Cleofina Bosco

Prediction of early and late pre-eclampsia from maternal characteristics, uterine artery Doppler and markers of vasculogenesis during first trimester of pregnancy.

To develop a predictive model for pre‐eclampsia using clinical, biochemical and ultrasound markers during the first trimester of pregnancy.

Rat kidney antioxidant response to long-term exposure to flavonol rich red wine.

This study evaluated the antioxidant defense system of the rat kidney following chronic exposure to red wine rich in flavonols. Both ethanol and antioxidant non-alcoholic wine components, mainly polyphenols, could contribute to the antioxidant status of kidney. Adult rats were given separately, water, ethanol (12.5%), red wine or alcohol-free red wine. After ten weeks of treatment, blood samples were obtained to determine plasma antioxidant capacity (FRAP, ferric reducing ability of plasma), uric acid and ethanol levels. Kidney tissues (cortex and papilla) were separated to perform measurements of reduced glutathione (GSH), glutathione disulfide (GSSG), lipid peroxidation (malondialdehyde, MDA) and the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). The activity of (Na + K)-ATPase, a membrane-bound enzyme, was also assessed. Red wine in plasma, elevated the FRAP without changing the concentration of uric acid; in kidney, it diminished the MDA production and elevated the GSH/GSSG ratio and the activity of CAT and GSH-Px. The activity of SOD did not change. Despite the finding that renal (Na + K)-ATPase activity was upregulated by ethanol, it was not altered by either red wine or alcohol-free red wine. The effects on the antioxidant enzymes could be attributed to ethanol, but the increase in the FRAP and GSH/GSSG ratio is attributed to the non-alcoholic components of red wine. These data suggest that there is an enhancement of the antioxidant defense potential in kidney and plasma, after chronic red wine consumption. Both ethanol and the non-alcoholic antioxidant constituents of red wine could be responsible for these effects.

Ganglionar nervous cells and telocytes in the pancreas of Octodon degus: Extra and intrapancreatic ganglionar cells and telocytes in the degus

This study shows for the first time the presence of intra and extrapancreatic ganglionar neurons and telocytes in Octodon degus such as those described in human and guinea pig pancreas. Pancreatic ganglionar neurons were identified by their histological characteristics as well as their positive immunostaining with mouse anti-human neuron specific enolase (NSE) antibody. Somatostatin secreting delta cells (D cells) in the islets of Langerhans were identified by positive immunostaining with rabbit antihuman polyclonal somatostatin antibody. Electron microscopy evidenced the presence of some unmyelinated axons in the interlobular spaces or septa, usually located adjacent to blood vessels and the exocrine epithelial ducts. The presence of telocytes with at least 2 telopodes was observed in the interlobular space, frequently in close spatial relationship with blood vessels and nerve endings. Telocytes were often observed in the vicinity or even in close proximity with both secretory acini and exocrine epithelial ducts and regulatory nerves and blood vessel apparatuses. A possible framework has been put forward within which such structures might contribute to elicit physiological responses in the pancreas. Further studies of synaptic interactions within and between pancreatic neuron cells are needed to help clarify the morphological results reported here. A broad overview of the field of neurogastroenterology with focus on the pancreas of O. degus related to the enteric nervous system (ENS) is provided in order to help design future studies on the connections of specific neurons forming pancreatic pathways, their neurotransmission processes and how disruption of these pathways may contribute to pancreatic disease.

Placental Hypoxia and Foetal Development Versus Alcohol Exposure in Pregnancy

AIMS To examine the causes of variability in the effect of maternal drinking on the foetus, with particular reference to the pattern, frequency and duration of the period of drinking, differences in maternal, foetal and placental metabolism of ethanol/acetaldehyde, and genetic factors. METHODS Narrative review of published studies of the pathogenesis of foetal alcohol syndrome (FAS) with emphasis in the development of the central nervous system. RESULTS Animal models suggest that acetaldehyde, the primary hepatic oxidative metabolite of ethanol, reaches the foetus either by placental production or by placental transference, which in turn could affect foetal growth and development. The most likely hypothesis regarding the decrease of foetal growth is via hypoxia and increased oxidative/nitrative stress, which interfere with cellular processes that require oxygen in order to function adequately, such as placental transport. CONCLUSION There seems to be an association between the teratogenic effect, hypoxia and oxidative stress, the molecular mechanism involved (e.g. apoptosis) and the range of effects. The review sums ups the evidence that could explain some of the abnormalities in the brain development that could be related to behavioural problems observed in individuals with FAS/foetal alcohol spectrum disorder. This suggests that alcohol consumption produces failures in the normal migration of radial cells, from which the rest of the brain cells would eventually develop.

