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Biomedical subjects

A Mas

Publications and source records attributed to A Mas.

At least 145 records · Page 8Linked to original sources

Binding, uptake and efflux of 65Zn by isolated human trophoblast cells.

The isolated trophoblast from human placenta at term has been used as model for placental transport. Binding to the cells showed to be of low specificity and very limited (less than 10%) in presence of serum. Uptake of zinc was 90% reduced at 4 degrees C and depended on the presence of sulfhydryl groups (as suggested with the inhibition produced by N-ethylmaleimide). There is considerable efflux (50%) of zinc from preloaded cells and the process was enhanced by presence of histidine in the medium. The model proved to be useful in studying the mode of zinc transport. The results indicate that the uptake of zinc by the trophoblast is probably the limiting process in the placental transport of this metal.

Acetates↗

[Liver transplantation: candidate selection and results of a program for adult patients].

During the first 18 months of liver transplantation program for adult patients we evaluated 98 potential candidates for this treatment. Forty five patients were refused for transplantation and 53 were accepted. Forty six out of these 53 cases were transplanted. Ten (22%) out of the 46 patients undergoing transplantation had chronic hepatic cholestasis, 31 (67%) chronic hepatic diseases of non biliary origin (3 patients had an associated hepatocarcinoma), and 5 patients (11%) suffered an acute hepatic failure. All transplanted patients with previous chronic hepatic diseases had clinical and biological signs of advanced hepatic failure. There were no operative deaths. During the follow-up period 6 transplanted patients (13%) died. The survival probability among the 46 operated patients was about 84% at 12 months after the transplant. This survival was theoretically higher than that expected to occur without transplantation. The survival probability among the 46 transplanted patients was significantly higher (p = 0.0001) than that recorded in 36 patients with comparable hepatic diseases who were evaluated during the same study period and who were not considered for transplantation due to several reasons. The survival probability at the first year in the later group of 36 patients was 20%.

Adult↗

Response to acute nickel toxicity in rats as a function of sex.

The effects of different nickel chloride doses upon blood and plasma glucose and essential metal homeostasis were studied in male and female rats. A definite sex-dependent response to injections of nickel has been observed for both the increase in plasma and blood glucose levels and the time at which these levels peak. Males showed a fast recovery from the rise in glucose levels and were much less affected by changes in the other parameters studied. In females, an extended rise in glucose levels was observed. All these effects are clearly nickel dose-dependent. Plasma, liver and kidney copper levels rose significantly in females while only a small decrease was observed in male kidneys. Zinc levels rose in all organs studied but males recovered to basal levels after the study period, whereas females maintained maximum levels at the end of the same period. An increase in urinary excretion of iron was observed. The present results show that the sex differences to acute nickel toxicity can be a helpful way to study metal interaction and discriminate between specific toxicity due to nickel or that induced by the associated hyperglucagonemia.

Animals↗

The influence of zinc-binding ligands in fetal circulation on zinc clearance across the in situ perfused guinea pig placenta.

Although zinc is essential for normal fetal growth and development, little is known about factors that influence its transfer across the placenta. The in situ perfused guinea pig placenta model was used to study the influence of zinc-binding ligands in fetal circulation on maternofetal placental zinc transfer. A placenta of each anesthetized sow was perfused (on the fetal side) with a physiological perfusate via the umbilical vessels, with the fetus excluded. The sow was infused intravenously with 65Zn as a tracer of placental zinc clearance and with antipyrine as an indirect indicator of maternal placental blood flow. Maternal plasma and placental effluent samples collected at intervals were counted for 65Zn with a gamma counter, and the absorbance of nitrosated antipyrine was measured at 350 nm. The addition of physiological levels of zinc-binding ligands (albumin, L-histidine and L-cysteine) to the perfusate increased the relative maternofetal clearance of zinc across the placenta calculated as zinc clearance/antipyrine clearance [mean +/- SEM; 0.113 +/- 0.016 vs. 0.062 +/- 0.012; ligands vs. no ligands; n = 8; P less than 0.05]. The results suggest that the availability of zinc-binding ligands in fetal circulation is one determinant factor of placental zinc transfer.

Animals↗

Effects of acute nickel toxicity upon plasma and liver metal homeostasis as a function of sex.

