutaneous injection of oestradiol benzoate (25 micrograms/kg) for 2 days or oestradiol benzoate (25 micrograms/kg) for 2 days plus a single dose of progesterone (5 mg/kg) on day three. On each day (0-5) of pregnancy and 24 h after the last dose in the case of the treated animals, animals were killed and lung was excised; total RNA was extracted and processed for Northern blot analysis. The results showed three main PR mRNA transcripts (6.1, 4.4 and 1.8 kb) in rabbit lung. The 4.4 kb species was the most abundant. PR mRNA content was markedly increased by oestradiol benzoate and downregulated by progesterone. It significantly increased on the first day of pregnancy and then diminished progressively, reaching its lowest value on day 5. These findings suggest that PR mRNA content in the rabbit lung is regulated by sex steroid hormones and changes according to the physiological concentrations of oestradiol and progesterone.
Assuntos
Hormônios Esteroides Gonadais/farmacologia , Pulmão/metabolismo , Prenhez/metabolismo , RNA Mensageiro/metabolismo , Receptores de Progesterona/genética , Animais , Northern Blotting , Densitometria , Estradiol/farmacologia , Feminino , Pulmão/efeitos dos fármacos , Gravidez , Progesterona/farmacologia , RNA Mensageiro/análise , CoelhosRESUMO
The effects of estradiol benzoate (EB) and progesterone (P4) upon progesterone receptor (PR) gene expression in the cerebral cortex and the hypothalamus of the rabbit were studied. Ovariectomized adult rabbits were subcutaneously treated with EB (25 micrograms/kg) for 2 days, and with EB (25 micrograms/kg) + a single dose of P4 (5 mg/kg) on day 3. Twenty-four hours after the last dose, the frontal cortex, the hypothalamus and the uterus were excised, total RNA was extracted and processed for reverse transcription-polymerase chain reaction. PR gene expression was induced by EB and down-regulated by P4 both in the frontal cortex and the hypothalamus in a manner similar to that observed in the uterus. The finding that PR gene transcription is regulated by steroid hormones in the cerebral cortex suggests that post-transcriptional processes are involved in the insensitivity of cortical PR protein to steroids regulation previously reported with binding techniques.
Assuntos
Córtex Cerebral/metabolismo , Estradiol/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hipotálamo/metabolismo , Progesterona/farmacologia , Receptores de Progesterona/genética , Animais , Regulação para Baixo , Feminino , Injeções Subcutâneas , Ovariectomia , Reação em Cadeia da Polimerase , Coelhos , Transcrição GênicaRESUMO
Progesterone (P4) and its metabolites are involved in several functions of the central nervous system (CNS). These steroids participate in neuronal excitability, reproduction and sexual behavior. P4 and its metabolites exert their effects on neurons and glial cells through several mechanisms that include the interaction of the steroids with: 1) intracellular specific receptors; 2) modulatory sites located in neurotransmitter receptors; and 3) ionic channels. By these mechanisms, modifications in gene expression, second messengers' production and ion conductance are induced. The activities of the P4 metabolites have been mainly related to membrane effects, whereas for P4, the transcriptional and translational effects are mediated by intracellular receptors. Thus, these steroids can modify the CNS functions at short (milliseconds), medium (minutes) or long term (hours or days) lapses. The knowledge of the molecular mechanisms involved in the actions of P4 and its metabolites in the CNS will contribute to the understanding of fundamental biological processes such as sexual behavior and reproduction, and it will open the possibility of alternative therapies in the treatment of some neurologic and psychiatric disorders such as epilepsy, anxiety, premenstrual syndrome, and cerebral tumors which possess hormonal regulation.
Assuntos
Sistema Nervoso Central/fisiologia , Progesterona/fisiologia , Animais , Estradiol/fisiologia , Regulação da Expressão Gênica/fisiologia , Humanos , Canais Iônicos/fisiologia , Progesterona/metabolismo , Receptores de Progesterona/fisiologia , Reprodução/fisiologia , Transdução de Sinais/fisiologia , Transmissão Sináptica/fisiologiaRESUMO
Norethisterone (NET) is a synthetic progestin, used as a contraceptive agent, that is biotransformed at target tissues into 5 alpha-NET and 3 beta,5 alpha-NET, which possess different pharmacological properties. The effects of these metabolites on the expression of uteroglobin (UG) and progesterone receptor (PR) genes, both regulated by progesterone (P4), were evaluated in the uterus of prepubertal female rabbits that were simultaneously treated with P4 (1.0 mg) for 5 consecutive days. As determined by Western and Northern blot analyses, 5 alpha-NET inhibited the P4-induced UG gene expression in a dose-dependent manner. A similar inhibition was observed with the administration of RU-486. The estrogenic agent 3 beta,5 alpha-NET and estradiol at a dose of 1.0 mg also inhibited the UG gene expression induced by P4. Both 5 alpha-NET and 3 beta,5 alpha-NET blocked the PR down-regulation induced by P4 as assessed by Western and Northern blot methods. The inhibition of UG synthesis and PR down-regulation by 5 alpha-NET and 3 beta,5 alpha-NET indicates that these NET metabolites possess antiprogestational properties.
