Placental growth hormone is not suppressed by oral glucose loading in normal human pregnancy

Placental growth hormone (PGH) progressively replaces pituitary growth hormone in the maternal circulation from mid-gestation onwards in human pregnancy. Our previous investigations have shown that placental growth hormone concentrations correlate well with foetal growth. Despite the apparent correlation between PGH and birthweight, the physiology of its secretion during pregnancy has not been well defined. We investigated the response of maternal serum PCH to oral glucose loading in pregnant women (n = 24) who demonstrated normal glucose tolerance at a mean gestation of 29 weeks. Mean (SEM) fasting PGH concentrations were high (36.9 [6.4] ng/ml). No suppression of PGH was noted at one, two or three hours after a 75 g oral glucose load. Similarly, no changes were noted in growth hormone binding protein or in calculated free PGH over the course of the glucose tolerance test. As expected, insulin concentrations rose sixfold and insulin like growth factor binding protein 1 concentrations fell by 20% with glucose loading. Cot-relation analysis showed maternal weight, BMI, fasting serum glucose serum insulin to be significantly correlated with the babies' birthweight. Our results support the proposition that PGH concentrations in maternal serum are not Suppressed by oral glucose loading in non-diabetic mothers.

Alterations in pulmonary vascular function in rats exposed to intermittent hypoxia

Vasoactive agents were examined in arteries from control rats and rats exposed to intermittent hypoxia (10% oxygen; 8 h/day) for 3, 5 or 20 days. Hypoxic rats developed right ventricular hypertrophy after 5 days, but became pulmonary hypertensive (elevated right ventricular systolic pressure; RVSP) only after 20 days. In pulmonary arteries (main and intralobar), responses to acetylcholine and ionomycin (endothelium-dependent vasodilators) were reduced after 20 and 5 days of intermittent hypoxia, whereas contractions to 5-hydroxytryptamine (5-HT) were enhanced (potency increase >10-fold) after 20, 5 and 3 days. Contractions to endothelin-1 and a thromboxane-mimetic, but not Ca-2divided by, were also increased. No changes in vascular function occurred in aorta. Since changes in pulmonary vascular function preceded the increase in RVSP they do not result from, but may contribute to, the development of hypoxia-induced pulmonary hypertension. If similar changes occur in humans, they may be important in conditions characterised by intermittent, as opposed to continuous, hypoxia. (C) 2003 Elsevier B.V. All rights reserved.

Alterations of neocortical pyramidal cell phenotype in the Ts65Dn mouse model of Down syndrome: Effects of environmental enrichment

Mental retardation in individuals with Down syndrome (DS) is thought to result from anomalous development and function of the brain; however, the underlying neuropathological processes have yet to be determined. Early implementation of special care programs result in limited, and temporary, cognitive improvements in DS individuals. In the present study, we investigated the possible neural correlates of these limited improvements. More specifically, we studied cortical pyramidal cells in the frontal cortex of Ts65Dn mice, a partial trisomy of murine chromosome 16 (MMU16) model characterized by cognitive deficits, hyperactivity, behavioral disruption and reduced attention levels similar to those observed in DS, and their control littermates. Animals were raised either in a standard or in an enriched environment. Environmental enrichment had a marked effect on pyramidal cell structure in control animals. Pyramidal cells in environmentally enriched control animals were significantly more branched and more spinous than non-enriched controls. However, environmental enrichment had little effect on pyramidal cell structure in Ts65Dn mice. As each dendritic spine receives at least one excitatory input, differences in the number of spines found in the dendritic arbors of pyramidal cells in the two groups reflect differences in the number of excitatory inputs they receive and, consequently, complexity in cortical circuitry. The present results suggest that behavioral deficits demonstrated in the Ts65Dn model could be attributed to abnormal circuit development.

Histological alterations in liver and testis of Astyanax aff. bimaculatus caused by acute exposition to zinc

This study investigated the effect of acute exposition to zinc (Zn) on histology of the liver and testes of yellow tail lambari (Astyanax aff. bimaculatus). The exposure consisted of six concentrations of Zn (0, 3, 5, 10, 15, and 20 mg/L) for 96 hours of exposure. Fragments of liver and testis were routinely processed and embedded in plastic resin based on glycol methacrylate. Fragments of bones, muscles, liver and testis were dehydrated and digested to quantify the absorption levels of Zn in the tissue. Acute exposure to concentrations above 10mg/L has produced structural changes in the liver and gonads. The changes found in the liver were vascular congestion; decrease of cellular volume; displacement of the hepatocyte nucleus; necrosis; disarrangement of cordon structure; leukocyte infiltrate and vacuolization. The changes found in the gonads were ruptured cyst, delayed development of germ cells, pyknotic nucleus, cell cluster, displacement of cyst wall and vacuolization. The histological changes observed were compatible with the increasing concentration of zinc in environment, compromising liver and reproductive functions, because there was an increase in relative frequency of hepatocytes and reduced sperm production

