Nonalcoholic fatty liver disease associated with metabolic syndrome: Influence of liver fibrosis stages on characteristics of very low-density lipoproteins.

BACKGROUND: We evaluated possible changes in VLDLcharacteristics, and metabolic related factors, in MetS-associated NAFLD and accompanying liver fibrosis. METHODS: We studied 36 MetS patients with biopsy-proven NAFLD (MetS+NAFLD) and 24 MetS without ultrasound NAFLD evidence. Further, MetS+NAFLD was sub-divided according to fibrosis stage into, non-to-moderate (F0-F2, n=27) and severe (F3-F4, n=9) fibrosis. We measured: lipid profile, VLDL composition and size (size exclusion-HPLC), CETP and lipoprotein lipase (LPL) activities and adiponectin. Additionally, in MetS+NAFLD type IV collagen 7S domain was measured. RESULTS: MetS+NAFLD showed increased VLDL-mass, VLDL particle number, VLDL-triglyceride% and large VLDL-% (p<0.04). CETP activity tended to increase in MetS+NAFLD (p=0.058), while LPL activity was unchanged. Moreover, in MetS+NAFLD, adiponectin was decreased (p<0.001), and negatively correlated with VLDL-mass and VLDL particle number (p<0.05), independently of insulin-resistance. Within MetS+NAFLD group, despite greater insulin-resistance, patients with severe fibrosis showed lower plasma triglycerides, VLDL-mass, VLDL-triglyceride%, large VLDL-% and CETP activity (p<0.05), while type IV collagen was increased (p=0.009) and inversely correlated with large VLDL-% (p=0.045). CONCLUSIONS: In MetS, NAFLD is associated with larger and triglyceride over-enriched circulating VLDLs, of greater atherogenicity. However, when NAFLD progresses to severe fibrosis, circulating VLDL features apparently improved, probably due to early alterations in hepatic synthetic function.

Physicochemical study of mixed systems composed by bovine caseinate and the galactomannan from Gleditsia amorphoides.

Model systems formed by sodium caseinate (NaCAS) and espina corona gum (ECG) were studied. There was no evidence of attractive interactions between NaCAS and ECG macromolecules. Aqueous mixtures of NaCAS and ECG phase-separate segregatively over a wide range of concentrations. According to the images obtained by confocal laser scanning microscopy, NaCAS particles form larger protein aggregates when ECG is present in the system. An increase in the hydrodynamic diameter of NaCAS particles, as a result of ECG addition, was also observed by light scattering in diluted systems. A depletion-flocculation phenomenon, in which ECG is excluded from NaCAS surface, is proposed to occur in the concentrated mixed systems, resulting in NaCAS aggregation. ECG raises the viscosity of NaCAS dispersions without affecting the Newtonian flow behaviour of NaCAS. These results contribute to improve the knowledge of a barely-studied hydrocolloid which may be useful in the development of innovative food systems.

[Hemobilia secondary to hepatic artery pseudoaneurysm]. / Hemobilia secundaria a pseudoaneurisma de la arteria hepática.

Hemobilia is defined as the presence of blood in the biliary tree characterized by the triad: jaundice, right hypochondrium pain (RH) and upper gastrointestinal bleeding (UGB). Among the etiologies highlighted in order of frequency there are: liver trauma (accidental and iatrogenic), inflammatory causes (acute and chronic cholecystitis), infections (cholangitis, liver abscesses, parasitic infections) and vascular diseases (aneurysms, vasculitis, arteriovenous malformations). There exist many complementary tests for the diagnosis of hemobilia, such as imaging (abdominal ultrasound, CT scan, angio CT), videoendoscopy, endoscopic retrograde cholangiopancreatography and angiography, the latter being considered the diagnostic tool and therapeutic modality of choice. We report the case of a 52-year-old male patient with hemobilia secondary to apseudoaneurysm ofthe hepatic artery, along with a review of the existing literature.

Brønsted Acid-Catalyzed Cascade Reactions Involving 1,2-Indole Migration.

A cascade reaction of indoles with propargylic diols involving an unprecedented metal-free 1,2-indole migration onto an alkyne was carried out. DFT calculations support a mechanism consisting of a concerted nucleophilic attack of the indole nucleus with loss of water, followed by the 1,2-migration and subsequent Nazarov cyclization. This Brønsted acid-catalyzed protocol affords indole-functionalized benzofulvene derivatives in high yields.

