Lack of methoxy-mycolates characterizes the geographically restricted lineage 7 of Mycobacterium tuberculosis complex.

Lineage 7 (L7) emerged in the phylogeny of the Mycobacterium tuberculosis complex (MTBC) subsequent to the branching of 'ancient' lineage 1 and prior to the Eurasian dispersal of 'modern' lineages 2, 3 and 4. In contrast to the major MTBC lineages, the current epidemiology suggests that prevalence of L7 is highly confined to the Ethiopian population, or when identified outside of Ethiopia, it has mainly been in patients of Ethiopian origin. To search for microbiological factors that may contribute to its restricted distribution, we compared the genome of L7 to the genomes of globally dispersed MTBC lineages. The frequency of predicted functional mutations in L7 was similar to that documented in other lineages. These include mutations characteristic of modern lineages - such as constitutive expression of nitrate reductase - as well as mutations in the VirS locus that are commonly found in ancient lineages. We also identified and characterized multiple lineage-specific mutations in L7 in biosynthesis pathways of cell wall lipids, including confirmed deficiency of methoxy-mycolic acids due to a stop-gain mutation in the mmaA3 gene that encodes a methoxy-mycolic acid synthase. We show that the abolished biosynthesis of methoxy-mycolates of L7 alters the cell structure and colony morphology on selected growth media and impacts biofilm formation. The loss of these mycolic acid moieties may change the host-pathogen dynamic for L7 isolates, explaining the limited geographical distribution of L7 and contributing to further understanding the spread of MTBC lineages across the globe.

Microscopic description of low-lying properties in 168≤A≤170 Yb nuclei by the pseudo-SU(3) shell model / Descripción microscópica de las propiedades de baja energía de los núcleos 168≤A≤170 Yb usando el modelo pseudo-SU(3)

Abstract The rare-earth nuclei have well-known collective properties. The theoretical description of these nuclei represents a challenge to nuclear models, due to the enormous dimensions of the valence space, making the problem unmanageable. This leads us to use symmetry-based models, where it is possible to calculate in a free-truncation environment. In this work we present results for the energy spectrum and the electromagnetic properties in even-even Yb isotopes using the pseudo-SU(3) shell model. The model considers a Nilsson Hamiltonian that additionally includes the quadrupole-quadrupole and pairing interactions, systematically parameterized. The results show that the model considered is a powerful theoretical tool, allowing us to describe the normal parity sector of deformed rare earth nuclei.

Resumen Las propiedades colectivas de los núcleos de las tierras raras están muy bien determinadas. La descripción teórica de estos núcleos representa un desafío para cualquier modelo nuclear debido a las dimensiones excesivas del espacio de valencia, lo que vuelve el problema inmanejable. Esto nos lleva a emplear modelos basados en simetrías, donde es posible realizar cálculos sin truncamiento del espacio. En este trabajo se presentan resultados para el espectro energético y las propiedades electromagnéticas en isótopos para-par de iterbio, utilizando el modelo de capas pseudo-SU(3). El modelo considera el hamiltoniano de Nilsson, al que adicionalmente se le han incluido las interacciones cuadrupolo-cuadrupolo y de apareamiento, parametrizadas de forma sistemática. El resultado muestra que el modelo utilizado es una herramienta poderosa que permite describir el sector de paridad normal del espectro de núcleos deformados de las tierras raras.

An open, randomized, multicenter clinical trial of oral tacrolimus in liver allograft transplantation: a comparison of dual vs. triple drug therapy.

Triple therapy combining an anticalcineurin agent, corticosteroids, and azathioprine (AZA) in liver transplantation has been frequently applied, particularly in Europe. Debates have arisen concerning the use of a third drug (AZA), mainly in patients receiving tacrolimus (TAC). An open-label, multicenter, prospective, and randomized trial was performed to assess the efficacy and safety of TAC and corticosteroids (dual therapy [D]) vs. TAC, corticosteroids, and AZA (triple therapy [T]) in liver transplantation. A total of 180 patients were randomized, 92 in D and 88 in T group. Patients were followed during 3 months for efficacy and safety and up to 24 months for patient and graft survival assessments. The rate of biopsy-proven acute rejection was higher in D than in T group (40.7% vs. 24.4%; P = 0.021). A higher incidence of positive HCV status in D group (55.6% vs. 40.7%; P = 0.049) may explain this difference, since significantly more patients of this HCV subpopulation experienced acute rejection when treated with D therapy (48% vs. 20%; P = 0.008). No treatment differences were apparent for HCV-negative patients. The 24-month graft survival tended to be inferior in T group, 69.8% vs. 75.8% (P = 0.283). Similar results were observed regarding patient survival at the same time point, with values of 72.9% vs. 76.9% (P = 0.573), favoring D group. Both regimens showed comparable safety profiles with the exception of hematological abnormalities, which were more frequently observed in T group. In conclusion, both regimens were shown to be effective although increased toxicity and a trend towards a lower graft and patient survival were observed in T group.

Melatonin prevents oxidative stress and hepatocyte cell death induced by experimental cholestasis.