Identification of neuronal alterations induced by Shank3 mutations using iPS cells from Phelan-McDermid Patients' Fibroblasts

A família de proteínas Shank é o principal conjunto de proteinas de suporte e está localizada na densidade pós-sináptica das sinapses excitatórias. Existem 3 genes na família Shank, Shank1, Shank2 e Shank3 e são caracterizados por múltiplos domínios repetidos de anquirina próximo ao N-terminal seguido pelos domínios Src homologo 3 e PDZ, uma região longa rica em prolina e um domínio de motivo α estéril próximo ao C-terminal. Shank proteínas conectam duas subunidades de receptors glutamatérgicos, recetores NMDA e recetores metabotrópicos de glutamato do tipo-I (mGluRs). O domínio PDZ da Shank conecta-se ao C-terminal do GKAP e este, liga-se, ao complexo recetor PSD-95-NMDA. Por outro lado, a proteína Homer interage com o domínio rico em prolina para confirmar a associação entre a proteína Shank com o mGluR tipo-I. A proteína específica em estudo, Shank3, é haploinsuficiente em pacientes com sindrome Phelan-McDermid devido à deleções no braço comprido do cromossoma 22 levando à danos intelectuais, ausência ou atraso no discurso, comportamentos semelhantes ao autismo, hipotonia e características dismórficas. Neste trabalho, investigamos o papel da Shank3 na função sináptica para compreender a relação entre alterações nesta proteína e as características neurológicas presente em Pacientes com síndrome Phelan-McDermid. Foram utilizados dois modelos diferentes, ratinhos knockout Shank3 e hiPSC de pacientes com PMS. Ratinhos geneticamente modificados são ferramentas uteis no estudo de genes e na compreensão dos mecanismos que experiências in vitro não são capazes de reproduzir, mas de maneira a compreender melhor as patologias humanas, decidimos trabalhar também com células humanas. Os fibroblastos dos pacientes com síndrome Phelan-McDermid fora reprogramados em hiPS cells, diferenciados em neurónios e comparados com os neurónios obtidos a partir de doadores saudavéis e da mesma idade. A reprogramação em iPSC foi realizada por infecção de lentivirus com quatro genes de reprogramação OCT4, c-MYC, SOX2 e KFL4 para posteriormente serem diferenciados em neurónios, com cada passo sendo positivamente confirmado através de marcadores neuronais. Através dos neurónios diferenciados, analisamos a expressão de proteínas sinápticas. Pacientes com haploinsuficiencia na proteína Shank3 apresentam níveis elevados de proteína mGluR5 e decrescidos de proteína Homer sugerindo que a haploinsuficiencia leva a desregulação do complexo mGluR5-Homer-Shank3 conduzindo também, a defeitos na maturação sináptica. Assim, a expressão da proteína mGluR5 está alterada nos pacientes com PMS podendo estar relacionada com defeitos encontrados na diferenciação neuronal e maturação sináptica observados nos neurónios de pacientes. Conclusivamente, iPS cells representam um modelo fundamental no estudo da proteína Shank3 e a sua influência no sindrome de Phelan-McDermid.

Metabolic alterations in pregnant women: gestational diabetes

Gestational diabetes mellitus (GDM) and controversy are old friends. The impact of GDM on maternal and fetal health has been increasingly recognized. Nevertheless, universal consensus on the diagnostic methods and thresholds has long been lacking. Published guidelines from major societies differ significantly from one another, with recommendations ranging from aggressive screening to no routine screening at all. As a result, real-world practice is equally varied. This article recaps the latest evidence-based recommendations for the diagnosis and classification of GDM. It reviews the current evidence base for intensive multidisciplinary treatment of GDM and provides recommendations for postpartum management to delay and/or prevent progression to type 2 diabetes.

