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Biomedical subjects

M Arrese

Publications and source records attributed to M Arrese.

At least 37 records · Page 2Linked to original sources

Adaptive regulation of hepatic bile salt transport: role of bile salt hydrophobicity and microtubule-dependent vesicular pathway.

BACKGROUND/AIMS: The hepatic transport of bile salts can be regulated by changes in bile salt pool size and/or in the flux of bile salts through the liver. Prolonged bile salt pool depletion is associated with down-regulation of maximum taurocholate transport and decreased canalicular membrane specific bile salt binding sites. This study was undertaken to investigate: a) whether adaptive down-regulation of maximum hepatic bile salt transport occurs to the same extent for bile acids of different hydrophobicity; and b) the role of microtubule-dependent vesicular pathway in the adaptive changes of bile salt transport capacity. METHODS: Male rats were subjected to 24-h or 48-h external biliary diversion to induce bile salt pool depletion. Basal bile flow, bile salt secretion and lipid secretion, maximum secretory rate of three bile salts of different hydrophobicity (tauroursodeoxycholate, taurocholate and taurochenodeoxycholate) and changes in the biliary excretion of two markers of the microtubule-dependent vesicular pathway (horseradish peroxidase and polyethyleneglycol molecular weight-900) were measured in control and bile salt-depleted rats. Taurocholate-stimulated horseradish peroxidase biliary excretion was also assessed in order to define whether the restoration of bile salt flux across the hepatocytes increased the excretion of this marker in bile salt-depleted rats. RESULTS: The reduction in the maximum secretory rate of the three bile salts under study observed after prolonged biliary diversion was clearly related to their hydrophobicity, with greater reduction for taurochenodeoxycholate and smaller reduction for tauroursodeoxycholate, compared with taurocholate. The biliary excretion of vesicular transport markers was significantly reduced in bile salt-depleted rats. However, when stimulated by taurocholate, biliary excretion of horseradish peroxidase was similar to controls. CONCLUSIONS: The magnitude of the decrease of the hepatic bile salt maximum transport capacity seen after bile salt pool depletion is directly related to the hydrophobicity of the bile salt infused. A functionally depressed vesicular transport pathway appears to be also a contributing factor to this phenomenon.

Adaptation, Biological↗

Implementation of conditions of the inoculum stage for Streptosporangium cultures.

Different factors concerning the inoculum stage of cultures classified within the genus Streptosporangium have been studied. These factors include a comparison among several inoculum media and sources, the influence of aeration and volume of medium in the growth of the cultures, and the effect of the inoculum size on the course of the production of two antibacterial substances. The results suggest that a slight variation in the status of the seed culture (age, biomass concentration, etc.) affect the course of the batch culture during its initial exponential phase (3-5 days), whereas, at longer times, the behavior of the culture does not depend greatly on the characteristics of the inoculum. The results obtained have allowed to define a set of conditions producing the maximum increase of biomass in the minimum time.

Actinomycetales↗

Accuracy of invasive and noninvasive tests to diagnose Helicobacter pylori infection after antibiotic treatment.

OBJECTIVES: To compare the diagnostic accuracy of the most widely available tests for diagnosis of Helicobacter pylori infection after antibiotic treatment. METHODS: A total of 59 H. pylori-positive, duodenal ulcer patients (mean age, 40.7 +/- 11.7 yr; 40 male and 19 female) were treated for 2 wk with either amoxicillin-metronidazole (n = 36) or omeprazole-amoxicillin-tinidazole (n = 23), and after 4 wk, were tested for H. pylori infection by [14C]urea breath test (UBT), serum IgG antibody level, and multiple antral biopsies for rapid urease testing, histology, Warthin-Starry stain, and polymerase chain reaction to detect H. pylori DNA. Infection status was established by a concordance of test results. RESULTS: H. pylori was eradicated in 47 patients (80%). UBT and rapid urease testing had the best sensitivity and specificity, although not statistically different to Warthin-Starry stain and polymerase chain reaction. Serology and histology had little diagnostic value in this setting due to high proportion of false-positive results. CONCLUSIONS: Noninvasive UBT is as accurate in predicting H. pylori status after antibiotic treatment as rapid urease testing and Warthin-Starry stain. Especially for duodenal ulcer patients, UBT could be considered the gold standard to confirm eradication of H. pylori.