Renal Effects of Experimental Obstructive Jaundice: Morphological and Functional Assessment

BACKGROUND The pathophysiology of renal impairments occurring in obstructive jaundice has been extensively studied, but the underlying mechanism of these derangements remains unclear. The aim of the present study was to investigate the time-related morphological and functional changes occurring in the kidneys of rats undergoing obstructive jaundice. METHODS Histological examination, renal function assessment and determination of (Na + K)-ATPase activity were performed in the kidneys of rats 7, 14, and 21 days following bile duct ligation (BDL) or sham operation (sham). RESULTS Glomerular filtration rate was unaffected by BDL throughout the period of the study. Tubular effects occurred at days 7 and 14, being more marked at day 7, and consisted of an increase of about twice in the fractional excretion of sodium and chloride, paralleled by a decreased proximal and distal tubular reabsorption of sodium of about 50 and 40%, respectively. Natriuresis was consistent with augmentation of osmolar clearance but it was not associated with changes in the activity of renal (Na+ + K+)-ATPase. The ability to dilute urine was impaired at days 14 and 21 after BDL. Additionally, these effects were accompanied by decreased tubulointerstitial fibrosis and vasodilation of inner medullary capillaries. At day 21, the parameters of tubular function in BDL and sham groups were not significantly different. CONCLUSIONS These data support the view that raised natriuresis taking place in the initial 2 weeks following BDL is due mainly to tubular effects. The contribution of hemodynamic, paracrine and humoral mediators is discussed.

Biochemical and Ultrastructural Lung Damage Induced by Rhabdomyolysis in the Rat

Rhabdomyolysis-induced oxidative stress is associated with morphological and functional damage to the kidney and other organs, but applications of this model in the lung are still lacking. The aim of the present study was to determine the relationship between oxidative stress and the morphological changes occurring in the lungs of rats subjected to rhabdomyolysis. Rhabdomyolysis was induced by intramuscular glycerol injection (50% v/v, 10 ml/kg), and the control group was injected with saline vehicle. Arterial blood samples were drawn at 0, 2, 4, and 6 hrs for measurement of arterial gases, creatine kinase activity, and plasma free F2-isoprostane levels. Six hours later, the lungs were removed to determine the wet-to-dry weight ratio, reduced glutathione (GSH) and GSH disulfide (GSSG) levels, and activity of antioxidant enzymes (cataiase [CAT], superoxide dismutase [SOD], and GSH peroxidase [GSH-Px]). Protein carbonylation and lipid peroxidation were assessed in the lungs by measurement of carbonyl and malondialdehyde (MDA) production, respectively. Bronchoalveolar lavage, cell counts, and lung ultrastructural studies were also performed. Six hours after glycerol injection, arterial PO2 and PCO2 were 23% and 38% lower, respectively, and plasma free F2-isoprostane levels were 72% higher, compared with control values. In lungs, protein carbonyl and MDA production were 58% and 12% higher, respectively; the GSH:GSSG ratio and GSH-Px activity were 43% and 60% lower, respectively; and activities of CAT and SOD showed no significant differences compared with controls. Rhabdomyolysis-induced ultrastructural impairment of the lung showed Type II cell damage, extracytoplasmic lamellar bodies and lack of tubular myelin reorganization, endothelial cellular edema, and no disruption of the alveolar-capillary barrier. These results provide evidence that rhabdomyolysis could induce tissue injury associated with increased oxidative stress, suggesting the contribution of oxidative stress to the pathogenic mechanism of acute lung injury.

