Leukocyte entry into the CNS of Leishmania chagasi naturally infected dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Maternal undernutrition and the offspring kidney: from fetal to adult life

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage

Background: Vaccination of neonates is generally difficult due to the immaturity of the immune system and consequent higher susceptibility to tolerance induction. Genetic immunization has been described as an alternative to trigger a stronger immune response in neonates, including significant Th1 polarization. In this investigation we analysed the potential use of a genetic vaccine containing the heat shock protein (hsp65) from Mycobacterium leprae (pVAXhsp65) against tuberculosis (TB) in neonate mice. Aspects as antigen production, genomic integration and immunogenicity were evaluated. Methods: Hsp65 message and genomic integration were evaluated by RT-PCR and Southern blot, respectively. Immunogenicity of pVAXhsp65 alone or combined with BCG was analysed by specific induction of antibodies and cytokines, both quantified by ELISA. Results: This DNA vaccine was transcribed by muscular cells of neonate mice without integration into the cellular genome. Even though this vaccine was not strongly immunogenic when entirely administered (three doses) during early animal's life, it was not tolerogenic. In addition, pVAXhsp65 and BCG were equally able to prime newborn mice for a strong and mixed immune response (Th1 + Th2) to pVAXhsp65 boosters administered later, at the adult life. Conclusion: These results suggest that pVAXhsp65 can be safely used as a priming stimulus in neonate animals in prime-boost similar strategies to control TB. However, priming with BCG or pVAXhsp65, directed the ensuing immune response triggered by an heterologous or homologous booster, to a mixed Th1/Th2 pattern of response. Measures as introduction of IL-12 or GM-CSF genes in the vaccine construct or even IL-4 neutralization, are probably required to increase the priming towards Th1 polarization to ensure control of tuberculosis infection. © 2007 Pelizon et al; licensee BioMed Central Ltd.

Drug addictions and sexual violence in childhood and adolescence: analyzing life stories

The sexual abuse suffered in childhood and adolescence, in addition to damage to physical and psychological health of the victim, is considered as an important risk factor for alcohol and drugs addiction, development of psychopathology and psychosocial damage in adulthood. In addition to the pain and humiliation that are submitted by the abuse, children and adolescents also experience shame and guilt which require them to adopt coping strategies to endure those feelings. The use of psychoactive substances is a recognized way of dealing with the pains of living. This work, which is of narrative style, analyses and discusses, through five case reports, chemical dependency as a result of sexual abuse suffered in childhood and/or adolescence. The eight subjects in this study are male and have suffered sexual violence in this age period of life. Their ages range from 23 years to 39 years, and all are admitted to a therapeutic community in a city in the interior of Sao Paulo state, in Brazil, for treatment of chemical dependency, being met by the Department of Psychology. The reasons for the choice of the participants for treatment modality for patients are: difficult to stop using drugs, even unwilling to take it, they have easy access to it; the feeling of losing control over their lives; by successive losses as a result of drug use, and for fear that their lives had a tragic ending. With the exception of two participants, the others do not classify that as a child suffered sexual violence. However, all attribute that facilitated their entry into the world of drugs. Seven participants experienced such violence in childhood (between 7 years and 9 years) and adolescence (age 14). The attackers were people closed to the victims—in the case of two victims, their families, with the exception of one participant who was raped by a stranger. Six participants declared themselves as homosexual. Another participant does not claim to be homosexual, but presents difficulties in terms of sexuality. Two participants are HIV positive. The start of psychoactive substances use occurred during adolescence (12 years to 17 years). The participants see drugs as an anesthetic to the pain of the soul, a way to get pleasure, but they get charged expensively, as it increases the feeling of emptiness, guilt, helplessness, worthlessness and hopelessness. Although participants have sought help to deal with addiction, it is noted that throughout the life course the issue of sexual violence was not treated. It was noted that the patients have a double stigma in society: the issue of drugs addiction and the orientation of sexual desire, because the majority of participants are homosexual. The results reinforce the need for effective action geared to accommodate the victims of sexual violence and effective preventive measures to prevent children and adolescents from being abused.

