Peripherally administered GM-CSF interferes with scopolamine-induced amnesia in mice: involvement of interleukin-1

We studied the effects of granulocyte-macrophage colony stimulating factor (GM-CSF) on the classical behavioral test of scopolamine-induced amnesia for a passive avoidance response in the mouse. Pre-training intraperitoneal administration of this cytokine (1.25, 2.5, 5.0 or 10 μg/mouse) partially, although significantly, reduced the amnesic action of the muscarinic receptor antagonist. The peripheral administration of a specific interleukin-1 receptor antagonist (IL-1 ra, 50 μg/mouse i.p.) blocked the effect of GM-CSF. Our results suggest that GM-CSF is able to exert neuromodulatory actions and that it is involved (probably via IL-1) in the interactions between the immune system and the central nervous system.     

Analgesic effects of μ antagonists after naloxone non-reversible stress-induced analgesia

Three antagonists at the mu opiate receptor site: naloxone, naltrexone and diprenorphine, and one agonist-antagonist compound nalorphine, at doses usually not analgesic elicited analgesia in rats when administered after non-naloxone-reversible shock-induced analgesia had disappeared. The chi receptor antagonist, MR 2266, and the delta antagonist, ICI 154129, were all ineffective. This effect was no longer present when non-naloxone-reversible shock-induced analgesia was inhibited by the administration of the chi receptor antagonist, MR 2266. These results suggest that the mu opiate receptor may change its conformation under particular conditions such as continuous inescapable shock.     

Psychoimmunoendocrine aspects of panic disorder.

Immunological, neuroendocrine and psychological parameters were examined in 14 psychophysically healthy subjects and in 17 panic disorder patients before and after a 30-day course of alprazolam therapy. T lymphocyte proliferation in response to the mitogen phytohemagglutinin, lymphocyte beta-endorphin (beta-EP) concentrations, plasma ACTH, cortisol and beta-EP levels were examined in basal conditions and after corticotropin-releasing hormone (CRH) stimulation. Cortisol inhibition by dexamethasone (DST) and basal growth hormone (GH) and prolactin levels were also examined. Depression, state or trait anxiety, anticipatory anxiety, agoraphobia, simple and social phobias, severity and frequency of panic attacks were monitored by rating scales. The immune study did not reveal any significant difference between patients and controls, or any effect of alprazolam therapy. The hormonal data for the two groups were similar, except for higher than normal basal ACTH and GH plasma levels, lower than normal ratios between the ACTH and cortisol responses to CRH, and blunted DST in some patients. All the impairments improved after alprazolam therapy, in parallel with decreases in anxiety and in severity and frequency of panic attacks.     

Bv8, the amphibian homologue of the mammalian prokineticins, induces a proinflammatory phenotype of mouse macrophages

1.--The small protein Bv8, isolated from the amphibian skin, belongs to a novel family of secreted proteins linked to several biological effects. We describe the expression of Bv8/prokineticins and their receptors in mouse macrophages, and characterize their proinflammatory activities. 2.--The rodent analogue of Bv8, prokineticin-2, is expressed by macrophages, as well as its G-protein-coupled receptor prokineticin receptor (PKR-1 and PKR-2). PKR-1 is expressed more abundantly. 3.-- Bv8 induces potent chemotaxis of macrophages at concentrations as low as 10(-12) M. 4.-- It stimulates lipopolysaccharide-induced production of the proinflammatory cytokines IL-1 and IL-12, reducing that of the anti-inflammatory cytokine IL-10. The effects are observed starting at the very low concentration of 10(-11) M. 5.--Effects on chemotaxis and cytokine are not pertussis-toxin sensitive, but are completely prevented by addition of the phospholipase inhibitor U73122, suggesting a G(q) protein is involved in the Bv8-induced effects. 6.--Studies in PKR-1 knockout mice indicate that all the activities exerted by Bv8 on macrophages are mediated by the PKR-1 receptor. 7.--In conclusion, Bv8 appears to be able to induce the macrophage to migrate and to acquire a proinflammatory phenotype.     

Randomized controlled trial: effect of nutritional counselling in general practice