Sulfoxide-Directed Metal-Free ortho-Propargylation of Aromatics and Heteroaromatics.

A sulfoxide-directed, metal-free ortho-propargylation of aromatics and heteroaromatics exploits intermolecular delivery of a propargyl nucleophile to sulfur followed by an intramolecular relay to carbon. The operationally simple cross-coupling procedure is general, regiospecific with regard to the propargyl nucleophile, and shows complete selectivity for products of ortho-propargylation over allenylation. The use of secondary propargyl silanes allows metal-free ortho-coupling to form carbon-carbon bonds between aromatic and heteroaromatic rings and secondary propargylic centres. The 'safety-catch' nature of the sulfoxide directing group is illustrated in a selective, iterative double cross-coupling process. The products of propargylation are versatile intermediates and they have been readily converted into substituted benzothiophenes.

Effectiveness of a brief primary care intervention to reduce passive smoking in babies: a cluster randomised clinical trial.

BACKGROUND: Tobacco smoke pollution (TSP) has major negative effects on infant health. Our objectives were to determine the effectiveness of a brief primary care intervention directed at parents who smoke in reducing babies' TSP exposure, and to establish variables related to greater exposure. METHOD: A multicentre, open, cluster-randomised clinical trial in Catalonia. The 83 participating primary health paediatric teams of the Catalan Health Service recruited 1101 babies whose parents were smokers. The intervention group (IG) received a brief TSP intervention; the control group (CG) received the usual care. Outcomes were measured by parents' reported strategies to avoid TSP exposure. Baseline clinical data and characteristics of each baby's TSP exposure were collected, along with infant hair samples and parents' tobacco use and related attitudes/behaviours. At 3-month and 6-month follow-up, behavioural changes to avoid TSP exposure were recorded; the association between reported parental behaviours and nicotine concentration in infant hair samples was tested in a random sample of 253 babies at baseline and 6 months. RESULTS: During follow-up, TSP-avoidance strategies improved more in the IG than in the CG: 35.4% and 26.9% ( p=0.006) at home, and 62.2% and 53.1% in cars (p=0.008). Logistic regression showed adjusted ORs for appropriate measures in the IG versus CG of 1.59 (95% CI 1.21 to 2.09) at home and 1.30 (95% CI 0.97 to 1.75) in cars. Hair samples showed that 78.7% of the babies tested were exposed. Reduced nicotine concentration was associated with improved implementation of effective strategies reported by parents at home (p=0.029) and in cars (p=0.014). CONCLUSIONS: The intervention produced behavioural changes to avoid TSP exposure in babies. The proportion of babies with nicotine (>=1ng/mg) in hair samples at baseline is a concern. TRIAL REGISTRATION NUMBER: Clinical Trials.gov Identifier: NCT00788996.

[Toxic nephropathy secondary to occupational exposure to metallic mercury]. / Nefropatía membranosa secundaria a exposición laboral con mercurio metálico.

Toxic nephrophaties secondary to occupational exposure to metals have been widely studied, including membranous nephropathy by mercury, which is rare. Occupational poisoning by mercury is frequent, neurological symptoms are the main form of clinical presentation. Secondary renal involvement in chronic exposure to metallic mercury can cause glomerular disease by deposit of immune-complexes. Membranous glomerulopathy and minimal change disease are the most frequently reported forms. Here we describe the case of a patient with occupational exposure to metallic mercury, where nephrotic syndrome due to membranous glomerulonephritis responded favorably to both chelation and immunosuppressive therapy.

Nefropatía membranosa secundaria a exposición laboral con mercurio metálico

Las nefropatías tóxicas secundarias a la exposición ocupacional a metales han sido ampliamente estudiadas. La nefropatía membranosa por mercurio es poco frecuente.La intoxicación ocupacional con mercurio sí es frecuente, siendo las principales formas de presentación las manifestaciones clínicas neurológicas. La afectación renal secundaria a la exposición crónica a mercurio metálico puede desarrollar enfermedad glomerular por depósito de inmunocomplejos. La glomerulopatía membranosa y a cambios mínimos son las más frecuentemente comunicadas.Se presenta el caso de un paciente con exposición ocupacional a mercurio metálico, con síndrome nefrótico y biopsia renal con glomerulopatía membranosa que presentó respuesta favorable luego del tratamiento quelante e inmunosupresor.