Adolescent↗

Serine 3 is critical for phosphorylation at the N-terminal end of the nucleoprotein of influenza virus A/Victoria/3/75.

The influenza A virus nucleoprotein (NP) is a phosphoprotein that encapsidates the viral genomic RNA. To map the in vivo phosphorylation site(s) of this protein, 32P-labeled NP was purified from cell cultures infected with influenza virus A/Victoria/3/75 by immunoaffinity chromatography. The purified protein was then subjected to chemical digestion with formic acid, which cleaves proteins at Asp-Pro bonds, and the resulting products were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two of the phosphorylated products obtained were identified as fragments corresponding to the N-terminal 88 amino acids and to the C-terminal 196 residues of the NP. To identify the phosphate acceptor site(s) at the N-terminal phosphorylated region of NP, each of the seven serines within this region was individually changed to alanine by site-directed mutagenesis. The mutant proteins were then transiently expressed in mammalian cells and analyzed for their phosphorylation state. It was observed that the S-to-A mutation at position 3 drastically reduced the amount of 32P label incorporated into NP, whereas the other substitutions did not have a discernible effect on the phosphorylation level of the protein. In addition, all serine-altered proteins were tested for their functionality in an artificial system in which expression of a synthetic chloramphenicol acetyl-transferase RNA molecule is driven by influenza virus proteins synthesized from cloned genes. The results obtained demonstrate that all mutant proteins were competent to cooperate with the subunits of the viral polymerase for expression of the synthetic virus-like chloramphenicol acetyltransferase RNA in vivo. These data are discussed regarding the possible roles of NP phosphorylation for the viral replicative cycle.

Amino Acid Sequence↗

Enhanced biliary excretion of canalicular membrane enzymes in ethynylestradiol-induced cholestasis. Effects of ursodeoxycholic acid administration.

Cholestasis is associated with a marked increase in the release of canalicular membrane enzymes into bile. This phenomenon has been related to an increased lability of these canalicular membrane integral proteins to the solubilizing effects of secreted bile salts. To further characterize the effects of oral ursodeoxycholic acid (UDCA) administration on ethynylestradiol (EE)-induced cholestasis, the influence of this bile acid on changes in biliary excretion of membrane-bound enzymes was investigated. Bile flow, basal bile salt and biliary lipid secretory rates, the maximum secretory rate of taurocholate (TC SRm), and the biliary excretion of the canalicular membrane-bound ectoenzymes alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) were measured in rats after EE and/or UDCA administration. The activities of ALP, GGT and Na+,K(+)-ATPase in purified isolated canalicular and sinusoidal membrane fractions and the ultrastructure of hepatic acinus, including histochemical studies of ALP distribution, were also examined. EE significantly reduced bile flow, bile salt and biliary lipid secretory rates, and TC SRm, and caused dilatation and loss of microvilli at the canalicular pole of hepatocytes. Biliary excretion of ALP increased 2-fold, whereas biliary excretion of GGT was unchanged. The relationship between biliary excretion of ALP or GGT and bile salt secretion (units of enzyme activity secreted per nanomole of bile salt) was greater in EE-treated rats compared with controls (2.1- and 1.5-fold greater for ALP and GGT, respectively), indicating that in EE-induced cholestasis more enzyme was released into bile per nanomole of bile salt. Na+,K(+)-ATPase activity in sinusoidal membrane fraction was reduced significantly, whereas ALP activity increased in both membrane fractions in EE-treated rats. The histochemical distribution of ALP in the acinus showed a strong reaction in acinar zone 3 and at both the canalicular and sinusoidal membranes. Oral administration of UDCA prevented EE-induced bile secretory failure by normalizing bile flow, bile salt and biliary phospholipid secretory rates, and TC SRm. UDCA also prevented the EE-induced changes in the biliary excretion of enzymes. On the contrary, UDCA did not modify either the enzyme activity in isolated membrane fractions or the morphological or ALP histochemical changes associated with EE administration. These data indicate that in EE-induced cholestasis changes occur at the canalicular membrane, enabling this portion of the plasma membrane to be more susceptible to the solubilizing effect of bile salt, and that oral administration of UDCA prevents bile secretory failure and changes in the biliary excretion of ALP and GGT in EE-treated rats.

