Individual differences in the effects of serotonergic anxiolytic drugs on the motivation to self-administer cocaine

Numerous clinical studies have indicated that lifetime anxiety is highly prevalent in drug addicts. In the treatment of drug abuse, dually diagnosed drug addicts may benefit from pharmacological intervention strategies that alleviate the psychiatric symptomatology. We have previously shown that rats with different coping strategies in a stressful environment show strong differences in the motivation to self-administer cocaine. That is, cocaine self-administration under a progressive ratio (PR) schedule of reinforcement was enhanced in high grooming (HG) rats as compared with low grooming (LG) rats. To identify the pharmacological basis of these differences, we tested the acute effects of several anxiolytic drugs on cocaine self-administration in HG and LG rats under a PR schedule of reinforcement. Chlordiazepoxide increased PR responding in both the HG and LG rats, while the selective corticotrophin releasing hormone 1 receptor antagonist R121919 had no effect on cocaine self-administration under the PR schedule. Interestingly, buspirone and fluoxetine decreased PR responding in HG rats only and thereby abolished the individual differences in PR responding between HG and LG rats. In support of the differential effects of the serotonergic drugs on PR responding in HG and LG rats, we found that the in vitro electrically evoked release of [3H]serotonin from mesocorticolimbic brain slices was reduced in the medial prefrontal cortex, substantia nigra and nucleus accumbens core, and increased in the nucleus accumbens shell of HG rats relative to LG rats. These findings show that serotonergic anxiolytics abolish the pre-existing individual differences in cocaine self-administration between HG and LG rats, which show differences in the reactivity of serotonergic neurons. This suggests that the effectiveness of pharmacological interference may depend on the neurochemical and motivational state of the individual.     

Localization of the HST/FGFK gene with regard to 11q13 chromosomal breakpoint and fragile site

The HST/FGFK gene, a member of the fibroblast growth factor gene family and a protooncogene, is localized on chromosomal band 11q13. Genes in this region are frequently involved in hematopoietic and solid tumors. Here we show that the HST gene lies telomeric to the BCL1 gene, the t(11;14)(q13;q32) breakpoint, and the FRA11A rare fragile site.     

Similarity of vegetative map and prophage map of bacteriophage Mu-1

The vegetative map of bacteriophage Mu was extended by the localization of three more amber mutations belonging to different complementation groups, and the position of the c gene on the vegetative map was approximately determined. The data confirm the previous finding that the vegetative map is linear (Wijffelman et al., 1972).Defective Mu lysogens were isolated from an Escherichia coli K12 strain, which has an insertion of Mu in the trp operon, by selecting for TonB colonies. All these defective lysogens were no longer immune to Mu infection, suggesting that the gene controlling immunity is located near to the end of the prophage proximal to tonB. By analyzing the remaining prophage genes in the defective lysogens, it was possible to determine the order of 16 amber mutations belonging to different complementation groups. The results show that the position of the genes on both the vegetative map and the prophage map is the same.The prophage map of Mu was determined by using the same method in another 9 independently isolated insertion mutants. In 7 of these mutants the gene order in the prophage is the same as found for the above-mentioned strain. The other two contain the prophage genes in the reversed order. All defective lysogens derived from these two insertion mutants by selection for TonB colonies were immune. The results show that Mu is integrated in a unique way and that both orientations may occur. The similarity between prophage map and vegetative map and the consequence for the mechanism of the integration process are discussed.     

Risk factors for asthma among children in Maputo (Mozambique)

BACKGROUND: Few studies have looked at risk factors for asthma in African children. We aimed to identify the risk factors associated with childhood asthma in Maputo (Mozambique). METHODS: This case-control study included 199 age-matched children (100 asthmatic and 99 nonasthmatic) who attended Maputo Central Hospital between January 1999 and July 2000. We collected information concerning their familial history of atopy, birth weight, environment and breast-feeding. Detailed information about morbidity and treatment was obtained for each asthmatic child. RESULTS: The children were aged between 18 months and 8 years; 60% were male. The asthmatic children were hospitalized more frequently than the nonasthmatic children (P < 0.0001). Most of the asthmatic children lived in the urban area of Maputo [odd ratio (OR) = 6.73, CI = 3.1-14.0, P < 0.0001], had a parental history of asthma (OR = 26.8, CI = 10.8-68.2, P < 0.0001) or rhinitis (OR = 4, CI = 1.2-13.3, P = 0.005), had at least parent who smoked and were weaned earlier than the nonasthmatic children (OR = 2.4, CI = 1.3-4.4, P < 0.001). CONCLUSION: Childhood asthma was strongly associated with a family history of asthma and rhinitis, the place of residence, having smokers as parents and early weaning from maternal breast milk. These results highlight the need to reassess the management of asthmatic children in Maputo.     