The effects of an acute dose of nickel chloride (4 mg Ni/kg body wt) upon liver and plasma essential metal homoeostasis were studied in male and female rats. Total levels of copper and zinc in the tissues and in the fractions of chromatographic profiles (Sephadex G-100 and G-150) were determined. Plasma and liver levels of both metals rose significantly. The higher levels of copper in plasma are associated with increased ceruloplasmin activity and the initial increase of zinc in plasma is due to higher zinc content in the plasma albumin fraction. In the liver, the higher levels of both metals similarly affected all the metal-containing chromatographic fractions, although a significant increase is only observed in metallothionein-containing fractions, which agrees with previous reports on increased levels of metallothionein after nickel treatment. Regarding the sex-dependent changes, both sexes showed the same alterations, yet males recovered faster than females from all the nickel-induced changes in metal homoeostasis.

Animals↗

[Predictive factors of mortality in a series of 61 patients with severe acute pancreatitis].

The predictive value of eight clinical variables and 20 analytical variables on mortality was retrospectively analyzed in 61 patients with severe acute pancreatitis, fulfilling at least three Ranson criteria, admitted to the ICU between 1977 and 1987. The mean age of the series was 57 +/- 16.6 years. Twenty seven were males and 34 females. The mortality rate was 60%. Univariate analysis demonstrated that the variables with greater predictive value of mortality were: age, days of hospitalization, presence of associated diseases, plasma lactodehydrogenase, more than 10% hematocrit decrease during the first 48 hours, plasma ureic nitrogen on admission and a value greater than 1.8 mmol/l during the first 48 hours, calcemia, arterial oxygen pressure, plasma albumin, and prothrombin time. A logistic regression multivariate analysis disclosed that the variables with independent predictive value of mortality were: age, serum ureic nitrogen, calcemia, arterial oxygen pressure, plasma albumin, and hematocrit decrease after 48 hours. When the patients were grouped according to the presence of less than three, three, four or more than four of these risk factors (being, the average the cutting point) we obtained a good prognostic discriminative power since the mortality in those groups was 0, 30%, 60%, and 100%, respectively.

Acute Disease↗

Cytosolic copper-binding proteins in rat and mouse hepatocytes incubated continuously with Cu(II).

The proteins that bind copper when it first enters cells are likely to play roles in its intracellular distribution and utilization. When hepatocytes were incubated with 64Cu(II), the time-dependence of the subcellular distribution of 64Cu was consistent with one or more cytosolic proteins distributing copper to the mitochondrial and nuclear fractions. Cytosolic copper was reproducibly distributed among four protein fractions from Sephadex G-150 columns at the earliest time (1 min) and at the lowest concentration used [2 microM-64Cu(II)] with both rat and mouse hepatocytes. Copper binding to proteins in these functions was sensitive to copper metabolic status. Hepatocytes from nutritionally copper-deficient rats or neonatal (9-30 days old) developing rats showed an inverse correlation between copper binding to metallothionein and copper binding to proteins in fraction I (approximately 88 kDa apparent) and fraction II (approximately 38 kDa apparent). The distribution of cytosolic 64Cu from the brindled-mouse model of Menkes disease indicated decreased binding by a protein in fraction I. Brindled-mouse hepatocytes also contain decreased levels of a approximately 55 kDa protein or subunit, which most likely represents a liver-specific secondary response to the primary defect. The results are consistent with one or more copper-binding proteins in fractions I and II having significant functions in intracellular copper metabolism.

Animals↗

Vasopressin/nitroglycerin infusion vs. esophageal tamponade in the treatment of acute variceal bleeding: a randomized controlled trial.

Vasopressin infusion and esophageal tamponade are still widely used to arrest variceal bleeding, but no objective evidence exists on the superiority of either of the two procedures. In this study, 108 cirrhotic patients bleeding from varices were included in a prospective, randomized trial to investigate the comparative effectiveness and safety of balloon tamponade (using the Sengstaken-Blakemore tube for esophageal varices and the Linton-Nachlas tube for gastric varices) (n = 52) and intravenous vasopressin infusion (0.4 to 0.8 mu/min) plus intravenous nitroglycerin infusion (40 to 400 micrograms/min) (n = 56). Both treatments were maintained for 24-hr. The hemostatic efficacy according to the intention to treat was 86.5% for tamponade and 66% for pharmacological therapy (p less than 0.01). No significant differences were found with respect to rebleeding during the first 72 hr after treatment, mortality rate or side effects. These results suggest that esophageal tamponade is more effective than vasopressin/nitroglycerin infusion in the treatment of variceal bleeding in cirrhotic patients.

