RESUMO
BACKGROUND: There is controversy in the literature concerning the effect of short-term insulin administration on blood pressure in different experimental situations, because in some experiments this association is clear, whereas in others it is nonexistent. OBJECTIVE: To investigate whether there is a difference in the effect of exogenous insulin administration on the blood pressure of normotensive Wistar-Kyoto (WKY) rats and hypertensive spontaneously hypertensive rats (SHR). METHODS: Hyperinsulinaemia was induced in normotensive WKY rats and in hypertensive SHR by the administration of long-acting insulin (insulin retard 0.4 U/kg body weight per day in one group and 0.8 U/kg body weight per day in another group) once a day, intraperitoneally, for 3 weeks. All of the rats drank a 10% sucrose solution, to prevent hypoglycaemia in those receiving insulin. RESULTS. Baseline serum levels were significantly higher in the SHR groups than in the WKY rat groups. At the end of the experiment, after 3 weeks' insulin therapy, systolic blood pressure measured by the tail-cuff method showed a significant increase in the SHR, but not in the WKY rats, possibly because of the genetic predisposition of the SHR to increase their blood pressure. The increase was similar in the SHR given 0.4 U/kg body weight per day insulin retard to that in those given 0.8 U/kg per day. CONCLUSIONS: Exogenous insulin increased systolic blood pressure in the SHR but not in the WKY rats. The rise was similar in rats receiving either 0.4 or 0.8 U/kg body weight per day insulin retard.
Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Hipoglicemiantes/efeitos adversos , Insulina/sangue , Animais , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/metabolismo , Insulina/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptor de Insulina/metabolismoRESUMO
BACKGROUND: Methimazole, an anti-thyroid drug, was recently found to be useful in the treatment of systemic lupus erythematosus and other autoimmune diseases. Moreover, decreased thyroid hormone production is associated with a variety of immunological manifestations, such as reduced activation of CD4+ cells, increased CD8+ cell activity and reduced soluble IL-2 receptors. In the present study we examined the effects of methimazole and propylthiouracil on a rat model of experimental colitis. METHODS: Colitis was induced by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB). Two weeks prior to induction of colitis, rats were treated by either methimaziole (0.04%) or propylthiouracil (0.01%) in drinking water after a week of free access to water. Rats were sacrificed 48 h or 7 days after induction of colitis. The colon was isolated, rinsed with ice-cold water and weighed. Damage was assessed both macroscopically and microscopically and myeloperoxidase (MPO) activity determined. RESULTS: All treated rats were hypothyroid as manifested by a significant elevation of thyroid stimulating hormone (TSH), by comparison with the control groups (mean -1.82 +/- 0.40 versus 0.11 +/- 0.02 mmol/L, respectively). The inflammatory response elicited by TNB resulted in severe mucosal damage 48 h after damage induction, which persisted for 7 days. Pre-treatment with either methimazole 0.04% or propylthiouracil 0.01% significantly decreased mucosal damage macroscopically (lesion area, lesion score and segmental weight) microscopically and also significantly decreased MPO level at both time points (P < 0.01). CONCLUSIONS: Methimazole and propylthiouracil significantly reduce mucosal damage and colonic weight in a rat model of colitis. The mode by which they do so remains to be studied.
Assuntos
Antitireóideos/farmacologia , Colite Ulcerativa/prevenção & controle , Mucosa Intestinal/efeitos dos fármacos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Mucosa Intestinal/enzimologia , Mucosa Intestinal/patologia , Masculino , Metimazol/farmacologia , Necrose , Peroxidase/metabolismo , Propiltiouracila/farmacologia , Ratos , Ratos Endogâmicos , Ácido Trinitrobenzenossulfônico/toxicidadeRESUMO
To investigate the effect of hyperinsulinemia on arteriolar hypertrophy, myocardial hypertrophy, and blood pressure, we administered insulin intraperitoneally to SHR and WKY rats for 3 consecutive weeks. To prevent hypoglycemia, the drinking water contained 10% sugar, and to accentuate the blood pressure, their chow contained 8% table salt. Blood pressure was measured by the tail-cuff method. Heart weights were factored with body weights. Arterioles of approximately 100 microns in diameter were examined at the end of the experiment and the vascular wall thickness was factored with the lumen diameter. At the end of 3 weeks, blood pressure rose in the SHR but not in the WKY rats. The heart weights in the WKY normotensive rats did not increase, whereas in the SHR they did. Furthermore, there was a significant rise in vessel wall thickness in the rats that received insulin, whether there was a rise in blood pressure or not and whether they had an increase in heart weight or not. There was a similar rise in blood glucose in all the groups, with slightly more accentuated rise in the SHR that received insulin. Nevertheless the increase in vascular wall thickness occurred only in the groups which received insulin. This seems to preclude the importance of hyperglycemia per se as the causative agent for the increase in vascular wall thickness in this study. The increase was in the form of medial hypertrophy without any sign of atherosclerosis. It seems, therefore, that hyperinsulinemia is associated with hypertrophy of the media of arterioles regardless of the increase in heart weight or the rise in blood pressure.