Alterations in psychosocial health of people affected by asbestos poisoning

OBJECTIVE To analyze the state of psychosocial and mental health of professionals affected by asbestos.METHODS A cross-sectional study was conducted with 110 professionals working in the Ferrolterra region of Spain, who were affected by asbestos poisoning. This group was compared with a group of 70 shipyard workers with no manifestation of work-related diseases. All the participants were male with a mean age of 67 years. This study was conducted in 2013, between January and June, and used the SCL-90 questionnaire by Derogatis as its primary measure for research. This questionnaire consists of 9 variables that measure psychosomatic symptoms. In addition, an overall index of psychosomatic gravity was calculated. The participants were also asked two questions concerning their overall perception of feeling good. Data were analyzed by ANOVA and logistic regression.RESULTS Participants affected by asbestos poisoning showed high occurrence rates of psychological health variables such as somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism, and global severity index.CONCLUSIONS Social interaction as a differentiating factor between workers affected by work-related chronic syndromes as compared to healthy participants will possibly aid in the development of intervention programs by improving the social network of affected individuals.

Prevention of electrocardiographic and histopathologic alterations in the murine model of Chagas' disease by preinoculation of an attenuated Trypanosoma cruzi strain

The effects of infection with Trypanosoma cruzi on the electrocardiographic tracings of mice were studied in 4.groups of animals: (1) normal; (2) infected with a pathogenic T. cruzi strain (TS COB); (3) immunized with 3 intraperitoneal inocula of 10(6) attenuated T. cruzi epimastigotes (TCC) and (4) immunized-infected, which sequentially received the treatments of groups 3 and 2. Infection and protection were confirmed by xenodiagnosis and histopathology. Isolated alterations such as extrasystolia, 1st degree atrioventricular block, arrhythmia and ST elevation were observed in normal as well as infected mice. However, tracings taken repeatedly on each mouse over a 293 day period revealed a set of alterations which were more frequently seen in infected (14/22) than in normal (4/27) animals (p = 0.00048). These alterations consisted of supraventricular tachycardia, sinus bradycardia and persisting, first degree AV blocks, often associated to pacemaker changes. Inoculation of attenuated T. cruzi (group 3) did not increase these alterations (2/27 mice) but significantly prevented their development after challenge with the pathogenic strain (1/19 versus 14/22 mice, p = 0.000095). Thus, preimmunization reduced not only parasitemia but also a pathogenic consequence of T. cruzi infection. This evidence is relevant for immunoprevention studies against Chagas' disease.

Hepatobiliary alterations in massive biliary ascariasis: histopathological aspects of an autopsy case

Hepatobiliary alterations found in an autopsy case of massive Biliary Ascariasis, are reported on histological grounds. Severe cholangitis was the main finding, but other changes were also detected, such as pyloric and intestinal metaplasia, hyperplasia of the epithelial lining, with intraductal papillomas and adenomatous proliferation. Remnants of the worm were observed tightly adhered to the epithelium, forming microscopic intrahepatic calculi. Mucopolysaccharides, especially acid, showed to be strongly positive on the luminal border, and in proliferated glands around the ducts. The authors discuss the similarity between such findings and Oriental Cholangiohepatitis, and suggest that inflammation and the presence of the parasitic remnants are responsible for the hyperplastic and metaplastic changes, similarly with what occurs in chlonorchiasis, fascioliasis and schistosomiasis.

Trypanosoma cruzi: modification of alkaline phosphatase activity induced by trypomastigotes in cultured human placental villi

Human term placental villi cultured ''in vitro" were maintained with bloodstream forms of Trypanosoma cruzi during various periods of time. Two different concentrations of the parasite were employed. Controls contained no T. cruzi. The alkaline phosphatase activity was determined in placental villi by electron microscopy and its specific activity in the culture medium by biochemical methods. Results showed that the hemoflagellate produces a significant decrease in enzyme activity as shown by both ultracytochemical and specific activity studies and this activity was lower in cultures with high doses of parasites. The above results indicate that the reduction in enzyme activity coincides with the time of penetration and proliferation of T. cruzi in mammalian cells. These changes may represent an interaction between human trophoblast and T. cruzi.

American trypanosomiasis and electrocardiographic alterations among industrial workers in São Paulo, Brazil

In this article, we evaluate electrocardiographic (ECG) alterations among urban workers from a mechanical-metallurgical industry in São Paulo, Brazil. In a cross-sectional survey carried out in 1980, we found 2.2% positive serological testing for Trypanosoma cruzi infection among 27,081 workers. A comparison between seropositive workers and a random sample of seronegative workers frequency-matched by age and occupation revealed that seropositive workers had a much lower educational level, and that a higher proportion of seropositive workers had ECG abnormalities (42.7%) when compared to those negative for T. cruzi infection (19.8%). The high frequency of ECG abnormalities suggests the need to provide medical assistance to these workers, without any kind of discrimination and to bring in a form of management that would decrease this dangerous risk to the workers and people around them.