Acute Disease↗

Hepatitis B virus and hepatitis D virus replication in HBsAg-positive fulminant hepatitis.

Hepatitis B virus DNA and hepatitis D virus RNA, the most sensitive markers of hepatitis B and hepatitis D virus replication, were sought by molecular hybridization with radioactive probes in serial serum samples from 29 consecutive patients with HBsAg-positive fulminant hepatitis. Nineteen patients had evidence of hepatitis D virus infection, as assessed by the presence in serum of delta antigen, anti-delta antibodies, or both. Hepatitis B virus DNA was found in only two patients: one was a chronic HBsAg carrier with hepatitis D virus superinfection and the other had fulminant hepatitis caused by hepatitis B and hepatitis D coinfection. Hepatitis D virus RNA was detected in three patients: two with hepatitis B and hepatitis D coinfection and also in the HBsAg carrier with positive hepatitis B virus DNA and hepatitis D virus superinfection. None of 10 patients with hepatitis B virus infection alone had detectable viral nucleic acids in serum. Overall, viral nucleic acids were detected in the sera of 4 of the 29 patients (14%). Hepatitis D virus antigenemia did not indicate hepatitis D virus replication because hepatitis D virus RNA was not detected in 9 of 12 patients with hepatitis D virus antigen in their sera. The low frequency of viral replication found in fulminant hepatitis B or D may explain the low recurrence rate of viral hepatitis in patients with fulminant hepatitis who have received liver transplantations.

Adolescent↗

Nickel binding by isolated human trophoblast cells.

Isolated human trophoblast cells were used for the first time to mimic the placental metabolism of nickel. The retention of nickel by the trophoblast cells was assessed in presence of different nickel ligands. Nickel chloride and nickel-albumin showed an initial rapid binding to human trophoblast cells reaching a quasi-steady state after 30 min. Albumin, however, reduced the binding of nickel to the cells. Nickel-histidine showed slow initial binding, although no saturation was achieved. The results for nickel-histidine complexes are similar to those observed in in vivo experiments.

Absorption↗

[Severe acute hepatitis as initial manifestation of chronic hepatitis B virus infection].

Chronic hepatitis B virus (HBV) infection was revealed by a severe acute hepatitis with positive HBsAg in a patient. The positivity of IgM anti-HBc antibody, the rapid negativization of DNA-HBV, the early normalization of liver function tests and the exclusion of other causes of acute hepatitis favored the diagnosis of recent HBV infection and were predictive of a rapidly favorable outcome. However, immunohistochemical study of a transjugular hepatic biopsy sample discovered HBsAg within the liver, with a characteristic topographic distribution of chronic HBV infection. The patient's evolution confirmed this diagnosis, because 20 months later he had chronic active hepatitis with persistent replicative activity of HBV. This case illustrates the heterogeneity of HBV infections, emphasizing the need of an accurate diagnosis and a careful follow up until the complete resolution of each case of acute hepatitis with positive HBsAg.

Acute Disease↗

Association of transdermal nitroglycerin to vasopressin infusion in the treatment of variceal hemorrhage: a placebo-controlled clinical trial.

The aim of this study was to evaluate, using a double-blind technique, the efficacy of the association of transdermal nitroglycerin to vasopressin infusion for the treatment of variceal bleeding. Sixty-nine cirrhotic patients with active variceal bleeding were randomly allocated to receive vasopressin (0.4 to 0.8 unit per min until variceal bleeding has been controlled for 12 hr) associated with nitroglycerin administered transdermically in a slow-release preparation (10 mg in 24 hr) or placebo. An initial control of variceal hemorrhage was achieved in 83% of the patients receiving vasopressin-nitroglycerin and in 74% in the vasopressin-placebo group. Owing to a lower frequency of recurrent bleeding during therapy (18 vs. 42%, p = 0.11), vasopressin-nitroglycerin achieved a definitive control of bleeding in a higher proportion of patients than vasopressin-placebo (73 vs. 54%, p = 0.13). The group treated with the drug combination showed favorable results in relation to transfusion requirements (2.9 +/- 0.4 vs. 4.2 +/- 0.5 units, p = 0.05), total dose of vasopressin required (453 +/- 47 vs. 587 +/- 50 units, p less than 0.05), need of balloon tamponade (6 vs. 15, p less than 0.05) and requirement for emergency surgery (0 vs. 4, p = 0.07). There were no significant differences in the undesirable effects associated with treatment, observed in 37 and 49% of cases, respectively. Hospital mortality was similar (33 vs. 25%). This study demonstrates that transdermal nitroglycerin improves the effectiveness of vasopressin for controlling variceal hemorrhage.