OBJECTIVES: To investigate the effectiveness of a non-structured 15-min educational intervention by general practitioners (GPs) on modifications of daily diet among healthy adults. DESIGN: Two arms randomized trial lasting 12 months. SETTING: Italian general practitioner wards. Subjects A total of 3,186 men and women aged 18-65 years recruited in the medical ward by their GPs. INTERVENTIONS: An educational intervention and a brochure on the basics of a healthy diet based on the Italian Guidelines for a Correct Nutrition, 1998. The main study goal was to attain an intake of fruits and vegetables >5 servings per day. Follow-up visit every 6 months. Main outcome measures Weight, blood pressure, and a 40-items Food Frequency Questionnaire. RESULTS: The intervention group showed a slightly reduced net intake of meat and a slightly increased net intake of fruits and vegetables, fish products, and olive oil. Body mass index (BMI) changed only in the treatment arm [-0.41 95% confidence interval (95% CI) -0.11 to -0.53]. The net change at 1 year in the intervention arm was +1.31 (CI 0.90-4.39) for fruits and vegetables, and -0.22 (-0.11 to -0.69) for meat (portions per week). We also computed a 'healthy diet score' reflecting compliance with recommended dietary habits. In the intervention group, the mean score at recruitment was significantly lower than the mean score at the end of follow-up (Crude score change = 0.29; CI 0.19-0.48). No differences were observed in the control group (Crude score change = -0.04; CI -0.22-0.02). The difference in score from baseline to the final visit, comparing the intervention vs the control group, was statistically significant (P < 0.001) (MANOVA adjusted by sex, BMI, education, and time). CONCLUSIONS: A brief educational intervention by GPs can induce multiple diet changes that may lower BMI and potentially reduce chronic disease risk in generally healthy adults.     

Fish consumption and breast cancer risk. The European Prospective Investigation into Cancer and Nutrition (EPIC)

There is current interest in fish consumption and marine omega-3 (n-3) fatty acids and breast cancer risk. Some in vitro and animal studies have suggested an inhibitory effect of marine n-3 fatty acids on breast cancer growth, but the results from epidemiological studies that have examined the association between fish consumption and breast cancer risk in humans are inconsistent. We examined fish consumption and breast cancer risk in 310,671 women aged between 25 and 70 yr at recruitment into the European Prospective Investigation Into Cancer and Nutrition (EPIC). The participants completed a dietary questionnaire between 1992-98 and were followed up for incidence of breast cancer for a median of 6.4 yr. Hazard ratio for breast cancer by intake of total and lean and fatty fish were estimated, stratified by study centre and adjusted for established breast cancer risk factors. During follow-up, 4,776 invasive incident breast cancers were reported. No significant associations between intake of total fish and breast cancer risk were observed, hazard ratio (HR) 1.01 (95% confidence interval [CI] 0.99-1.02; p = 0.28 per 10 g fish/day). When examining lean and fatty fish separately, we found a positive significant association only in the highest quintile for fatty fish (HR 1.13, 95% CI 1.01-1.26), but test for trend was not significant (p = 0.10). No associations with breast cancer risk were observed when the study participants were subdivided by menopausal status. Although the period of follow-up is relatively short, the results provide no evidence for an association between fish intake and breast cancer risk.     

Serum C-peptide levels and breast cancer risk: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)

It has been hypothesized that chronic hyperinsulinemia, a major metabolic consequence of physical inactivity and excess weight, might increase breast cancer risk by direct effects on breast tissue or indirectly by increasing bioavailable levels of testosterone and estradiol. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we measured serum levels of C-peptide--a marker for pancreatic insulin secretion--in a total of 1,141 incident cases of breast cancer and 2,204 matched control subjects. Additional measurements were made of serum sex hormone binding globulin (SHBG) and sex steroids. Conditional logistic regression models were used to estimate breast cancer risk for different levels of C-peptide. C-peptide was inversely correlated with SHBG and hence directly correlated with free testosterone among both pre and postmenopausal women. C-peptide and free estradiol also correlated positively, but only among postmenopausal women. Elevated serum C-peptide levels were associated with a nonsignificant reduced risk of breast cancer diagnosed up to the age of 50 years [odds ratio (OR)=0.70, (95% confidence interval (CI), 0.39-1.24); ptrend=0.05]. By contrast, higher levels of C-peptide were associated with an increase of breast cancer risk among women above 60 years of age, however only among those women who had provided a blood sample under nonfasting conditions [OR=2.03, (95% CI, 1.20-3.43); ptrend=0.01]. Our results do not support the hypothesis that chronic hyperinsulinemia generally increases breast cancer risk, independently of age. Nevertheless, among older, postmenopausal women, hyperinsulinemia might contribute to increasing breast cancer risk.     

Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.     

Euthanasia of companion animals: a legal and ethical analysis

In Italy, the conditions under which euthanasia of small pets is justified are only partially regulated by law n. 281/1991, article 2 n. 6 and 9, by the later Ministry Circular n. 9 made on 10/03/1992 and by law n. 189/2004. Law n. 281/1991, besides delegating the job of birth control in cat and dog populations to the regions, has made it statutory that stray dogs may only be euthanised when they are 'seriously or incurably ill or proven to be dangerous'. The Ministry Circular underlines the fact that 'euthanasia of dogs is prohibited except in special justified cases'. On the other hand, due to the legal classification of animals as property, the owner has the right of ownership over his animal so that he can sell it and kill it (ius vitae ac necis). In this view a request for euthanasia is licit, whatever the animal's state of health may be. The authors feel that further legislation to regulate the question more completely would be opportune and thus they analyse the problems of legal-ethics and public health that a veterinarian faces when carrying out euthanasia, also bearing in mind the laws and codes of professional ethics. They suggest possible solutions which could be adopted by the competent authorities.