Assuntos
Expressão Gênica/efeitos dos fármacos , Noretindrona/metabolismo , Receptores de Progesterona/genética , Uteroglobina/genética , Animais , Northern Blotting , Western Blotting , Regulação para Baixo/efeitos dos fármacos , Feminino , Noretindrona/farmacologia , Progesterona/antagonistas & inibidores , Progesterona/farmacologia , RNA Mensageiro/metabolismo , Coelhos , Útero/efeitos dos fármacos , Útero/metabolismoRESUMO
Norethisterone (NET) has been used as a contragestational postcoital agent. It is biotransformed to 5 alpha dihydro-NET (5 alpha-NET) and 3 beta,5 alpha tetrahydro-NET (3 beta,5 alpha-NET) in target tissues. The participation of these metabolites in NET effects is unknown. We have examined the antiimplantation and antiprogestational effects of NET and its metabolites, in adult mated female rabbits, by assessing the number of implantation sites and the expression products of the uteroglobin (UTG) gene in the uterus, and by comparing them with those of RU-486 and estradiol. Steroids were daily administered s.c. at several doses for 7 consecutive days, starting 24 hr after coitus. To assure that fertilization occurred in all animals, the presence of early pregnancy factor was determined. The results demonstrated that high doses (5 mg/kg) of NET reduced both implantation and the expression of the UTG gene. On the other hand, lower doses (1.5 mg/kg) of 5 alpha-NET produced an antiimplantation effect and suppressed UTG synthesis and its mRNA. These effects were similar to those of RU-486. At lower doses (1 mg/kg), both estradiol and the estrogenic metabolite 3 beta,5 alpha-NET were also effective in inhibiting implantation and UTG gene expression. The overall results suggest that NET metabolites exert antiimplantation and antiprogestational effects through their interaction with progesterone and estrogen receptors, and provide an explanation for the molecular mechanisms involved in the postcoital contraceptive action of NET.
Assuntos
Implantação do Embrião/efeitos dos fármacos , Endométrio/metabolismo , Noretindrona/análogos & derivados , Noretindrona/farmacologia , Uteroglobina/biossíntese , Útero/fisiologia , Animais , Biotransformação , Relação Dose-Resposta a Droga , Endométrio/efeitos dos fármacos , Estradiol/farmacologia , Feminino , Fertilização , Masculino , Mifepristona/farmacologia , Noretindrona/metabolismo , Gravidez , Coelhos , Fatores de Tempo , Útero/efeitos dos fármacos , Útero/metabolismoRESUMO
There is a high incidence of rheumatic endocarditis in our environment. Therefore it is important to know the structural characteristics of the valvular lesions in order to better understand the physiopathologic pathways of tissue injury. We have chosen a non-conventional method, the scanning electron microscopy. There were very few such reports in the current literature. We analyzed ten mitral valve with rheumatic scarring lesion and five normal, as a control group. We were able to establish three structural patterns. 1) Stone pavement like (endocardium with nuclear bulge cells and marginal folds at the cell boundaries, abundant number of microvillous projections and few areas of endothelial loosening). 2) Cerebroid (subendothelium with wrinkles caused by deformity of the valve with or without endothelial loosening) and 3) Smooth pattern (flattened endothelium with scanty microvillous projections and abundant areas of endothelial denundation and exposition of subendothelium). More damage was noted in the auricular surface of the rheumatic group, characterized by a predominance of the smooth pattern. We found Lambl's excrecences in two mitral leaflets, they were formed by collagen break fascicles of the subendothelium. This technique allowed us to analyze integrity of the endocardial selective barrier and the interactions between the damaged surface of the valve and elements of the peripheral blood and showed more endocardial injury in the rheumatic group. These alterations could play an important role in the pathogenesis of this disease.
Assuntos
Valva Mitral/ultraestrutura , Cardiopatia Reumática/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Doenças das Valvas Cardíacas/patologia , Humanos , Microscopia Eletrônica de Varredura , Pessoa de Meia-IdadeRESUMO
The knowledge about rheumatic diseases in Latin American children is scanty. The features of Juvenile Rheumatoid Arthritis (J.R.A.) in the islands of the Caribbean had not been described. In this retrospective study, fifty cases of J.R.A. in a pediatric population of Puerto Rico and the Virgin Islands followed at a formal pediatric rheumatology service in San Juan, Puerto Rico, were demographically and clinically characterized. There was a female predominance of 1.4:1. The peak of occurrence was at 1-2 years of age. Pauciarticular onset was the most common through all ages. Antinuclear antibodies and rheumatoid factor were positive in 40% and 10% respectively. Although a larger and prospective study is necessary to determine if these clinical trends will prevail, the present findings suggest that the characteristics of J.R.A. among children in the Caribbean are similar to other previously published series in U.S.A. and Europe.