Protective Effect of Oral Acetylcysteine against the Hepatorenal Toxicity of Carbon Tetrachloride Potentiated by Ethyl Alcohol

Considering the well-documented protection of acetylcysteine (AC) in hepatotoxicity related to acetaminophen, we studied the preventive potential of AC against mild hepatotoxicity of CCl4, potentiated with ethyl alcohol (ETH) and the role of tissue glutathione. Rats fed a liquid diet with 30% of energy from ETH, had-intraperitoneal CCl4 administered in three injections, at 7-day intervals. AC was ingested at the level for acetaminophen overdose. ETH markedly potentiated the injury induced by CCl4, as evidenced by higher values of serum alanine aminotransferase (ALT), urinary bile acids (BA), serum creatinine, histological score of liver cell necrosis, mortality and by lower body weights and lower liver glutathione, when compared with CCl4 alone. Protective effect of AC consisted of a lesser hepatocytic necrosis, better body weights and higher liver glutathione. We conclude, that AC favorably modifies liver damage induced by CCl4 and potentiated with ETH. There is a preventive role for AC in subjects who combine ETH overuse with exposure to hepatotoxic xenobiotics, whose toxicity is modified by tissue glutathione.     

Frontal white matter volume and delta EEG sources negatively correlate in awake subjects with mild cognitive impairment and Alzheimer's disease.

OBJECTIVE: A relationship between brain atrophy and delta rhythmicity (1.5-4 Hz) has been previously explored in Alzheimer's disease (AD) subjects [Fernandez A, Arrazola J, Maestu F, Amo C, Gil-Gregorio P, Wienbruch C, Ortiz T. Correlations of hippocampal atrophy and focal low-frequency magnetic activity in Alzheimer disease: volumetric MR imaging-magnetoencephalographic study. Am J Neuroradiol. 2003 24(3):481-487]. In this study, we tested the hypothesis that such a relationship does exist not only in AD patients but also across the continuum of subjects with mild cognitive impairment (MCI) and AD. METHODS: Resting, eyes-closed EEG data were recorded in 34 MCI and 65 AD subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by LORETA. Cortical EEG sources were correlated with MR-based measurements of lobar brain volume (white and gray matter). RESULTS: A negative correlation was observed between the frontal white matter and the amplitude of frontal delta sources (2-4 Hz) across MCI and AD subjects. CONCLUSIONS: These results confirmed for the first time the hypothesis that the sources of resting delta rhythms (2-4 Hz) are correlated with lobar brain volume across MCI and AD subjects. SIGNIFICANCE: The present findings support, at least at group level, the 'transition hypothesis' of brain structural and functional continuity between MCI and AD.     

A mating deficient and temperature-sensitive lethal mutant of Schizosaccharomyces pombe defines a new fertility locus

Summary A recessive mutant allele, mef1-84, of a novel locus mapping on the left arm of chromosome I, between ade3 and ura1, 5 cM apart from lys5, confers temperature-sensitive growth and mating deficiency at the nonrestrictive temperatures for growth. Two other mutations suppress the phenotype conferred by mef1-84: sts1-1 suppresses the temperature-sensitive growth only, and smd1-35 suppresses both temperature-sensitive growth and mating deficiency.     

Infectious lymphocytes in lymphocytic choriomeningitis virus carrier mice.

The infectivity of blood and lymphoid organs of mice persistently infected with lymphocytic choriomeningitis virus was found to be predominantly associated with lymphocytes and both T and B cells were infectious. A hypothesis is presented in which it is assumed that lymphocytes in carrier mice are infected via their LCM virus-specific antigen receptors, thereby leading to their antigen-triggered clonal expansion followed by infection and functional inactivation.     

Liver-First Approach for Synchronous Colorectal Metastases: Analysis of 7360 Patients from the LiverMetSurvey Registry

Annals of Surgical Oncology - The liver-first approach in patients with synchronous colorectal liver metastases (CRLM) has gained wide consensus but its role is still to be clarified. We aimed to...     

BCL-2--general considerations

BCL-2 protein is a oncoprotein considered to have an important role in the regulation of programmed cell death--apoptosis. The intracellular localization, the relation with other oncoproteins, the antioxidant function and the pathological implications are discussed.     

The xenotransplantation of goat and human hematopoietic cells to sheep fetuses

Hematopoietic xenografts were carried out in three experiments using goat fetal liver (44-48 days, experiments I and II) or purified human CD 34+ cells (experiment III) as the donor cells. Recipients were sheep fetuses at 41-47 days of gestation. Goat fetal liver cells were either injected without any pretreatment or stimulated by preincubation in a culturing in goat phytohemagglutinin-stimulated lymphocyte supernatant. Human CD 34+ myeloid progenitor cells were purified from bone marrow by minimacs immunomagnetic purification and cultured in medium supplemented with stem cell factor, IL3, and IL6. Goat-sheep chimerism was assessed by flow cytometry analysis (FCA) of peripheral blood and bone marrow cells using a mouse anti-goat CD 45 monoclonal antibody and by karyotype analysis of peripheral blood from goat/sheep chimeras. Human cell engraftment was assessed by polymerase chain reaction amplification of the human DAX1 gene in blood and bone marrow DNA from sheep which had received human cells. In the three experiments, a mean of 76% (26 of 34) of injected fetuses were born alive without any clinical evidence of graft-versus-host disease. Three lambs were found to be goat/sheep chimeric after flow cytometry analysis (peripheral blood and bone marrow) and karyotype (peripheral blood) analysis. Both tissues continued to express goat cells at 6 or 12 months (last assessment) depending on the experiment. No human chimerism was detected using polymerase chain reaction amplification in peripheral blood and bone marrow of any of the six sheep grafted with human cells. These data and those also obtained on other species (human, pig/sheep) show that it is possible to carry out hematopoietic xenografts using the sheep fetus as recipient provided both donor and recipient fetal cells are processed during the period of tolerance to foreign antigens.     

The effect of etafenone on the subcellular distribution of calcium and some oligoelements in heart muscle. Ultracytochemical and x-ray microanalytical study.

In order to detect the subcellular localization of calcium in the myocardium of laboratory animals (rats and guinea-pigs) under the influence of 2'-(2-diethylaminoethoxy)-3-phenyl-propiophenone (etafenone, Baxacor) (4 mg, 20 mg and 100 mg/kg body weight) two ultracytochemical methods, with lead acetate and with potassium pyroantimonate, were used. In addition, X-ray microanalysis of myocardial fragments was performed. The correlation of ultrastructural, ultracytochemical and X-ray microanalytical findings provides direct evidence of the hypothesis that etafenone acts on myocardium as a so-called "calcium antagonist". The subcellular targets of etafenone action are mainly the sarcoplasmic reticulum and mitochondria. Etafenone modifies also the concentration of copper, zinc and selenium in myocardium. The effect of etaferone on myocardial calcium and oligoelements appears to be dose-dependent.