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Biomedical subjects

M Arevalo

Publications and source records attributed to M Arevalo.

13 recordsLinked to original sources

Effect of maternal cholestasis on biliary lipid and bile acid secretion in the infant rat.

Partial and reversible impairment of bile formation has been reported to occur in the offspring of rats undergoing common bile duct ligation during the last third of pregnancy. This situation was defined as latent cholestasis of the neonate and was suggested to be related to the multilamellar bodies partially occupying the canalicular lumen. The current study was undertaken to investigate the presence of alterations in the secretion of biliary lipids in these infant rats. Using both high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) analyses, no changes caused by maternal cholestasis were found in either the conjugation pattern, or in the ratio of primary to secondary major bile acids in bile samples collected from 4-week-old and 8-week-old rats. However, a decrease in the proportion of cholate together with an increase in the amount of alpha- and omega-muricholate were found at 4 weeks of age. These changes were different from those observed in the pattern of maternal plasma bile acids, in which beta-, but not alpha-muricholate, concentrations were increased. Moreover, studies performed by labeling the bile acid pool of the cholestatic mother-fetus tandem with [14C]glycocholic acid (GC) at day 16 of pregnancy indicated that only a minor proportion (approximately 10%) of bile acids found in 4-week-old pups was of maternal origin. Changes in the bile acid pool composition were fully reversed by 8 weeks of age. Bile lecithin and cholesterol output were determined by enzymatic techniques, both under basal conditions and during stepwise taurocholate (TC) infusion. At the time when multilamellar bodies were found, i.e., 4 weeks after birth, no change in either nonstimulated or TC-induced cholesterol output was observed. By contrast, both spontaneous and TC-induced lecithin secretion were markedly higher (+200%) in pups of cholestatic mothers as compared with control rats. These differences were abolished at 8 weeks of age. At this time, cholesterol output was significantly lower than that found in younger animals. This reduction was more pronounced in the control than in the cholestatic group. Histological examination of liver samples collected from the cholestatic group at 4 weeks of age revealed the presence of multilamellar bodies not only in the canalicular lumen but also within vesicular structures located in the pericanalicular area or near the Golgi apparatus. Both intracellular and intracanalicular bodies were present before and after TC infusion for 2 hours. These results indicate that maternal cholestasis in rats induces profound alterations in biliary lipids and bile acid secretion in their pups. Because bile acids are important activators of different steps responsible for biliary lipid secretion (intracellular trafficking, releasing into bile, and solubilization), alterations in maternal bile acid pool size and composition may affect the fetal development of biliary lipid secretion mechanisms, which may result in the appearance of multilamellar bodies within bile canaliculi, which in turn may be involved in the reversible latent cholestasis observed in these infants rats.

Aging

Reversible impairment of neonatal hepatobiliary function by maternal cholestasis.

The effect of total blockage of maternal biliary excretion during the last third of the pregnancy on the maturation of hepatobiliary function was investigated in neonatal rats. Extrahepatic obstruction of the common bile duct on day 14 of pregnancy induced a marked enhancement in serum bilirubin--mainly conjugated bilirubin--and bile acid concentrations as compared with sham-operated pregnant rats. Excretion of bile acids by the kidney was significantly increased, whereas fecal elimination of these compounds was almost abolished. Most of the cholestatic mothers (CMs) (77%) were able to carry pregnancy to term and lactation until weaning (21 days after birth). The body and liver weights of their offspring were lower than for offspring of control healthy mothers in all postnatal periods considered. Serum bile acid concentrations were higher in the fetuses and neonates of CMs. This difference was evident up to 1 week after weaning and disappeared in young adult animals (8 weeks old). When the bile secretion rate was investigated in these animals at 4 or 8 weeks of age, no significant difference was found as far as nonstimulated bile flow and bile acid output was concerned. However, the biliary response to stepwise sodium taurocholate (TC) intravenous infusion showed that 4-week-old neonates of CMs had impaired bile acid secretion. Moreover, the maximal secretion rate (SRmax) for TC was significantly reduced (-30%), whereas the choleretic ability of taurocholate was not modified. This alteration was not selective for bile acids. The SRmax for bromosulfophthalein (BSP) was also significantly lowered (-40%). These dysfunctions were overcome during subsequent development. No impaired biliary response to either TC or BSP infusion was observed at 8 weeks of age. Morphological abnormalities in the canaliculi were found in animals with impaired biliary function. In summary, these results indicate that maternal cholestasis may profoundly but transiently impair the normal liver maturation. The importance of the implications derived from these findings both in the nutrition and management of human neonates demands further evaluation of the hepatobiliary function of babies born after alterations of fetal-maternal bile acid homeostasis, such as in maternal obstetric cholestasis.

