Polimorfismos do gene MSX1 e a fenda labio e/ou palatina não-sindrômica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

A influência do esqueleto açúcar-fostato no transporte da molécula de DNA

This dissertation analyses the influence of sugar-phosphate structure in the electronic transport in the double stretch DNA molecule, with the sequence of the base pairs modeled by two types of quasi-periodic sequences: Rudin-Shapiro and Fibonacci. For the sequences, the density of state was calculated and it was compared with the density of state of a piece of human DNA Ch22. After, the electronic transmittance was investigated. In both situations, the Hamiltonians are different. On the analysis of density of state, it was employed the Dyson equation. On the transmittance, the time independent Schrödinger equation was used. In both cases, the tight-binding model was applied. The density of states obtained through Rudin-Shapiro sequence reveal to be similar to the density of state for the Ch22. And for transmittance only until the fifth generation of the Fibonacci sequence was acquired. We have considered long range correlations in both transport mechanism

Imunoexpressão das proteínas APE-1 e XRCC-1 em carcinoma epidermoide de língua oral

DNA repair systems play a critical role in protecting the human genome from damage caused by carcinogens present in the environment. Mutations in DNA repair genes may be responsible for tumor development and resistance of malignant cells to chemotherapeutic agents. The major pathway for oxidative DNA damage repair is the base excision repair pathway. The objective of this study was to investigate the immunoexpression of APE-1 and XRCC-1, which are proteins involved in DNA base excision repair and its association with clinical and histopathological parameters in oral tongue squamous cell carcinoma (OTSCC), in order to investigate a possible prognostic value for those proteins. The expression of APE-1 and XRCC-1 was evaluated semi-quantitatively by immunohistochemistry in 50 OTSCC cases. Clinical data was collected from patients’ medical charts and histopathological grading was performed for each case. Statistical analysis (Chi-square and Fisher’s exact tests; significance of 5%) was performed to determine the association between protein expressions and clinico-pathological characteristics. APE-1 was highly expressed in nucleus and cytoplasm in 56% of cases. XRCC-1 showed overexpression only in nucleus in 60% of cases. High expression of XRCC-1 was significantly associated to clinical stages I and II (P=0.02). Both proteins were not associated to other clinical parameters or histopathological grading. Our findings demonstrate that DNA base excision repair proteins APE-1 and XRCC-1 are upregulated in OTSCC, however, they are not related to clinical and histologic parameters, except for XRCC-1 association to better clinical staging. Our results indicate that the immunohistochemical expression of these proteins has no association with prognostic parameters in this tumor.

Imunoexpressão das proteínas APE-1 e XRCC-1 em carcinoma epidermoide de língua oral

DNA repair systems play a critical role in protecting the human genome from damage caused by carcinogens present in the environment. Mutations in DNA repair genes may be responsible for tumor development and resistance of malignant cells to chemotherapeutic agents. The major pathway for oxidative DNA damage repair is the base excision repair pathway. The objective of this study was to investigate the immunoexpression of APE-1 and XRCC-1, which are proteins involved in DNA base excision repair and its association with clinical and histopathological parameters in oral tongue squamous cell carcinoma (OTSCC), in order to investigate a possible prognostic value for those proteins. The expression of APE-1 and XRCC-1 was evaluated semi-quantitatively by immunohistochemistry in 50 OTSCC cases. Clinical data was collected from patients’ medical charts and histopathological grading was performed for each case. Statistical analysis (Chi-square and Fisher’s exact tests; significance of 5%) was performed to determine the association between protein expressions and clinico-pathological characteristics. APE-1 was highly expressed in nucleus and cytoplasm in 56% of cases. XRCC-1 showed overexpression only in nucleus in 60% of cases. High expression of XRCC-1 was significantly associated to clinical stages I and II (P=0.02). Both proteins were not associated to other clinical parameters or histopathological grading. Our findings demonstrate that DNA base excision repair proteins APE-1 and XRCC-1 are upregulated in OTSCC, however, they are not related to clinical and histologic parameters, except for XRCC-1 association to better clinical staging. Our results indicate that the immunohistochemical expression of these proteins has no association with prognostic parameters in this tumor.