Assuntos
Arteríolas/patologia , Vasos Coronários/patologia , Insulina/sangue , Animais , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Hipertrofia , Injeções Intraperitoneais , Masculino , Tamanho do Órgão , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
Twenty-five women scheduled for hysterectomy for nonmalignant disease participated in the study. Sperm storage in endocervical crypts was examined in three groups of patients: nine women pretreated with estrogen and inseminated with normal semen, nine women pretreated with gestagen and inseminated with normal semen, and seven women pretreated with estrogen and inseminated with abnormal semen. The number of crypts containing spermatozoa (colonized crypts) and the sperm density per crypt were examined in serially sectioned cervices. In estrogen-pretreated cervices both the percentage of colonized crypts and the sperm density were significantly higher than in gestagen-pretreated cervices. Large and giant crypts proved to be the main storage facility for spermatozoa. The localization of crypts along the endocervical canal did not influence sperm storage. The quality of semen appeared to be of critical importance to sperm storage. The percentage of colonized crypts and sperm density were severly reduced in patients inseminated with abnormal semen.
PIP: This study investigated whether estrogen and gestagen influence the capacity pattern and retention time of sperms in endocervical crypts, determined whether the mean number of sperms in the lower part of the cervix was similar to or different from that in the upper part, and established whether the retention time of sperms in cervical crypts differed in the case of abnormal semen as compared with normal semen. 25 women, scheduled for hysterectomy for nonmalignant indications were studied. 3 groups of patients were studied for sperm storage measurements: 9 women were pretreated with estrogen and inseminated with normal semen; 9 women were pretreated with gestagen and inseminated with normal semen; and 7 women were pretreated with estrogen and inseminated with abnormal semen. Serially sectioned cervixes were studied to quantitate the number of crypts containing sperm (colonized crypts). In estrogen-pretreated subjects, the percents colonized crypts and sperm density were significantly higher than in gestagen-pretreated subjects' cervixes. The main storage of sperm occurred in large and giant crypts. Localization of crypts along the endocervical canal had no influence on sperm storage. Semen quality was of critical importance in sperm storage; the percentages of colonized crypts and sperm density were severely reduced in subjects inseminated with abnormal semen.
Assuntos
Colo do Útero/fisiologia , Espermatozoides/fisiologia , Muco do Colo Uterino/fisiologia , Colo do Útero/efeitos dos fármacos , Etinilestradiol/farmacologia , Feminino , Humanos , Inseminação Artificial , Masculino , Medroxiprogesterona/farmacologia , Contagem de Espermatozoides , Transporte Espermático/efeitos dos fármacosRESUMO
The AKR lymphoma-leukemia is a T lymphocyte neoplasm, most suitable as a model for human T cell malignancies. We have been interested in the process of tumor progression in the AKR lymphoma system. In the present study, two newly isolated variants, the TAU-42 and TAU-44, were characterized with respect to their biological behavior, by comparing them to a previously studied low-malignancy variant, the TAU-39. While the TAU-44 variant formed large s.c. local tumors, the TAU-42 variant formed only small growths or none at all. The TAU-42 lymphoma was found to have the highest malignant potential: it displayed very marked dissemination to spleen, lymph nodes, liver and lungs. The TAU-44 variant had an intermediate degree of metastatic potential but presented a predilection for spread to lymph nodes and spleen and was sometimes found to metastasize to peculiar organs, such as heart and pancreas. Cells derived from the different lymphoma variants varied in their immunophenotype: the highly malignant variant cells expressed more CD4 antigen than the low-malignancy one. The opposite was observed with regard to CD8. The variant cells also differed in their migrating capacity, the more malignant one exhibiting a higher motile activity. Studies on the tumor progression model of AKR lymphoma might contribute to the elucidation of the features determining the aggressiveness of T lymphocytic malignancies.
