RESUMO
Little is known about the impact of standardized imaging surveillance on anxiety levels and well-being of patients after endovascular aortic aneurysm repair (EVAR). We hypothesize that patient anxiety levels increase just before receiving the imaging results compared with standard anxiety levels. METHODS: Prospective cohort study from November 2018 to May 2020 including post-EVAR patients visiting the outpatient clinics of 4 Dutch hospitals for imaging follow-up. The Patient-Reported Outcomes Measurement Information System (PROMIS) was used. Patients completed the PROMIS Anxiety v1.0 Short Form (SF) 4a, PROMIS-Global Health Scale v1.2, and PROMIS-Physical Function v1.2 SF8b at 2 time points: prior to the result of the imaging study (T1: pre-visit) and 6-8 months later (T2: reference measurement). Mean T-scores at T1 were compared to T2, and T2 to the general 65+ Dutch population. RESULTS: Altogether 342 invited patients were eligible, 214 completed the first questionnaire, 189 returned 2 completed questionnaires and 128 patients did not participate. Out of 214 respondents, 195 were male (91.1%) and the mean (standard deviation) age was 75.2 (7.0) years. There were no significant differences between T1 and T2 in anxiety levels (0.48; 95% confidence interval[CI] -0.42-1.38), global mental health (0.27; 95% CI -0.79-0.84), global physical health (0.10; 95% CI -0.38-1.18) and physical function (0.53; 95% CI -0.26-1.32). Compared with the 65+ Dutch population, at T2 patients experienced more anxiety (3.8; 95% CI 2.96-5.54), had worse global physical health (-3.2; 95% CI -4.38 - -2.02) and physical function (-2.4; 95% CI -4.00 - -0.80). Global mental health was similar (-1.0; 95% CI -2.21 - 0.21). CONCLUSIONS: Post-EVAR patients do not experience more anxiety just before receiving surveillance imaging results than outside this period, but do suffer from more anxiety and worse physical outcomes than the 65+ Dutch population.
Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/etiologia , Aneurisma da Aorta Abdominal/cirurgia , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Qualidade de Vida , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Exposure to methyl isocyanate and other toxic gases in Bhopal, India, on December 3, 1984 resulted in thousands of acute deaths, pregnancy loss and long-term effects. METHODS: From 1985 to 2007, we conducted successive surveys of vital status and health to determine whether the exposure of parents to toxic gases in the Bhopal incident affected the 5-year survival and anthropometric variables of their offspring. RESULTS: Initial 5-year mortality of offspring of exposed parents was very high. Male but not female offspring who were exposed to gases in utero or who were born to exposed parents were stunted in growth until puberty, which was followed by a period of accelerated growth. Results also suggest a post-puberty effect on head circumference of females exposed to gases in utero. CONCLUSION: Exposure of pregnant women to toxic gases in Bhopal in 1984 resulted in high pregnancy loss, increased first 5-year mortality and delayed development of male progeny.
Assuntos
Transtornos do Crescimento/induzido quimicamente , Isocianatos/toxicidade , Exposição Materna/efeitos adversos , Exposição Paterna/efeitos adversos , Praguicidas/toxicidade , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Análise de Variância , Antropometria , Antidrepanocíticos/toxicidade , Estatura , Tamanho Corporal , Peso Corporal , Vazamento de Resíduos Químicos/estatística & dados numéricos , Pré-Escolar , Feminino , Transtornos do Crescimento/epidemiologia , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , Índia/epidemiologia , Lactente , Mortalidade Infantil/tendências , Recém-Nascido , Masculino , Pico do Fluxo Expiratório , Gravidez , Puberdade , Fatores Sexuais , Estresse FisiológicoRESUMO
OBJECTIVE: To evaluate the mechanical properties of gastrointestinal (GI) tissue segments and to compare them with the urinary bladder for urinary tract reconstruction. METHODS: Urinary bladders and GI tissue segments were sourced from porcine models (n = 6, 7 months old [5 male; 1 female]). Uniaxial planar tension tests were performed on bladder tissue, and Cauchy stress-stretch ratio responses were compared with stomach, jejunum, ileum, and colonic GI tissue. RESULTS: The biomechanical properties of the bladder differed significantly from jejunum, ileum, and colonic GI tissue. Young modulus (kPa-measure of stiffness) of the GI tissue segments was on average 3.07-fold (±0.21 standard error) higher than bladder tissue (P < .01), and the strain at Cauchy stress of 50 kPa for bladder tissues was on average 2.27-fold (±0.20) higher than GI tissues. There were no significant differences between the averaged stretch ratio and Young modulus of the horizontal and vertical directions of bladder tissue (315.05 ± 49.64 kPa and 283.62 ± 57.04, respectively, P = .42). However, stomach tissues were 1.09- (±0.17) and 0.85- (±0.03) fold greater than bladder tissues for Young modulus and strain at 50 kPa, respectively. CONCLUSION: An ideal urinary bladder replacement biomaterial should demonstrate mechanical equivalence to native tissue. Our findings demonstrate that GI tissue does not meet these mechanical requirements. Knowledge on the biomechanical properties of bladder and GI tissue may improve development opportunities for more suitable urologic reconstructive biomaterials.
