Produção da nucleoproteína recombinante do vírus da influenza aviária para aplicação no imunodiagnóstico

Pós-graduação em Microbiologia Agropecuária - FCAV

Desenvolvimento e aplicação do Elisa indireto com a nucleoproteína recombinante (NPR) do vírus da doença de Newcastle

Pós-graduação em Medicina Veterinária - FCAV

Endogenous and uric acid-induced activation of NLRP3 inflammasome in pregnant women with preeclampsia

Preeclampsia (PE) is a specific syndrome of pregnancy, characterized by hypertension and proteinuria. This pathology is associated with hyperuricemia and elevated serum levels of inflammatory cytokines. Uric acid crystals may activate an intracellular complex called inflammasome, which is important for processing and release of inflammatory cytokines. This study investigated the state of monocyte activation, both endogenous and stimulated with monosodium urate (MSU), by gene expression of NLRP1 and NLRP3 receptors as well as their association with inflammatory cytokines expression. Monocytes were obtained from peripheral blood of 23 preeclamptic pregnant women, 23 normotensive pregnant women (NT) and 23 healthy non-pregnant women (NP). Inflammasome activation was evaluated by the gene expression of NLRP1, NLRP3, caspase-1, IL-1 beta, IL-18 and TNF-alpha by RT-qPCR in unstimulated monocytes (endogenous expression), or after cell stimulation with MSU (stimulated expression). The concentration of cytokines was assessed by ELISA. In preeclamptic pregnant women, gene expression of NLRP1, NLRP3, caspase-1, IL-1 beta and TNF-alpha by monocytes stimulated or not with MSU was significantly higher than in NT and NP groups. Stimulation of monocytes from preeclamptic and non-pregnant women with MSU induced increased gene expression of NLRP3, caspase-1 and TNF-alpha in relation to the endogenous expression in these groups, while this was not observed in the NT group. The cytokine determination showed that monocytes from women with PE produced higher endogenous levels of IL-1 beta, IL-18 and TNF-alpha compared to the other groups, while the stimulus with MSU led to higher production of these cytokines in preeclamptic group than in the NT group. In conclusion, the results showed increased basal gene expression of NLRP1 and NLRP3 receptors in monocytes from PE group. These cells stimulation with MSU demonstrates that uric acid plays a role in NLRP3 inflammasome activation, suggesting the participation of this inflammatory complex in the pathogenesis of preeclampsia.

Correlations among antiangiogenic factors and trace elements in hypertensive disorders of pregnancy

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A flexible lab-on-a-chip for the synthesis and magnetic separation of magnetite decorated with gold nanoparticles

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

Nanoparticles increase the efficacy of cancer chemopreventive agents in cells exposed to cigarette smoke condensate

Lung cancer is a leading cause of death in developed countries. Although smoking cessation is a primary strategy for preventing lung cancer, former smokers remain at high risk of cancer. Accordingly, there is a need to increase the efficacy of lung cancer prevention. Poor bioavailability is the main factor limiting the efficacy of chemopreventive agents. The aim of this study was to increase the efficacy of cancer chemopreventive agents by using lipid nanoparticles (NPs) as a carrier. This study evaluated the ability of lipid NPs to modify the pharmacodynamics of chemopreventive agents including N-acetyl-L-cysteine, phenethyl isothiocyanate and resveratrol (RES). The chemopreventive efficacy of these drugs was determined by evaluating their abilities to counteract cytotoxic damage (DNA fragmentation) induced by cigarette smoke condensate (CSC) and to activate protective apoptosis (annexin-V cytofluorimetric staining) in bronchial epithelial cells both in vitro and in ex vivo experiment in mice. NPs decreased the toxicity of RES and increased its ability to counteract CSC cytotoxicity. NPs significantly increased the ability of phenethyl isothiocyanate to attenuate CSC-induced DNA fragmentation at the highest tested dose. In contrast, this potentiating effect was observed at all tested doses of RES, NPs dramatically increasing RES-induced apoptosis in CSC-treated cells. These results provide evidence that NPs are highly effective at increasing the efficacy of lipophilic drugs (RES) but are not effective towards hydrophilic agents (N-acetyl-L-cysteine), which already possess remarkable bioavailability. Intermediate effects were observed for phenethyl isothiocyanate. These findings are relevant to the identification of cancer chemopreventive agents that would benefit from lipid NP delivery.

