Effect of hypothermia on the pharmacokinetics of ethanol in piglets

The effect of hypothermia (29 C) on the pharmacokinetics of ethanol was studied in eight piglets serving as their own normothermic controls. Ten milliliters of 12% ethanol per kilogram were infused over 30 minutes, and serum ethanol concentrations were measured for seven hours. Ethanol concentration data were fitted to one-compartment open model assuming Michaelis Menten elimination kinetics. During hypothermia, ethanol concentrations were consistently higher than during normothermia. This observation could be explained by both a significantly smaller distribution volume of ethanol during hypothermia (0.71 +/- 0.03 L/kg at 29 C and 0.84 +/- 0.05 L/kg at 37 C, P less than .02) and a significantly slower maximum velocity of metabolism of ethanol (Vm) during hypothermia (1.12 +/- 0.11 mg/kg.min vs. 1.83 +/- 0.21 mg/kg.min, P less than .01). Our study indicates that during hypothermia, ethanol stays significantly longer in the circulation in piglets. Potentially, this may contribute to a more profound effect from the ethanol.     

Oncornavirus-like particles in baboon type C virus-infected chimpanzee lung cells (SFRE:CL-1).

Intracytoplasmic type A particles were observed in a fetal chimpanzee lung culture (SFRE:CL-1) inoculated with type C virus-containing supernatants from a coculture of baboon placenta and SFRE:CL-1 cells. Budding, immature, and mature type C particles were also noted. In thin section, spike-like structures were rarely detected on budding intracytoplasmic type A particles but were occasionally observed on some immature and mature virus particles. Unlike mouse mammary tumor virus or Mason-Pfizer monkey virus, infected SFRE:CL-1 cells contained no eccentric or rodshaped nucleoids.     

A comparison of the effects of flurazepam 30 mg and triazolam 0.5 mg on the sleep of insomniacs

The effects of oral, bedtime triazolam 0.5 mg and flurazepam 30 mg, on the laboratory sleep of 12 insomniacs were compared in a double blind, crossover study. A 22 consecutive night schedule was used: Nts. 1–2 placebo; 3–6 first drug; 7–8 placebo; 9–14 no drugs; 15–16 placebo; 17–20 second drug; 21–22 placebo. In 6 Ss first drug was triazolam and second drug was flurazepam. In the other 6 Ss the drug order was reversed. Effects on sleep were assessed objectively by conventional EEG/EOG/EMG sleep recordings and subjectively by questionnaires administered each morning. Side or toxic effects were assessed by physical exams, clinical lab tests, and twice daily questionnaires. During their administration the two drugs were practically indistinguishable in their effects. Both significantly reduced objective and subjective measures of insomnia, such as total wake time and sleep latency. On discontinuation the drugs differentially affected sleep, e.g., on the first post flurazepam night total sleep time was significantly more than baseline whereas on first post triazolam night, total sleep time was significantly less than baseline. There were no remarkable side or toxic effects with either drug.     

Induction of lupus-related specific autoantibodies by non-specific inflammation caused by an intraperitoneal injection of n-hexadecane in BALB/c mice

A single intraperitoneal (i.p.) injection of pristane, incomplete Freund's adjuvant (IFA), or the adjuvant oil squalene, but not high molecular weight medicinal mineral oils, induces lupus-related autoantibodies to nRNP/Sm and -Su in non-autoimmune strains of mice. This ability appears to be associated with the low molecular weight and adjuvanticity of hydrocarbon. n-Hexadecane (C(16)H(34)), which is present in petroleum, has adjuvant activity and induces arthritis in rodents like other lupus-inducing oils. In addition to dietary exposure to n-hexadecane in mineral oils, exposure also occurs via inhalation of oil mist, jet fuel, or diesel exhaust or by absorption through the skin. Since n-hexadecane is a low molecular weight adjuvant hydrocarbon oil similar to other lupus-inducing hydrocarbons, the present study examined whether it can also induce lupus-related autoantibodies in mice. Female BALB/cJ mice received a single i.p. injection of 0.5 ml of n-hexadecane, pristane, or saline (control). Pathology and serology (immunoglobulin levels, autoantibodies by immunofluorescence, immunoprecipitation, and ELISA) were examined 3 months later. Unexpectedly, all n-hexadecane-treated mice, but none in the other groups, developed inflammatory ascites within 2.5 months. n-Hexadecane induced hypergammaglobulinemia (IgG1, IgG2a), antinuclear (titer>1:160, 67%) and -cytoplasmic antibodies (58%) and autoantibodies to nRNP/Sm (25%), Su (33%), ssDNA (83%), and chromatin (100%). Therefore, non-specific inflammation caused by n-hexadecane resulted in the production of a limited set of specific autoantibodies. These previously unrecognized immunological effects of n-hexadecane may have implications in monitoring human exposure to hydrocarbons and in the pathogenesis of autoimmune diseases.     