Assuntos
Íleo/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Engenharia Tecidual/métodos , Sistema Urinário/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Animais , Materiais Biocompatíveis , Fenômenos Biomecânicos , Feminino , Íleo/transplante , Masculino , Teste de Materiais , Modelos Animais , Sensibilidade e Especificidade , Estresse Mecânico , Retalhos Cirúrgicos/transplante , Suínos , Bexiga UrináriaRESUMO
We have previously characterized an activity from human plasma that markedly stimulates triglyceride synthesis in cultured human skin fibroblasts and human adipocytes. Based on its in vitro activity we named the active component acylation stimulating protein (ASP). The molecular identity of the active serum component has now been determined. NH2-terminal sequence analysis, ion spray ionization mass spectroscopy, and amino acid composition analysis all indicate that the active purified protein is a fragment of the third component of plasma complement, C3a-desArg. As well, reconstitution experiments with complement factors B, D, and complement C3, the components necessary to generate C3a, have confirmed the identity of ASP as C3a. ASP appears to be the final effector molecule generated by a novel regulatory system that modulates the rate of triglyceride synthesis in adipocytes.
Assuntos
Complemento C3a/análogos & derivados , Triglicerídeos/metabolismo , Sequência de Aminoácidos , Complemento C3a/química , Complemento C3a/isolamento & purificação , Complemento C3a/metabolismo , Fator D do Complemento , Humanos , Dados de Sequência Molecular , Serina Endopeptidases/metabolismoRESUMO
Autoimmunity involves immune responses directed against self, which are a result of defective self/foreign distinction of the immune system, leading to proliferation of self-reactive lymphocytes, and is characterized by systemic, as well as tissue-specific, inflammation. Numerous mechanisms operate to ensure the immune tolerance to self-antigens. However, monogenetic defects or genetic variants that weaken immune tolerance render susceptibility to the loss of immune tolerance, which is further triggered by environmental factors. In this review, we discuss the phenomenon of immune tolerance, genetic and environmental factors that influence the immune tolerance, factors that induce autoimmunity such as epigenetic and transcription factors, neutrophil extracellular trap formation, extracellular vesicles, ion channels, and lipid mediators, as well as costimulatory or coinhibitory molecules that contribute to an autoimmune response. Further, we discuss the cellular and molecular mechanisms of autoimmune tissue injury and inflammation during systemic lupus erythematosus and lupus nephritis.