Estudo dos genes do complexo do antígeno leucocitário humano (hla) associados à susceptibilidade ao diabetes mellitus tipo 1

Of all of the genes associated with the development of Diabetes mellitus type 1 (T1D), the largest contribution comes from the genes in the Human Leukocyte Antigen (HLA) region, mostly the class II DR e DQ genes. Specific combinations of alleles DRB1, DQA1 and DQB1 constituting haplotypes, and further, a combination of more than one haplotype, providing multilocus genotypes are associated with susceptibility, protection and neutrality to DM1. Thus, the aim of present study was to verified the association of polymorphisms of HLA genes class II with susceptibility to type 1 diabetes mellitus (T1D). Ninety-two patients with T1D and 100 individuals normoglycemics (NG) aged between 6 and 20 years were studied. Genomic DNA was obtained from peripheral whole blood, collected in EDTA tube, using the extraction kit Illustra Triple Prep®, GE Healthcare. For HLA typing was used DNA LABType system by One Lambda kit applying Luminex® technology to the method of PCRSSO typing reverse. The alleles DRB1*03:01, *04:05, *04:01, *04:02, DQA1*03:01g, *05:01g, DQB1*02:01g, *03:02, the haplotypes DRB1*03:01-DQA1*05:01-DQB1*02:01, DRB1*04:05-DQA1*03:01g-DQB1*03:02, DRB1*04:02-DQA1*03:01g-DQB1*03:02, DRB1*04:01-DQA1*03:01g-DQB1*03:02 and DR3-DQ2/DR4-DQ8 genotype were significantly associated with the chance of developing T1D. The alleles DRB1*11:01, *15:03, *15:01, *13:01, DQA1*01:02, *04:01g, *01:03, DQB1*06:02, *03:01g, *06:03, *04:02, the haplotypes DRB1*11:01-DQA1*05:01-DQB1*03:01, DRB1*13:01-DQA1*01:03-DQB1*06:03 and DRX-DQX/DRX-DQX genotype, formed by other than the DR3-DQ2 or DR4-DQ8 haplotypes, were significantly associated with T1D protection Despite the major racial Brazilian, even at the regional level, these results are similar to the majority of alleles, genotypes and haplotypes of HLA class II-related susceptibility or resistance to T1D, extensively described in the literature for Caucasian population. Children with age at diagnosis less than 5 years of age had significantly higher frequency of the heterozygous genotype DR3-DQ2/DR4-DQ8 compared to children with age at diagnosis than 5 years old. These results also demonstrate strong association of the genetic profile of the class II HLA for this age group, possibly associated with the severity and rapid progression to the onset of T1D. The knowledge of HLA class II genes may be useful in genetic screens that allow the prediction of T1D

A cultura organizacional influenciando o comportamento do capital humano na biblioteca universitária

DUARTE, E. N. ; CARVALHO, Andréa Vasconcelos ; PINHEIRO, E. G. ; CARVALHO, Luciana Moreira ; NOGUEIRA, N. M. F. . A cultura organizacional influenciando o comportamento do capital humano na biblioteca universitária. Informação & Sociedade. Estudos, João Pessoa - PB, v. 10, n. 2, p. 190-210, 2000

Educação complementar e desenvolvimento humano: alcances e limites da estratégia socioeducativa do projeto OASIS de intervivência universitária

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Influência do estado nutricional materno em vitamina A sobre os níveis de imunoglobulina A no colostro humano

Mothers with good vitamin A nutritional status during gestation and lactation are better able to nourish and protect their infant with maternal milk. Our hypothesis is that women with more serum retinol have more retinol and secretory immunoglobulin A in colostrum. 190 healthy puerperal women from a Brazilian public maternity were recruited and divided according to the cutoff point for serum retinol (30 μg/dL). A number of the women was supplemented with 200000 UI (60 mg) of retinyl palmitate in the immediate postpartum. Serum and colostrum were collected on the 1st day postpartum and colostrum again on the following day. Retinol (serum and colostrum) was analyzed by HPLC and SIgA (colostrum) by turbidimetry. The mothers presented with adequate biochemical indicators of nutritional status, according to serum retinol (44.6 μg/dL). There were significant differences (p= 0.0017 and p= 0.043, respectively) in retinol and SIgA levels in the colostrum of mothers with serum retinol > 30 μg/dL and < 30 μg/dL. The concentration of SIgA in the colostrum of non-supplemented mothers on the 1st day postpartum was 822.6 mg/dL, decreasing after 24 hours to 343.7 mg/dL. Supplemented mothers showed levels of SIgA in colostrum of 498.9 mg/dL on the 2nd day postpartum (p= 0.00006). The colostrum of women with good vitamin A nutritional status had more retinol and SIgA. Additionally, maternal supplementation increases the levels of SIgA in colostrum. The higher levels of SIgA on the 1st day postpartum showed the importance of early breastfeeding, given that it provides considerable immunological benefits to newborn infants

Efeito de glucanas do fungo Caripia montagnei em modelo de inflamação intestinal induzida por tnbs em ratos Wistar e em células de carcinoma de cólon humano HT-29