Attribute charts for monitoring the mean vector of bivariate processes

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Gestational protein malnutrition impairs c-myc and p63 protein expression, increases prostatic intraepithelial neoplasia incidence and prostatitis aggressiveness in adult male offspring subjected to hormonal handling

Background: Prostate cancer is the second most common cancer diagnosed in men; however its etiology remains unknown. Previous studies have shown that environmental adverse factors, such as maternal nutritional status during pregnancy, can influence fetal development and predispose people to diseases in adult life. The feeding of low-protein diets to pregnant rats result in fetal growth disturbance, androgen/estrogen unbalance and changes in the expression and sensibility of hormone receptors in male offspring. These alterations can promote permanent changes in androgen dependent organs, such as in the prostate. In this sense, we hypothesized that the hormonal unbalance that occurs during aging can lead to an increase in the susceptibility to prostatic disorders. Aim: To evaluate our hypothesis, malnourished male rat offspring were submitted to simultaneous estrogen and testosterone exposure in adulthood, to drive lesions in the rat ventral prostate gland (VP). Methods: 17 week-old Wistar rats (n=48) that received in utero normal protein diet (NP group, AIN93G=17% protein) or low protein diet (RP group, AIN93G modified=6% protein) were given implants with 17β-estradiol plus testosterone administration (NPH and RPH groups) for 17 weeks. The animals were killed at the age of 34 weeks and the VP were excised, weighted and processed for histopathological, immunohistochemical (Ki67, AR, p63, e-caderin, laminin, c-myc and GSTP), biochemical and ultrastructural analysis. Results: Both absolute and relative VP weight from NPH animals were about 30% higher than RPH. Serological data showed that estradiol levels were similar in both groups, but testosterone levels were lower in the RPH male offspring. The steroid hormone exposure in adult life promoted prostate lesions in both RPH and NPH offspring associated with reactive stroma. VP from RPH group exhibited heightened susceptibility to prostatic intraepithelial neoplasia (mainly cribriform and signet ring-cell patterns) and increased the incidence and aggressiveness of prostatitis. In this group, a higher proportion of basal cells, increased proliferation index, lower expression ofthe androgen receptor and increased focus of collagenous micronodules closely associated to epithelial neoplasias were also observed. Conclusion:These observations suggest that maternal protein restriction alters adult prostate response to androgen/estrogen handling and increases susceptibility to prostate diseases. Ethical protocol:CEEA,476/2013 IBB-UNESP; Funding Support: 2009/50204-6 and 2013/09649-0.

Effect of age and endometrial degenerative changes on uterine blood flow during early gestation in mares

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

Análise de inflamassoma induzido por urato monossódico em monócitos de gestantes portadoras de pré-eclampsia

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

Desenvolvimento de dispersões sólidas e nanopartículas poliméricas mucoadesivas de Zidovudina e avaliação da interação biológica com a mucosa intestinal

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

Indicadores antropométricos do estado nutricional entre idosas praticantes e não praticantes de exercício físico na zona norte de São José do Rio Preto-SP

Although the regular practice of physical exercise for the maintenance of the nutritional state and quality of life is important, it is not a common habit among the elderly, especially those of the lower income social bracket. The objective was to characterize and compare according to social-economic conditions and anthropometric indexes of the nutritional state of the elderly who regularly practice and those who do not practice exercises, offered at no cost, in the Northern zone of São José do Rio Preto-SP. In this study, 110 elderly women participated, of which 60 (group P) exercised regularly and 50 did not (group NP). Group P participated in a special gym program, free of charge, for at least 2 years, 2 to 3 times a week, one hour a day. Group NP was recruited from the same location as Group P. The comparison between the groups of elderly women was proportionately distributed according to marital status, level of education, means of locomotion, results of body mass index (IMC), waist to hip ratio (RCQ) and calf circumference, using the chi-square test. Comparisons were also made of average age, per capita family income, individual income, IMC, arm and triceps skin fold measured by t-Test. Differences were not found in all the comparisons made. The variables that stood out were the IMC (overweight) and RCQ (risk of chronic diseases) results, which were above what was expected, and the high frequency of walking and riding buses for both groups of elderly women (about 60%). We came to the conclusion that the low-intensity exercise program evaluated made no difference in the nutritional profi le of the elderly who also used walking as a means of getting around.

