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Biomedical subjects

G Ugarte

Publications and source records attributed to G Ugarte.

At least 19 recordsLinked to original sources

Putative ClC-2 chloride channel mediates inward rectification in Drosophila retinal photoreceptors.

We report that Drosophila retinal photoreceptors express inwardly rectifying chloride channels that seem to be orthologous to mammalian ClC-2 inward rectifier channels. We measured inwardly rectifying Cl(-) currents in photoreceptor plasma membranes: Hyperpolarization under whole-cell tight-seal voltage clamp induced inward Cl(-) currents; and hyperpolarization of voltage-clamped inside-out patches excised from plasma membrane induced Cl(-) currents that have a unitary channel conductance of approximately 3.7 pS. The channel was inhibited by 1 mM: Zn(2+) and by 1 mM: 9-anthracene, but was insensitive to DIDS. Its anion permeability sequence is Cl(-) = SCN(-)> Br(-)>> I(-), characteristic of ClC-2 channels. Exogenous polyunsaturated fatty acid, linolenic acid, enhanced or activated the inward rectifier Cl(-) currents in both whole-cell and excised patch-clamp recordings. Using RT-PCR, we found expression in Drosophila retina of a ClC-2 gene orthologous to mammalian ClC-2 channels. Antibodies to rat ClC-2 channels labeled Drosophila photoreceptor plasma membranes and synaptic regions. Our results provide evidence that the inward rectification in Drosophila retinal photoreceptors is mediated by ClC-2-like channels in the non-transducing (extra-rhabdomeral) plasma membrane, and that this inward rectification can be modulated by polyunsaturated fatty acid.

Animals↗

Changes in microsomal activity in alcoholism and obesity.

BACKGROUND: Liver damage is more prevalent among obese alcoholics, and cytochrome P-4502E1(CYP2E1) induction is involved in its pathogenesis. OBJECTIVES: The study was undertaken to assess microsomal function, in alcoholic and nonalcoholic male subjects with different body compositions, through pharmacokinetics of chlorzoxazone (CLZ). We also intended to study the relationship between CLZ hydroxylation and urinary levels of 8-hydroxydiguanosine, and between CLZ levels and liver histology. METHODS: Serial measurements of CLZ serum concentration, after a 750 mg dose, were performed in 17 alcoholics (9 normal weight and 8 obese) and 21 nonalcoholic subjects (10 normal weight and 11 obese). Concentration of 6-hydroxy-chlorzoxazone (6-OH-CLZ) was determined at the second hour. Anthropometry, clinical laboratory tests, and urinary 8-hydroxydiguanosine concentrations were measured. Liver biopsies were performed in alcoholics. RESULTS: Five biopsies revealed severe lesions, one in normal-weight and four in obese patients (p = NS). Area under the curve (AUC) of CLZ was higher in normal-weight controls compared with the rest of the groups (ANOVA p = 0.001). This parameter correlated negatively with adiposity in nonalcoholic subjects and did not correlate with liver histology. 6-OH-CLZ/CLZ ratio was lower in normal-weight controls, compared with obese subjects and normal-weight alcoholics (p = 0.02). Both alcoholism and obesity were included as predictors of CLZ AUC in a multiple regression analysis. The two-factor ANOVA showed an additive effect of centripetal body fat distribution and alcoholism. Urinary 8-hydroxydiguanosine levels were extremely variable. CONCLUSIONS: Centripetal adiposity and alcoholism are associated with induction of CYP2E1. This may explain the higher prevalence of liver damage among obese alcoholics and also nonalcoholic steatohepatitis.

Adult↗

How do calcium channels transport calcium ions?