Animals

Immune depression induced by protein calorie malnutrition can be suppressed by lesioning central noradrenaline systems.

Depressed immune function is well documented in protein calorie malnutrition (PCM). Also, central noradrenergic hyperactivity has recently been reported in malnourished animals. Increase in central noradrenaline activity could be responsible for cell-mediated immune depression. The present study is designed to address this hypothesis by testing whether neurotoxic lesion of central noradrenergic systems by 6-hydroxydopamine (6-OHDA) could improve lymphoproliferative response to mitogens and interleukin (IL)-1 production in PCM rats. A significant enhancement of lymphoproliferative response to concanavalin A (ConA) and in IL-1 production was observed in spleen mononuclear cells of PCM rats injected intracerebroventricularly with 120 micrograms of 6-OHDA, as compared with solvent injected and untreated PCM animals. A significant decrease in brain noradrenaline levels was produced in the drug-injected animals. These results suggest that central noradrenergic hyperactivity is one of the mechanisms involved in the immunodepression produced by malnutrition.

Animals

Idiopathic bronchiolitis obliterans organizing pneumonia with multiple cavitary lung nodules.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a pulmonary disorder with a wide spectrum of radiological features. We report the case of a 58 year old woman, in whom the radiological appearance was multiple cavitary nodules in both lungs, that responded with a complete resolution after corticosteroid therapy. This finding justifies the inclusion of BOOP in the differential diagnosis of multiple cavitary nodules.

Biopsy

Zinc supplementation impairs monocyte function.

Zinc has been shown to be involved in many functions of the immune system. This study was conducted to examine the effect of zinc supplementation on phagocytic, fungicidal and metabolic activity of blood monocytes of marasmic infants during nutritional rehabilitation. A controlled, double-blind design was used in which 19 infants fed a zinc-fortified formula were compared with 20 infants fed the same, unfortified formula. Evaluation of phagocytic-fungicidal capacity, growth, zinc, copper and iron status was performed in both groups on admission and after 60 and 105 days of nutritional rehabilitation. Although energy, copper and iron intakes were similar in the two groups, a decrease in the number of infants able to phagocytose one or more Candida buds was observed after 60 days of zinc supplementation compared to admission (p < 0.03). No change in phagocytic ability was detected between admission and 60 days in the control group. The number of infants with depressed fungicidal activity increased significantly after 105 days of nutritional rehabilitation in the zinc-fortified group as compared to controls (p < 0.04). The number and duration of impetigo episodes was significantly greater in the group fed the zinc-fortified formula. These results suggest that zinc supplements at the RDA level may impair monocyte function.

Candida albicans

Effect of a zinc-fortified formula on immunocompetence and growth of malnourished infants.

This study attempted to define the possible contribution of zinc nutrition to immunocompetence and growth in severely malnourished infants. The effect of zinc supplementation was evaluated in marasmic infants during nutritional rehabilitation by using a controlled double-blind design in which 19 infants fed a zinc-fortified formula were compared with 20 infants fed the same non-supplemented formula. Evaluation of immunocompetence, growth, and zinc, copper, and iron status was performed on admission and at 30, 60, and 105 d of nutritional rehabilitation. Although energy intake was similar in both groups, the zinc-supplemented infants had significantly higher linear growth gain, and their immune function improved as demonstrated by conversion of their delayed hypersensitivity skin reactions, enhanced lymphoproliferative response to PHA, and increased salivary IgA concentrations. Thus, the use of a zinc-fortified formula during nutritional rehabilitation can prevent the development of zinc deficiency and improve growth and immune function.

Copper

Familial alloimmune neutropenia of NA-2 specificity.

Three siblings with alloimmune neonatal neutropenia are presented. An immunoglobulin G (IgG) antineutrophil antibody specific for NA-2 antigen was demonstrated in maternal serum and in both of the three affected infants who were studied as neonates. The mother's neutrophils were negative for NA-2 antigen. The father and all four children, including the three known to be affected, had neutrophils that expressed NA-2 antigen. One patient studied sequentially demonstrated an inverse relationship between the antineutrophil antibody titer and the absolute neutrophil count. Exchange transfusions did not appear to benefit two of the infants.

Antibody Specificity

Functional capacity of colostral leukocytes from women delivering prematurely.