Administration, Cutaneous↗

Initial permeability of the 19-day foetus to nickel.

The administration of 63NiCl2 to 19-day pregnant rats produced a limited transfer of nickel to the foetus. An experimental model based on the incubation of the conceptuses still connected to the maternal organism resulted in an appreciable net transfer of nickel through the amniotic membranes. The placenta retained a significant amount of radioactive nickel as did the lining of the uterine wall. The circulation of nickel through the foetus following the direction maternal blood----placenta----foetus----amniotic membranes----endometrium----maternal venous blood, is postulated. This transfer could provide an additional protection to placental barrier against metal toxicity.

Animals↗

The metabolism of metals in rat placenta.

The status and transfer of metals across the rat placenta were studied by subcellular and molecular fractionations of this organ at 2 and 24 h after iv injection of radiolabeled metals. The soluble and nuclear fractions showed higher contents of copper and zinc, whereas most of the nickel was associated with the soluble fraction. Cadmium was almost evenly distributed between the microsomal and nuclear fractions. Gel filtration of the soluble fractions showed nickel associated with an unknown low molecular weight form; zinc with high molecular weight proteins; copper with metallothionein, ceruloplasmin, and high molecular weight proteins; and cadmium with high molecular weight proteins and metallothionein.

Animals↗

Analysis of factors predicting early seroconversion to anti-HBe in HBeAg-positive chronic hepatitis B.

To investigate whether data obtained at the time of diagnosis may serve to predict early seroconversion to anti-HBe in chronic hepatitis B virus infection, we have compared the clinical, pathological and virological features of two groups of patients with untreated HBeAg-positive chronic hepatitis B who showed a markedly different outcome. One group (early seroconverters) included 20 patients who developed a typical seroconversion to anti-HBe within the first year of prospective follow-up. The other group (non-seroconverters) was formed by 21 patients who remained seropositive for HBeAg and still had raised aminotransferase serum levels after at least 2 years of follow-up. The serum aminotransferases, the degree of periportal and lobular lesions, the amount of liver fibrosis and the total score index of histological activity were significantly higher but the amount of HBcAg in liver was smaller in early seroconverters. Stepwise logistic regression analysis demonstrated that the alanine aminotransferase serum levels, the Knodell's index of histological activity and the amount of HBcAg in liver had significant value as independent predictors of early seroconversion. Calculation of the probability of seroconversion for individual cases showed marked differences between the two groups of patients, suggesting that early seroconversion to anti-HBe may be predicted in some patients with chronic hepatitis B.

Adult↗

Chronic hepatitis D in intravenous drug addicts and non-addicts. A comparative clinico-pathological study.

In recent years chronic infection by the hepatitis delta virus (HDV) has become an important cause of chronic liver disease among drug addicts. To evaluate the influence of addiction to i.v. drugs on the course of this disease we have analyzed the clinical, histopathological, virological and evolutive features in 18 addicts and 11 non-addicts with chronic delta infection. Recent acute hepatitis D, documented as HDV superinfection, was observed in 14 addicts (77%) and in 2 non-addicts (18%) (P less than 0.02). At the time of evaluation for chronic liver disease, the frequency of symptoms, the degree of biochemical disturbances and the histopathological severity were similar in the two groups but the duration of HDV infection was probably shorter in drug addicts. HBV replication, as indicated by the presence of HBeAg and HBV-DNA in serum and HBcAg in liver, was more frequent in addicts. The amount of HDAg in liver tissue was also greater in addicts (P less than 0.005). Antibodies against the human immunodeficiency virus were detected in all of the addicts (P less than 0.001). Although most patients remained asymptomatic, significant histological worsening occurred in one half of the cases after a relatively short period of follow-up (25.1 +/- 16.3 months). The tendency to deteriorate in addicts (61% of cases) was greater than in non-addicts (36%). These observations suggest that the prognosis of chronic HDV infection is particularly poor in drug addicts in whom rapid deterioration may be related to simultaneous and inadequately controlled replication of hepatotropic viruses.

Chronic Disease↗