Assuntos
Autoimunidade/genética , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Animais , Predisposição Genética para Doença , Humanos , Tolerância Imunológica/genética , Inflamação/patologia , Receptores de Reconhecimento de Padrão/metabolismoRESUMO
The effect of streptozocin (STZ)-induced maternal diabetes in rats on fetal erythropoiesis was studied in short-term cultures of fetal liver cells at the time of switch from embryonic to adult hemoglobins. Liver erythroid cell functions were monitored by measuring the incorporation of [3H]-uridine in trichloroacetic acid (TCA)-soluble and -insoluble cell fractions and of [3H]-leucine in hemoglobin chains. Fetal liver cells of diabetic rats showed a higher incorporation of [3H]-uridine compared with controls when the cells were obtained from 14-day-old fetuses. However, there were no significant differences in the uptake of uridine when cells were obtained from 16-day-old fetuses. In parallel cell cultures, incorporation of [3H]-leucine into adult and embryonic globin chains was studied by separation of the globin chains by high-performance liquid chromatography (HPLC). The overall globin chain synthesis was higher in the fetuses of diabetic mothers compared with controls on day 14 of gestation. Erythropoietin had similar effects on the stimulation of globin chains in the two groups of fetuses. However, in the fetuses of diabetic mothers, erythropoietin had a specific stimulatory effect on embryonic-type globins that was significantly higher in the fetuses of diabetic mothers compared with controls. Differences between fetuses of control and diabetic mothers completely disappeared at 16 days of gestation. It is concluded that maternal diabetes has an effect on the cells synthesizing embryonic hemoglobins on day 14 of gestation, but by the time the switch from embryonic to adult-type hemoglobins is complete, these differences are abolished.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Hemoglobinas/biossíntese , Fígado/embriologia , Uridina/metabolismo , Animais , Glicemia/análise , Células Cultivadas , Eritropoetina/farmacologia , Feminino , Feto/metabolismo , Idade Gestacional , Globinas/biossíntese , Insulina/sangue , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Gravidez , Ratos , Ratos EndogâmicosRESUMO
Rabbit (r) ACTH was extracted from 600 pituitaries, and 2 forms of immunoreactive ACTH were identified with the least polar form accounting for approximately 90% of the total. Peptide mapping and sequence analysis indicated that three tryptic peptides had retention times identical to those obtained from human (h) ACTH. The least polar tryptic fragment from rACTH had a shorter retention time than the corresponding one from hACTH. Sequence analysis indicated that rACTH differed from hACTH at three different loci, namely, an Asn in place of Asp in position 29; a Val in place of Leu in position 37, and a Val in place of Phe in position 39. Biological activity of the ACTH was compared with synthetic hACTH in 2 bioassays with adrenals from 10-day-old pups, the first using dispersed rabbit adrenal cells and the second using monolayer adrenal cells in culture. The biological potencies of the two ACTH preparations were identical with respect to corticosterone (B) release in the short term bioassay, with an ED50 value of 1.67 X 10(-10) M. The ED50 value for cortisol (F) release for rACTH and hACTH were 1.1 X 10(-10) M and 1.67 X 10(-10) M, respectively, which were not statistically different. The biological potency of rACTH in the monolayer adrenal cell system for both F and B was significantly greater than the hACTH, and the ED50 values were 4.4 X 10(-10) M and 8.9 X 10(-10) M, respectively. There was a progressive decrease in the B/F ratios with increasing concentrations of ACTH in both the bioassay systems suggesting that ACTH stimulated the 17 alpha-hydroxylase activity even when the exposure of cells to ACTH was as short as 2 h.
Assuntos
Hormônio Adrenocorticotrópico/isolamento & purificação , Coelhos/metabolismo , Hormônio Adrenocorticotrópico/imunologia , Hormônio Adrenocorticotrópico/metabolismo , Aminoácidos/análise , Animais , Cromatografia Líquida de Alta Pressão , Peptídeo da Parte Intermédia da Adeno-Hipófise Semelhante à Corticotropina , Hormônios Estimuladores de Melanócitos/isolamento & purificação , Fragmentos de Peptídeos/isolamento & purificação , Adeno-Hipófise/análiseRESUMO
Three structural variants of the joining peptide (JP) fragment of POMC have been purified from human pituitaries. Ion exchange and reverse phase tissue extraction procedures were combined with reverse phase HPLC to achieve complete purification of each form of JP. Fragments resulting from tryptic hydrolysis of each form were characterized by amino acid analysis and fast atom bombardment mass spectrometry. The predominant form of human JP, accounting for about 50% of the total purified, was found to be conjugated to glutathione through the lone cysteine residue at position 9. The other two variants were identified as human JP with a free cysteine residue and human JP dimer and accounted for 35% and 15%, respectively, of the total purified. Recently, human JP-(1-18) has been suggested as having adrenal androgen-stimulating activity. None of the three JP variants or their respective 1-20 amino-terminal fragments resulting from tryptic hydrolysis showed any ability to promote the secretion of dehydroepiandrosterone sulfate by cultured human fetal adrenal cells. Similarly, no potentiation of the stimulatory effects of ACTH-(1-39) was observed. The three variants of human JP as well as JP purified from rat, porcine, and bovine pituitaries were tested for their ability to stimulate androgenic steroids from dispersed fetal rabbit adrenal cells. None showed any significant biological activity either in stimulating steroid secretion or in potentiating the action of ACTH-(1-39).
Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Desidroepiandrosterona/análogos & derivados , Fragmentos de Peptídeos/isolamento & purificação , Hipófise/química , Pró-Opiomelanocortina/análise , Glândulas Suprarrenais/embriologia , Glândulas Suprarrenais/metabolismo , Adulto , Sequência de Aminoácidos , Animais , Bovinos , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Desidroepiandrosterona/metabolismo , Sulfato de Desidroepiandrosterona , Humanos , Substâncias Macromoleculares , Dados de Sequência Molecular , Peso Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacologia , Pró-Opiomelanocortina/química , Ratos , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Suínos , TripsinaRESUMO
A RIA method is described for the measurement of dexamethasone in maternal, cord, and neonate plasma in a collaborative multicenter clinical trial to evaluate the efficacy of antenatal steroid therapy in the prevention of respiratory distress syndrome. The antiserum raised against dexamethasone-3-carboxymethyloxime-BSA conjugate was highly specific in that the endogenous steroids and 11-dehydrodexamethasone, a metabolite of dexamethasone, had a cross-reaction of less than 2.0%. Both pregnancy and cord plasma had to be purified by either gel filtration and/or paper chromatography. The overall recoveries of dexamethasone were 75.3 +/- 6.7% and 48.9 +/-6.7% for maternal and cord plasma samples, respectively. The intra- and interassay coefficients of variance for maternal plasma were 8.4% ad 9.1%, respectively, and for cord plasma were 11.9% and 10.9%, respectively. There was a good correlation between the dexamethasone values obtained by RIA when compared with those obtained by performance liquid chromatography in some cord plasma specimens. The recoveries of added dexamethasone and its metabolite by high performance liquid chromatography were also found to be good. The average maternal plasma dexamethasone level was 37 ng/ml 2 h after im injections of 5 mg dexamethasone phosphate every 12 h. The half-life of dexamethasone measured after the discontinuation of the drug was 216 min. Dexamethasone appeared too be cleared very rapidly from the circulation of the fetus and neonate. Because 11-dehydrodexamethasone was not present in significant amounts in the neonate, it was concluded that other factors in addition to the conversion of dexamethasone to its 11 dehydro metabolite were responsible for the rapid clearance of dexamethasone from fetal and neonatal circulation.
Assuntos
Dexametasona/sangue , Sangue Fetal/análise , Recém-Nascido , Radioimunoensaio/métodos , Especificidade de Anticorpos , Cromatografia , Ensaios Clínicos como Assunto , Dexametasona/imunologia , Dexametasona/isolamento & purificação , Dexametasona/uso terapêutico , Feminino , Humanos , Soros Imunes/imunologia , Gravidez , Radioimunoensaio/normas , Síndrome do Desconforto Respiratório do Recém-Nascido/prevenção & controleRESUMO
The influence of streptozotocin-diabetes on the pharmacokinetics, placental transfer and tissue localization of dexamethasone was determined in Sprague-Dawley rats. Diabetes significantly increased the volume of distribution of dexamethasone in pregnant but not in nonpregnant rats; plasma half-life was not significantly increased. Concentrations of maternally administered dexamethasone in all tissues studied (maternal and foetal serum and livers, foetal lungs and placentas) except the amniotic fluid were lower in diabetic than in control animals. Diabetes did not alter the binding of dexamethasone to maternal or foetal serum proteins. Insulin treatment partially reversed the effects of diabetes on the maternal-foetal exchange of dexamethasone. Diabetes-induced decrease in the foetal localization of dexamethasone appears to be caused by a decrease in the maternal serum levels as well as by an increase in the foetal excretion of the steroid into the amniotic fluid. In so far as the rat model reflects the human situation, the present data suggest that a standard dose of dexamethasone might not be adequate in promoting foetal lung maturation in diabetic pregnancies.