Alkaline Phosphatase↗

Is dietary erucic acid hepatotoxic in pregnancy? An experimental study in rats and hamsters.

The hypothesis that dietary erucic acid may contribute to the pathogenesis of intrahepatic cholestasis of pregnancy has been examined in pregnant rats and hamsters after prolonged feeding of diets containing 25% rapeseed oil rich in erucic acid (40% of fatty acids) or corn oil, without erucic acid. Both dietary oils were well tolerated, although weight gain was 17% to 20% less in animals receiving rapeseed oil. Rats and hamsters were studied on the last day of pregnancy and compared with age- and diet-matched nonpregnant animals. Histological examination showed no major morphologic abnormalities in liver, heart, kidneys, and adrenals. Similar microscopic deposits of fat were found in the livers and hearts of pregnant hamsters of both dietary groups. Chromatographic analysis of fatty acids in liver, heart, and kidney homogenates of hamsters and in isolated rat liver cells reflected the fatty acid composition of the dietary oils: oleic (18:1) and linoleic (18:2) acids were among the predominant fatty acids. Erucic acid was found in a higher proportion in the heart (14% by weight of total fatty acids) than in the liver (3%) and kidneys (3%) of animals fed rapeseed oil. Bile flow and biliary lipid composition was similar in rats and hamsters fed rapeseed or corn oil. Bile flow tended to be less in pregnant than in nonpregnant animals. Pregnant hamsters fed rapeseed oil tended to have the lowest bile flow. The lithogenic index of bile was slightly decreased in pregnant rats and increased in pregnant hamsters, although these proportional changes were similar for both diets. In all circumstances the lithogenic index remained below a value of 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

[Vital prognosis in severe acute hepatic failure. Value of the quantitative indexes of evaluation].

The aim of this study was to assess the predictive value for mortality of admission and daily APACHE II score, mortality due to multiple organ failure and the Organ Failure Score in patients with acute hepatic failure. We retrospectively studied 15 such patients admitted to an intensive care unit. Thirteen patients died (87%) and their admission APACHE II score was 22 +/- 7.5 compared to 21 +/- 8.5 in survivors. Daily APACHE II score, mortality due to multiple organ failure and multiple organ failure score had a 100% sensitivity to predict mortality and a 69.2, 76.9 and 76.9% specificity respectively. The predictive accuracies of multiple organ failure and multiple organ failure score were 80% and significantly better than the accuracy of admission APACHE II score (53%). We conclude that these prognostic scores can be useful in the assessment of patients with acute hepatic failure.

APACHE↗

Protective role of biliary cholesterol and phospholipid lamellae against bile acid-induced cell damage.

BACKGROUND/AIMS: Bile salts (BS) are cytotoxic agents, but cell damage is not observed in the hepatobiliary system. We hypothesized that biliary lipid vesicles (unilamellae and multilamellae) could have a protective role against BS-induced cytotoxicity. METHODS: Biliary lipid lamellar secretion was induced by feeding rats with 0.5% diosgenin. Cytoprotection was assessed in bile duct-obstructed rats and by incubating human erythrocytes with sodium taurocholate. RESULTS: Biliary cholesterol concentration increased > 300% in diosgenin-fed rats; electron microscopic examination showed a great abundance of lipid lamellar vesicles in bile and within the canaliculi. After bile duct obstruction, serum hepatic enzyme activities were significantly lower in diosgenin-fed rats. Histologically severe and confluent hepatocellular necrosis was only observed in control rats. Biliary lamellar lipid material significantly reduced the BS-induced hemolytic effect in vitro in a concentration-dependent manner. This protective effect correlated to a progressive decrease in the intermicellar BS concentration. Phosphatidylcholine or cholesterol, alone or as lamellar structures, also showed cytoprotective effect in vitro but always less than native biliary lamellae. CONCLUSIONS: These results support the concept that native biliary cholesterol phospholipid lamellae represent an important cytoprotective factor for hepatocytes and biliary epithelial cells against BS-induced damage.

Animals↗

[Multiple organ failure syndrome in fulminant hepatic failure].

