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Biomedical subjects

J Quiroga

Publications and source records attributed to J Quiroga.

At least 19 recordsLinked to original sources
PubMed2006

Insulin-like growth factor I improves intestinal barrier function in cirrhotic rats.

BACKGROUND AND AIMS: In liver cirrhosis, disruption of the intestinal barrier facilitates bacterial translocation and spontaneous bacterial peritonitis. Insulin-like growth factor I (IGF-I) is an anabolic hormone synthesised by hepatocytes that displays hepatoprotective activities and trophic effects on the intestine. The aim of this study was to investigate the effect of IGF-I on intestinal barrier function in cirrhotic rats. METHODS: In rats with carbon tetrachloride induced cirrhosis, we investigated the effect of IGF-I therapy on: (a) portal pressure; (b) intestinal histology and permeability to endotoxin and bacteria; (c) intestinal expression of cyclooxygenase 2 (COX-2) and tumour necrosis factor alpha (TNF-alpha), two factors that influence in a positive and negative manner, respectively, the integrity of the intestinal barrier; (d) intestinal permeability to 3H-mannitol in rats with bile duct ligation (BDL); and (e) transepithelial electrical resistance (TER) of polarised monolayers of rat small intestine epithelial cells. RESULTS: IGF-I therapy reduced liver collagen expression and portal pressure in cirrhotic rats, induced improvement in intestinal histology, and caused a reduction in bacterial translocation and endotoxaemia. These changes were associated with diminished TNF-alpha expression and elevated COX-2 levels in the intestine. IGF-I reduced intestinal permeability in BDL rats and enhanced barrier function of the monolayers of epithelial intestinal cells where lipopolysaccharide (LPS) caused a decrease in TER that was reversed by IGF-I. This effect of IGF-I was associated with upregulation of COX-2 in LPS treated enterocytes. CONCLUSIONS: IGF-I enhances intestinal barrier function and reduces endotoxaemia and bacterial translocation in cirrhotic rats. IGF-I therapy might be useful in the prevention of spontaneous bacterial peritonitis in liver cirrhosis.

Animals↗
PubMed2006

[Liver transplantation].

Liver transplantation is an efficient therapeutic option for terminal hepatic diseases. The principal indications of liver transplantation are hepatic cirrhosis, hepatic tumours (mainly, hepatocellular carcinoma) and acute liver failure. Over the years, the absolute contraindications for a transplant have lessened. Surgical techniques have also undergone changes. The results of liver transplant have improved so that survival one year after the transplant is close to 90% and after five years some 80% of transplanted patients continue to live.

Age Factors↗
PubMed2004

[Acute infection by hepatitis B virus].

The clinical spectrum of acute hepatitis B virus infection is very broad, with clinical manifestations that range from anicteric and sub-clinical hepatitis to severe acute icteric hepatitis and even, in some cases, to fulminant hepatitis. Diagnosis depends to a large extent on the degree of clinical suspicion of hepatitis, establishing the aetiological origin of the B virus through the study of serological markers and/or DNA in the blood. Although in the majority of cases there is a favourable evolution of acute hepatitis B virus infection, with spontaneous resolution of the clinical manifestations in 4-8 weeks, progression to chronic hepatitis is not unusual in certain cases, above all in infancy. No specific treatment exists for acute hepatitis B virus infection that would reduce its severity or prevent its evolution into chronic hepatitis. However, relative rest and the administration of an hypercaloric diet are recommended. In cases of severe acute hepatitis hospital admission should be recommended; in cases of fulminant hepatitis, admission to the intensive care unit for intensive monitoring and evaluation of a liver transplantation is recommended if spontaneous improvement does not occur. This paper reviews briefly the clinical manifestations, diagnosis, prognosis and treatment of acute hepatitis B virus infection.

Acute Disease↗
PubMed2003

Conversion from calcineurin inhibitors to mycophenolate mofetil in liver transplant recipients with diabetes mellitus.

Diabetes mellitus, a frequent metabolic complication in liver transplant recipients, may be produced by the diabetogenic effect of calcineurin inhibitors cyclosporine and tacrolimus. The aim of this study was to investigate the safety and metabolic effects of a gradual switch from cyclosporine or tacrolimus to mycophenolate mofetil among 12 diabetic liver transplant recipients. One patient was withdrawn from the study due to gastrointestinal side effects. Of the 11 remaining patients, cyclosporine or tacrolimus was completely withdrawn in five patients. Two patients developed suspected acute rejection episodes that were controlled by increasing the tacrolimus dosage. Glycosylated hemoglobin A1C and C-peptide levels were significantly lower at 3 and 6 months after the initiation of mycophenolate mofetil (P<.03 in all cases). Furthermore, urea and uric acid levels were significantly reduced after the change of treatment. In conclusion, a switch from cyclosporine/tacrolimus to mycophenolate mofetil may produce beneficial metabolic effects in diabetic liver transplant recipients, but poses a risk of graft rejection.