Compounds derived from fungi has been the subject of many studies in order to broaden the knowledge of their bioactive potential. Polysaccharides from Caripia montagnei have been described to possess anti-inflammatory and antioxidant properties. In this study, glucans extracted from Caripia montagnei mushroom were chemically characterized and their effects evaluated at different doses and intervals of treatment. It was also described their action on colonic injury in the model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS), and its action on cells of the human colon carcinoma (HT-29). Compounds extracted of C. montagnei contain high level of carbohydrates (96%), low content of phenolic compounds (1.5%) and low contamination with proteins (2.5%). The (FT-IR) and (NMR) analysis showed that polysaccharides from this species of mushroom are composed of α- and β-glucans. The colonic damage was evaluated by macroscopic, histological, biochemical and immunologic analyses. The results showed a reduction of colonic lesions in all groups treated with the glucans of Caripia montagnei (GCM). GCM significantly reduced the levels of IL-6 (50 and 75 mg/kg, p < 0.05), a major inflammatory cytokine. Biochemical analyses showed that such glucans acted on reducing levels of alkaline phosphatase (75 mg/kg, p < 0.01), nitric oxide (p < 0.001), and myeloperoxidase (p < 0.001). These results were confirmed microscopically by the reduction of cellular infiltration. The increase of catalase activity suggest a protective effect of GCM on colonic tissue, confirming their anti-inflammatory potential. GCM displayed cytostatic activity against HT-29 cells, causing accumulation of cells in G1 phase, blocking the cycle cell progression. Those glucans also showed ability to modulate the adhesion of HT-29 cells to Matrigel® and reduced the oxidative stress. The antiproliferative activity against HT-29 cells displayed by GCM (p <0.001) can be attributed to its cytostatic activity and induction of apoptosis by GCM

Indução de morte celular em células de adenocarcinoma cervical humano (HeLa) pela lectina da esponja Cinachyrella apion (CaL)

Cancer is a term used to represent a set of more than 100 diseases, including malignant tumors from different locations. The malignancies are the second leading cause of death in the population, representing approximately 17% of deaths of known cause. Strategies that induce differentiation have had limited success in the treatment of established cancers. In this work, a lectin purified from the marine sponge Cinachyrella apion (CaL) was evaluated due to its hemolytic, cytotoxic and antiproliferative properties, besides the ability to induce cell death via apoptosis in tumor cells. The antiproliferative activity of CaL was tested against cell lines, with the highest inhibition of tumor growth for HeLa, reducing cell growth at a dose dependent manner, with a concentration of 10 μg/mL. The hemolytic activity and toxicity against peripheral blood cells were tested using the concentration of IC50 for both trials and twice the IC50 for analysis in flow cytometry, indicating that CaL is not toxic to these cells. To assess the mechanism of cell death caused by CaL in HeLa cells, we performed flow cytometry and western blotting. The results showed the lectin probably induces cell death by apoptosis activation by pro-apoptotic protein Bax, promoting mitochondrial membrane permeabilization, cell cycle arrest in S phase, with accumulation of cells of approximately 57% in this phase, and acting as both dependent and/or independent of caspases pathway. These results suggest that CaL has the potential to be used as drug treatment against cancer.

Estudo do genoma do vírus causador da mionecrose infecciosa em camarões e desenvolvimento de métodos para detecção de diferentes variantes

Shrimp farming is one of the activities that contribute most to the growth of global aquaculture. However, this business has undergone significant economic losses due to the onset of viral diseases such as Infectious Myonecrosis (IMN). The IMN is already widespread throughout Northeastern Brazil and affects other countries such as Indonesia, Thailand and China. The main symptom of disease is myonecrosis, which consists of necrosis of striated muscles of the abdomen and cephalothorax of shrimp. The IMN is caused by infectious myonecrosis virus (IMNV), a non-enveloped virus which has protrusions along its capsid. The viral genome consists of a single molecule of double-stranded RNA and has two Open Reading Frames (ORFs). The ORF1 encodes the major capsid protein (MCP) and a potential RNA binding protein (RBP). ORF2 encodes a probable RNA-dependent RNA polymerase (RdRp) and classifies IMNV in Totiviridae family. Thus, the objective of this research was study the IMNV complete genome and encoded proteins in order to develop a system differentiate virus isolates based on polymorphisms presence. The phylogenetic relationship among some totivirus was investigated and showed a new group to IMNV within Totiviridae family. Two new genomes were sequenced, analyzed and compared to two other genomes already deposited in GenBank. The new genomes were more similar to each other than those already described. Conserved and variable regions of the genome were identified through similarity graphs and alignments using the four IMNV sequences. This analyze allowed mapping of polymorphic sites and revealed that the most variable region of the genome is in the first half of ORF1, which coincides with the regions that possibly encode the viral protrusion, while the most stable regions of the genome were found in conserved domains of proteins that interact with RNA. Moreover, secondary structures were predicted for all proteins using various softwares and protein structural models were calculated using threading and ab initio modeling approaches. From these analyses was possible to observe that the IMNV proteins have motifs and shapes similar to proteins of other totiviruses and new possible protein functions have been proposed. The genome and proteins study was essential for development of a PCR-based detection system able to discriminate the four IMNV isolates based on the presence of polymorphic sites

