Inhibition of CBrCl3-induced lipid peroxidation in rats in vivo by (+)-cyanidanol-3

(+)-Cyanidanol-3 given to rats in vivo decreased the ethane production induced by treatment with 100 mg CBrCl₃/kg. The extent of this inhibitory effect was dependent on the dose of (+)-cyanidanol-3. It is concluded that (+)-cyanidanol-3 prevents the lipid peroxidation induced in vivo by CBrCl₃.     

Production of reactive oxygen species due to metabolic activation of butylated hydroxyanisole

The synthetic antioxidant butylated hydroxyanisole (BHA) stimulates superoxide formation in rat liver microsomes up to 10-fold. This stimulation is prevented by the monooxygenase inhibitor metyrapone and does not occur when NADH is consumed instead of NADPH indicating that metabolic activation is required for superoxide production. The BHA metabolite tert-butylhydroquinone (TBHQ) is much more active than BHA in stimulating superoxide production, and the amounts of TBHQ and formaldehyde formed from BHA in microsomes are sufficient to explain the effect of BHA. In buffer and in a xanthine oxidase system, superoxide production by TBHQ also takes place. TBHQ autoxidizes to tert-butylquinone (TBQ) and TBQ exceeds TBHQ by far in its capacity for superoxide production in microsomes. Thus, a 30-fold increase of basal superoxide production is induced by 5 microM TBQ. In rat forestomach, the target organ of BHA carcinogenicity in rodents, stimulation of superoxide production by BHA and more markedly by TBHQ and TBQ is also observed. Excess production of superoxide in microsomes by TBHQ is accompanied by excess production of hydrogen peroxide and of hydroxyl radicals. It is concluded that TBQ undergoes redox cycling leading to an oxidative burst in the presence of enzymes capable of one electron reduction of TBQ and that the BHA metabolite TBHQ enters the redox cycle by autoxidation. No oxygen activating properties can be ascribed to BHA itself.     

Dengue in the Seychelles

Epidemics of dengue-like illness occurred in the Seychelles from December 1976 to April 1977 and from December 1978 to January 1979. Dengue 2 virus was isolated from individuals who had been in the Seychelles in 1977. From February to April 1979, sera were collected from outpatients in Mahé, Seychelles, who had not previously been hospitalized with a dengue-like illness. Results of neutralization tests with these sera indicated that prevalence rates for the four dengue viruses were between 81% and 91.8% and that dengue 2 was the most probable etiological agent in the epidemics. In addition, antibodies to chikungunya (8.7%) and Sindbis (7.4%) viruses were found, providing, for the first time, evidence of the presence of these two alphaviruses in the Seychelles.     

Die Zentralambulanz für Betrunkene

The outpatient center for drunkards (OCD) has been in operation in Hamburg since 1974. Helpless inebriated persons can be detoxified under medical supervision. The Hamburg Law on the Protection of Public Safety and Order provides the legal basis for their temporary confinement. A physician and nursing personnel from the state hospital system originally staffed the facility. Due to necessary consolidation of the public budget, a more economical solution had to be found to continue operating the OCD in 2002. The Hamburg Fire Department developed a plan for their emergency service personnel to assume the responsibilities of medical support and supervision. A physician is no longer on the premises. Operation of a central facility for drying out by the agency for emergency services is a model for emulation. This article describes the development and structure of the OCD. It also reports on the new building where the center moved in July 2004 and the experiences gathered with regard to patient safety since the Hamburg Fire Department took over the management.     

Lack of in vivo lipid peroxidation in experimental paraquat poisoning

Summary Ethane evolution was measured in rats breathing pure oxygen. Animals injected i.p. with a lethal dose of paraquat (50 mg/kg) developed signs of pulmonary insufficiency within 3 hours and died within 24 hours. Ethane evolution, a parameter of lipid peroxidation in vivo, was increased over control levels only by 26% after 4 hours. It is concluded that this increase is too small to support the theory that lipid peroxidation is the biochemical mechanism of paraquat toxicity.     

Redox cycling of bleomycin-Fe(III) and DNA degradation by isolated NADH-cytochrome b5 reductase: involvement of cytochrome b5

Isolated and purified microsomal NADH-cytochrome b5 reductase (EC 1.6.2.2) was incubated with bleomycin (BLM) and FeCl3 in the presence of NADH. Only when purified cytochrome b5 was added could an increased NADH consumption be observed indicating redox cycling of the BLM-Fe(III) complex. In the presence of DNA, BLM-Fe(III)-related NADH consumption was accompanied by malondialdehyde (MDA) formation, further evidence for BLM activation yielding oxidative DNA cleavage. BLM, FeCl3, cytochrome b5 and NADH were absolutely necessary to provide these effects. Addition of DNA changed the initial velocity (V0) and the shape of the NADH consumption curves, both probably due to an interaction between DNA and BLM-Fe(III). Furthermore, DNA effectively protected BLM-Fe(III) from autoxidative degradation during redox cycling. BLM-Fe(III)-related, reductase-catalyzed NADH consumption and MDA formation were also dependent on oxygen, showing the involvement of oxygen in the reduction process and in the action of the drug-metal complex in attacking DNA. However, superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6) did not affect NADH consumption. Also, superoxide dismutase and catalase were almost without influence on MDA formation, suggesting that no free (or freely accessible) reactive oxygen species occurred during the redox cycle and DNA damage. The results reveal that the BLM-Fe(III) complex undergoes redox cycling by the microsomal NADH-dependent cytochrome b5 reductase-cytochrome b5 system. The significance of this effect for the action of BLM and the involvement of cytochrome b5 is discussed with regard to the presence of these enzymes in the cell nucleus.     

Moxalactam for obstetric and gynecologic infections. In vitro and dose-finding studies

Moxalactam (LY 127935), a "third-generation" beta-lactam antimicrobial, has been shown to have promising in vitro activity against a wide spectrum of pathogens similar to those isolated from women with pelvic infections. Pharmacodynamic studies have shown that its serum half life is longer than 2 hours, which permits less frequent dosing. The current investigation was carried out in two parts: In the first phase, the minimal inhibitory concentration of moxalactam against 519 clinical isolates was determined and compared to antimicrobials used in infections caused by these microbes. In vitro activity of moxalactam comparable to that of clindamycin was demonstrated against B. fragilis and other Bacteroides species. There was similar activity to penicillin G and clindamycin against anaerobic gram-positive cocci and activity superior to amikacin was demonstrated against Enterobacteriaceae. The second part of this investigation was a clinical one and 100 women with pelvic infections were given treatment with moxalactam. With an initial dose of 3 gm/day, women with posthysterectomy cellulitis and pelvic inflammatory disease did well. Women with pelvic infections following cesarean section responded less readily to this dose; however, when the initial dose was increased to 6 gm/day, a 91% cure rate was effected. The results of these investigations indicate that moxalactam is useful as a single-agent antimicrobial for treatment of polymicrobial female pelvic infection.