Studies on the mechanism of paracetamol-induced protection against paracetamol hepatotoxicity.

In rats, 3 days treatment with paracetamol (1 oral dose of 1 g/kg daily) produced a complete protection against the hepatotoxic actions of a further dose of paracetamol as documented by determination of serum enzyme activities (glutamic-oxaloacetic transaminase, (GOT), glutamic-pyruvic transaminase (GPT), sorbitol dehydrogenase (SDH), bromsulphthalein retention and histological investigations. Subacute paracetamol treatment decreased liver glutathione levels by 46%, liver microsomal cytochrome P-450 content by 23%, hepatic hydroxylation of aniline by 29% and hepatic demethylation of aminopyrine by 46%. It afforded also some protection against the hepatotoxic actions of carbon tetrachloride, bromobenzene and thioacetamide, but did not influence the antiphlogistic activity of paracetamol (carrageenan paw edema test). Plasma and liver concentrations of free paracetamol after oral administration of 1 g/kg paracetamol were somewhat higher in the subacutely paracetamol-pretreated rats than in the non-pretreated control animals whereas no differences in the concentrations of conjugated paracetamol were found between the 2 groups. Pretreatment with paracetamol did not influence the urinary excretion of free paracetamol but caused some shift in the urinary excretion of paracetamol conjugates: pretreated rats excreted 23% less of the paracetamol glucuronide and sulfate and 33% more of the paracetamol mercapturate than the control animals. A depression of the microsomal mixed-function oxidase activity is presumed to be the main cause of the paracetamol-induced protection against paracetamol hepatotoxicity.     

Arcuate ligament vascular compression syndrome in infants and children

Background

Arcuate ligament vascular compression syndrome has not been described previously in the pediatric or pediatric surgical literature. However, it is mentioned in the literature of vascular and general surgery and in journals of radiology and orthopedics. In this review, the intraoperative pathological anatomy and the principles of treatment for 8 children will be presented.

Methods

The chart records and the anatomical sketches that were documented by the surgeon immediately after each procedure were analyzed retrospectively. In addition, preoperative courses and long-term follow-up (range, 3-18 years) were evaluated by a defined program.

Results

The diagnosis of celiac artery compression by an arcuate ligament was suspected in children presenting with a history of several years of recurrent acute abdominal pain associated with a typical arterial bruit in the midline of the epigastric region.

Conclusions

Other diseases with recurrent abdominal pain and an arterial bruit must be excluded before making the decision for an operative intervention. Duplex ultrasound and angiography are possibly helpful tools to establish the respective diagnosis, but in the patients of the present series, these techniques neither confirmed compression of the celiac axis nor demonstrated decreased perfusion of the superior mesenteric artery. However, as the clinical symptoms clearly announce the disease, these diagnostic measures are not mandatory.     

The factor V G1691A mutation is a risk for porencephaly: A case-control study

This study was initiated to investigate prothrombotic risk factors in children with porencephaly. 76 porencephalic and 76 healthy infants were investigated for factor V (FV) G1691A mutation, factor II G20210A variant, methylenetetrahydrofolate reductase (MTHFR) C677T genotype, lipoprotein (a), protein C, protein S, and antithrombin. Only the FV mutation (p = 0.005) and combinations of two or three different risk factors (p = 0.003) were significantly associated with porencephaly. These data give evidence that the FV G1691A mutation and a combination of prothromboic factors play a major role in the development of childhood porencephaly.     

Acute and subacute intracerebral hemorrhages: comparison of MR imaging at 1.5 and 3.0 T--initial experience

PURPOSE: To assess and describe the appearance of intracerebral hemorrhage (ICH) at 3.0-T magnetic resonance (MR) imaging as compared with the appearance of this lesion type at 1.5-T MR imaging. MATERIALS AND METHODS: Sixteen patients with 21 parenchymal ICHs were examined. ICHs were classified as hyperacute, acute, early subacute, late subacute, or chronic. Patients underwent 1.5- and 3.0-T MR imaging with T2-weighted fast spin-echo, fluid-attenuated inversion-recovery (FLAIR), and T1-weighted spin-echo (1.5-T) and gradient-echo (3.0-T) sequences within 4 hours of each other. The central (ie, core) and peripheral (ie, body) parts of the ICHs were analyzed quantitatively by using contrast-to-noise ratio (CNR) calculations derived from signal intensity (SI) measurements; these values were statistically evaluated by using the Mann-Whitney U test. Two readers qualitatively determined SIs of the cores and bodies of the ICHs, degrees of apparent susceptibility artifacts, and lesion ages. The chi(2) test was used to determine statistically significant differences. RESULTS: With the exception of the bodies of late subacute ICHs at 3.0-T T2-weighted imaging, which had increased positive CNRs and SI scores (P .05). With the exception of minor susceptibility artifacts seen in acute and early subacute ICHs at 3.0-T T1-weighted gradient-echo imaging, no susceptibility artifacts were noticed. The ages of most lesions were identified correctly without significant differences between the two field strengths (P >.05), with the exception of the ages of acute ICHs, which were occasionally misinterpreted as early subacute lesions at 3.0 T. CONCLUSION: At 3.0 T, all parts of acute and early subacute ICHs had significantly increased hypointensity on FLAIR and T2-weighted MR images as compared with the SIs of these lesions at 1.5 T. However, 1.5- and 3.0-T MR images were equivalent in the determination of acute to late subacute ICHs.     