Association between neuropathic pain and A-Waves in Leprosy patients with type 1 and 2 reactions

Summary: Neuropathic pain (NP) is a well-recognized feature of leprosy neuropathy. However, the diagnosis of NP is difficult using only clinical criteria. In the study reported here, by means of conventional nerve conduction studies, the authors sought for an association between long-latency responses and NP complaints in leprosy patients with type 1 and 2 reactions. Of the 27 ulnar nerves of leprosy patients, 18 with type 1 reaction (T1R) and 9 with type 2 reaction (T2R) were followed-up for 6 months before and after steroid treatment. Clinical characteristics of pain complaints and clinical function were assessed, as well as the presence of F- and A-waves of the ulnar nerve using nerve conduction studies. The clinical and the neurophysiologic findings were compared to note positive concordances (presence of NP and A-waves together) and negative concordances (absence of NP and A-waves together) before and after treatment. Both reactions presented a high frequency of A-waves (61.1% in T1R and 66.7% in T2R, P < 0.05) and prolonged F-waves (69.4% in T1R and 65.8% in T2R, P = 0.4). No concordances were seen between pain complaints and F-waves. However, significant concordances between NP and A-waves were observed, although restricted to the T2R group ([chi]2 = 5.65, P = 0.04). After treatment, there was a significant reduction in pain complaints, as well as the presence of F- and A-waves in both groups (P < 0.05 for all comparisons). In conclusion, the presence of A-waves correlates well with pain complaints of neuropathic characteristics in leprosy patients, especially in those with type 2 reaction. Probably, such response shares similar mechanisms with the small-fiber dysfunction seen in these patients with NP, such as demyelination, intraneural edema, and axonal sprouting. Further studies using specific tools for small-fiber assessment are warranted to confirm our findings.

Development of numerical cognition among Brazilian school-aged children

The Numerical Cognition is influenced by biological, cognitive, educational, and cultural factors and entails the following systems: Number Sense (NS) represents the innate ability to recognize, compare, add, and subtract small quantities, without the need of counting; Number Production (NP) which includes reading, writing and counting numbers or objects; Number Comprehension (NC), i.e., the understanding the nature of the numerical symbols and their number, and the calculation (CA). The aims of the present study were to: i) assess theoretical constructs (NS, NC, NP and CA) in children from public schools from 1 st -to 6 th - grades; and ii) investigate their relationship with schooling and working memory. The sample included 162 children, both genders, of 7-to 12-years-old that studied in public school from 1 st -to 6 th -grades, which participated in the normative study of Zareki-R (Battery of neuropsychological tests for number processing and calculation in children, Revised; von Aster & Dellatolas, 2006). Children of 1 st and 2 nd grades demonstrated an inferior global score in NC, NP and CA. There were no genderrelated differences. The results indicated that the contribution of NS domain in Zareki-R performance is low in comparison to the other three domains, which are dependent on school-related arithmetic skills.

Desempenho de crianças com deficiência auditiva e implante coclear em tarefas de seleção de e de nomeação de figuras

The aim of this study was to investigate the development of specific domains of Numerical Cognition (Number Sense – NS, Number Comprehension – NC, Number Production – NP, and Calculation – CA) in Brazilian children with Specific Learning Disorders. The study included 72 children (36 boys), from 9-to 10-years-old, enrolled in 4th and 5th years of elementary school of public schools at countryside of Sao Paulo State, Brazil. They were divided into three groups: control (CT, N = 42), Developmental Dyslexia (DL, N = 11) and Developmental Dyscalculia combined with dyslexia (DDc, N = 19). All participants had intellectual level within the normal range, however, children from the last two groups had Learning Disorders classified by School Achievement Test - TDE (Stein, 1994) and DDc children received necessarily classification as 'inferior' in Arithmetic Test of TDE. The children did not differ in NS. DL and DDc children showed slight deficits in NC. However, DDc children had moderate in NP and mild to moderate deficits in CA, which indicates a more generalized impairment in Numerical Cognition. Furthermore, DDc children showed discrepancy in Numerical Cognition performance when compared to the other groups. Thus, children with Learning Disorders showed different performances in Numerical Cognition, although both groups had preserved SN, DDc children showed higher deficits and discrepancy in relation DL and typically developing children.