Multivariate Analysis of Dopaminergic Gene Variants as Risk Factors of Heroin Dependence

BACKGROUND: Heroin dependence is a debilitating psychiatric disorder with complex inheritance. Since the dopaminergic system has a key role in rewarding mechanism of the brain, which is directly or indirectly targeted by most drugs of abuse, we focus on the effects and interactions among dopaminergic gene variants. OBJECTIVE: To study the potential association between allelic variants of dopamine D2 receptor (DRD2), ANKK1 (ankyrin repeat and kinase domain containing 1), dopamine D4 receptor (DRD4), catechol-O-methyl transferase (COMT) and dopamine transporter (SLC6A3) genes and heroin dependence in Hungarian patients. METHODS: 303 heroin dependent subjects and 555 healthy controls were genotyped for 7 single nucleotide polymorphisms (SNPs) rs4680 of the COMT gene; rs1079597 and rs1800498 of the DRD2 gene; rs1800497 of the ANKK1 gene; rs1800955, rs936462 and rs747302 of the DRD4 gene. Four variable number of tandem repeats (VNTRs) were also genotyped: 120 bp duplication and 48 bp VNTR in exon 3 of DRD4 and 40 bp VNTR and intron 8 VNTR of SLC6A3. We also perform a multivariate analysis of associations using Bayesian networks in Bayesian multilevel analysis (BN-BMLA). FINDINGS AND CONCLUSIONS: In single marker analysis the TaqIA (rs1800497) and TaqIB (rs1079597) variants were associated with heroin dependence. Moreover, -521 C/T SNP (rs1800955) of the DRD4 gene showed nominal association with a possible protective effect of the C allele. After applying the Bonferroni correction TaqIB was still significant suggesting that the minor (A) allele of the TaqIB SNP is a risk component in the genetic background of heroin dependence. The findings of the additional multiple marker analysis are consistent with the results of the single marker analysis, but this method was able to reveal an indirect effect of a promoter polymorphism (rs936462) of the DRD4 gene and this effect is mediated through the -521 C/T (rs1800955) polymorphism in the promoter

The Role of Central Serotonin Neurons and 5-HT Heteroreceptor Complexes in the Pathophysiology of Depression : A Historical Perspective and Future Prospects

Serotonin communication operates mainly in the extracellular space and cerebrospinal fluid (CSF), using volume transmission with serotonin moving from source to target cells (neurons and astroglia) via energy gradients, leading to the diffusion and convection (flow) of serotonin. One emerging concept in depression is that disturbances in the integrative allosteric receptor-receptor interactions in highly vulnerable 5-HT1A heteroreceptor complexes can contribute to causing major depression and become novel targets for the treatment of major depression (MD) and anxiety. For instance, a disruption and/or dysfunction in the 5-HT1A-FGFR1 heteroreceptor complexes in the raphe-hippocampal serotonin neuron systems can contribute to the development of MD. It leads inter alia to reduced neuroplasticity and potential atrophy in the raphe-cortical and raphe-striatal 5-HT pathways and in all its forebrain networks. Reduced 5-HT1A auto-receptor function, increased plasticity and trophic activity in the midbrain raphe 5-HT neurons can develop via agonist activation of allosteric receptor-receptor interactions in the 5-HT1A-FGFR1 heterocomplex. Additionally, the inhibitory allosteric receptor-receptor interactions in the 5-HT1AR-5-HT2AR isoreceptor complex therefore likely have a significant role in modulating mood, involving a reduction of postjunctional 5-HT1AR protomer signaling in the forebrain upon activation of the 5-HT2AR protomer. In addition, oxytocin receptors (OXTRs) play a significant and impressive role in modulating social and cognitive related behaviors like bonding and attachment, reward and motivation. Pathological blunting of the OXTR protomers in 5-HT2AR and especially in 5-HT2CR heteroreceptor complexes can contribute to the development of depression and other types of psychiatric diseases involving disturbances in social behaviors. The 5-HTR heterocomplexes are novel targets for the treatment of MD

ARTICULO ORIGINAL COMPLETO/FULL ORIGINAL PAPER - IMMUNITY AND PROTECTION ELICITED BY A RECOMBINANT VACCINE AGAINST ENTEROTOXIGENIC E. coli.

We studied the effectiveness of a recombinant vaccine capable of protecting piglets from enterotoxigenic E. coli during lactation and after weaning. Following this purpose, we vaccinated some pregnant sows with the recombinant vaccine VACOLI^TM (Heber Biotec S.A, P.O.Box 6162, Havana, CUBA), composed of enterotoxigenic E. coli K88ab and K99 recombinant antigens, plus an oil adjuvant. Before weaning piglets were reimmunized to extend protection, and serum samples were tested by an enzyme-linked immunoassay in solid phase to determine the antibody levels against K88ab and K99. The control of E. coli infections was performed by plating stool samples in selective media. There were no death recorded in piglets from vaccinated sows by collibacillosis during lactation, while in piglets from the control sows mortality was of 21%. The morbility and the number of deaths by other causes in the vaccinated group were significantly lower than in the control group. Total protection achieved was 93%. After weaning, mortality caused by E. coli was 0.37% in the vaccinated group of piglets and 21.7% in the control group. The total protection in this period was 98%. RESUMEN Para estudiar la efectividad de una vacuna recombinante capaz de proteger a cerdos contra la E. coli enterotoxica durante la lactancia y despues del destete, se realizo la vacunacion de cerdas gestantes con la vacuna recombinante VACOLI^T

Tuberculose na cidade de Salvador, Bahia, Brasil: o perfil na década de 1990 Tuberculosis in Salvador, Bahia, Brazil, in the 1990s

Com o objetivo de caracterizar o perfil epidemiológico da tuberculose (incidência e mortalidade) no Município de Salvador, Bahia, Brasil, na década de 1990, foram analisadas as características demográficas, clínicas e laboratoriais dos casos e óbitos por esta doença ocorridos no período. Foram calculadas as taxas médias anuais de mortalidade e da incidência por sexo, faixa etária e formas clínicas da doença com base nas informações dos bancos de dados do Sistema de Informações de Tuberculose da Secretaria de Saúde do Estado da Bahia e do Sistema de Informações de Mortalidade do Ministério da Saúde. Analisou-se a distribuição espacial da tuberculose segundo distritos sanitários. Ficou evidente o predomínio dos casos e óbitos no sexo masculino e na faixa etária de 15 a 39 anos. A forma pulmonar apresentou uma maior taxa de incidência e de mortalidade. Sobre a hipótese de que, a co-infecção AIDS/tuberculose possa contribuir para manter elevadas taxas de mortalidade, os dados existentes não corroboram para esta associação. A maior ocorrência de tuberculose em determinados distritos sanitários pode estar associada à densidade populacional e às condições desfavoráveis de vida.<br>The characteristics of tuberculosis (TB) cases and deaths were analyzed in order to characterize the epidemiological profile of TB (incidence and mortality) in Salvador, Bahia, Brazil, in the 1990s. Annual incidence and mortality rates were calculated by gender, age bracket, and clinical forms of the disease using databases from the Tuberculosis Information System of the Bahia State Health Secretariat and the Mortality Information System of the Brazilian Ministry of Health. TB spatial distribution was analyzed according to health district. Cases and deaths were predominantly in males in the 15 to 39 year group. The pulmonary form showed the highest incidence and mortality. The existing data did not corroborate the hypothesis that AIDS/TB co-infection might contribute to maintaining the high mortality rates. The greater occurrence of tuberculosis in certain health districts may be associated with population density and unfavorable living conditions