Vaccine protection in the elderly: are Austrian seniors adequately protected by vaccinations?

OBJECTIVE: The aim of the study was to evaluate, if elderly persons are sufficiently protected against infectious diseases by vaccination. PROBANDS AND METHODS: 300 elderly (> 60 years) and 300 young (< 35 years) persons from five Austrian cities were recruited according to the criteria of a field study. Antibody concentrations against tetanus, diphtheria, tickborne encephalitis and influenza were assessed by ELISA or by haemagglutination inhibition test. Disease and vaccination histories were recorded. RESULTS: The results of the study demonstrate that protection against infectious diseases was frequently insufficient in the elderly. This was partly due to the fact that old persons were not vaccinated according to recommended strategies. However, low antibody concentration and a short duration of protective humoral immunity were also observed in many elderly persons in spite of regular vaccination. This was not only the case in frail, but also in healthy elderlies. CONCLUSION: The data demonstrate that vaccination has a relatively weak and short-lasting effect in old age. The results of the study should stimulate discussions about strategies how vaccinations can be made more effective in old age. Improved campaigns, shortened vaccination intervals as well as the design of novel vaccines tailored to fulfill the specific demands of the aging immune system are imaginable.     

Comparison of single,homologous prime-boost and heterologous prime-boost immunization strategies against H5N1 influenza virus in a mouse challenge model

Preparation for an H5N1 influenza pandemic in humans may involve priming the population with a vaccine produced from an existing, available H5N1 strain. We have used a mouse challenge model to compare the immunogenicity and efficacy of inactivated, Vero cell-derived, whole virus H5N1 vaccines in single immunization and homologous or heterologous prime-boost regimes. A single immunization was sufficient to protect against a lethal challenge with strains from matched and unmatched H5N1 clades. Homologous and heterologous prime-boost regimes induced cross-neutralizing antibodies and cross-protection against representative viruses of H5N1 clade 1, clade 2.1, clade 2.2 and clade 2.3. Moreover, the results indicate that heterologous prime-boost immunization regimes might broaden the specificity of the anti-H5N1 antibody response.     

Enhancement of acute ethanol hepatotoxicity under conditions of low oxygen supply and ischemia/reperfusion. The role of oxygen radicals

Using isolated hemoglobin-free perfused rat livers we studied the effect of low oxygen supply on ethanol hepatotoxicity in two models. In the first model resembling low blood supply, perfusion rate was lowered from 60 to 10 ml/min after a 30 min-equilibration phase and kept low for 60 min. As a consequence, oxygen consumption fell from 1.76 +/- 0.15 mumol/min/g to 0.51 +/- 0.02 mumol/min/g. In the second model, total ischemia was accomplished by interruption of the perfusion for 30 min and was followed by reperfusion at a perfusion rate of 60 ml/min for a further 30 min. In this model, oxygen consumption returned immediately to normal values upon reperfusion. In both models, low oxygen supply had no toxic effects of its own on livers from fed rats. While ethanol (3 g/l) given under normoxic conditions led to a moderate hepatotoxicity, its application in both models of partial as well as total ischemia and reperfusion resulted in a marked liver damage as evidenced by a strong release of sorbitol dehydrogenase, glutamate-pyruvate-transaminase, lactate dehydrogenase and glutathione, as well as by an increase in hepatic calcium content. Inhibition of ethanol metabolism by 4-methylpyrazol prevented liver damage in both models indicating that metabolism of ethanol is a prerequisite for its toxicity to occur. Also, hepatotoxicity was inhibited partially by catalase and superoxide dismutase and nearly totally by deferrioxamine and allopurinol. Thus, reactive oxygen species which are produced during ethanol metabolism as well as under conditions of low oxygen supply are mediators of hepatic damage in both models employed.     

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