Toxic nephrophaties secondary to occupational exposure to metals have been widely studied, including membranous nephropathy by mercury, which is rare. Occupational poisoning by mercury is frequent, neurological symptoms are the main form of clinical presentation. Secondary renal involvement in chronic exposure to metallic mercury can cause glomerular disease by deposit of immune-complexes. Membranous glomerulopathy and minimal change disease are the most frequently reported forms. Here we describe the case of a patient with occupational exposure to metallic mercury, where nephrotic syndrome due to membranous glomerulonephritis responded favorably to both chelation and immunosuppressive therapy.

Nefropatía membranosa secundaria a exposición laboral con mercurio metálico

Las nefropatías tóxicas secundarias a la exposición ocupacional a metales han sido ampliamente estudiadas. La nefropatía membranosa por mercurio es poco frecuente.La intoxicación ocupacional con mercurio sí es frecuente, siendo las principales formas de presentación las manifestaciones clínicas neurológicas. La afectación renal secundaria a la exposición crónica a mercurio metálico puede desarrollar enfermedad glomerular por depósito de inmunocomplejos. La glomerulopatía membranosa y a cambios mínimos son las más frecuentemente comunicadas.Se presenta el caso de un paciente con exposición ocupacional a mercurio metálico, con síndrome nefrótico y biopsia renal con glomerulopatía membranosa que presentó respuesta favorable luego del tratamiento quelante e inmunosupresor.(AU)

Toxic nephrophaties secondary to occupational exposure to metals have been widely studied, including membranous nephropathy by mercury, which is rare. Occupational poisoning by mercury is frequent, neurological symptoms are the main form of clinical presentation. Secondary renal involvement in chronic exposure to metallic mercury can cause glomerular disease by deposit of immune-complexes. Membranous glomerulopathy and minimal change disease are the most frequently reported forms. Here we describe the case of a patient with occupational exposure to metallic mercury, where nephrotic syndrome due to membranous glomerulonephritis responded favorably to both chelation and immunosuppressive therapy.(AU)

Nefropatía membranosa secundaria a exposición laboral con mercurio metálico. / [Toxic nephrophaty secondary to occupational exposure to metallic mercury].

Toxic nephrophaties secondary to occupational exposure to metals have been widely studied, including membranous nephropathy by mercury, which is rare. Occupational poisoning by mercury is frequent, neurological symptoms are the main form of clinical presentation. Secondary renal involvement in chronic exposure to metallic mercury can cause glomerular disease by deposit of immune-complexes. Membranous glomerulopathy and minimal change disease are the most frequently reported forms. Here we describe the case of a patient with occupational exposure to metallic mercury, where nephrotic syndrome due to membranous glomerulonephritis responded favorably to both chelation and immunosuppressive therapy.

Regioselective synthesis of elusive 4,9-dihydro-1H-carbazoles by gold-catalyzed cycloisomerization of 3-allenylmethylindoles.

A general and efficient synthesis of 4,9-dihydro-1H-carbazoles from 3-allenylmethylindoles is reported. The process, catalyzed by a cationic gold(I) complex, involves a formal C2-H bond activation of the indole unit by reaction with the allene. The nature of the substituents at the allylic and terminal positions of the allene moiety has a crucial effect on the regioselectivity of the cyclization, which is also influenced by the catalyst and the solvent employed. Moreover, some evidence of the contribution of different reaction routes is provided, which led us to propose a plausible multipathway mechanism consistent with all of the results described.

Incidence of hepatocellular carcinoma in hepatitis C cirrhotic patients with and without HIV infection: a cohort study, 1999-2011.