Assuntos
Dexametasona/metabolismo , Diabetes Mellitus Experimental/metabolismo , Troca Materno-Fetal , Gravidez em Diabéticas/metabolismo , Animais , Proteínas Sanguíneas/metabolismo , Dexametasona/sangue , Feminino , Feto/metabolismo , Insulina/farmacologia , Cinética , Gravidez , Ligação Proteica , Ratos , Ratos Endogâmicos , Frações Subcelulares/metabolismo , Distribuição TecidualRESUMO
1. The influence of progesterone on the activity of atrial natriuretic factor (ANF) on rat myometrial motor activity was determined in vitro. 2. ANF inhibited the tension development by myometrium from cycling or oestrogen-treated rats in a dose-dependent manner; maximal inhibition was 100%. 3. Injections of progesterone into rats inhibited the tocolytic activity of ANF in a dose and time-dependent manner. The tocolytic effects of ANF were completely abolished by 3 daily injections of 1 mg kg-1 progesterone. 4. Pregnancy-related increase in plasma progesterone was accompanied by a corresponding decrease in the tocolytic effects of ANF; myometria from gestational day 10 to 21 were completely refractory and those from earlier gestational age and immediate postpartum were responsive to ANF to varying degrees. 5. Treatment of pregnant rats with the progesterone antagonist, RU486, caused abortions and vaginal bleeding, decreased plasma progesterone concentrations and restored the tocolytic activity of ANF. Tocolytic activity of ANF on virgin rat myometria was potentiated by RU486. 6. Progesterone also inhibited the effects of ANF on myometria from ovariectomized rats. 7. Tocolytic activity of isoprenaline was not modified by progesterone, pregnancy, RU486 or ovariectomy. 8. It is concluded that progesterone antagonizes myometrial effects of ANF by an oestrogen-independent mechanism and the pregnancy-induced refractoriness to the tocolytic effects of ANF is caused by progesterone.
Assuntos
Fator Natriurético Atrial/antagonistas & inibidores , Mifepristona/farmacologia , Progesterona/farmacologia , Receptores de Progesterona/antagonistas & inibidores , Tocolíticos/antagonistas & inibidores , Animais , Sinergismo Farmacológico , Estro/fisiologia , Feminino , Técnicas In Vitro , Ovário/fisiologia , Gravidez , Progesterona/sangue , Ratos , Ratos EndogâmicosRESUMO
1. Negative inotropic effects of several beta-adrenoceptor (betaAR) antagonists on electrically-stimulated right atria, left atria, right ventricles and left ventricular papillary muscles from reserpine-treated rats were used as a measure of their inverse agonist activities. 2. Beta1AR antagonists acebutolol, atenolol and metoprolol, beta2AR antagonist ICI-181,551 and nonselective betaAR antagonists alprenolol, nadolol, propranolol and timolol produced negative inotropic effects, which were most marked on the right atria. 3. The nonselective betaAR antagonist pindolol did not exhibit inverse agonist activity but inhibited the negative inotropic activities of ICI-118,551, atenolol and propranolol. 4. The negative inotropic effects of lidocaine, nifedipine and pentobarbitone were similar on all the four myocardial preparations. 5. The positive inotropic efficacy of salbutamol on right and left atria but not on right ventricles and papillary muscles was comparable to that of isoprenaline. The antagonist activity of ICI-118,551 against isoprenaline was greater on right atria than on other cardiac regions. 6. Beta1AR proteins were expressed in all regions of the heart but of beta2AR were primarily localized in the right atrium. 7. It is concluded that beta2AR play a greater role in right atria than in other cardiac regions and almost all betaAR antagonists behave as inverse agonists.
Assuntos
Agonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Contração Miocárdica/efeitos dos fármacos , Propanolaminas/farmacologia , Albuterol/farmacologia , Animais , Western Blotting , Técnicas In Vitro , Isoproterenol/farmacologia , Masculino , Pindolol/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos beta 1/fisiologia , Receptores Adrenérgicos beta 2/fisiologiaRESUMO
Experiments were carried out on Sprague-Dawley rats to determine whether changes in fetal corticosterone levels during maternal diabetes were caused by the accompanying fetal hyperinsulinaemia or fetal hyperglycaemia. Diabetes was induced by injecting streptozotocin (30-45 mg/kg, i.v.) on day 2 of gestation. Fetal adrenals were removed on day 20 of gestation and cultured. Streptozotocin caused moderate (blood glucose 14-22.5 mmol/l) to severe (blood glucose greater than 25 mmol/l) diabetes. Both moderate and severe diabetes caused a decrease in fetal body weights. Relative to non-diabetic controls, maternal and fetal plasma concentrations of corticosterone were higher in the severely and lower in the moderately diabetic rats. Corticosterone production by fetal adrenal cells from control and moderately diabetic rats was comparable, but cells from the severely diabetic animals produced significantly greater amounts of corticosterone than did control cells. Neither glucose (28 mmol/l) nor insulin (1 nmol/l) exerted significant effects on [3H]thymidine uptake or corticosterone production by fetal adrenal cells from non-diabetic, moderately diabetic or severely diabetic rats. Human ACTH (0.02-20 nmol/l) caused a concentration-dependent increase in corticosterone output of comparable magnitude by cells from all three groups of animals. These data suggest that fetal growth abnormalities during diabetic pregnancy are not directly related to changes in glucocorticoid levels and that changes in glucocorticoid levels are not caused by any direct action of fetal hyperinsulinaemia or hyperglycaemia on adrenal cells.