Effect of epitope density on the induction of the IgE immune response in mice

The effect of hapten density on benzylpenicilloyl (BPO)-protein conjugates upon the induction of BPO-specific IgE immune response was investigated in BALB/c and C3H mice. Bovine gamma-globulin (BGG) and ovalbumin (OA) were employed as carrier proteins. In both strains of mice, moderately substituted conjugates (BPO19-BGG, and BPO-OA with an epitope density from 2 to 7.5) elicited a persistent BPO-specific IgE, while heavily substituted conjugates (BPO38-BGG) induced only a transient response. In contrast, lightly substituted conjugates (BPO3.2-, BPO9.5-BGG, and BPO1-OA) failed to produce BPO-specific IgE antibodies. There was no significant difference in carrier-specific IgE immune response among these various conjugates. These results suggest that moderately substituted hapten-protein conjugates are one of the favorable conditions for eliciting hapten-specific IgE immune response in mice.     

Modulation of immune responses in mice by oral administration of niflumic acid

The in vivo effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the host immune system are still poorly understood. However, through inhibition of prostaglandin synthesis, NSAIDs may exhibit immunomodulating properties. The present work was aimed at evaluating the influence of niflumic acid on immune responses when administered orally for 7 consecutive days to 8-week-old inbred mice. Immunological tests were performed 24 h after the arrest of the treatment. At a dosage of 50 mg/kg/day, niflumic acid exerted noticeable immunostimulating effects, as shown by an increase in plaque-forming cell numbers after in vivo immunization with sheep red blood cells, an augmentation of spleen cell proliferation responses to stimulation with T- or B-cell mitogens and of T-cell cytotoxic response to allogenic cells. Phagocytosis-induced chemiluminescence of peritoneal macrophages was also enhanced whereas interleukin-1 production by these cells was depressed, but without concomitant modification in interleukin-2 production by T-cells. Increasing the niflumic acid dosage to 75 mg/kg resulted in the disappearance of the immunostimulatory effects on lymphocytes responses. Macrophage activities were affected similarly in mice receiving 50 mg/kg. These results demonstrate that niflumic acid is able to stimulate in vivo several immunological functions and, consequently, to maintain host immune defenses. Interestingly, it depressed interleukin-1 production, known to play a major role in the inflammatory process.     

Studies of the solubility of different calcium phosphate ceramic particles in vitro

In vitro solubility tests of hydroxyapatite, tetracalcium phosphate or tricalcium phosphate particles were performed in lactate, citrate, Gomoris or Michaelis buffer with pH 6.2 or 7.2 and in aqua destillata. The results showed that in general the solubility decreased in the order tetracalcium phosphate greater than tricalcium phosphate greater than hydroxyapatite, except for lactate or citrate buffer where the solubility order was tetracalcium phosphate = tricalcium phosphate greater than hydroxyapatite. The influence of the specific buffer used is much larger than either pH or specific calcium phosphate salt tested. The pH stability of lactate buffer and aqua destillata is very low, the other buffer solvents had a rather stable pH value.     

A crude extract of Artocarpus integrifolia contains two lectins with distinct biological activities.

The crude extract derived from seeds of Artocarpus integrifolia (jack fruit) contains two fractions with different biological activities for lymphocytes. One fraction is the D-galactose-binding lectin, jacalin, obtained by affinity purification on a D-galactose agarose column. The other, which is a component of the flow-through fraction (FT), is responsible for the mitogenic activity observed with human PBMC and murine spleen cells. In contrast, jacalin inhibits FT- and ConA-induced proliferative activity of human PMBC and murine spleen cells. This inhibition is not due to toxicity, because: (1) jacalin induces significant levels of IL-3/GM-CSF but not of IL-2 and/or IL-4 in murine spleen cells; (2) jacalin does not affect the capacity of these cells to secrete IL-2 or IL-4 as supernatants obtained from spleen cells sequentially stimulated with jacalin and ConA contain IL-2 and/or IL-4 as well as IL-3/GM-CSF. The ligand for the mitogen contained in the FT fraction is D-mannose as determined by sugar inhibition studies.     

A “Stopper” mutant of Neurospora crassa containing two populations of aberrant mitochondrial DNA

Summary [E35], an extranuclear mutant of Neurospora crassa has all the phenotypic characteristics of the stopper mutants (De Vries et al. 1980). In the present work, the mitochondrial DNA as well as the mitochondrial translation products are characterized further. The primary mutational event appears to have been the deletion of about 4 kbp from the wild-type genome. Moreover, after prolonged vegetative growth the mutant accumulates an 8-m circular mtDNA, which was demonstrated both by electronmicroscopy and by restriction enzyme analysis. Hence, the mutant contains two populations of aberrant mitochondrial DNA, the smaller of which is an amplification of the rRNA-tRNA part of the larger. We propose that the primary deletion has generated a signal in the larger DNA which can cause premature termination of replication at the deletion site, and subsequent circularization of the unfinished daughter molecule. Finally, the deleted part may contain a determinant for synthesis of a protein of 11 kDal. The function of this protein, which is not a subunit of the F₀ ATPase, is not yet known.Abbreviations (k)bp (kilo)basepairs - kDal kilodalton - mt mitochondrial