Calcium channel activity is crucial for many fundamental physiological processes ranging from the heart beat to synaptic transmission. The channel-forming protein, of about 2000 amino acids, comprises four domains internally homologous to each other. Voltage-dependent Ca2+ channels are the most selective ion channels known. Under physiological conditions, they prefer Ca2+ over Na+ by a ratio of about 1000:1. To explain at the same time the exquisite ion selectivity and the large Ca2+ ion turnover rate of Ca2+ channels (approximately 3 x 10(6) ions/s), two kind models have been proposed. In one, the conduction pathway possesses two high-affinity binding sites. When two Ca2+ ions are bound to each site, the mutual repulsion between them speeds the exit rate for the ions, causing greater ion permeation through the pore. The second model hypothesizes the existence of a single site having a charged structure able to attract multiple, interacting ions, simultaneously. Recent studies that combine mutagenesis and electrophysiology show that the high-affinity binding site is formed by a ring of glutamate residues located in the pore forming region of the Ca2+ channel. As proposed in the second class of models, the results suggest that four glutamate residues, one glutamate donated by each repeat, combine to form a single high-affinity site. In this review the different conduction models for Ca2+ channels are discussed and confronted with structural data.

Binding Sites↗

Protein turnover in abstinent and non-abstinent patients with alcoholic cirrhosis.

OBJECTIVE: This study was designed to measure the effect of chronic alcohol intake on leucine turnover in outpatients with stable alcoholic liver cirrhosis. METHODS: Protein turnover rate was measured using L [1-14C] leucine in ten outpatients with proven alcoholic cirrhosis and in five healthy controls. After the performance of the turnover, the patients were divided in two groups depending on the evidence of alcohol ingestion in the previous month. RESULTS: Non-abstinent patients had a significantly higher leucine flux and non-oxidative disposal (73.8 +/- 25.4 and 65.9 +/- 21.6) than abstinent cirrhotic patients (48.9 +/- 9.5 and 43.7 +/- 9.0) and normal controls 37.3 +/- 8.9 and 31.1 +/- 7.6 mumol/m2/min (p < 0.01). Leucine oxidation and serum leucine levels were similar in the three groups. CONCLUSION: Alcohol intake in alcoholic cirrhotic patients has a catabolic effect that could be associated with the nutritional imbalances observed in alcoholic liver disease.

Adult↗

[Major histocompatibility system as a risk factor for alcoholic liver disease].

Several associations between alleles of the major histocompatibility system and alcoholic liver disease have been described. However, these are weak and change from one population to another. The aim of this work was to search for a possible genetic risk factor for alcoholic liver disease among Chilean alcoholics. We studied blood groups, serum proteins and HLA antigens in 39 alcoholic cirrhotics, 104 asymptomatic alcoholics and 44 non alcoholic controls. Asymptomatic alcoholics were also subjected to a percutaneous liver biopsy that showed moderate to severe histological liver damage in 46 subjects (44%). No differences in the studied genetic markers, were found among the four groups. It is concluded that this study does not confirm previously reported associations between genetic markers and alcoholic liver disease.

Adult↗

Inhibitory K+ current activated by odorants in toad olfactory neurons.

Odorant responses of isolated olfactory neurons from the toad Caudiverbera caudiverbera were monitored by using patch-clamp techniques. Depending on the stimulus, the same neuron responded with an increase or a decrease in action potential firing. Odorants that activate the cAMP cascade in olfactory cilia increased electrical activity, caused membrane depolarization, and triggered inward currents. In contrast, odorants that do not activate the cAMP cascade inhibited electrical activity, produced membrane hyperpolarization, and activated outward currents in a dose-dependent fashion. Such currents were carried by K+ and blocked by tetraethylammonium. Similar currents were recorded from Xenopus laevis. Our results suggest that this K+ current is responsible for odorant-induced inhibition of action potential firing in olfactory neurons.

Acyclic Monoterpenes↗

[Liver cirrhosis and pregnancy].

A clinical case of a woman 25 year old with Laennec's cirrhosis at 18th, week of gestation was admitted in our hospital. In the 30th week a cesarean section was performed, resulting a healthy infant. The infrequency relationship between pregnancy and cirrhosis is discussed an a review of the literature is presented.

Adult↗

[Prediction of histological liver damage in asymptomatic alcoholic patients by means of clinical and laboratory data].