Repercussions of mild diabetes on pregnancy in Wistar rats and on the fetal development

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Neonatally-induced diabetes: lipid profile outcomes and oxidative stress status in adult rats

INTRODUÇÃO: Modelos experimentais são desenvolvidos com propósito de ampliar o entendimento dos mecanismos fisiopatológicos envolvidos no diabete. Os achados experimentais levam ao desenvolvimento de tratamentos alternativos para a manutenção das condições metabólicas normais. Existem vários estudos sobre o diabete induzido por streptozotocin mimetizando o quadro clínico do DM2. No entanto, a interação entre os níveis de glicose, perfil lipídico e estresse oxidativo nestes animais são escassos. Portanto, o objetivo do trabalho foi avaliar estes parâmetros em ratas Wistar adultas com diabete induzido com streptozotocin no período neonatal. MÉTODOS: Fêmeas recém-nascidas receberam streptozotocin (70mg/Kg, ip) no 5º dia de vida (n5-STZ). A glicemia foi medida no terceiro e quarto meses de vida dos animais. No final do quarto mês de vida, amostras de sangue foram coletadas e processadas para a dosagem de lipídios e marcadores de estresse oxidativo. RESULTADOS: A glicemia das ratas do grupo n5-STZ foi significativamente maior comparada às ratas do grupo controle (p<0,05). Não houve alteração nos níveis de colesterol total e triglicérides, peroxidação lipídica (TBARS), atividade da SOD e determinação da GSH-t (p>0,05) nas ratas n5-STZ em relação às ratas do grupo controle. No entanto, houve diminuição significativa no HDL-colesterol (p<0,05). CONCLUSÃO: Este modelo de indução de diabete em ratas causou hiperglicemia (120-360mg/dL), caracterizando o diabete moderado. Essa glicemia levou a alterações no HDL-colesterol, a qual não foi suficiente para prejudicar a atividade das enzimas antioxidantes ou marcadores da peroxidação lipídica na vida adulta. Além disso, esta investigação experimental contribuiu para entender os diferentes resultados encontrados em outros modelos deindução do diabete moderado em animais de laboratório, como também para a melhor compreensão dos mecanismos fisiopatológicos do diabete moderado ou da hiperglicemia em humanos.

Inhibition of 5-alpha-reductase activity induces stromal remodeling and smooth muscle de-differentiation in adult gerbil ventral prostate

Prostatic differentiation during embryogenesis and its further homeostatic state maintenance during adult life depend on androgens. Dihydrotestosterone, which is synthesized from testosterone by 5alpha-reductase (5alpha-r), is the active molecule triggering androgen action within the prostate. In the present work, we examined the effects of 5alpha-reductase inhibition by finasteride in the ventral prostate (VP) of the adult gerbil, employing histochemical and electron microscopy techniques to demonstrate the morphological and organizational changes of the organ. After 10 days of finasteride treatment at a dose of 100 mg/kg/day, the prostatic complex (VP and dorsolateral prostate) absolute weight was reduced to about 18%. The epithelial cells became short and cuboidal, with less secretory blebs and reduced acid phosphatase activity. The luminal sectional area diminished, suggestive of decreased secretory activity. The stromal/epithelial ratio increased, the stroma becoming thicker but less cellular. There was a striking accumulation of collagen fibrils, which was accompanied by an increase in deposits of amorphous granular material adjacent to the basal lamina and in the clefts between smooth muscle cells (SMC). Additionally, the periacinar smooth muscle became loosely packed. Some SMC were atrophic and showed a denser array of the cytoskeleton, whereas other SMC had a highly irregular outline with numerous spine-like projections. The present data indicate that 5alpha-r inhibition causes epithelial and stromal changes by affecting intra-prostatic hormone levels. These alterations are probably the result of an imbalance of the homeostatic interaction between the epithelium and the underlying stroma.

A New and Fast Technique to Generate Offspring after Germ Cells Transplantation in Adult Fish: The Nile Tilapia (Oreochromis niloticus) Model

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Influence of δβ-thalassemia or regulatory elements in individuals with increased fetal Hb levels in the São Paulo northwest population