Blood Glucose↗
PubMed2002

IGF1 gene transfer into skeletal muscle using recombinant adeno-associated virus in a rat model of liver cirrhosis.

Systemic administration of recombinant IGF1 at low levels has been shown to improve hepatic function, nutritional status and testicular atrophy in rats with CCl4-induced cirrhosis. We have developed a recombinant adeno-associated (rAAV) viral vector containing the cDNA for rat IGF1 and confirmed the expression of IGF1 after intramuscular injection of this vector in a rat model of liver cirrhosis. Although weight of injected muscles was significantly increased in rats with mild cirrhosis, this was not the case in rats with advanced, de-compensated cirrhosis. Furthermore, we found no significant amelioration of liver damage in treated rats at any stage of liver cirrhosis. Our results suggest that IGF1 gene transfer into muscle results in a local effect, at least at the vector dose employed here.

Animals↗
PubMed2002

Effect of ursodeoxycholic acid on methionine adenosyltransferase activity and hepatic glutathione metabolism in rats.

BACKGROUND AND AIMS: Both bile salts and glutathione participate in the generation of canalicular bile flow. In this work, we have investigated the effect of different bile salts on hepatic glutathione metabolism. METHODS: Using the isolated and perfused rat liver, we studied hepatic glutathione content, and metabolism and catabolism of this compound in livers perfused with taurocholate, ursodeoxycholate, or deoxycholate. RESULTS: We found that in livers perfused with ursodeoxycholate, levels of glutathione and the activity of methionine adenosyltransferase (an enzyme involved in glutathione biosynthesis) were significantly higher than in livers perfused with other bile salts. In ursodeoxycholate perfused livers, methionine adenosyltransferase showed a predominant tetrameric conformation which is the isoform with highest activity at physiological concentrations of substrate. In contrast, the dimeric form prevailed in livers perfused with taurocholate or deoxycholate. The hepatic activities of gamma-glutamylcysteine synthetase and gamma-glutamyltranspeptidase, enzymes involved, respectively, in biosynthetic and catabolic pathways of glutathione, were not modified by bile salts. CONCLUSIONS: Ursodeoxycholate specifically enhanced methionine adenosyltransferase activity and hepatic glutathione levels. As glutathione is a defensive substance against oxidative cell damage, our observations provide an additional explanation for the known hepatoprotective effects of ursodeoxycholate.

Animals↗
PubMed2002

Integration of telemedicine into emergency medical services.

We developed an integrated model of telemedicine services in emergency medical care. The architecture was designed to support pre-hospital management. The experimental work was carried out with the collaboration of the emergency medical services (EMS) in Madrid. Two different study populations were defined: a control population using conventional EMS protocols and a population using the telemedicine system. The telemedicine system was based on a telepresence service; electrocardiograms and images were transmitted from the ambulance to the health emergency coordination centre. The cost of dealing with 100 patients using telemedicine was C6030 less than the cost of conventional care. The response times using telemedicine were significantly lower.

Attitude of Health Personnel↗
PubMed2001

An epidemiological study of Taenia solium cysticercosis in a rural population in the Bolivian Chaco.

A survey of 100 rural households in a village in the Chaco region of Bolivia revealed a serious problem of Taenia solium cysticercosis, with a seroprevalence of 99/447 (22%) in humans and 102/273 (37%) in pigs. Risk factors for humans were being in older age groups, absence of sanitary facilities, poor formal education and inability to recognise infected pork. Significant risk indicators were a history of seizures and the reported elimination of worms in the faeces. Risk factors for pigs were being in older age groups and absence of sanitary facilities in the owner's house. The proportion of households with evidence of human cysticercosis was similar for those who owned pigs (48%) and those that did not (55%). This unexpected finding was attributed to the high overall prevalence of cysticercosis in pigs and the probability that everyone, regardless of pig-ownership, had ample opportunity to become infected in such communities. The main recommendation for reducing the prevalence of human cysticercosis was to provide more effective education campaigns, aimed at preventing both T. solium infection and cysticercosis.

Adolescent↗
PubMed2001

4-(4-Chlorophenyl)-3,7,7-trimethyl-1-[2-(4-nitrobenzoyl)ethyl]-4,7,8,9-tetrahydro-1H-pyrazolo[3,4-b]quinolin-5(6H)-one-ethanol (1/1).