Assuntos
Glândulas Suprarrenais/embriologia , Hormônio Adrenocorticotrópico/farmacologia , Corticosterona/biossíntese , Diabetes Mellitus Experimental/metabolismo , Glucose/farmacologia , Insulina/farmacologia , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Animais , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Gravidez , Ratos , Ratos Endogâmicos , Estreptozocina/farmacologia , Fatores de TempoRESUMO
Administration of a dose of 45 mg streptozotocin/kg on day 2 of gestation produced a diabetic state in pregnant rats and was associated with fetal hyperinsulinaemia. Although there was no evidence of fetal macrosomia, the ratio of fetal liver and lung weight to body weight was greater in fetuses of diabetic rats, suggesting an increase in the size of these organs relative to the body weight. Maternal and fetal plasma corticosterone levels of diabetic rats between 19 and 22 days of gestation was significantly lower than the corresponding control values. Maternal plasma progesterone levels of diabetic rats were lower than controls on days 19 and 20 of gestation, but higher than controls on day 21 of gestation. The absence of pregnancy-related changes in maternal and fetal plasma corticosterone levels and maternal progesterone levels in diabetic rats suggest that adrenocortical function as well as ovarian and/or placental function may be impaired, which may in turn be related to the observed delay in parturition of approximately 18 h as well as to the low survival rate of the pups. There was a small increase in the cytoplasmic glucocorticoid receptor concentration in the lung but not in the liver of fetuses of diabetic mothers when compared with fetuses of controls, suggesting that the increased receptor concentration may be a compensatory mechanism to overcome the effect of decreased corticosterone levels and increased insulin levels in the fetuses of diabetic rats.
Assuntos
Corticosterona/sangue , Diabetes Mellitus Experimental/sangue , Feto/metabolismo , Gravidez em Diabéticas , Progesterona/sangue , Receptores de Glucocorticoides/metabolismo , Receptores de Esteroides/metabolismo , Animais , Citoplasma/metabolismo , Feminino , Fígado/metabolismo , Pulmão/metabolismo , Gravidez , Ratos , Ratos Endogâmicos , EstreptozocinaRESUMO
The influence of maternal diabetes on fetal development was studied in rats made diabetic by administration of streptozotocin on day 2 of gestation as well as in genetically diabetic BB Wistar rats. A dose of 65 mg streptozotocin/kg produced severe diabetes with plasma glucose levels of approximately 36 mmol/l, this was associated with fetal growth retardation but not fetal hyperinsulinaemia. In contrast, a smaller dose of streptozotocin (45 mg/kg) produced moderate diabetes with plasma glucose levels of approximately 20 mmol/l and was associated with fetal hyperinsulinaemia but only a marginal effect on fetal size. In both groups of diabetic animals, maternal body weight gain was decreased, maternal plasma insulin levels were low and fetal glucose levels were similar. In a small group of genetically diabetic BB rats on insulin therapy the fetuses were macrosomic and hyperinsulinaemic. The specific binding of 125I-labelled insulin to partially purified liver and lung membranes of fetuses of both groups of streptozotocin-induced diabetic rats was significantly lower than the binding to membranes from fetuses of control animals. The specific binding of 125I-labelled insulin to fetal liver and lung membranes from the diabetic BB Wistar rats also appeared to be reduced when compared to tissues from controls. Decreased insulin receptors in fetal lung and liver of diabetic rats suggest a role for insulin in the development of these organs during the fetal and neonatal period.
