Effect of cocaine on periadolescent rats with or without early maternal separation

Cocaine-induced behavioral sensitization and weight loss were investigated in periadolescent Wistar rats kept with their mothers or subjected to repeated maternal separation. Litters allocated to the separation procedure were placed in a temperature-controlled (33ºC) chamber for 3 h per day from postnatal day 6 (P6) to P20. Non-handled rats were left undisturbed until weaning. Treatments were started on P30-31 and the test was performed on P36-37. Animals received injections of saline or cocaine (10 mg/kg, sc) twice daily for 5 days. On day 6 all animals received saline. On day 7 animals were challenged with 10 mg/kg cocaine and their locomotion was evaluated in activity cages. A third group received saline throughout the 7-day period. Body weights were recorded on P30-31 and P36-37. Two-way ANOVA on body weights showed a main effect of treatment group (F(1,35) = 10.446, P = 0.003; N = 10-12). Non-handled rats treated with cocaine for 5 days gained significantly less weight, while no significant effect was observed in maternally separated rats. Two-way ANOVA revealed a main effect of drug treatment on locomotor activity (F(2,32) = 15.209, P<0.001; N = 6-8), but not on rearing condition (F(1,32)<0.001, P = 0.998). Animals pretreated with cocaine showed a clear behavioral sensitization relative to the saline group. No difference in the magnitude of sensitization was found between separated and non-handled animals. Only the effect of cocaine on weight gain was significantly affected by repeated episodes of early maternal separation during the pre-weaning period.

Clinical features of panic patients sensitive to hyperventilation or breath-holding methods for inducing panic attacks

Our aim was to compare the clinical features of panic disorder (PD) patients sensitive to hyperventilation or breath-holding methods of inducing panic attacks. Eighty-five PD patients were submitted to both a hyperventilation challenge test and a breath-holding test. They were asked to hyperventilate (30 breaths/min) for 4 min and a week later to hold their breath for as long as possible, four times with a 2-min interval. Anxiety scales were applied before and after the tests. We selected the patients who responded with a panic attack to just one of the tests, i.e., those who had a panic attack after hyperventilating (HPA, N = 24, 16 females, 8 males, mean age ± SD = 38.5 ± 12.7 years) and those who had a panic attack after breath holding (BHPA, N = 20, 11 females, 9 males, mean age ± SD = 42.1 ± 10.6 years). Both groups had similar (chi² = 1.28, d.f. = 1, P = 0.672) respiratory symptoms (fear of dying, chest/pain disconfort, shortness of breath, paresthesias, and feelings of choking) during a panic attack. The criteria of Briggs et al. [British Journal of Psychiatry, 1993; 163: 201-209] for respiratory PD subtype were fulfilled by 18 (75.0%) HPA patients and by 14 (70.0%) BHPA patients. The HPA group had a later onset of the disease compared to BHPA patients (37.9 ± 11.0 vs 21.3 ± 12.9 years old, Mann-Whitney, P < 0.001), and had a higher family prevalence of PD (70.8 vs 25.0%, chi² = 19.65, d.f. = 1, P = 0.041). Our data suggest that these two groups - HPA and BHPA patients - may be specific subtypes of PD.

Control of the rat angiotensin I converting enzyme gene by CRE-like sequences

We characterized the role of potential cAMP-responsive elements (CRE) in basal and in induced angiotensin converting enzyme (ACE) gene promoter activity in order to shed light on the regulation of somatic ACE expression. We identified stimulators and repressors of basal expression between 122 and 288 bp and between 415 and 1303 bp upstream from the transcription start site, respectively, using a rabbit endothelial cell (REC) line. These regions also contained elements associated with the response to 8BrcAMP. When screening for CRE motifs we found pCRE, a proximal sequence between 209 and 222 bp. dCRE, a distal tandem of two CRE-like sequences conserved between rats, mice and humans, was detected between 834 and 846 bp. Gel retardation analysis of nuclear extracts of REC indicated that pCRE and dCRE bind to the same protein complexes as bound by a canonical CRE. Mutation of pCRE and dCRE in REC established the former as a positive element and the latter as a negative element. In 293 cells, a renal cell line, pCRE and dCRE are negative regulators. Co-transfection of ATF-2 or ATF-2 plus c-Jun repressed ACE promoter activity, suggesting that the ACE gene is controlled by cellular stress. Although mapping of cAMP responsiveness was consistent with roles for pCRE and dCRE, mutation analysis indicated that they were not required for cAMP responsiveness. We conclude that the basal activity of the somatic ACE promoter is controlled by proximal and distal CREs that can act as enhancers or repressors depending on the cell context.