Avaliação do efeito da megadose de vitamina A no colostro humano

The mothers supplementation of vitamin A in the postpartum comes being a measure of intervention sufficiently used in the combat to the vitamin deficiency. The objective of this work was to evaluate the effect of the mother megadose of vitamin A under the levels of retinol in colostrum of postpartum mothers receiving care at the Januário Cicco Maternity School (MEJC), Natal, RN, as well as analyzing the influence of the maternal nutritional status in the reply to this supplementation. The study it was transversal type, with participation of 91 women in labor divided in group had participated of the study have controlled (44 women) and supplemented group (47 women). In the period of the morning blood and milk had been collected (milk 0h). After that a capsule of retinil palmitate of (200 000 UI or 60 mg) was supplied to the supplemented group. Another aliquot of colostro was after gotten 24h of the first collection (milk 24h). Retinol in milk and serum was quantified through the High Pressure Liquid Chromatography. The vitamin ingestion was evaluated by the questionnaire of frequency of alimentary consumption. The levels of serum retinol were 40.6 ± 10.6 and 35.9 ± 10.9 µg/dL in the groups controlled and supplemented, respectively. The women had presented a satisfactory average ingestion of vitamin (1492,4 µgRAE/dia), however with high prevalence of inadequate consumption (23%). Average values of retinol in milk 0h had been found and 24h of 93.5 ± 50.3 µg/dL and 99.1 ± 49.3 µg/dL has the group controlled group, respectively (p>0.05). After the supplementation had a significant increase in the levels of retinol of the supplemented group, being found values of 102.0 ± 56.0 µg/dL and 196.1 ± 74.0 µg/dL for milk 0h and 24h, respectively (p<0.0001). The women in labor presented different answers to the supplementation influenced for the basal levels of retinol in colostrum. It was possible to verify that women with deficient levels of retinol in milk had transferred more retinol to milk 24h than ones with adjusted levels, showing a percentage of reply equivalent to 326.1% and 86.5% of increase, respectively (p< 0.0001). Although the apparent normality found in the serum, the studied women are considered of risk to the development of the vitamin deficiency, and megadose was efficient in first 24h after the supplementation and wakes up with the mechanisms considered for transference of vitamin A to the milk

Prevalência da infecção por papilomavírus humano, herpes simplex tipo 1 e 2 e Chlamydia trachomatis em um segmento da população feminina da grande Natal/RN

Sexually transmitted diseases (STDs) are among the largest public health problems, especially in developing countries. The acquisition of these infections during early sexual activity is common and many infections have a benign course. However, in some pathogens remain in the state of latency can be reactivated and cause productive infection that may progress to severe forms. In addition, some of them are transmitted vertically resulting in congenital infection, causing immediate damage or long-term child. The classic risk factors for sexually transmitted agents are: early onset of sexual and reproductive health, multiple sexual partners throughout life, use of oral contraceptives and co-infections with different pathogens. We present the results of a cross-sectional study aimed to estimate the prevalence of genital infection by human papillomavirus (HPV), Herpes simplex virus (HSV) and Chlamydia trachomatis (CT) in a segment of the female population of the metropolitan area Christmas, among those who enrolled voluntarily sought, Basic Health Units for the examination of cancer screening cervix in the period 2008 to 2010. All participants, a total of 261 women answered a standard questionnaire by which identified the socio-demographic characteristics, classical risk factors for STDs, reproductive and sexual activity and smoking. Of each patient were obtained two samples, one for the completion of the Pap test for detection of cellular changes and the other processed for DNA extraction and analyzed by PCR (polymerase chain reaction) to detect the three pathogens studied. The population of the study was composed of sexually active women aged between 13 and 79 years, mean 38.7 years, most of them being married, low education levels and low incomes. The majority (87%) had normal results on cytology and only 2.7% had low-grade cytological abnormalities. Prevalence rates were 37.9% for HPV, 4.6% for CT and 26% for HSV. HPV prevalence was higher in women under 25, unmarried and in those who had multiple sexual partners. Women with simultaneous infection by HSV-1 and 2 had higher prevalence of HPV infection. The prevalence of HSV infection showed no association whatsoever with the risk factors analyzed and HSV-1 was the predominant type among the cases of genital HSV infection. The overall prevalence of C. Trachomatis was relatively low, thus providing greater value in younger women aged less than or equal to 20 years