Oxidative damage to pre-eclamptic placenta: immunohistochemical expression of VEGF, nitrotyrosine residues and von Willebrand factor

Objective: To determine the relationship of biomarkers of placental damage by oxidative stress in pre-eclamptic placenta. Methods: A case-control study was performed on a population of 14 pregnant women with PE and 12 women with normal pregnancies. Immunohistochemical expressions of VEGF, vWF distribution, (Na + K)-ATPase activity, and abundance of nitrotyrosine residues, were assessed in the placental tissue. Results: Women with pre-eclampsia showed increased VEGF expression and abundance of nitrotyrosine residues in placental villous, and plasma vWF levels (p < 0.05), whereas placental (Na + K)-ATPase activity were significantly reduced. The syncytiotrophoblast and the maternal space of pre-eclamptic placenta showed diminished and increased vWF expression, respectively, but no significant differences in its expression were found in the placental endothelium and stroma (p < 0.05). Conclusions: It could be suggested that increased oxidative stress and VEGF contribute to enhance the impairment of placental perfusion by increasing peroxynitrite formation, product of the NO and superoxide reaction, thereby partly contributing to account for the pathophysiology of this disease. The presence of vWF in the maternal space and its diminished expression in syncytiotrophoblast of pre-eclamptic placenta also might have pathogenic implications.

Immunohistochemical identification of the extravillous trophoblast during the placentation of the degu (Octodon degus)

Recent data indicate that placentation in Octodon degus is similar to that in humans, making it a potential animal model for studies in human placental pathologies related to alterations in the migration of the extravillous trophoblast (EVT). Our objective was to immunohistochemically identify degu EVT during placentation by using cytoskeletal protein markers to establish the normal migratory pattern of the EVT. Fifteen O.degus were divided into three equal groups: day 27, 60, and 84 of gestation. The placentas were immunostained for cytokeratin (CK) and alpha smooth muscle actin (SMA). At day 27, the migrating EVT immunostained for SMA but not for CK. Once the EVT was incorporated in the maternal vessels (day 60) it was positive for CK but negative for SMA. The smooth muscle cells of the mesometrial arteries that remained after EVT invasion were positive for SMA. At day 84, the media muscular layer had partially regenerated but some EVT was still present. Furthermore, at day 27 cyclooxygenase-1 (COX-1) was detected in the endothelium of the maternal decidual vessels. Our results suggest that during the early stages of placentation, the cytoskeletal organization of the actin network of the migrating EVT corresponds to that of a cell with motile behavior. Once the EVT invaded the spiral arteries, the cytoskeleton reorganized, adopting the structure of an epithelial-like cell, expressing CK intermediate filaments. The media muscle layer regenerated near the end of gestation but some EVT remained. During EVT formation the endothelium of the maternal decidual vessels immunostained for COX-1.

Renal effects of chronic exposure to malathion in Octodon degus

We studied the effects of chronic exposure to malathion in the kidney of Octodon degus, a caviomorph whose habitat may be exposed to pesticides currently used in Chilean agriculture. A group of adult female animals received malathion (200 ppm) as sole drinking fluid for 90 days. Kidneys showed signs of histologic damage, marked by hyperplasia and hypertrophy of tubular cells. Exposed animals had unchanged glomerular filtration rates and renal handling of sodium and chloride, but a significant increase in fractional excretion of potassium resulted from this treatment. The activities of Na+/K(+)-ATPase and Mg(2+)-ATPase in renal cortex and outer medulla were not affected by malathion exposure. This study provides evidence of both morphologic and functional renal damage elicited by chronic exposure of O. degus to a low dose of malathion. Morphologic alterations in glomerulus were accompanied by either morphologic and functional impairments of the distal nephron.

Effects of Maternal Alcoholism on Placental Function and Lung Fetal Development

Epidemiological and clinical data indicate that alcohol consumption during pregnancy remains a substantial public-health problem as many pregnant women continue to drink alcohol despite clinical recommendations and public health campaigns warning about the risks associated. It is well known that maternal ethanol consumption during pregnancy results in deleterious effects on the developing fetus. Among these effects is the so called Fetal Alcohol Spectrum Disorder (FASD). Fetal Alcohol Syndrome (FAS) is a severe form of FASD and also an irreversible condition. Although all children born to alcoholic mothers show abnormalities, in some cases these may not be clearly observable. There is a wide spectrum of abnormalities regardless of the amount and pattern of alcohol exposure, differences in maternal, foetal and placental metabolism of ethanol/acetaldehyde, as well as genetic factors. In this article we present some of the effects of maternal alcoholism on placental functions and how it affects lung development