Looking for a noninvasive method to predict liver histologic alterations in alcoholic patients without clinical signs of liver failure, we studied 187 chronic alcoholics recently abstinent, divided in 2 series. In the model series (n = 94) several clinical variables and results of common laboratory tests were confronted to the findings of liver biopsies. These were classified in 3 groups: 1. Normal liver; 2. Moderate alterations; 3. Marked alterations, including alcoholic hepatitis and cirrhosis. Multivariate methods used were logistic regression analysis and a classification and regression tree (CART). Both methods entered gamma-glutamyltransferase (GGT), aspartate-aminotransferase (AST), weight and age as significant and independent variables. Univariate analysis with GGT and AST at different cutoffs were also performed. To predict the presence of any kind of damage (Groups 2 and 3), CART and AST > 30 IU showed the higher sensitivity, specificity and correct prediction, both in the model and validation series. For prediction of marked liver damage, a score based on logistic regression and GGT > 110 IU had the higher efficiencies. It is concluded that GGT and AST are good markers of alcoholic liver damage and that, using sample cutoffs, histologic diagnosis can be correctly predicted in 80% of recently abstinent asymptomatic alcoholics.

Adult↗

[Controlled study of the effect of silymarin on alcoholic liver disease].

A controlled trial on the use of Silymarin in patients with alcoholic liver disease was performed. Seventy two patients were admitted to the trial and randomly assigned to an experimental or controls group. Experimentals received 280 mg/day of Silymarin and controls an equal number of placebo tablets. Three patients on placebo and nine on Silymarin were lost from control (p = 0.035), remaining in control 34 patients receiving placebo and 25 patients receiving the drug. Both groups did not differ in their initial laboratory assessment and were followed up for an average of 15 months. Ten patients died during the follow up (5 in placebo and 5 in Silymarin); life table analysis did not show significant differences in mortality. Patients who died had lower serum albumin and prothrombin time and higher total bilirubin, alkaline phosphatases and CCLI on the initial clinical and laboratory assessment. Final laboratory values and their changes in those who survived did not differ between Silymarin and placebo. Twenty two patients on placebo (65%) and 14 on Silymarin (58%) recognized alcohol ingestion or had a positive urine sample analysis for alcohol during follow up. Those who abstained from alcohol had a significant fall in gamma glutamyl transferase during follow up. No other significant differences were observed between these two groups. It is concluded that in this trial, Silymarin did not change the evolution or mortality of alcoholic liver disease.

Double-Blind Method↗

Glucose turnover rate and peripheral insulin sensitivity in alcoholic patients without liver damage.

Glucose intolerance is frequently found in alcoholic patients and an impaired insulin response has been documented in them. To look for alternative mechanisms that could explain this intolerance, a glucose turnover using tritiated glucose and an euglycemic glucose clamp were performed to measure the glucose production rate and peripheral insulin sensitivity, respectively. Two groups of recently abstinent chronic male alcoholic patients without evidence of liver damage were studied. The glucose turnover technique showed a higher basal glucose production rate in alcoholics, compared with normal volunteers (2.83 +/- 0.29 vs. 1.84 +/- 0.22 mg/kg/min); an intravenous ethanol load significantly increased this rate. The euglycemic glucose clamp did not show peripheral insulin resistance in alcoholics, compared with controls.

Adult↗

Nutritional support in hospitalized patients with alcoholic liver disease.

The effects of a nutritional support in hospitalized patients with alcoholic cirrhosis and liver failure were studied in a controlled protocol. Thirty-six patients were included, 17 were randomly assigned to an experimental group and the rest to a control group. Experimentals received a diet aiming at 50 kcal (209 kJ)/kg bodyweight/d and 1.5 g protein/kg bodyweight/d (as proteins of high biological value). Controls received the standard diet prescribed by the attending physician. The severity of liver failure and the nutritional status on admission were similar in both groups. The measured energy intake in controls was 1813 +/- 121 kcal/d (7589 +/- 506 kJ/d) and 2707 +/- 71 kcal/d (1131 +/- 297 kJ/d) in experimentals (P less than 0.001). The protein intake in controls was 47 +/- 3.8 g/d and in experimentals 80 +/- 3 g/d (P less than 0.001). There were seven deaths during the study period (two experimentals and five controls). No differences were observed in the evolution of liver failure, hepatic encephalopathy or nutritional status between both study groups. It is concluded that a higher energy and protein intake in these patients does not have adverse effects and is associated with a non-significant reduction in mortality.