BACKGROUND: in fulminant hepatic failure, different organs systems become involved and a multiple systems organic failure may ensure. AIM: to perform a retrospective analysis of patients with fulminant hepatic failure admitted to UC Hospital Intensive Care Unit. PATIENTS AND METHODS: the charts of fourteen patients (8 male) were analyzed. Multiple systems organic failure was defined as the presence of 2 or more organic dysfunctions. The evolution and mortality of these patients was analyzed. RESULTS: patient's ages ranged from 30 to 74 years. The etiology of hepatic failure was B hepatitis in 4, non A non B hepatitis in 5, acute fatty liver of pregnancy in 3 and use of halothane and HIN in 2. ICU stay ranged from 1 to 44 days and 2 patients survived (one with drug induced liver failure and one with acute fatty live of pregnancy). Mean prothrombin time was 19 +/- 9.5%, total bilirrubin was 24 +/- 8.9 mg/dl and 12 patients reached grade IV encephalopathy. Mean admission APACHE II score was 21.5 +/- 6. Twelve patients developed multiple systems organic failure, that appeared 1.5 days after or was already present at ICU admission; it lasted a mean of 2.5 days and all these 12 patients died. Neurologic involvement occurred in 13 patients, renal in 10, cardiovascular in 9, respiratory in 5 and hematological involvement in 1. CONCLUSIONS: multiple systems organic failure is frequent in fulminant hepatic failure and is associated with a high mortality.

Adult↗

[Ursodeoxycholic acid in the treatment of cholestatic liver diseases].

Ursodeoxycholic acid (UDCA) is a hydrophilic biliary acid that has been used in the medical therapy of cholelithiasis. In the last decade, its use in the treatment of some liver diseases renewed the interest on its hepato-protective properties. Controlled trials have demonstrated that UDCA has symptomatic and laboratory beneficial effects in primary biliary cirrhosis and sclerosing cholangitis. However its effects on the long-term and patients survival have not been determined. Uncontrolled trials on the effects of UDCA on a series of cholestatic liver diseases (cystic fibrosis, chronic hepatitis, cholestasis of pregnancy, etc) have communicated promising results that require confirmation with methodologically rigorous studies. The research in this area has significantly stimulated the study of the mechanisms of cellular injury associated to cholestatic phenomena and its prevention or attenuation with UDCA. The present review analyzes the most outstanding aspects of UDCA mechanisms of action, pharmacology and clinical efficacy in the treatment of liver diseases.

Bile↗

Postcholestatic alkaline phosphatase activity after relief of bile duct obstruction in the rat.

The effects of obstructive cholestasis on the activity of alkaline phosphatase have been extensively studied in serum and liver tissue. However, very little is known about the activity of this enzyme in the postcholestatic condition after relief of the biliary obstruction. The purpose of this study has been to characterize alkaline phosphatase activity in serum, liver and bile in the postcholestatic period and to relate it to changes in bile acid secretory rate. Serum activity and biliary secretory rates of alkaline phosphatase were markedly increased in rats subjected to a reversible obstructive cholestasis for 24 hr or 48 hr and progressively declined along the postcholestatic period to values not significantly different from those of control rats within 48 hr. A significant direct linear relationship between the biliary secretory rates of enzyme activity and bile salts was apparent both in cholestatic groups and in the control groups. The slope of the regression line (units of alkaline phosphatase secreted per micromole of bile salts) was 1.5-fold to 3-fold higher in cholestatic animals. Remarkably, a positive y-intercept of regression lines suggested that a significant fraction of the enzyme was secreted independently of bile salts; this fraction was 18-fold and 34-fold greater in 24-hr and 48 hr cholestatic rats, respectively, compared with that in controls. Sodium taurocholate administered intravenously, either as a bolus or as an infusion at increasing submaximal rates, resulted in parallel increases of bile salt and alkaline phosphatase secretory rates into bile. The enzyme activity secreted per micromole of taurocholate was significantly greater in cholestatic than in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

[Miliary tuberculosis as a complication of BCG immunotherapy in cancer of the bladder. Case report].

Intravesical administration of BCG may be used as an ancillary immunotherapy after endoscopic resection for cancer of the bladder. Local side effects are usually mild. Here is reported a patient who developed miliary tuberculosis after this form of therapy. Radiologic studies of the thorax and liver biopsy confirmed the diagnosis. The patient recovered after treatment with anti-tuberculosis drugs (TA-81 scheme). Epithelial trauma may be invoked as an alteration facilitating this complication. Although it develops infrequently, patients with bladder cancer treated with BCG must be monitored for this complication.