Role of oxidative stress-induced systemic and cavernosal molecular alterations in the progression of diabetic erectile dysfunction

Background Erectile dysfunction (ED) is a prevalent complication of diabetes, and oxidative stress is an important feature of diabetic ED. Oxidative stress-induced damage plays a pivotal role in the development of tissue alterations. However, the deleterious effects of oxidative stress in the corpus cavernosum with the progression of diabetes remain unclear. The aim of this study was to evaluate systemic and penile oxidative stress status in the early and late stages of diabetes. Methods Male Wistar streptozotocin-diabetic rats (and age-matched controls) were examined 2 (early) and 8 weeks (late) after the induction of diabetes. Systemic oxidative stress was evaluated by urinary H2O2 and the ratio of circulating reduced/oxidized glutathione (GSH/GSSG). Penile oxidative status was assessed by H2O2 production and 3-nitrotyrosine (3-NT) formation. Cavernosal endothelial nitric oxide synthase (eNOS) was analyzed by quantitative immunohistochemistry. Dual immunofluorescence was also performed for 3-NT and α-smooth muscle actin (α-SMA) and eNOS–α-SMA. Results There was a significant increase in urinary H2O2 levels in both diabetic groups. The plasma GSH/GSSG ratio was significantly augmented in late diabetes. In cavernosal tissue, H2O2 production was significantly increased in late diabetes. Reactivity for 3-NT was located predominantly in cavernosal smooth muscle (SM) and was significantly reduced in late diabetes. Quantitative immunohistochemistry revealed a significant decrease in eNOS levels in cavernosal SM and endothelium in late diabetes. Conclusions The findings indicate that the noxious effects of oxidative stress are more prominent in late diabetes. Increased penile protein oxidative modifications and decreased eNOS expression may be responsible for structural and/or functional deregulation, contributing to the progression of diabetes-associated ED.

Aerobic Exercise Does Not Predict Brain Derived Neurotrophic Factor And Cortisol Alterations in Depressed Patients

The pathophysiology of depression is related to neurobiological changes that occur in the monoamine system, hypothalamic-pituitary-adrenal axis, neurogenesis system and the neuroimmune system. In recent years, there has been a growing interest in the research of the effects of exercise on brain function, with a special focus on its effects on brainderived neurotrophic factor (BDNF), cortisol and other biomarkers. Thus, the aim of this study is to present a review investigating the acute and chronic effects of aerobic exercise on BDNF and cortisol levels in individuals with depression. It was not possible to establish an interaction between aerobic exercise and concentration of BDNF and cortisol, which may actually be the result of the divergence of methods, such as type of exercises, duration of the sessions, and prescribed intensity and frequency of sessions.

Alterations in lipid transfer to High-Density Lipoprotein (HDL) and activity of paraoxonase-1 in HIV+ patients

HIV+ patients often develop alterations of the plasma lipids that may implicate in development of premature coronary artery disease. High-density lipoprotein (HDL) has an important role in preventing atherogenesis and the aim of this study was to investigate aspects of HDL function in HIV+ patients. HIV+ patients (n = 48) and healthy control subjects (n = 45) of both sexes with similar age were studied. Twenty-five were not being treated with antiretroviral agents, 13 were under reverse transcriptase inhibitor nucleosidic and non-nucleosidic (NRTI+NNRTI) and 10 were under NRTI + protease inhibitors (NRTI+PI) treatment. Paraoxonase 1 (PON1) activity and the transfer of free and esterified cholesterol, tryglicerides and phospholipids from a lipidic nanoemulsion to HDL were analyzed. In comparison with healthy controls, HIV+ patients presented low PON-1 activity and diminished transfer of free cholesterol and tryglicerides. In contrast, phospholipid transfer was increased in those patients, whereas the transfer of cholesteryl esters was unchanged. NRTI+NNRTI increases the transfer of cholesteryl esters and triglycerides but in NRTI+PI there was no difference in respect to non-treated HIV+ patients. HDL from HIV+ patients has smaller antioxidant properties, as shown by lower PON-1 activity, and the transfer of lipids to this lipoprotein fraction is also altered, suggesting that HDL function is defective in those patients.