Body Weight↗

Overweight as a risk factor or a predictive sign of histological liver damage in alcoholics.

This study analyzes whether increased body weight is related to histological liver damage in chronic alcoholic patients. Data from 152 recently abstinent alcoholics without evidences of liver failure were analyzed. Liver biopsies were scored for the presence of fat, necrosis, fibrosis, inflammation, and Mallory material. Total histological score correlated significantly with body weight (BW), length of alcoholism (L), and age (A) but not with the amount of ethanol ingested (E). Forward stepwise multiple regression analysis with histological score as the dependent variable gave significant F values for BW and L but not for A. Patients with severe damage had higher BW than patients with mild damage. The group with BW greater than 110% showed a higher histological score. These results confirm the association between increased BW and liver damage in asymptomatic alcoholic patients suggesting that overweight is a risk factor for alcoholic liver disease.

Alcoholism↗

Nitrogen economy in alcoholic patients without liver disease.

Nitrogen balance was studied in five alcoholic patients during alcohol consumption and after 1 or 2 weeks of abstinence, under metabolic ward conditions. Patients had a history of excessive ethanol intake for five years or more. They were intoxicated and otherwise asymptomatic on admission and had been drinking 150 g or more of ethanol daily, for at least one month. Subjects consumed a diet providing vitamins and minerals exceeding RDA values, 45 kcal/kg of body weight and 0.6 g/kg of proteins (as egg protein), for 33 days. During the first 11 days patients received 200 g of ethanol that were isocalorically substituted later by dietary fat and carbohydrates. The results of this study show that, in alcoholic patients while drinking and after seven days of alcohol withdrawal, nitrogen balance is significantly decreased compared to that performed after two weeks of abstinence. Ethanol metabolic rate was found to be increased, compared to controls. It was lower in four of five patients after the second week of abstinence. These results suggest that alcohol abuse increases protein requirements in chronic alcoholic patients even without histologic liver disease or clinical signs of gastroenterologic disorders.

Adult↗

Cutaneous leishmaniasis in Bolivia. A study of 185 human cases from Alto Beni (La Paz Department). Isolation and isoenzyme characterization of 26 strains of Leishmania braziliensis braziliensis [corrected].

A clinical, serological, parasitological and therapeutic study of cutaneous leishmaniasis was carried out in a low sub-andean area (250-800 metres) of the La Paz Department, Bolivia. A team of seismic prospectors (350 workers) was surveyed for 12 months. Of 200 suspected cases of cutaneous leishmaniasis, 185 were serologically or parasitologically confirmed (incidence 52.8%). Those exposed to the greatest risk of infection were working in a virgin forest environment. Leishmanial organisms were isolated from 26 of the workers, either by in vitro cultivation or inoculation into hamsters. Isoenzyme characterization of the organisms by cellulose acetate electrophoresis showed them to be Leishmania braziliensis braziliensis [corrected]. The results of treatment of 168 patients with a pentavalent antimonial drug are also reported.

Animals↗

Glucose tolerance and the insulin response in recently drinking alcoholic patients: possible effects of withdrawal.

To investigate possible effects of withdrawal on carbohydrate metabolism in chronic alcoholic patients, intravenous glucose tolerance tests were performed in three periods in 11 alcoholic patients: early abstinence (less than three days), early abstinence plus ethanol (1 g/kg/BW IV), and late abstinence (three weeks later). According to liver biopsy results and laboratory tests, patients were classified as a group with liver damage (four cases) and a group without it (seven cases). In the group without damage, glucose tolerance expressed as K% and compared to a control group, was significantly decreased in early and late abstinence but not after the infusion of ethanol. Cases with damage also had glucose intolerance at admission. Plasma insulin levels after the glucose load were significantly lower at ten and 30 minutes in the group without damage, in early or late abstinence. They were normal in the presence of ethanol. Patients with liver damage presented higher basal and postglucose plasma insulin concentrations. It was concluded that glucose intolerance in alcoholic patients is a common finding that occurs in the presence or absence of liver damage. In cases with liver damage it seems to be due to peripheral insulin resistance. In those without damage it is related to low peripherovenous insulin levels.

Acute-Phase Proteins↗