INTRODUCTION. High activity antiretroviral therapy (HAART) has allowed people infected with human immunodeficiency virus (HIV) to live longer. In the course of time, hepatocellular carcinoma (HCC) began to be found in these patients. Investigations have suggested that, as it has been described for other tumors, HIV infection raises the risk of developing HCC. However, convincing evidence is still required. Our aim was to quantify the incidence of HCC in hepatitis C cirrhotic patients with and without human immunodeficiency virus infection in the HAART era. MATERIAL AND METHOds. This prospective cohort study was conducted in hepatitis C cirrhotic patients with and without HIV co-infection, between june 1, 1999 and May 21, 2010. Ultrasound screening for HCC was performed every 6 to 12 months to all the patients until January 15, 2011. Incidence rate and cumulative incidence (Kaplan-Meier) were calculated. RESULTS. One hundred and forty eight patients (69 hepatitis C virus mono-infected and 79 HIV/hepatitis C virus co-infected) were followed for a median time of 43 months, with a total follow-up of 555 person-years (324 for co-infected and 231 for mono-infected patients). Twelve patients developed HCC (5 co-infected and 7 mono-infected). The incidence of HCC in co-infected patients and mono-infected patients was 1.54 (95% confidence interval = 0.5 to 3.6) and 3.03 (95% confidence interval = 1.22 to 6.23) cases per 100 person-year respectively (log-rank p = 0.3225). CONCLUSION. In the HAART era, HIV co-infection is not associated with a higher incidence of HCC in hepatitis C cirrhotic patients.

Effect of cirrhosis at baseline on the outcome of type 1 autoimmune hepatitis.

MATERIAL AND METHODS: With the aim of analyzing the influence of presence of cirrhosis at baseline on the outcome, we revised the evolution of a cohort of patients with type 1 autoimmune hepatitis, prospectively followed at a single hospital. 139 patients (113 females, 26 males), median age 45.7 years, interquartile range 13-59 years, were followed-up for a median period of 58 months (interquartile range 27-106). RESULTS: At baseline, 55 patients had cirrhosis and they were significantly older, had lower prothrombin activity and serum albumin than patients without cirrhosis. In contrast, patients without cirrhosis had significantly higher bilirubin, AST and ALT levels at diagnosis time. There was no significant difference in the follow-up time between patients with and without cirrhosis at baseline and either in the percentage of patients receiving immunosupresor treatment (80 vs. 91%, respectively) or in the response to therapy (complete response in 82 vs. 95%, respectively). However, patients with cirrhosis had a significantly lower probability of remaining free of cirrhosis complications (49.1% at 102 months, 95%CI, 35.5-67.9% vs. 86.7%, 95%CI, 77.1%-97.5%, respectively) (p = 0.0000) and a significantly lower overall survival at 120 months (67.1%, 95%CI, 51.3-87.6 vs. 94.4%, 95%CI, 86.9-100%, respectively) (p = 0.003) than those without cirrhosis at presentation. CONCLUSION: Patients with type 1 autoimmune hepatitis and cirrhosis at presentation have a lower survival than those without cirrhosis despite a similar response to treatment.

Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans.

A new route to regioselectively dialkoxy-functionalized benzo[b]furan derivatives has been developed from 3-halo-2-iodoanisoles bearing an additional methoxy group, which have been accessed through an ortho-zincation/iodination reaction. Two palladium-catalyzed processes, namely a Sonogashira coupling followed by a tandem hydroxylation/cyclization sequence, give rise to new and interesting dimethoxy-substituted benzo[b]furans.

Solvent- and ligand-induced switch of selectivity in gold(I)-catalyzed tandem reactions of 3-propargylindoles.

The selectivity of our previously described gold-catalyzed tandem reaction, 1,2-indole migration followed by aura-iso-Nazarov cyclization, of 3-propargylindoles bearing (hetero)aromatic substituents at both the propargylic and terminal positions, was reversed by the proper choice of the catalyst and the reaction conditions. Thus, 3-(inden-2-yl)indoles, derived from an aura-Nazarov cyclization (instead of an aura-iso-Nazarov cyclization), were obtained in moderate to good yields from a variety of 3-propargylindoles.