The phagocytic, bactericidal, and metabolic activity of colostral leukocytes from mothers delivering preterm infants was compared with that of colostral leukocytes from mothers of term infants. In addition, the proliferative capacity of colostral lymphocytes was compared. Preterm adherent colostral leukocytes had a significantly higher phagocytic index than term colostral adherent leukocytes. Mean +/- SEM values were 5.4 +/- 0.5 versus 2.7 +/- 0.2, respectively (p less than 0.001). Bactericidal capacity against Escherichia coli and nitroblue tetrazolium reduction of preterm and term colostral leukocytes were comparable. Lymphocyte proliferative response was equivalent in preterm and term milk. We conclude that colostral leukocytes from preterm mothers are at least as functional in their antimicrobial activity and possibly phagocytose even better than the colostral cells of mothers of term infants.

Adult

Prevalence of hepatitis B in an indigent, multi-ethnic community clinic prenatal population.

Perinatal infection of hepatitis B virus (HBV) from an infected asymptomatic woman to her offspring is now a preventable disease. A chart review was undertaken to document the prevalence of asymptomatic HBV infection in a high-risk, predominantly minority, indigent, and immigrant family practice clinic population and to evaluate the frequency of accepted known risk factors for those subjects with positive hepatitis B surface antigen (HBsAg) screening tests. Records for 464 pregnant women entering the prenatal program between January 1, 1983, and April 30, 1987, were reviewed. Twenty-three (5.3%) were found positive for the HBsAG, all were asymptomatic. Results of a logistic regression on multiple risk factors for HBV infection revealed that ethnicity was the sole predictor of a positive HBsAg screening test, with 13% of the Asian patients and 1% of the Latino subjects positive for HBsAg. Other historical factors such as previous sexually transmitted disease and past history of transfusion were not predictive. These results reaffirm that a screening program for asymptomatic HBV infection in selected prenatal populations can identify a significant number of infants at risk for risk for perinatal infection.

Adolescent

Cytogenetic findings in an effusion secondary from pleural mesothelioma.

Cytogenetic analysis was performed on cells from pleural effusion secondary to an epithelial mesothelioma. Although chromosomal findings (pseudodiploid stemline, including marker chromosomes involving chromosomes #1, #3, #5, and #6) suggested the neoplastic origin of the effusion, routine cytologic diagnosis was negative.

Adult

Interleukin-1 beta in human colostrum.

The two forms of interleukin-1, IL-1 alpha and IL-1 beta respectively, and tumour necrosis factor (TNF) are polypeptides sharing different biological activities which are often associated with host defence mechanisms. Because of the well-recognized benefits of breast feeding for newborns, colostrum from 9 healthy lactating women was analysed for the presence of these 3 cytokines. Specific radioimmunoassay revealed that colostrum contains a significant amount of IL-1 beta (mean +/- SEM values of 1,130 +/- 259 pg/ml). The concentrations of IL-1 alpha and TNF were negligible. Colostral leukocytes are able to produce IL-1 since high activity was found after stimulation with Staphylococcus epidermidis. In addition, these cells produced IL-1 spontaneously in vitro, in contrast to resting maternal blood monocytes. As IL-1 increases resistance to infection, the presence of this cytokine represent a beneficial aspect of breast feeding.

Adult

Effect of gentamicin treatment on glutamine and lactate metabolism by the renal cortex of the rat.

The present study was performed to measure the uptake of main renal cortical fuel substrates (glutamine and lactate) and the release of the main renal cortical products (ammonia and glucose) by cortical slices from gentamicin-treated rats. Experiments were done in 2 groups of female Wistar rats (250 g): In gentamicin group (n = 13), rats were injected s.c. with gentamicin-sulphate 100 mg/Kg body wt/day for 5 days. Control rats (n = 13) received isotonic saline. After anesthesia and blood sampling, renal cortical slices were obtained and incubated with L-glutamine and/or lactate at 1 or 5 mM concentration, containing L-glutamate and/or pyruvate at 0.1 or 0.5 mM. Creatinine clearance was reduced to a 50% in gentamicin-treated rats. In addition these animals showed a sharp increase in urinary excretion of N-acetyl-beta-D-glucosaminidase and alkaline phosphatase. Light microscopy examination revealed extensive cell necrosis and tubular obstruction of the proximal tubules in kidneys of rats injected with gentamicin. The renal cortical gentamicin concentration of rats injected with gentamicin was 310 +/- 43 mu/g, whereas it was undetectable in control rats. Cortical slices from gentamicin-treated rats, compared to control ones, showed a reduced production of ammonia and glucose, without differences in glutamine or lactate extraction. These alterations can be explained by both the increased rate of anabolic reactions to recover cell damage associated to renal failure, as well as by a direct effect of gentamicin on the rate of carboxylation reactions.

Ammonia