Molecules of the title compound, C(28)H(27)ClN(4)O(4).C(2)H(6)O, form a C(6) chain via an N--H...O hydrogen bond along the c axis by the operation of a c-glide plane, with N...O = 2.761 (3) A and N--H...O = 165 degrees. The molecules are further linked by a weak C--H...O interaction, with C.O = 3.344 (4) A and C--H...O = 150 degrees. Pendant hydrogen-bonded ethanol solvent molecules are attached to the chains by O--H...N hydrogen bonds, with O...N = 2.904 (3) A and O--H...N = 175 degrees.

Antiviral Agents↗
PubMed2001

Antifibrogenic effect in vivo of low doses of insulin-like growth factor-I in cirrhotic rats.

Insulin-like growth factor-I (IGF-I) is produced mainly in the liver and it induces beneficial effects on the nutritional status, the liver function and oxidative hepatic damage in cirrhotic rats. The aim of this work was to analyze the effect of IGF-I on mechanisms of fibrogenesis in cirrhotic rats. Liver cirrhosis was induced by CCl(4) inhalation and phenobarbital in Wistar rats. Ten days after stopping CCl(4) administration (day 0), rats received either IGF-I (2 microg/100 g bw/day) (CI+IGF) or saline (CI) subcutaneously during 14 days. Animals were sacrificed on day 15. As control groups were used: healthy rats (CO) and healthy rats treated with IGF-I (CO+IGF). Liver histopathology, hydroxyproline content, prolyl hydroxylase activity, collagen I and III mRNA expression and the evolution of transformed Ito cells into myofibroblasts were assessed. Among the two control groups (CO+IGF), no differences were found in hydroxyproline content and these levels were lower than those found in the two cirrhotic groups. Compared with untreated cirrhotic rats, the CI+IGF-I animals showed a significant reduction in hydroxyproline content, prolyl hydroxylase activity and collagen alpha 1(I) and alpha1(III) mRNA expression. A higher number of transformed Ito cells (alpha-actin +) was observed in untreated cirrhotic animals as compared to CO and CI+IGF groups. In summary, treatment with IGF-I reduced all of the studied parameters of fibrogenesis. In conclusion, low doses of IGF-I induce in vivo an antifibrogenic effect in cirrhotic rats.

Actins↗
PubMed2001

Feature subset selection by genetic algorithms and estimation of distribution algorithms. A case study in the survival of cirrhotic patients treated with TIPS.

The transjugular intrahepatic portosystemic shunt (TIPS) is an interventional treatment for cirrhotic patients with portal hypertension. In the light of our medical staff's experience, the consequences of TIPS are not homogeneous for all the patients and a subgroup dies in the first 6 months after TIPS placement. Actually, there is no risk indicator to identify this subgroup of patients before treatment. An investigation for predicting the survival of cirrhotic patients treated with TIPS is carried out using a clinical database with 107 cases and 77 attributes. Four supervised machine learning classifiers are applied to discriminate between both subgroups of patients. The application of several feature subset selection (FSS) techniques has significantly improved the predictive accuracy of these classifiers and considerably reduced the amount of attributes in the classification models. Among FSS techniques, FSS-TREE, a new randomized algorithm inspired on the new EDA (estimation of distribution algorithm) paradigm has obtained the best average accuracy results for each classifier.

Algorithms↗
PubMed2001

Disturbed synthesis of insulinlike growth factor I and its binding proteins may influence renal function changes in liver cirrhosis.

Insulinlike growth factor-1 (IGF-1) is an anabolic hormone synthesized by the liver upon stimulation by growth hormone (GH). IGF-1 exerts important effects on renal hemodynamics and renal sodium handling. The bioactivity of this hormone is influenced by its binding proteins (BP) of which IGF-BP3 favors retention in the capillary lumen while IGF-BP1 facilitates the transport to the target tissues. IGF-BP1 modulates the actions of IGF-1 on target cells including renal tubules. Although a number of reports have dealt with disturbances of the IGF-1/IGF-BP system in cirrhosis, no studies have yet addressed the relationship between alterations in this system and renal function changes in cirrhosis. In the present study we have included 20 patients with cirrhosis and 10 healthy subjects (control group). As compared with the controls, patients showed lower circulating levels of IGF-1 and IGF-BP3, higher IGF-BP1 levels, and a tendency to higher insulinemia and GH values. The index IGF-1 x IGF-BP1/IGF-BP3 (IGF-1-IGF-BP index, reflecting the accessibility of circulating IGF-1 to target cells) was higher in patients with ascites. IGF-1 directly correlated with renal blood flow (P < 0.05), with IGF-BP3 (P < 0.001) and inversely with the Pugh's score (P < 0.02). A negative correlation was found between IGF-1-IGF-BP index and fractional sodium excretion (P < 0.01) and between IGF-BP1 and urinary sodium excretion (P < 0.02). Our findings support the hypothesis that the disturbance of the IGF-1/IGF-BP axis may be related to the degree of renal vasodilation and renal sodium retention in cirrhotic patients.

