Flecainide overdose: is cardiopulmonary support the treatment?

Flecainide toxicity can impair cardiac function and precipitate circulatory collapse, which in turn depresses clearance and redistribution of flecainide. Treatment directed at improving cardiac function is often ineffective in the presence of persistently increased flecainide levels. We report a novel approach to severe flecainide overdose using peripheral cardiopulmonary bypass support (CBS) to maintain perfusion of the liver, thereby allowing clearance of the drug. CBS was initiated to resuscitate a young woman who had ingested flecainide in a suicide attempt. The patient had an agonal rhythm, no effective blood pressure, and a flecainide level of 5.4 micrograms/mL (therapeutic range, .2 to 1.0 microgram/mL). During 10 hours of CBS, the flecainide level decreased to 1.4 micrograms/mL, a half-life of 6 hours. Effective cardiac rhythm and blood pressure returned. CBS successfully supported this patient until the flecainide level decreased as a result of redistribution and normal clearance mechanisms. Unfortunately, because of severe neurologic damage sustained at the time of overdose, the patient died 4 days after admission.     

Correlates of battering among 997 men: family history, adjustment, and attitudinal differences

In order to identify the characteristics associated with physical abuse of female partners, a detailed questionnaire was administered to 997 men who were recruited from either a forensic out-patient clinic (780) or from a community based employment center (217). This questionnaire sampled family and personal history, criminal behavior, psychopathology, and attitudes towards violence. Based upon self-report, the sample was divided into 184 non-abusive men, 517 moderately abusive men, and 296 severely abusive men. The full sample (997) was randomly divided into two subsamples and then, using a cross-validation design, group differences were identified in both subsamples on 46 of the 93 variables examined in this study. All significant effects were linear, such that the average scores of the severely abusive men were worse than the scores of the abusive men who, in turn, scored worse than the non-abusive men. In general, both groups of abusive men reported high rates of violence during childhood (both as victims and perpetrators), antisocial personality disorder, subjective distress, marital maladjustment, attitudes tolerant of spouse assault, and a range of impulsive behaviors (impulsive violence, substance abuse, motor vehicle accidents). The factors that correlated with abuse in the total sample also correlated with abuse in the community sample.     

Metanil yellow: a bifunctional inducer of hepatic phase I and phase II xenobiotic-metabolizing enzymes

Metanil yellow, a non-permitted food colour, has been found in various foodstuffs. The induction potential of metanil yellow on hepatic microsomal cytochrome P-450 (P-450)-dependent monooxygenases and cytosolic detoxification enzymes, namely, glutathione S-transferase (GST) and quinone reductase (QR), was investigated. Oral administration of metanil yellow (430 mg/kg body weight) to four animals for seven days caused significant induction of hepatic P-450 (48%) and its dependent aryl hydrocarbon hydroxylase (100%) activity and cytosolic GST (136%) and QR (92%) activities. Parenteral administration of metanil yellow (80 mg/kg body weight) to another set of four animals for 3 days resulted in higher induction of ethoxyresorufin-O-deethylase (228%) as compared to other monooxygenases (64-92%), while GST and QR were also found to be induced (59-95%). Spectra of metanil yellow-induced microsomes showed an increase in P-450 with a shift of 2.2 nm in the soret region. The results suggest that metanil yellow acts as a bifunctional inducer of specific isozymes of P-450 and cytosolic enzymes and thus may involve the cytosolic aryl hydrocarbon (Ah) receptor for this type of induction.     

