Opiate induced feeding is not dependent on the hippocampus

It has been shown that spreading depression of the hippocampus can elicit feeding, and that several opioid peptides elicit spreading depression when injected into the hippocampus. To determine whether such depression is the primary mechanism by which opiates induce feeding, we tested the feeding effects of naloxone, an opiate antagonist, and butorphanol tartrate, a kappa-sigma agonist, on feeding in rats with and without hippocampal lesions. Naloxone tended to reduce intake approximately equally in the two groups. Similarly, the doses of butorphanol that increased intake in sham rats were equally effective in lesioned rats. It was concluded that the hippocampus is not the major structure mediating opiate-induced feeding.     

A modified Sindbis vector for prolonged gene expression in neurons

Sindbis viruses have been widely used in neurobiology to express a variety of genes in cultured neurons, in cultured slices, and in vivo. They provide fast onset and high levels of expression of foreign genes, but the expression is limited to a short time window due to a shut-off of host protein synthesis. We have used a mutation in an essential gene (nsP2) of the life cycle of Sindbis, which allows the functional analysis of changes in protein expression for >/=6 days after infection. This Sindbis mutant (nsP2) was used to express enhanced green fluorescent protein (EGFP) in hippocampal neurons in culture and in vivo without any sign of toxicity, based on two-photon imaging and electrophysiology. In addition, the EGFP mutant virus can be injected in vivo to visualize spines and other details of neuronal structure. The Sindbis mutant described here provides an improved tool in neurobiology with reduced cytotoxicity and a prolonged time window of expression for novel applications in imaging and behavior. In addition, the use of this vector for the functional expression of mammalian voltage-gated ion channels in organotypic slices is demonstrated.     

Aspirin downregulates homocysteine formation in stimulated human peripheral blood mononuclear cells

Moderate hyperhomocysteinaemia is established as an independent risk factor for atherosclerosis, thrombosis, stroke and dementia. Hyperhomocysteinaemia is mostly caused by the deficiency of B-vitamins folate and vitamin B12, which are essential cofactors in the remethylation of homocysteine to methionine. Interestingly, moderate hyperhomocysteinaemia is also often observed in chronic diseases, in which also elevated immune activation markers such as neopterin or sTNFR-II are found. In order to simulate immune activation in vitro, human peripheral blood mononuclear cells (PBMC) were stimulated with mitogens. Stimulation significantly increased homocysteine production in comparison with unstimulated PBMC; in parallel also neopterin formation was induced. Homocysteine formation was due to cell proliferation, proliferating T lymphocytes, and also the myelomonocytic cell line U-937 produced homocysteine. Treatment with the anti-inflammatory drug aspirin dose-dependently inhibited homocysteine production and also neopterin formation in human PBMC. Treatment with salicylic acid showed similar effects as aspirin; FACS analysis showed that both compounds inhibited cell proliferation by arresting cells in the G0/G1-phase. In U-937, both compounds also slightly induced apoptosis at 5 mm. Proliferation-induced homocysteine formation and in parallel also monocyte activation can be suppressed effectively by aspirin and salicylic acid in vitro, suggesting that also in vivo aspirin may downregulate not only inflammation but also formation of homocysteine.     

Academic underachievement and the disruptive behavior disorders

Academic underachievement (AU) was studied among 177 clinic-referred boys reliably diagnosed as having attention-deficit hyperactivity disorder (ADHD) or conduct disorder (CD). Unlike previous studies, the present study assessed AU using a formula that determined the discrepancy between a child's predicted level of achievement and actual level of achievement while controlling for regression and age effects. AU was associated with both ADHD and CD when the disorders were examined individually. However, when examined in multivariate logit model analyses, the apparent relation between CD and AU was found to be due to its comorbidity with ADHD. When boys with ADHD were divided into those with attention deficits only and those with co-occurring hyperactivity, findings did not support the hypothesis that the association with AU is stronger for attention deficits without co-occurring hyperactivity.     

Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease

In a randomized, double-blind five-year trial, we tested the efficacy of simultaneously elevating serum levels of high-density lipoprotein (HDL) cholesterol and lowering levels of non-HDL cholesterol with gemfibrozil in reducing the risk of coronary heart disease in 4081 asymptomatic middle-aged men (40 to 55 years of age) with primary dyslipidemia (non-HDL cholesterol greater than or equal to 200 mg per deciliter [5.2 mmol per liter] in two consecutive pretreatment measurements). One group (2051 men) received 600 mg of gemfibrozil twice daily, and the other (2030 men) received placebo. Gemfibrozil caused a marked increase in HDL cholesterol and persistent reductions in serum levels of total, low-density lipoprotein (LDL), and non-HDL cholesterol and triglycerides. There were minimal changes in serum lipid levels in the placebo group. The cumulative rate of cardiac end points at five years was 27.3 per 1,000 in the gemfibrozil group and 41.4 per 1,000 in the placebo group--a reduction of 34.0 percent in the incidence of coronary heart disease (95 percent confidence interval, 8.2 to 52.6; P less than 0.02; two-tailed test). The decline in incidence in the gemfibrozil group became evident in the second year and continued throughout the study. There was no difference between the groups in the total death rate, nor did the treatment influence the cancer rates. The results are in accord with two previous trials with different pharmacologic agents and indicate that modification of lipoprotein levels with gemfibrozil reduces the incidence of coronary heart disease in men with dyslipidemia.     

Anti-IgE and Con A-induced histamine release from mast cells of four rat strains: Correlation with total serum IgE

Anti-IgE- and Con A-induced histamine release from serosal mast cells were compared to each other and to total serum levels of IgE in non-immunized, alum-injected, and Silica gel-injected rats of the BN, Fischer, PVG, and SD strains. The results indicate that the degree of anti-IgE-and Con A-induced release is strain-dependent and varies with immunization conditions. Furthermore, there is a gross but not complete correlation between the degree of serosal mast cell histamine release induced by the two secretagogues. However, Con A- or anti-IgE-induced release could significantly be correlated to serum levels of total IgE only in the Fischer strain but not in the BN or the PVG strains. In the SD strain, Con A-induced release correlated to serum IgE levels in Silica gel-injected but not in alum-injected animals.Subsidiary of AB Astra, Sweden.     

Development of allergy in children. I. Association with virus infections.

Children born into allergic families, with two allergic parents, are at high risk of developing allergy within the first 5 years of life. In order to observe possible external factors in the sensitization process, a prospective study of 13 such children was done, in which serial clinical and immunologic observations were made at 3- to 6-month intervals over a period of 1 to 4 yr. Eleven of these children are now clinically allergic; 5 have asthma. Immunologic evidence for allergic sensitization was observed in these 11 children by RAST, antigen-induced leukocyte histamine release, lymphoblastogenesis, and rise in serum IgE. Upper respiratory infections (URI) occurred in these 11 allergic children 1 to 2 months prior to the onset of allergic sensitization. In 10 of these 11 URI children, complement-fixing antibodies to viruses (parainfluenza, RSV, CMV) increased in the same blood samples in which immunologic allergic sensitization was first evidenced. This coincidence suggests that certain viruses may contribute to the allergic sensitization process.     

Association of dopamine D3-receptor gene variants with neuroleptic induced akathisia in schizophrenic patients: a generalization of Steen's study on DRD3 and tardive dyskinesia

Neuroleptic induced akathisia is a common and distressful extrapyramidal side effect of antipsychotic treatment. A significant proportion of the variability of its development has been left unexplained and has to be attributed to individual susceptibility. Since hereditary factors have been discussed in the etiology of acute akathisia (AA), part of the individual susceptibility might be of genetic origin. Moreover, AA is regarded as a forerunner of tardive dyskinesia, a drug-induced chronic movement disorder, which may be associated with homozygosity for the Ser9Gly variant of the DRD3 gene. Considering expression studies, which demonstrated functional variants of DRD3 polymorphisms, we investigated whether homozygosity for the Ser9Gly variant of the DRD3 gene is associated with AA. Homozygosity for the Ser9Gly variant of the DRD3 gene was connected to an 88% incidence of AA as compared with a considerably lower 46.9% incidence of AA in schizophrenic patients nonhomozygous for the 2-2 allele (exact P = 0.0223). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:187-191, 2000.