Influence of the polymorphisms of the α-major regulatory element HS-40 on in vitro gene expression

The α-MRE is the major regulatory element responsible for the expression of human α-like globin genes. It is genetically polymorphic, and six different haplotypes, named A to F, have been identified in some population groups from Europe, Africa and Asia and in native Indians from two Brazilian Indian tribes. Most of the mutations that constitute the α-MRE haplotypes are located in flanking sequences of binding sites for nuclear factors. To our knowledge, there are no experimental studies evaluating whether such variability may influence the α-MRE enhancer activity. We analyzed and compared the expression of luciferase of nine constructs containing different α-MRE elements as enhancers. Genomic DNA samples from controls with A (wild-type α-MRE) and B haplotypes were used to generate C-F haplotypes by site-directed mutagenesis. In addition, three other elements containing only the G→A polymorphism at positions +130, +199, and +209, separately, were also tested. The different α-MRE elements were amplified and cloned into a plasmid containing the luciferase reporter gene and the SV40 promoter and used to transiently transfect K562 cells. A noticeable reduction in luciferase expression was observed with all constructs compared with the A haplotype. The greatest reductions occurred with the F haplotype (+96, C→A) and the isolated polymorphism +209, both located near the SP1 protein-binding sites believed not to be active in vivo. These are the first analyses of α-MRE polymorphisms on gene expression and demonstrate that these single nucleotide polymorphisms, although outside the binding sites for nuclear factors, are able to influence in vitro gene expression.

Impairment of locomotor activity induced by the novelN-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in mice

The N-acylhydrazone (NAH) analogues N-methyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-785) and N-benzyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-786) were prepared from 2-thienylidene 3,4-methylenedioxybenzoylhydrazine (LASSBio-294). The ability of LASSBio-785 and LASSBio-786 to decrease central nervous system activity was investigated in male Swiss mice. LASSBio-785 or LASSBio-786 (30 mg/kg, ip) reduced locomotor activity from 209 ± 26 (control) to 140 ± 18 (P < 0.05) or 146 ± 15 crossings/min (P < 0.05), respectively. LASSBio-785 (15 or 30 mg/kg, iv) also reduced locomotor activity from 200 ± 15 to 116 ± 29 (P < 0.05) or 60 ± 16 crossings/min (P < 0.01), respectively. Likewise, LASSBio-786 (15 or 30 mg/kg, iv) reduced locomotor activity from 200 ± 15 to 127 ± 10 (P < 0.01) or 96 ± 14 crossings/min (P < 0.01), respectively. Pretreatment with flumazenil (20 mg/kg,ip) prevented the locomotor impairment induced by NAH analogues (15 mg/kg, iv), providing evidence that the benzodiazepine (BDZ) receptor is involved. This finding was supported by the structural similarity of NAH analogues to midazolam. However, LASSBio-785 showed weak binding to the BDZ receptor. LASSBio-785 or LASSBio-786 (30 mg/kg,ip, n = 10) increased pentobarbital-induced sleeping time from 42 ± 5 (DMSO) to 66 ± 6 (P < 0.05) or 75 ± 4 min (P < 0.05), respectively. The dose required to achieve 50% hypnosis (HD50) following iv injection of LASSBio-785 or LASSBio-786 was 15.8 or 9.5 mg/kg, respectively. These data suggest that both NAH analogues might be useful for the development of new neuroactive drugs for the treatment of insomnia or for use in conjunction with general anesthesia.

Organofosforados e carbamatos no leite produzido em quatro regiões leiteiras no Brasil: ocorrência e ação sobre Listeria monocytogenes e Salmonella spp.

Organofosforados e carbamatos são compostos utilizados no controle de parasitas em animais e podem gerar resíduos nos produtos alimentícios derivados, representando um risco para o consumidor. O presente estudo objetivou pesquisar a presença de resíduos de organofosforados e carbamatos em leite cru produzido em quatro regiões leiteiras no Brasil e verificar se a presença desses compostos teria alguma relação com a ausência de Listeria monocytogenes e Salmonella spp., anteriormente observada nessas amostras. Entre 209 amostras analisadas, a presença de ao menos um desses compostos foi detectada em 196 (93,8%). Para a avaliação da sua interferência na detecção de L. monocytogenes e Salmonella spp., 28 amostras de leite positivas e negativas para esses compostos foram submetidas à fervura por 10 minutos e adicionadas desses patógenos, monitorando-se sua multiplicação durante armazenamento a 4 °C e a 25 °C. Não houve diferença significativa (p < 0,05) entre as taxas médias de multiplicação de L. monocytogenes e Salmonella spp. nas amostras de leite com diferentes resultados para resíduos de organofosforados ou carbamatos, indicando que esses patógenos não foram afetados pela presença desses resíduos. Entretanto, a alta freqüência de amostras de leite cru positivas para esses compostos é preocupante devido ao grande risco que representam para os consumidores, mesmo após o beneficiamento por tratamento térmico.