Assuntos
Linfoma de Células T/classificação , Linfoma de Células T/imunologia , Animais , Biomarcadores , Linfócitos T CD4-Positivos/química , Linfócitos T CD8-Positivos/química , Modelos Animais de Doenças , Neoplasias Cardíacas/secundário , Imunofenotipagem , Neoplasias Renais/secundário , Cinética , Neoplasias Hepáticas/secundário , Linfonodos/imunologia , Linfonodos/patologia , Camundongos , Camundongos Endogâmicos AKR , Neoplasias Pancreáticas/secundário , Neoplasias Esplênicas/secundário , Proteínas tau/análiseRESUMO
Massive splenomegaly is defined as a spleen weighing about 10 times normal weight. We describe a 36-year-old man who had huge splenomegaly and secondary pancytopenia simulating malignant lymphoma for about 3 months. Splenectomy was necessary because of the suspicion of hematologic malignancy, especially isolated lymphoma of the spleen, and pain and mechanical abdominal disturbances. On operation, the spleen was 25 cm long and weighted 250 g. There was florid, reactive follicular lymphoid hyperplasia. Immunohistochemical staining with CD-20(L26), CD-45Ro(UCHL), bcl-2 oncoprotein (Dakopatts), EBV (anti-EBV mol weight 60 KD, Dakopatts) was consistent with reaction to EBV infection and not with follicular lymphoma. Lack of PCR amplification using DNA extracted from paraffin-embedded splenic tissue indicated absence of a monoclonal B cell population carrying rearranged immunoglobulin genes. The lymphocytic population was proven polyclonal by the negative results of PCR for the bcl-2 gene rearrangement. EBV seroconversion from high titer antibodies of anti-EBV-VCA-IgM to negative, and from negative EBNA to positive was consistent with an apparent primary EBV infection. We have not found on computerized search a previous report of reactive follicular splenic hyperplasia to EBV infection causing huge splenomegaly, with or without EBV-induced infectious mononucleosis.
Assuntos
Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/isolamento & purificação , Baço/patologia , Esplenomegalia/etiologia , Adulto , Diagnóstico Diferencial , Humanos , Hiperplasia , Masculino , Reação em Cadeia da Polimerase , Esplenectomia , Esplenomegalia/patologia , Esplenomegalia/cirurgiaRESUMO
Iron supplementation is one of the principal therapies in inflammatory bowel disease. Iron is a major prooxidative agent; therefore therapeutic iron as well as heme iron from chronic mucosal bleeding can increase the iron-mediated oxidative stress in colitis by facilitating the Fenton reaction, namely production of hydroxyl radicals. In the present study colitis was induced in the iodoacetamide rat model. Forty male Whistar rats were divided into four groups, each group receiving a different diet regimen in parallel with colitis induction: Malondialdehyde was measured to assess the degree of tissue oxidative stress. There were microscopic changes, and significantly more severe colitis was seen in colonic biopsies when iron was supplemented. It was concluded that iron supplementation can amplify the inflammatory response and enhance the subsequent mucosal damage in a rat model of colitis. We suggest that the resultant oxidative stress generated by iron supplementation leads to the extension and propagation of crypt abscesses.
Assuntos
Colite/patologia , Suplementos Nutricionais , Mucosa Intestinal/patologia , Ferro da Dieta , Animais , Colite/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo , Peroxidase/metabolismo , Ratos , Ratos WistarRESUMO
The coexistence of hyperkinetic circulation, hypermetabolism, and hyperactivity of the sympathetic nervous system is encountered in both cirrhosis and hyperthyroidism. Several drugs, such as propylthiouracil and propranolol, that are beneficial for treating some patients with chronic liver diseases are also prescribed for the treatment of thyrotoxicosis. We investigated the effects of experimentally induced hypo- and hyperthyroidism on the development of cirrhosis induced in rats by thioacetamide (TAA). We specifically examined whether hypothyroidism could prevent and hyperthyroidism could aggravate liver damage. Hypothyroidism induced by methimazole (MMI, 0.04%), propylthiouracil (PTU 0.05%), and by thyroidectomy was confirmed by a significant elevation of thyroid-stimulating hormone (TSH) levels. Hyperthyroidism (decreased TSH levels) was induced by eltroxin (ELT:50 micrograms/kg). Thirteen groups of 10 rats each were studied: euthyroid controls (3 groups: water, TAA 1.5 months, and TAA 3 months), hypothyroid (6 groups: MMI, PTU, surgical, MMI-TAA, PTU-TAA, surgical-TAA), and hyperthyroid (4 groups:ELT 1.5 months and 3 months, and ELT-TAA for 1.5 months and 3 months). Hepatic fibrosis (scored from 0 to 3) was significantly reduced (P < .0001) in hypothyroid rats as compared with euthyroid controls, and was aggravated in TAA-treated hyperthyroid rats (P < .0001). Quantitative microscopic analysis of liver biopsy specimens from all groups confirmed the semiquantitative histopathological scores (P < .001). Direct intrasplenic pressure measurement revealed a significant portal pressure elevation in the TAA and the ELT-treated rats (from 4.7 +/- 0.1 in the euthyroid group to 8.1 +/- 2.3 and 10.2 +/- 2.1 and 12.5 +/- 1.6 in the TAA, ELT and ELT-TAA groups, respectively). However, in the hypothyroid-TAA groups, the portal pressure was found to be within the euthyroid normal range (4.6 +/- 1.2 and 5.8 +/- 0.6 in the PTU-TAA and surgical-TAA, respectively). After 12 weeks, the mean spleen weight of rats receiving only TAA was significantly higher than the TAA-treated hypothyroid rats (P < .0001), indicating that the hypothyroid TAA-treated rats were less portal hypertensive. These results suggest that induced hypothyroidism can inhibit, whereas hyperthyroidism can aggravate, the development of cirrhosis in a rat model.