Prevalência da infecção pelo Papilomavírus humano, Chlamydia Trachomatis e Herpes Simples do tipo 2 em adolescentes atendidas em unidades de saúde pública de Natal

This study assessed the level of knowledge, attitude and practice of Pap smear and human papillomavirus (HPV), in addition to analyzing the prevalence of genital HPV infection, Herpes Simplex Type 2 (HSV-2) and Chlamydia trachomatis in teenagers. The study consisted of two approaches, one based only on interviews conducted with adolescents enrolled in public schools or in public health facilities in the city of Natal. The other approach involved only a group of 132 adolescents enrolled among those admitted to two health units in Natal-RN. This second group of participants two specimens were collected for laboratory analysis: one was directed to prepare the blade for the Pap test, and other processed for DNA extraction for molecular analysis, focusing on the detection of HPV, HSV-2 and C . trachomatis. The presence of DNA of the three pathogens was investigated by the technique of polymerase chain reaction (PCR). The presence of each of the three pathogens was analyzed in terms of socio-demographic characteristics, as well as sexual and reproductive activity to identify risk factors for infection and development of lesions of the uterine cervix. The results show that the adolescents in this study had levels of knowledge and attitude very low, both in relation to cytology to HPV as though they have made a reasonable percentage of adequate practice exam and prevention of HPV infection. The overall prevalence of HPV infection was 54.5% and 48.2% in adolescents with normal cytology and 86.4% in those with abnormal cytology. We observed a higher proportion of cases of infection in the age group of 18 to 21. The prevalence of HPV infection was slightly higher among pregnant teenagers. The overall prevalence of HSV-2 infection was 13.6% and 11.8% in women with normal cytology and 22.7% in those with abnormal cytology. A higher proportion of cases of infection was found in the age group from 14 to 17, with a slightly higher prevalence among pregnant women. The C. trachomatis was found with an overall prevalence of 19.7% and 21.8% in adolescents with normal cytology and 9.1% in those with abnormal cytology. The prevailing rate was highest in the age group 18 to 21 years and in nonpregnant

Correlação entre a infecção genital pelo vírus do papiloma humano, a resposta imune e os achados colpocitológicos em mulheres grávidas e não grávidas

The genital HPV infection is very common between men and women worldwide, affecting particularly young women, constituting a serious public health problem in less developed regions, favored by the poor living conditions of population. The cytology and colposcopy have notorious importance in the diagnosis of precursor lesions of cervical cancer and therefore its prevention. However, even with such diagnostic tools, the number of women who develop cervical cancer is still high. This study aims to assess the prevalence of genital tract infection by HPV in pregnant and nonpregnant women, evaluating the profile of the immune response presented by the women of these two groups in order to establish correlations among profile of immune response, presence of virus and occurrence of lesions of the uterine cervix. We analyzed specimens obtained from the cervix of 221 patients, 91 pregnant and 130 non-pregnant, aged 14-72 years. The women were subjected to colposcopic and cytologic evaluation detect possible changes in the cervix and then samples were collected in order to perform HPV detection by PCR and real-time PCR for detection of mRNA of pro-inflammatory and anti-inflammatory cytokines. In the present study, the overall prevalence of HPV genital infection was 28.1%; of which 31.9% were pregnant patients and 25.4% in non-pregnant women. Young women under 30 years and those with low educational level education showed a higher risk of HPV infection. Colposcopy showed better correlation with detection of HPV DNA by PCR, when compared to cytology. Generally, HPV infected patients, pregnant or not, exhibited reduced mRNA expression of both pro-inflammatory (IFN-γ, TNF-α) and anti-inflammatory (IL -10) cytokines, when compared to patients not infected by HPV. Nonpregnant patients infected presented increase mRNA expression of IL-17 in patients without injury, whereas those with lesion showed higher mRNA expression of TGF-β. Pregnant women without injury infected exhibited increased mRNA expression of TGF-β. There was no difference in HPV prevalence between pregnant and nonpregnant women. There was a reduction of pro-inflammatory cytokines, except IL-17, in all women infected by HPV. Moreover, we observed an increase of TGF-β in HPV-infected women who are pregnant or not. The results suggest that, in women in this study, HPV infection promoted changes in the profile of cytokines necessary for activation of effective immune response, possibly favoring viral persistence