Human granulocytes contain an opiate alkaloid-selective receptor mediating inhibition of cytokine-induced activation and chemotaxis

Human peripheral blood granulocytes previously were found to contain opioid delta 2-receptors mediating stimulation by opioid peptides of chemotaxis. Studies presented in this work indicate that granulocytes also contain opiate alkaloid-selective, opioid peptide-insensitive receptors mediating inhibition by morphine and other opiates of cytokine-induced activation and chemotaxis. Binding studies with [3H]morphine and [3H]diprenorphine ([3H]DPN) indicated the presence of receptor sites, at considerable density with affinities and selectivity for opiates comparable with those of the mu 3-receptor of human peripheral blood monocytes (macrophages). The influence of the guanosine 5'-triphosphate (GTP) analogue GppNHp on binding indicated that the granulocyte receptor was linked to a G protein. Morphine but not opioid peptides interfered with activation and/or chemotaxis of the granulocytes induced by TNF-alpha, IL-1 alpha, IL-8, and FMLP (chemotactic peptide). These effects of morphine were blocked by the antagonist naloxone. Levorphanol inhibited TNF-alpha-induced activation, and also potentiated the inhibition by morphine. Furthermore, in binding assays, levorphanol enhanced the affinity of the receptor for morphine. Dextrorphan had no effect on activation or chemotaxis, and it also had no effect on binding, indicative of stereoselectivity for the effect of levorphanol. It is concluded that human granulocytes contain opiate alkaloid-selective mu 3-receptors that mediate inhibitory effects of morphine on cellular activation by cytokines.     

Invasion of hereditary ovalocytes by Plasmodium falciparum in vitro and its relation to intracellular ATP concentration

Hereditary ovalocytes (stomatocytic ovalocytes), when examined within 1-2 days from the time that the blood sample is drawn, are invaded by Plasmodium falciparum in culture to the extent of at least 55% of normal control cells. The ovalocytes have extremely rigid membranes, characterised by a shear elastic modulus some 3-4 times greater than that of normal cells. The extent of invasion falls off very much more rapidly than that into normal cells on storage, and we surmise that this is the reason for earlier reports of resistance of ovalocytes to malarial invasion in vitro. The initial loss of susceptibility to invasion with time is not accompanied by any change in membrane rigidity, but is primarily a consequence of a rapid decline in intracellular ATP concentration: this falls to below the threshold level required for invasion (approx. 0.1 mM) over a period in which the ATP in normal cells remains almost constant. Incubation in a metabolic regenerating medium leads to a rise in the intracellular ATP concentration and invasion by P. falciparum is recovered, though to a much lower extent than in normal cells. The resistance of ovalocytes to invasion becomes irreversible, due possibly to degradative processes in the membrane, on further storage. The developing parasites in ovalocytes have a reduced number of merozoites and show distinct morphological abnormalities.     

Metabolism-reproduction interactions in domestic animals

In farm animals as in human, reproduction is affected by changes in the level of energetic balance. The main factors that link metabolism and reproduction, like insulin, IGFs, glucose, FFA, leptin and NPY, act on hypothalamo-pituitary axis as well as on gonads by directly altering gametogenesis.     

Assessment of alcohol consumption and alcoholism in the elderly

This study evaluates characteristics associated with alcohol consumption or alcohol-related problems in an elderly population, as detected by CAGE questionnaire and self-reported alcohol intake respectively. Data were obtained from a multidimensional study carried out in a community-dwelling population aged 70-75 (n = 1205, 389 males and 816 females) living in the city center of Brescia, in northern Italy. All information was gathered by self-report. Male gender, better mood, daily function, somatic health, not living alone, and being married were significantly associated with self-reported alcohol consumption. Male gender, poorer cognitive function, and income dissatisfaction were significantly associated with alcohol problems as detected by CAGE. Data suggest that self-report of alcohol intake, though intrinsically loaded with imperfect internal consistency, does not necessarily indicate risk of alcoholism; on the contrary, it can reveal the positive psychological attitude of the drinking habit. CAGE questionnaire, which is sensitive to alcohol related problems, is associated with poor psychosocial conditions.     

Benefits of collecting local data on breast cancer and mammography practices in northwestern Pennsylvania

OBJECTIVES: A randomized trial was conducted to evaluate the effectiveness of a work-site health promotion program in reducing obesity and the prevalence of cigarette smoking. METHODS: Thirty-two work sites were randomized to treatment or no treatment for 2 years. Treatment consisted of health education classes combined with a payroll-based incentive system. Evaluation was based on cohort and cross-sectional surveys. RESULTS: Of 10,000 total employees in treatment work sites, 2041 and 270 participated in weight control and smoking cessation programs, respectively. Weight losses averaged 4.8 lbs, and 43% of smoking participants quit. Net 2-year reductions in smoking prevalence in treatment vs control work sites were 4.0% and 2.1% in cross-sectional and cohort surveys, respectively. No treatment effect was found for weight. Treatment effects for smoking prevalence and weight were both positively correlated with participation rates in the intervention programs (r = .45 for smoking and r = .55 for weight). CONCLUSIONS: This work-site health promotion program was effective in reducing smoking prevalence at a cost that is believed to make the investment worthwhile.     

The relationship between coffee consumption and serum cholesterol under consideration of smoking history

To provide insight into the stream of Medicare payments over time, a sixteen-year longitudinal study examines three age cohorts of beneficiaries, looking separately at beneficiaries who died during the study period and those who survived. The common wisdom that a small minority of the population accounts for a large majority of health care expenditures is tempered when health care use is examined over an extended period of time. By putting high average costs in the final years of life in the context of a cohort's total lifetime experience, the study shows a leveling of spending over time, resulting in a lower concentration of health care resources on a small fraction of the population.     

Hypothalamic paraventricular nucleus lesions differentially affect serotonin-1A (5-HT1A) and 5-HT2 receptor agonist-induced oxytocin, prolactin, and corticosterone responses

A number of receptor subtypes mediate hormonal responses to serotonin (5-HT). To test the hypothesis that the hypothalamic paraventricular nucleus (PVN) mediates 5-HT1A and 5-HT2 receptor-mediated oxytocin, PRL, and corticosterone responses, we studied the effects of the 5-HT1A agonist ipsapirone and the 5-HT2A/2C agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI) after surgical PVN lesions or sham operations. Chronically cannulated, conscious, freely moving, male Wistar rats were injected iv (1 mg/kg) shortly after (3-4 days) and 5 weeks after (35-37 days) the operations. In sham-operated rats, ipsapirone caused marked elevations in plasma PRL and corticosterone, but not oxytocin concentrations, whereas DOI increased plasma concentrations of all three hormones. Short term PVN lesions prevented ipsapirone-induced corticosterone and DOI-induced oxytocin responses. DOI-induced PRL and corticosterone responses were also markedly inhibited 3-4 days after lesioning, although small rises over the baseline values were still observed. The ipsapirone-induced PRL response was unaffected by the lesioning. Five weeks after PVN lesioning, partial recoveries were observed in ipsapirone- and DOI-induced corticosterone and DOI-induced oxytocin responses, whereas DOI-induced PRL responses remained suppressed. The present findings suggest that the PVN or neural pathways close to it mediate oxytocin, PRL, and corticosterone responses to the 5-HT2 receptor agonist DOI as well as corticosterone, but not PRL, responses to the 5-HT1A receptor agonist ipsapirone. The results after long term PVN lesioning show that the oxytocin and corticosterone responses may be partially restored with time after lesioning.