Assuntos
Retardo do Crescimento Fetal/etiologia , Fígado/metabolismo , Pulmão/metabolismo , Gravidez em Diabéticas/complicações , Receptor de Insulina/metabolismo , Animais , Feminino , Retardo do Crescimento Fetal/metabolismo , Insulina/metabolismo , Fígado/embriologia , Pulmão/embriologia , Gravidez , Ratos , Ratos Endogâmicos , EstreptozocinaRESUMO
It was observed in the course of other studies that rat fetal lung extracts inhibited proliferation of fetal lung cells in culture. The purpose of the present study was to isolate and characterize this cytostatic factor. It was found that fetal lungs contained a 16 kDa cytostatic factor and its concentration was twofold greater in fetal lungs of diabetic rats compared with control rats. This fetal lung cytostatic protein (FLCP) was purified by reversed-phase, heparin-affinity and gel filtration high-performance liquid chromatography and SDS-PAGE. The purified protein was electroblotted onto polyvinylidene difluoride membrane and subjected to sequence analysis. The amino-terminal sequence of this fetal lung cytostatic protein was P E P A K S A P A P X K G I G K Q X X K A X X K A ... and showed significant homology with histone H2B; however, the amino acid composition of FLCP suggested that it may be structurally distinct from histone H2B. Ion-spray mass spectrometry suggested that FLCP was made up of at least two species of the protein with molecular weights of 13,776.1 and 14,007.3 and was different from the molecular weight of rat histone H2B predicted by its cDNA sequence. The concentration of FLCP, based on amino acid compositions, was 0.32 nmol/g and 0.83 nmol/g wet fetal lung from non-diabetic and diabetic rats respectively. These findings suggest that the fetal rat lung produces a regulatory factor bearing considerable homology with but possibly different from histone H2B and that fetal lung immaturity during diabetic pregnancy might be contributed to by an increase in this factor.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Proteínas Fetais/isolamento & purificação , Pulmão/embriologia , Sequência de Aminoácidos , Animais , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental/embriologia , Eletroforese em Gel de Poliacrilamida , Proteínas Fetais/genética , Histonas/genética , Pulmão/química , Dados de Sequência Molecular , Ratos , Ratos Sprague-Dawley , Homologia de Sequência de AminoácidosRESUMO
The main purpose of these studies was to determine whether diabetic pregnancy altered maternal and fetal atrial natriuretic peptide (ANP). Diabetes was induced in rats by intravenous injection of 40 mg streptozotocin/kg on day 2 of gestation. Immunoreactive ANP in plasma, amniotic fluid and hearts on day 20 of gestation was measured by radioimmunoassay; fetal cardiac natriuretic peptides (ANP, proANP and BNP) were separated by reverse-phase high pressure liquid chromatography. Diabetes caused an increase in fetal plasma insulin, placental weight, amniotic fluid volume, the ratio of the fetal heart to body weight, maternal and fetal plasma ANP, fetal cardiac ANP and fetal cardiac BNP. It is suggested that the maternal diabetes-induced increase in fetal ANP might be related to fetal myocardial hypertrophy and could contribute to hydramnios.
Assuntos
Fator Natriurético Atrial/metabolismo , Diabetes Mellitus Experimental/metabolismo , Coração Fetal/metabolismo , Gravidez em Diabéticas/metabolismo , Líquido Amniótico/metabolismo , Animais , Fator Natriurético Atrial/sangue , Cromatografia Líquida de Alta Pressão , Feminino , Sangue Fetal/metabolismo , Coração Fetal/química , Insulina/sangue , Peptídeo Natriurético Encefálico , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
The influence of dietary protein deficiency on maternal plasma corticosterone and progesterone levels as well as on maternal and fetal liver and lung cytoplasmic glucocorticoid receptors has been studied in Sprague-Dawley rats during the last 3 days of gestation. Plasma corticosterone levels of control but not protein-deficient rats increased on days 20 and 21 of gestation; corticosterone levels of protein-deficient rats decreased on day 21 of gestation. Maternal adrenalectomy caused only a moderate decrease in corticosterone levels in both groups of pregnant rats. Fetal corticosterone levels of the two groups of rats were similar. Progesterone levels were consistently lower in protein-deficient than in control animals from day 20 of gestation until 2-12 h after parturition. There were no differences in the binding of [3H]dexamethasone to liver cytosol of non-pregnant control and protein-deficient rats. However, receptor levels were lower in pregnant controls than in pregnant protein-deficient rats. Maternal protein deficiency led to an increase in fetal liver glucocorticoid receptor levels but exerted no significant effect on receptor levels in fetal lung. It is suggested that lower levels of plasma corticosterone and progesterone and high levels of liver glucocorticoid receptors in protein-deficient rats might be related to some of the adverse consequences of maternal malnutrition on fetal development.