RNA-protein interactions within the 3 ' untranslated region of vimentin mRNA

Several functions have been attributed to protein binding within the 3'untranslated region (3'UTR) of mRNA, including mRNA localization, stability, and translational repression. Vimentin is an intermediate filament protein whose 3'untranslated sequence is highly conserved between species. In order to identify sequences that might play a role in vimentin mRNA function, we synthesized32P-labeled RNA from different regions of vimentin's 3'UTR and assayed for protein binding with HeLa extracts using band shift assays. Sequences required for binding are contained within a region 61-114 nucleotides downstream of the stop codon, a region which is highly conserved from Xenopus to man. As judged by competition assays, binding is specific. Solution probing studies of 32P-labeled RNA with various nucleases and lead support a complex stem and loop structure for this region. Finally, UV cross-linking of the RNA-protein complex identifies an RNA binding protein of 46 kDa. Fractionation of a HeLa extract on a sizing column suggests that in addition to the 46 kDa protein, larger complexes containing additional protein(s) can be identified. Vimentin mRNA has been shown to be localized to the perinuclear region of the cytoplasm, possibly at sites of intermediate filament assembly. To date, all sequences required for localization of various mRNAs have been confined to the 3'UTR. Therefore, we hypothesize that this region and associated protein(s) might be important for vimentin mRNA function such as in localization.     

Conversion of D-arabinose to D-erythroascorbic acid and oxalic acid in Sclerotinia sclerotiorum

D-glycero-Pent-2-enono-1,4-lactone (trivial name: D-erythroascorbic acid) occurs in the phytopathogen, Sclerotinia sclerotiorum (Lib.) de Bary, where it has a potential role as precursor of oxalic acid. On Glc/yeast/malt medium, S. sclerotiorum produces only nominal amounts of D-erythroascorbic acid but even partial replacement of Glc by D-Ara increases production of erythroascorbic acid and oxalic acid. Use of D-[1-14C]-, -[3-14C]-, or -[6-14C]Glc and D-[5-3H]-, -[2-14C,5-3H]-, or -[UL-14C]Ara provide additional information on erythroascorbic acid biosynthesis and cleavage. The latter process resembles that obtained by peroxygenation of erythroascorbic acid in alkaline solution. An unknown erythroascorbic acid-like compound also occurs in both Glc- and Ara-based cultures.     

Inhibition of murine renal carcinoma pulmonary metastases by systemic administration of interferon gamma: mechanism of action and potential for combination with interleukin 4

We have previously demonstrated that IFN-gamma causes cell growth inhibition and up-regulation of MHC antigens in human renal cell carcinoma cell lines. In this study, we have investigated the therapeutic potential of IFN-gamma for the treatment of 5-day established pulmonary metastases induced by i.v. injection of Renca cells, a murine renal adenocarcinoma. We found that systemic injections of IFN-gamma significantly reduced the number of lung metastases in a dose-dependent manner and increased mouse survival. Histological evaluation of IFN-gamma-treated lungs showed residual small tumor nodules containing extensive necrosis and mononuclear infiltrates. Immunohistochemistry studies on lung sections showed macrophage infiltration into tumor nodules, and in vivo depletion of macrophages partially inhibited IFN-gamma antitumor effect, suggesting a role for the macrophages in tumor destruction. Lymphocyte depletion of either natural killer (NK) cells or CD4+ or CD8+ T-cell subsets or both T-cell subsets did not affect the IFN-gamma effect, whereas depletion of both NK and T cells decreased the antitumor activity of IFN-gamma. These data indicate that neither T cells nor NK cells are essential for this activity but that either lymphocyte population can contribute to the IFN-gamma effect. An optimal dose of IFN-gamma inhibited by 60% the growth of Renca cells treated for 3 days in vitro, but this effect was transient and less pronounced in a long-term colony assay, suggesting that IFN-gamma direct growth inhibition may play a role but may not be sufficient to mediate its antitumor effect in vivo. In vitro, IFN-gamma caused up-regulation of class I MHC antigens and induction of class II antigen expression in Renca cells, an effect that may enhance Renca immunogenicity but may be relevant only when a T-cell response is elicited. A sequential administration of IFN-gamma followed by interleukin 4 was therapeutically better than IFN-gamma alone for the treatment of advanced pulmonary metastases, probably due to different antitumor mechanisms induced by these two cytokines.