Female↗
PubMed2001

Insulin-like growth factor-I restores the reduced somatostatinergic tone controlling growth hormone secretion in cirrhotic rats.

BACKGROUND/AIMS: An altered growth hormone/insulin-like growth factor-I (GH/IGF-I) axis occurs in advanced liver cirrhosis, characterised by diminished serum levels of IGF-I and increased concentrations of GH. Under normal conditions, GH release is mediated by somatostatin (SS) inhibition. However, the influence of SS on GH release in cirrhosis is not well known. IGF-I supplementation has beneficial effects in experimental cirrhosis, and - under physiological conditions - IGF-I increases SS, inhibiting GH. The aims of this work were to study SS tone in cirrhotic animals and to evaluate whether IGF-I treatment influences SS tone, controlling GH secretion in cirrhosis. METHODS: We studied the influence of SS on GH secretion by assessing GH response to pyridostigmine (PD) in cirrhotic rats treated and untreated with IGF-I. Liver cirrhosis was induced with CCl4-inhalation for 11 weeks in male Wistar rats. The animals were randomly divided into two groups: CI+IGF (n=12), which received IGF-I treatment for 12 days (2 microg/100 g body wt-1 x d-1) and CI (n=12), which received saline. Healthy controls (CO, n=12) were studied at the same time. On day 13, animals from each group were subdivided into two groups (n=6) in order to explore the effect of a PD intrajugular bolus (10 microg x 100 gbw-1) on serum GH levels (at 0,10,20,30 and 60 min), which were assessed by RIA. RESULTS: PD bolus did not exert any effect on GH serum levels in the CI group, suggesting a low SS tone in cirrhotic rats. However, PD induced an increase in GH levels into CO and CI+IGF groups. In conclusion, as occurs under normal conditions, the cholinergic system is a significant modulator of GH secretion in experimental liver cirrhosis. CONCLUSION: Cirrhotic rats have a reduced somatostatinergic tone which can be restored by IGF-I supplementation, suggesting that somatostatin is the main factor involved in the feed-back regulation between GH and IGF-I in cirrhosis.

Administration, Inhalation↗
PubMed2001

Liver transplantation in cirrhotic patients with diabetes mellitus: midterm results, survival, and adverse events.

Liver cirrhosis is frequently associated with diabetes mellitus (DM), and this metabolic complication is also frequent after orthotopic liver transplantation (OLT). The aim of our study is to investigate which factors are associated with DM before and after OLT and their impact on post-OLT evolution. We evaluated the prevalence of DM among 115 liver transplant candidates with cirrhosis and assessed their evolution after OLT (median follow-up, 41 months). Sixteen candidates had DM requiring pharmacological therapy (group A), 45 candidates had DM controlled with diet (group B), and 54 candidates did not have DM (group C). One-year and 3-year actuarial survival rates were 100% and 100% for group A, 91% and 85% for group B, and 77% and 74% for group C, respectively (P <.03). Post-OLT DM was more frequent in group A. The incidence of other metabolic complications, major infections, rejection, and arterial hypertension; the need for hospitalization; and renal and graft function of patients in groups A, B, and C were similar. The only risk factor for DM 1 year after OLT on multivariate analysis was pre-OLT DM requiring pharmacological treatment. The incidence of complications, need for hospitalization, and renal and graft function 1 year after OLT for patients with post-OLT DM were similar to those of patients without post-OLT DM. In conclusion, patients with cirrhosis who have DM have a greater risk for post-OLT DM, but their midterm survival is not worse than the survival of those without DM.

Adult↗
PubMed2001

Prognostic model for early acute rejection after liver transplantation.

Hepatic graft rejection is a common complication after liver transplantation (LT), with a maximum incidence within the first weeks. The identification of high-risk patients for early acute rejection (EAR) might be useful for clinicians. A series of 133 liver graft recipients treated with calcineurin inhibitors was retrospectively assessed to identify predisposing factors for EAR and develop a mathematical model to predict the individual risk of each patient. The incidence of EAR (< or =45 days after LT) was 35.3%. Multivariate analysis showed that recipient age, underlying liver disease, and Child's class before LT were independently associated with the development of EAR. Combining these 3 variables, the following risk score for the development of EAR was obtained: EAR score [F(x)] = 2.44 + (1.14 x hepatitis C virus cirrhosis) + (2.78 x immunologic cirrhosis) + (2.51 x metabolic cirrhosis)--(0.08 x recipient age in years) + (1.65 x Child's class A) [corrected]. Risk for rejection = e(F(x))/1 + e(F(x)). The combination of age, cause of liver disease, and Child's class may allow us to predict the risk for EAR.

Calcineurin Inhibitors↗