Assuntos
Corticosterona/sangue , Progesterona/sangue , Deficiência de Proteína/metabolismo , Receptores de Glucocorticoides/metabolismo , Receptores de Esteroides/metabolismo , Animais , Citoplasma/metabolismo , Dexametasona/metabolismo , Dieta , Feminino , Feto/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Gravidez , Ratos , Ratos EndogâmicosRESUMO
Diabetic pregnancy is associated with a high incidence of fetal growth abnormalities which cannot be solely ascribed to fetal hyperglycaemia and hyperinsulinaemia. We therefore examined the possibility of other contributing factors using rats made diabetic with streptozotocin as the experimental model. Blood serum from virgin diabetic rats and, to a much greater extent, from pregnant diabetic rats inhibited [3H]thymidine incorporation by fetal lung cells in culture in a concentration- and time-dependent manner; cell number was also decreased. The cytotoxic activity of the serum was decreased by treatment of pregnant diabetic rats with insulin. Sera from non-diabetic rats and from rats at 6 h and 24 h after the injection of streptozotocin were not cytotoxic. The cytotoxic activity of diabetic rat serum was retained after dialysis and was not destroyed by heating it for 60 min at 60 degrees C. Diabetic rat serum antagonized the stimulatory effects of fetal bovine serum, insulin and insulin-like growth factors on thymidine incorporation by lung cells and inhibited corticosterone production by adrenal cells. Ultrafiltration of diabetic rat serum and high-performance gel permeation chromatography in phosphate buffer suggested that the molecular weight of the cytotoxic factor was approximately 40 kDa. However, gel permeation chromatography in 40% acetonitrile of the cytotoxic eluate from reversed-phase high-performance liquid chromatography using a C18 and C4 column revealed that the cytotoxic factor was a low molecular weight substance, which contained no amino acids. The apparent discrepancy in molecular weights using different separation procedures suggests that the cytotoxic factor is bound to serum proteins. The u.v. spectrum of this factor was different from those of ketone bodies but its exact chemical identity could not be established because of the scarcity of the material. It is suggested that the sera of pregnant diabetic rats and their fetuses contain a cytotoxic factor, which may contribute to fetal developmental abnormalities.
Assuntos
Fatores Biológicos/sangue , Anormalidades Congênitas/etiologia , Diabetes Mellitus Experimental/sangue , Complicações na Gravidez/etiologia , Gravidez em Diabéticas/sangue , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Animais , Contagem de Células , Células Cultivadas , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Anormalidades Congênitas/sangue , Corticosterona/biossíntese , Diálise , Relação Dose-Resposta a Droga , Feminino , Antagonistas da Insulina , Pulmão/embriologia , Pulmão/metabolismo , Peso Molecular , Gravidez , Complicações na Gravidez/sangue , Ratos , Somatomedinas/antagonistas & inibidores , Timidina/metabolismoRESUMO
The main objective of this study was to find out if the reported changes in the aldosterone-suppressant activity of atrial natriuretic peptide (ANP) during different hormonal states in rats are due to a modulation of ANP receptors. In zona glomerulosa cells, ribonuclease protection assay detected mRNAs for guanylate cyclase (GC)-coupled ANP GC-A and GC-B receptors, and for ANP C receptors, which are not coupled to GC. Western analysis using polyclonal anti-GC-A and anti-GC-B receptor antibodies revealed the presence of GC-A but not GC-B receptor proteins in zona glomerulosa cells. Pregnancy (days 7, 16 and 21), oestradiol-17 beta and progesterone decreased mRNAs for all the three ANP receptors in zona glomerulosa cells. Pregnancy decreased GC-A receptor proteins in zona glomerulosa cells, but these recovered to virgin values on day 2 postpartum. ANP receptor mRNAs in zona glomerulosa cells increased by postpartum day 2, but did not reach the values found in virgin rats. Zona fasciculata mainly contained GC-A receptor mRNA. It is concluded that ANP receptors in rat adrenal zona glomerulosa are modulated by pregnancy, oestrogen and progesterone; a decrease in ANP GC-A receptors during pregnancy might explain the accompanying decrease in the aldosterone-suppressant effects of ANP.