Fetal hemoglobin (Hb F), formed by two alpha globin chains (α) and two gamma chains (γ) (α2 γ2), has reduced expression in adults, ranging from 0 to 1% of total hemoglobin. Increased levels of Hb F are due to mutations in the β-globin family, which cause hereditary persistence of fetal hemoglobin (HPFH) and delta-beta thalassemia (δβ-thalassemia).The control of the production takes place by the regulatory region and regions outside the β-globin family, among them 2q16, 6q23, 8q, and Xp22.2.The aims of this study were to determine the presence and frequency of two mutations for δβ-thalassemia, the XmnI polymorphism and β-globin haplotypes in healthy individuals with increased Hb F in the State of São Paulo. We analyzed 60 samples of peripheral blood of healthy adults, without complaints of anemia. The samples were separated into two groups according to Hb F level: group I - 34 samples with Hb F ranging from 2 to 15% and group II - 26 samples with Hb F over 15%. In relation to the polymorphisms examined, we found three heterozygous individuals (5%) for Spanish δβ-thalassemia, belonging to group I, whose Hb F levels were within the normal range.The Sicilian δβ-thalassemia mutation was not found, indicating the need to study other polymorphisms related to the increase of Hb F in adult life.The frequency of XmnI polymorphism was 33.3% and the mean Hb F levels were 15.48 ± 11.69%.The frequency observed in our study for this polymorphic site is higher than that found in the literature for healthy subjects.This polymorphism was more prevalent in individuals with Hb F levels below 15%. For four samples positive for this polymorphism, the Hb F levels were explained by the presence of HPFH and Spanish δβ-thalassemia mutations, so that the presence of the XmnI polymorphic site was not a determinant in the overexpression of γ-globin genes. Regarding β-globin haplotypes, 18 alleles and 27 distinct genotypic patterns were found.The pattern Atp1/Atp2 was the mostfrequent genotype (13.72%).Of the 18 alleles, 13 showed atypical patterns.The results show that the haplotype V was the most frequent (27.45%), followed by atypical Atp2 (13.72%) and Atp1 (11.76%), and that there was a higher correlation with the presence of HPFH and XmnI polymorphism.The high frequency of haplotype V in our samples and high frequency of atypical haplotypes may reflect a high rate of miscegenation in this population, suggesting an ethnic characteristic for the Brazilian population, requiring the evaluation of population genetic markers to corroborate this hypothesis. © FUNPEC-RP.

Implications of intrauterine protein malnutrition on prostate growth, maturation and aging

Aims Maternal malnutrition by low protein diet is associated with an increased incidence of metabolic disorders and decreased male fertility in adult life. This study aimed to assess the impact of maternal protein malnutrition (MPM) on prostate growth, tissue organization and lesion incidence with aging. Main methods Wistar rat dams were distributed into two groups, which were control (NP; fed a normal diet containing 17% protein) or a restricted protein diet (RP, fed a diet containing 6% protein) during gestation. After delivery all mothers and offspring received a normal diet. Biometrical parameters, hormonal levels and prostates were harvested at post-natal days (PND) 30, 120 and 360. Key findings MPM promoted low birth weight, decreased ano-genital distance (AGD) and reduced androgen plasma levels of male pups. Prostatic lobes from RP groups presented reduced glandular weight, epithelial cell height and alveolar diameter. The epithelial cell proliferation and collagen deposition were increased in RP group. Incidences of epithelial dysplasia and prostatitis were higher in the RP offspring than in the NP offspring at PND360. Significance Our findings show that MPM delays prostate development, growth and maturation until adulthood, probably as a result of low testosterone stimuli. The higher incidence of cellular dysplasia and prostatitis suggests that MPM increases prostate susceptibility to diseases with aging. © 2013 Elsevier Inc.

Influência da δβ-Talassemia ou de elementos de regulação em indivíduos com hemoglobina fetal aumentada na população da região Noroeste do Estado de São Paulo

Pós-graduação em Genética - IBILCE

Influência do meio hiperglicêmico intrauterino em diferentes fases de vida dos descendentes de ratas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Livros de autoajuda adaptados ao público infantojuvenil: estratégias linguístico-discursivas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A civilização no meio rural: o livro de leitura como instrumento modernizador

In search of Brazil's entry into modernity, educators pledged to develop mechanisms for the construction of the brazilian man, and modern. Thales Castanho de Andrade was one of those educators who found in the educational destination book this possibility. This article is concerned to examine the ways that are served by reading books models of urban life to cite the country life. These books are part of the Coleção de leitura escolar: série Thales de Andrade. The books carry a model school reading ideologized as they meet, in addition to teaching reading, build civility of the countryside, through images or words, or the organization that goes through all the books of the collection.