Antagonism of the toxicity of cocaine by MK-801: Differential effects in spontaneously hypertensive and Wistar-Kyoto rats

A putative role for endogenous excitatory amino acid systems in the mediation of the cardiovascular and toxic responses to acute administration of cocaine, was examined in spontaneously hypertensive and normal Wistar-Kyoto rats. Conscious, restrained, male hypertensive and normal rats (12 weeks of age) received either the non-competitive excitatory amino acid receptor antagonist, MK-801 (0.01–10 mg/kg, i.v.) or vehicle, 30 min prior to initiation of infusion of cocaine hydrochloride (1.25 mg/kg min, i.v.). Administration of MK-801 produced increases in mean blood pressure and heart rate in both hypertensive and normal rats. Resting rectal temperature was reduced by MK-801 only at the largest dose tested (10 mg/kg). Infusion of cocaine caused convulsions and death at doses of 27.8 ± 2.3 and 48.2 ± 5.7 mg/kg, respectively in the normals, and 21.2 ± 2.5 (P < 0.05) and 31.1± 3.4 (P < 0.05) in the hypertensive rats. Pretreatment with MK-801 abolished the enhanced sensitivity of the hypertensive rats to the toxicity of cocaine. The doses of cocaine required to cause death were significantly increased, in the hypertensive rats at doses 0.05 mg/kg, an effect which was not evident, at any dose, in the normals. The maximally effective dose of MK-801 (0.5 mg/kg) increased the dose of cocaine required to cause lethality by 272% (P < 0.05) in the hypertensive rats; the increase produced by MK-801 in the normals (163%) was not significant. Cocaine-induced convulsions were abolished in both hypertensive and control rats with doses of MK-801 >0.1 mg/kg. Progressively developing hypotensive and bradycardiac effects were noted during infusion of cocaine in hypertensive and control rats, pretreated with MK-801. The drug MK-801 was an effective antagonist of cocaine-induced convulsions in both hypertensive and normal rats but protected against cocaine-induced lethality only in the hypertensive rats.     

Interleukin-11 receptor signaling is required for normal bone remodeling.

IL-6 and -11 regulate bone turnover and have been implicated in estrogen deficiency-related bone loss. In this study, deletion of IL-11 signaling, but not that of IL-6, suppressed osteoclast differentiation, resulting in high trabecular bone volume and reduced bone formation. Furthermore, IL-11 signaling was not required for the effects of estradiol or estrogen deficiency on the mouse skeleton. INTRODUCTION: Interleukin (IL)-6 and -11 stimulate osteoclastogenesis and bone formation in vitro and have been implicated in bone loss in estrogen deficiency. Because of their common use of the gp130 co-receptor signaling subunit, the roles of these two cytokines are linked, and each may compensate for the absence of the other to maintain trabecular bone volume and bone cell differentiation. MATERIALS AND METHODS: To determine the interactions in bone between IL-11 and IL-6 in vivo and whether IL-11 is required for normal bone turnover, we examined the bone phenotype of mature male and female IL-11 receptor knockout mice (IL-11Ralpha1-/-) and compared with the bone phenotype of IL-6-/- mice and mice lacking both IL-6 and IL-11Ralpha. To determine whether IL-11 is required for the effects of estrogen on trabecular bone, mature IL-11Ralpha1-/- mice were ovariectomized and treated with estradiol. RESULTS: In both male and female IL-11Ralpha1-/- mice, trabecular bone volume was significantly higher than that of wildtype controls. This was associated with low bone resorption and low bone formation, and the low osteoclast number generated by IL-11Ralpha1-/- precursors was reproduced in ex vivo cultures, whereas elevated osteoblast generation was not. Neither trabecular bone volume nor bone turnover was altered in IL-6-/- mice, and compound IL-6-/- :IL-11Ralpha1-/- mice showed an identical bone phenotype to IL-11Ralpha1-/- mice. The responses of IL-11Ralpha1-/- mice to ovariectomy and estradiol treatment were the same as those observed in wildtype mice. CONCLUSIONS: IL-11 signaling is clearly required for normal bone turnover and normal trabecular bone mass, yet not for the effects of estradiol or estrogen deficiency on the skeleton. In the absence of IL-11Ralpha, increased trabecular bone mass seems to result from a cell lineage-autonomous reduction in osteoclast differentiation, suggesting a direct effect of IL-11 on osteoclast precursors. The effects of IL-11Ralpha deletion on the skeleton are not mediated or compensated for by changes in IL-6 signaling.     

Petroleum-Vergiftungen bei Kindern

Ohne Zusammenfassung     

Falling incidence of HIV infection in a cohort of clinic attenders

Abstract: It is widely accepted that changes in sexual behaviour in the mid-1980s drastically reduced the spread of human immunodeficiency virus (HIV) through male homosexual contact in Western countries, but documentation of changes in infection rates has been based on observation of subjects enrolled in cohort studies, who may be highly selected and motivated. In this study, the incidence of HIV seroconversion was investigated among people attending a major site of HIV testing, counselling and patient care in Sydney. Over the period March 1985 to June 1990, 2 301 people were tested for HIV antibody on more than one occasion, following a negative result at the first test. On the basis of subsequent tests, 107 were found to have seroconverted during the study period, including 91 men who reported homosexual or bisexual contact as their only exposure to HIV. Overall, the incidence rate of HIV infection among men reporting homosexual or bisexual contact was 404 per 100 person-years of follow-up. Under various methods of calculation, the incidence was estimated to have declined between 1985 and 1989–1990. However, there was continuing HIV seroconversion in 1989–1990 and no indication of declining incidence in younger men. The fall in HIV incidence documented in this study supports the role of HIV prevention programs aimed at homosexual and bisexual men.     

Molecular cloning and characterization of an invertebrate homologue of a neuropeptide Y receptor

Neuropeptide Y is an abundant and physiologically important peptide in vertebrates having effects on food intake, sexual behaviour, blood pressure and circadian rhythms. Neuropeptide Y homologues have been found in invertebrates, where they are very likely to play similar, important roles. Although five neuropeptide Y-receptor subtypes have been identified in mammals, none has been reported from invertebrates. Here we describe the cloning of a neuropeptide Y-receptor from the brain of the snail Lymnaea stagnalis. The identity of the receptor was deduced by expressing the neuropeptide Y-receptor-encoding cDNA in Chinese Hamster Ovary cells, which were subsequently challenged with size-fractionated Lymnaea brain extracts. An active peptide, selected on the basis of its ability to induce changes in cAMP levels, was purified to homogeneity, analysed by mass spectrometry and amino acid sequence determination, and turned out to be a Lymnaea homologue of neuropeptide Y.     

Disruption and infection of median sternotomy: a comprehensive review.

Disruption and infection of median sternotomy wounds are grave complications often associated with prolonged hospitalization, high cost, and significant mortality. Effective prevention techniques are still debated. Successful management requires early recognition based on a high index of suspicion, detailed physical examination, appreciation of the clinical signs and symptoms, timely imaging studies, and prompt surgical therapy. Improvements in perioperative management and critical care of patients with multisystem organ failure can reduce morbidity and mortality rates. Sternal salvage and direct sternal reclosure are possible when the infection is diagnosed early. Techniques utilizing lateral sternal support should be first-line options in the condition. Muscle flap techniques should be the next consideration when direct closure has failed or cannot be attempted.