Comparison of NAFLD fibrosis score and BARD score in predicting fibrosis in nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Liver biopsy (LB) is the only means to evaluate fibrosis in NAFLD. Two scoring systems, NAFLD fibrosis score and BARD score, were proposed to separate cases with and without severe fibrosis (SF). Our aim was to compare the utility of both scores in patients with biopsy-proven NAFLD. METHODS: 138 consecutive patients of our series were included (67 male, median age 49 years). A NAFLD fibrosis score lower than -1.455 would exclude SF. A score greater than 0.676 would predict SF. An intermediate score is defined as indeterminate. The BARD score ranges from 0 to 4. Scores 0-1 are considered to have a high negative predictive value (NPV) for SF. The results of the scores were compared with LB staging. NPV, positive predictive value (PPV) and area under the ROC curve (AUROC) were calculated for both systems. RESULTS: A total of 37 patients had SF. NAFLD fibrosis score was indeterminate in 42 cases. Among the 91 patients with low score, 74 did not have SF but 17 patients had SF. All of 5 patients with a high score had SF. Sensitivity was 22.7%; specificity, 100%; NPV, 81.3%; and PPV, 100%. The BARD score was low in 96 patients and high in 42. Among the 96 patients with a low score, 78 did not have SF but 18 did. Among 42 patients with a high score, 19 had SF. Sensitivity was 51.4%; specificity, 77.2%; NPV, 81.3%; and PPV, 45.2%. AUROC were 0.68 (95% CI, 0.57-0.78) and 0.67 (95% CI, 0.56-0.77) for NAFLD fibrosis and BARD scores, respectively. CONCLUSIONS: Both systems were useful in identifying patients without SF (NPV 81.3%) but the BARD score is easier to estimate and does not have indeterminate results.

Tumores estromales (GISTs) del tubo digestivo / Estromales tumors (GISTs) of the alimentary canal

Antecedentes: Los tumores estromales del tubo digestivo son tumores mesenquimáticos distintos a los tumores musculares o nerviosos. Objetivo: Estudiar su incidencia, cuadro clínica, método de diagnóstico, localización, tratamiento, malignidad y evolución. Lugar: Hospital Nacional "Profesor Alejandro Posadas" y práctica privada. Diseño: Estudio retrospectivo, observacional. Población: 16 pacientes. período 2000-2005. Método: Fueron analizadas las historias clínicas y documentación diagnóstica. Se dividio a los pacientes de acuerdo con la localización de su patología. Resultados: Fueron tratados 16 pacientes . 11 con tumores gástricos, 3 de intestino delgado y 2 de colon. La hemorragia digestiva se presentó en 7 de los gástricos y 1 de intestino delgado. La endoscopia fue útil en las hemorragias digestivas. La ecografía y tomografía computarizada sirvieron para el diagnóstico. La certificación se hizo en todos los casos con CD 117. La malignidad se demostró en 6 por tener más de 5 cm y 3 de éstos tenían más de 5 mitosis por 50 campos de gran aumento. Conclusiones: Los tumores estromales se originan en las células de Cajal. Se diagnostican por inmunohistoquímica (CD 117). Son más frecuentes en estómago. La endoscopia, la TAC y la ecoendoscopia son los métodos auxiliares de diagnóstico de mayor utilidad. El número de mitosis y el tamaño son los marcadores más importantes para establecer la malignidad.

Alagille syndrome: cutaneous manifestations in 38 children.

The Alagille syndrome is one of the most common inherited disorders causing chronic liver disease during childhood. During the 1990s, 38 children with Alagille syndrome were evaluated at two pediatric centers in Buenos Aires, Argentina. Characteristic clinical, humoral, and cutaneous features were analyzed. The average age of diagnosis was 29 months old (range of between 2 months and 15 years). Cholestasis was evident in 92% of patients during the neonatal period. Family antecedents related to the syndrome were found in 18.5% of the patients. Peculiar facies developed in 85% of patients. Chronic cholestasis and pruritus were observed in all of the patients and jaundice was evident in 78%. Eighty-four percent of the patients had heart disease (pulmonary stenosis, intraauricular communication, intraventricular communication), 76% of them showed growth retardation, and vertebrae abnormalities were found in 63%. Embryotoxon appeared in 76% of patients, and renal disturbances in 21%. Eleven children (28%) had xanthomas, in the neck, elbows, palms, helixes, inguinal area, gluteus, and knees. The earliest findings appeared in the first months of life, and the latest at 5 years of age. The xanthomas located in the folds had a stony aspect. Cholesterol levels ranging from 220 to 1600 mg percentage (mg%) were demonstrated in all of the children with xanthomas. Liver transplantation was performed in seven of the patients (18.4%). Two of them died after this operation. The disappearance of xanthomas after transplantation was remarkable in all of the patients.