BCG Vaccine↗

[Eosinophilic pneumonia causing severe respiratory insufficiency. Clinical case].

A 37 year-old previously healthy woman developed severe respiratory failure and diffuse pulmonary infiltrates. A diagnosis of Eosinophilic pneumonia was made based on elevated blood counts of eosinophils and high numbers of them in the broncho-alveolar lavage. The patient recovered after steroid therapy and remained well six months later. Most cases of eosinophilic involvement of the lung have a chronic course and only recently has acute eosinophilic pneumonia been recognized. Typical findings on bronchoalveolar lavage and cure with steroid therapy provide the basis for diagnosis.

Acute Disease↗

S-adenosyl-L-methionine in the treatment of patients with intrahepatic cholestasis of pregnancy: a randomized, double-blind, placebo-controlled study with negative results.

S-Adenosyl-L-methionine has been reported to induce beneficial effects in intrahepatic cholestasis of pregnancy. Because cholestasis of pregnancy has a high prevalence in Chile and a deleterious effect on fetal prognosis, we decided to verify the efficacy of S-adenosyl-L-methionine in this disease. Eighteen patients with pruritus that appeared during pregnancy and with elevated serum levels of bile salts (68.1 +/- 15.9 mumol/L; mean +/- S.E.M.) and ALT (226 +/- 50 KU/L) were enrolled in a prospective double-blind study comparing the effects of the drug with a placebo. S-Adenosyl-L-methionine, 900 mg, or placebo was administered in daily intravenous infusions for 20 days. Every 5 days liver function tests were done and pruritus was assessed using a preestablished score. No significant differences in pruritus or in serum levels of bile salts, ALT, bilirubin and alkaline phosphatases were seen during or after treatment between patients who received S-adenosyl-L-methionine (n = 9) or placebo (n = 9). No relevant adverse reactions were detected. Most patients had cesarean sections because of reasons unrelated to the therapeutic trial. All newborns had Apgar scores greater than 7 and normal postnatal development. Our patients had moderately severe to severe cholestasis of pregnancy as indicated by the onset of pruritus before wk 32 of pregnancy. Seven of nine multiparous patients had a past history of recurrent cholestasis of pregnancy. In this study, the administration of S-adenosyl-L-methionine during 20 days did not improve intrahepatic cholestasis of pregnancy.

Apgar Score↗

[Munchausen's syndrome: a study of 6 cases].

We report 6 patients with Munchausen syndrome, a fictitious disorder with physical symptoms. There were 4 females and 2 males, the age ranged from 21 to 29 years. Abdominal pain (2), hemoptysis, shock and hypoglycemia were the presenting symptoms. The diagnosis was made after a prolonged and costly hospital course, including invasive and non invasive diagnostic procedures. Two patients were ill enough to be at risk of death. An early diagnosis may help prevent unnecessary or risky procedures in these patients.

Adult↗

Intrahepatic cholestasis of pregnancy in twin pregnancies.

To clarify whether the increase in estrogen levels occurring during twin pregnancies (TP) is associated with a greater risk of developing intrahepatic cholestasis of pregnancy (ICP), we followed up 62 consecutive patients with TP and compared them with single pregnancies delivered in our hospital during 1 year. The prevalence of ICP was significantly higher in twin than in single pregnancies (20.9% versus 4.7%, respectively; P less than 0.001). Urinary estriol excretion was also significantly higher in twin compared to single pregnancies, although no quantitative differences were detected in TP with or without ICP. In multiparous patients with a proband TP affected by ICP, the disease recurred only in further TP, emphasizing the important role that estrogens seem to play in the pathogenesis of ICP. In contrast, in multiparous patients with a proband single pregnancy affected by ICP, the disease occurred in 70.5% of their other single pregnancies, suggesting the presence of a metabolic predisposition in these cases. However, in both groups of multiparous women a notable number of single pregnancies were not affected by the disease, supporting the postulate that the pathogenesis of ICP is multifactorial and that some as yet unidentified environmental factor needs to be present in order to develop the disease and also to modulate its expressivity.

Alanine Transaminase↗