The induction of oxidative stress precedes liver injury during experimental obstructive jaundice (OJ). In this sense, different evidences suggest that melatonin (MEL), as antioxidant, may be useful in the protection against apoptosis and necrosis during experimental cholestasis. In addition, we will also assess if MEL-dependent protection is related to a recovery of antioxidant status disturbances induced by OJ. Cholestasis was achieved by double ligature and sectioning of the principal bile duct. MEL was injected intraperitoneally (500 microg/kg/day). Lipid peroxidation was evaluated by the measurement of malondialdehyde (MDA) content in liver. Different parameters related to antioxidant status, such as reduced glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) were determined in liver. Liver injury was assessed by alanine amino-transferase (ALT) in serum, histological examination, DNA fragmentation and TUNEL assay. The activation of perisinusoidal stellate cells was evaluated by immunohistochemical measurement of alpha-smooth muscle actin in liver sections. The induction of OJ increased all the parameters related to apoptosis and necrosis in liver. The induction of liver injury was associated with stellate cell activation, as well as an increase in MDA (p < 0.0001) and a reduction in GSH, GPx, catalase and SOD content (p < 0.0001) in liver. MEL reduced hepatic apoptosis and necrosis (p < 0.004) with a significant improvement in all oxidative stress markers. In conclusion, our results showed that MEL recovered the antioxidant status and reduced apoptosis and necrosis induced by experimental cholestasis.

Effect of melatonin on cholestatic oxidative stress under constant light exposure.

This study was designed to evaluate the effect of melatonin on cholestatic oxidative stress under constant light exposure. Cholestasis was induced by double ligature and section of the extra-hepatic bile duct. Melatonin was injected i.p.(1000 microg kg(-1) day(-1)). Malondialdehyde, reduced glutathione, catalase, superoxide dismutase, glutathione reductase, peroxidase and transferase were determined in liver. After bile-duct obstruction and under constant light exposure, an increase in malondialdehyde (p < 0.05) and a slight decrease in reduced glutathione were seen. Enzyme activity, with the exception of glutathione reductase, had significantly diminished. After melatonin administration, malondialdehyde fell (p < 0.001), whereas there was an increase in reduced glutathione (p < 0.0001) compared with untreated controls. Constant light exposure was associated with an increase in hepatic oxidative stress. Treatment with melatonin decreased lipid peroxide synthesis, and permitted a recovery of both reduced glutathione and scavenger enzyme activity.

Effect of internal biliary drainage on plasma levels of endotoxin, cytokines, and C-reactive protein in patients with obstructive jaundice.

Preoperative biliary drainage may improve the cytokine and acute-phase response derangements observed in patients with obstructive jaundice. We conducted a prospective longitudinal, before-after trial in our 600-bed teaching hospital. Twenty-four patients with obstructive jaundice were investigated, 11 with benign obstruction and 13 with malignant disease. Endoscopic internal biliary drainage was performed in all patients (7 by papillotomy and 17 by endoprostheses). Endotoxin, tumor necrosis factor alpha (TNF-a), interleukin-6 (IL-6), nitric oxide production, and C-reactive protein (CRP) were determined at admission and on days 2 and 7 after internal biliary drainage was accomplished. Bile cultures were obtained before and at the time of drainage. Endotoxin, IL-6, TNF-a, and CRP were significantly higher in patients with cancer. After internal drainage, endotoxin (11.4 vs. 2 EU/L; p <0.05), TNF-a (87.5 vs. 48 pg/ml; p = 0.03), and IL-6 (324 vs. 232 pg/ml; p <0.05) plasma levels decreased significantly in the early postdrainage period in patients with cancer. Endotoxin, cytokines, as well as the CRP plasma values, however, increased again on day 7 after drainage. This trend was less marked in patients with benign obstruction. Patients with positive bile cultures after drainage displayed higher levels of CRP (115 vs. 62 mg/L; p = 0.03), IL-6 (598 vs. 330 pg/ml; p = 0.04), and endotoxin (10.6 vs. 4.8 EU/L; p = 0.02) than those with negative bile cultures. Biliary tract obstruction is associated with an increase in endotoxin levels, a positive acute-phase response, and plasma cytokine elevation. After biliary drainage a transitory improvement of these alterations was observed, although values remained high 1 week postdrainage. These findings were associated with positive bile cultures.

Carcinoma suprarrenocortical. Abordaje terapéutico en estadio avanzado / Adrenal cortical carcinoma: therapeutic approach in advanced-stage disease

Presentamos el caso clínico de una mujer de 33 años diagnosticada de carcinoma suprarrenocortical en estadio avanzado. Describimos la forma de presentación clínica, los métodos diagnósticos empleados y el tratamiento, especialmente en su aspecto quirúrgico, que puede precisar en determinadas ocasiones conocimientos y habilidades en cirugía hepática y vascular para intentar conseguir la resección completa del tumor y mejorar la supervivencia en estos pacientes, generalmente muy jóvenes; asimismo, realizamos una actualización bibliográfica diagnosticoterapéutica de esta neoplasia, rara en su frecuencia pero agresiva en su evolución (AU)

Masas del ovario en niñas / Ovary masses in girls

Objetivo: revisar los casos de masas de ovario en niñas que ingresan al hospital. Metodología: estudio retrospectivo basado en la revisión de casos durante el período de 1985 a 1995. Resultados: Se encontraron 21 casos en niñas menores de 13 años de edad. Masas benignas en 15 casos (71/100) y 6 casos malignas (29/100). La mayor parte de las masas malignas fueron en niñas mayores de 9 años (83/100). El uso de ultrasonido fue útil en los 11 casos en que se empleó. No hubo relación entre gran tamaño de las masas y malignidad, de 11 casos mayores de 15 cms de diámetro, 8 fueron masas benignas. En 10 casos (48/100) la masa ovárica sufrió torsión. Conclusiones: las masas de ovario en niñas son raras y la presentación clínica es muy variada. Su patología varía de quistes benignos a tumores malignos muy agresivos