O controle de pragas urbanas na qualidade do alimento sob a visão da legislação federal

A qualidade do alimento oferecido à população sempre foi uma preocupação do governo federal, observada com a publicação, em 27 de fevereiro de 1967, do Decreto Lei 209 que institui o Código Brasileiro de Alimentos. A Portaria 1.428 de 26 de novembro de 1993/ANVISA inova na relação dos fatores contribuintes para a contaminação alimentar, apresentando, nas diretrizes para o estabelecimento de boas práticas de produção e de prestação de serviços na área de alimentos, a desinfestação que compreende o plano de sanitização utilizado pelo estabelecimento. A partir deste momento cria-se uma nova visão dos fatores determinantes de contaminação alimentar, o controle de ratos e insetos. Este procedimento passa a integrar todos os documentos legais que foram sendo gerados pelo Ministério da Saúde e da Agricultura no que se refere ao controle de alimentos. Até a publicação da RDC 275/2002-ANVISA, o controle de pragas urbanas poderia ser feito por equipes treinadas dos estabelecimentos que realizassem: produção/industrialização, fracionamento, armazenamento e transportes de alimentos industrializados, manipulação, preparação, fracionamento, armazenamento, distribuição, transporte, exposição à venda e entrega de alimentos preparados ao consumo, tais como cantinas, bufês, confeitarias, cozinhas industriais, cozinhas institucionais, delicatéssens, lanchonetes, padarias, pastelarias, restaurantes, e congêneres. A partir de sua publicação, o controle químico passa a ser realizado apenas pelas desinsetizadoras que estejam em conformidade com a RDC 18/2000-ANVISA. Entretanto isto não tira a responsabilidade legal da empresa de alimentos que deverá ter em seu POP (Procedimento Operacional Padronizado) a inclusão do controle de pragas, seja físico e/ou químico.

Avaliação de influências sociais e econômicas sobre a pressão arterial de adolescentes de escolas públicas e privadas: um estudo epidemiológico

INTRODUÇÃO: Anteriormente, a alta prevalência de hipertensão arterial em alunos do Ensino Médio de Sorocaba, em São Paulo, foi descrita. Neste estudo, em nova amostra de alunos da mesma faixa etária, oriundos de escolas públicas e privadas, foi avaliado se as diferenças socioeconômicas e o modo de vida podem influenciar os valores da pressão arterial. MÉTODOS: Trata-se de um estudo epidemiológico, inserido entre as atividades de um trabalho comunitário, em que estudantes de Medicina fazem palestras para alunos do Ensino Médio, objetivando estimular hábitos de vida saudáveis e a prevenção primária da hipertensão arterial. Em amostra aleatória de 410 alunos do segundo ano do Ensino Médio (209 de escolas públicas e 201 de escolas privadas), foram determinados o peso, a altura e a pressão arterial, e foi aplicado um questionário epidemiológico e socioeconômico. RESULTADOS: Não há diferenças estatísticas entre os alunos das escolas públicas e privadas quanto à distribuição de sexo, ao índice de massa corporal (IMC), à pressão arterial sistólica e diastólica, à prevalência de hipertensão arterial (16,3%), à porcentagem de fumantes (5,9%), à atividade física regular e aos antecedentes familiares de hipertensão arterial. Nas escolas públicas há maior porcentagem de afro-descendentes, os alunos trabalham fora de casa com maior frequência e têm menor renda familiar. Nas escolas públicas e privadas, os homens têm maior prevalência de hipertensão arterial e a média da pressão arterial é maior que nas mulheres. O IMC tem correlação positiva com a pressão arterial sistólica e diastólica. CONCLUSÕES: A hipertensão arterial e outros fatores de risco cardiovasculares têm início precoce e necessitam de intervenções educativas para a prevenção primária. Fatores socioeconômicos não influenciam a pressão arterial na adolescência.

Impact of social vulnerability on the outcomes of predialysis chronic kidney disease patients in an interdisciplinary center

Introduction: Numerous studies examined the associations between socio-demographic, economic and individual factors and chronic kidney disease (CKD) outcomes and observed that the associations were complex and multifactorial. Socioeconomic factors can be evaluated by a model of social vulnerability (SV). Objective: To analyze the impact of SV on the outcomes of predialysis patients. Methods: Demographic, clinical and laboratory data were collected from a cohort of patients with predialysis stage 3 to 5 who were treated by an interdisciplinary team (January 2002 and December 2009) in Minas Gerais, Brazil. Factor, cluster and discriminant analysis were performed in sequence to identify the most important variables and develop a model of SV that allowed for classification of the patients as vulnerable or non-vulnerable. Cox regression was performed to examine the impact of SV on the outcomes of mortality and need for renal replacement therapy (RRT). Results: Of the 209 patients examined, 29.4% were classified as vulnerable. No significance difference was found between the vulnerable and non-vulnerable groups regarding either mortality (log rank: 0.23) or need for RRT (log rank: 0.17). In the Cox regression model, the hazard ratios (HRs) for the unadjusted and adjusted impact of SV on mortality were found to be 1.87 (confidence interval [CI]: 0.64-5.41) and 1.47 (CI: 0.35-6.0), respectively, and the unadjusted and adjusted impact of need for RRT to be 1.85 (CI: 0.71-4.8) and 2.19 (CI: 0.50-9.6), respectively. Conclusion: These findings indicate that SV did not influence the outcomes of patients with predialysis CKD treated in an interdisciplinary center.