Dietary chelators as antioxidant enzyme mimetics: implications for dietary intervention in neurodegenerative diseases

Following recent reviews on the role of metal ions in oxidative stress and neurodegenerative diseases, this article reports advances in the study of dietary components for the control of these conditions. Poor metal ion homeostasis is credited with pathological roles in the progression of a number of disorders including Alzheimer's disease, Parkinson's disease and multiple sclerosis. Synthetic metal ion chelators continue to show promise as a new therapeutic approach for neurodegenerative disorders. Dietary chelators, unlike most vitamins, are, however, capable of negating or even reversing the roles of metal ions by: (i) decorporation of metal ions, (ii) redox silencing, (iii) dissolution of deposits, and (iv) generation of an antioxidant enzyme mimetic. This review gives a critical evaluation of recent progress in, and potential for, dietary control of neurodegeneration on the basis of the formation of antioxidant enzyme mimetics.     

Non-steroidal anti-estrogens in the treatment of breast cancer

The non-steroidal selective estrogen receptor modulator (SERM) tamoxifen has been used as standard first-line therapy for postmenopausal breast cancer since the 1970s, during which time over 400,000 lives have been saved. Nevertheless, much attention has been paid to the side effect profile of tamoxifen, particularly in terms of cardiovascular and endometrial abnormalities. Third generation non-steroidal aromatase inhibitors, such as anastrozole and letrozole, have been approved as an alternative, although it is still too early to judge what long-term adverse effects might be associated with prolonged restriction of the supply of estrogen. Novel SERMs have demonstrated improved characteristics over tamoxifen, reducing or eliminating certain adverse events while retaining breast tumor-reducing efficacy. Thus, these agents could provide a direct substitute for tamoxifen. In addition, other estrogen receptor (ER) subtype-selective modulators are under investigation, and the importance of ERbeta as a positive prognostic indicator may open up further therapeutic opportunities. Resistance to hormonal therapies is still a major problem and identifiying the onset of the development of resistance, together with earlier intervention with inhibitors of growth-factor driven cell survival pathways, in combination or sequentially, requires more intense study.     

Mining the Wnt pathway for cancer therapeutics

Aberrant activation of the Wnt pathway is implicated in driving the formation of various human cancers, particularly those of the digestive tract. Inhibition of aberrant Wnt pathway activity in cancer cell lines efficiently blocks their growth, highlighting the great potential of therapeutics designed to achieve this in cancer patients. Here we provide an overview of the promise and pitfalls of current drug development strategies striving to inhibit the Wnt pathway and present new opportunities for therapeutic intervention.     

Results of 100 consecutive femoropopliteal vein grafts for limb salvage.

One hundred consecutive patients with femoropopliteal autogenous vein grafts for limb salvage were reviewed five years later. In this group 40% died and 30% of the limbs had been lost at the end of five years. Limb survival correlated best with adequacy of distal run-off, but not with the presence or absence of diabetes. Forty-seven per cent of the grafts were still patent among surviving patients, and when combined with the limbs that were viable despite failure of the original graft, 70% of the limbs were salvaged among the survivors at five years. Temporary graft patency was effective in preserving ischemic tissue by facilitating healing of ulcers or limited amputations. Femoral-popliteal bypass grafting in the presence of advanced ischemia is capable of improving the quality of life for many of these patients.