Distúrbios de aprendizagem e fracasso escolar na visão de professores e licenciandos / Learning disorders and school failure in the view of teachers and graduates / Distúrbios de aprendizaje y fracaso escolar en la visión de docentes y estudiantes universitários

O estudo teve por objetivo conhecer a visão e a prática de professores de ciências e alunos de curso de licenciatura em Ciências Biológicas em relação aos distúrbios de aprendizagem e ao fracasso escolar, de modo a compreender os sentidos e significados construídos por eles em relação à crescente atribuição de responsabilidade biológica ao suposto fracasso no ensino. Trata-se de pesquisa qualitativa, que se utilizou de aplicação de questionário e entrevista semiestruturada com professores de escolas pública e particular e com alunos de um curso de graduação/licenciatura de uma universidade pública. Como resultados, é possível identificar a sobreposição em relação ao entendimento e uso de terminologias como "distúrbios", "problemas" e "dificuldades" de aprendizagem, sendo utilizadas pelos professores e estudantes participantes da pesquisa, como sinônimos para designar um processo análogo. Verificou-se a atribuição de causa biológica a qualquer dificuldade ou problema de aprendizado do aluno, ainda que a causa seja, de fato, devido a fatores sociais ou psicológicos. Evidenciou-se o despreparo para com a realização do diagnóstico, bem como desconhecimento em relação às formas de se fazer, atribuindo esse papel a outros profissionais que acreditam estar mais preparados para lidar com esses casos, considerando-se que o tratamento medicamentoso possa ser o mais efetivo. Desse modo, os resultados obtidos demonstram a importância de investigações e elucidações mais profundas a respeito do cotidiano escolar no que se refere às questões atreladas ao processo ensino-aprendizagem e à crescente medicalização de crianças e adolescentes.

The purpose of this study was to understand the vision and practice of science teachers and students of a licentiate degree course in Biological Sciences in relation to learning disorders and school failure, in order to understand the senses and meanings they constructed in relation to the increasing attribution of biological responsibility to the supposed school failure. It is a qualitative research, in which was used a questionnaire application and a semi-structured interview with public and private school teachers and with students of a undergraduate/licentiate course from a public university. As results it is possible to identify the overlap in terms of understanding and use of terminologies such as "disturbs", "problems" and "difficulties" of learning, by teachers and students participating in the research, as synonyms to designate the same process. The attribution of biological cause to any difficulty or learning problem of the student has been verified, even if the cause is, in fact, due to social or psychological factors. The lack of preparation for diagnosis was evidenciated, as well as lack of knowledge about the ways of doing it, attributing this role to other professionals who believe that they are better prepared to assist these cases, considering that drug treatment may be the most effective. Thus, the results obtained demonstrate the importance of investigations and more profound elucidations about the school daily life in relation to the issues linked with the teaching-learning process and the increasing medicalization of children and adolescents.

El estudio tuvo como objetivo conocer la visión y la práctica de los profesores de ciencias y los estudiantes de la licenciatura en Ciencias Biológicas en relación a los trastornos de aprendizaje y fracaso escolar, con el fin de comprender los significados construidos por ellos en relación al crecente aumento de la asignación de la responsabilidad biológica al supuesto fracaso en la enseñanza. Se trata de una investigación cualitativa, en la cual se utilizo la aplicación de cuestionarios y entrevistas semiestructuradas a maestros de escuelas públicas y privadas y a estudiantes en un curso de grado / licenciatura de una universidad pública. Como resultado, es posible identificar la superposición en relación con la comprensión y el uso de terminología como "trastornos", "problemas" y "dificultades" de aprendizaje, siendo utilizados por los profesores y estudiantes que participaron de la encuesta, indistintamente para describir un mismo proceso. Se encontró la asignación de causa biológica a cualquier dificultad o problema de aprendizaje de los estudiantes, aun que la causa sea de hecho, debido a factores sociales o psicológicos. La falta de preparación para realización de diagnóstico se hizo evidente, así como el desconocimiento de formas de hacer, asignando ese papel a otros profesionales que creen estar mejor preparados para hacer frente a estos casos, teniendo en cuenta que el tratamiento farmacológico puede ser más eficaz. Por lo tanto, los resultados demuestran la importancia investigaciones y mejores esclarecimiento sobre el cotidiano de la escuela cuando se trata de cuestiones relacionadas al proceso de enseñanza-aprendizaje y la creciente medicalización de niños y adolescentes.

Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells.

B cells constitute an essential line of defense from pathogenic infections through the generation of class-switched antibody-secreting cells (ASCs) in germinal centers. Although this process is known to be regulated by follicular helper T (TfH) cells, the mechanism by which B cells initially seed germinal center reactions remains elusive. We found that NKT cells, a population of innate-like T lymphocytes, are critical for the induction of B cell immunity upon viral infection. The positioning of NKT cells at the interfollicular areas of lymph nodes facilitates both their direct priming by resident macrophages and the localized delivery of innate signals to antigen-experienced B cells. Indeed, NKT cells secrete an early wave of IL-4 and constitute up to 70% of the total IL-4-producing cells during the initial stages of infection. Importantly, the requirement of this innate immunity arm appears to be evolutionarily conserved because early NKT and IL-4 gene signatures also positively correlate with the levels of neutralizing antibodies in Zika-virus-infected macaques. In conclusion, our data support a model wherein a pre-TfH wave of IL-4 secreted by interfollicular NKT cells triggers the seeding of germinal center cells and serves as an innate link between viral infection and B cell immunity.

Alloreactive Regulatory T Cells Allow the Generation of Mixed Chimerism and Transplant Tolerance.

The induction of donor-specific transplant tolerance is one of the main goals of modern immunology. Establishment of a mixed chimerism state in the transplant recipient has proven to be a suitable strategy for the induction of long-term allograft tolerance; however, current experimental recipient preconditioning protocols have many side effects, and are not feasible for use in future therapies. In order to improve the current mixed chimerism induction protocols, we developed a non-myeloablative bone-marrow transplant (NM-BMT) protocol using retinoic acid (RA)-induced alloantigen-specific Tregs, clinically available immunosuppressive drugs, and lower doses of irradiation. We demonstrate that RA-induced alloantigen-specific Tregs in addition to a NM-BMT protocol generates stable mixed chimerism and induces tolerance to allogeneic secondary skin allografts in mice. Therefore, the establishment of mixed chimerism through the use of donor-specific Tregs rather than non-specific immunosuppression could have a potential use in organ transplantation.

Validación del cuestionario para graduación de dolor crónicoen pacientes chilenos con patología musculoesquelética / Validation of the graduation of chronic pain in patients with chilean musculoskeletal pathology

Introducción: el dolor crónico es una condición que afecta a 1 de cada 5 personas en el mundo, comprometiendo diferentes áreas de la calidad de vida. El cuestionario para graduación de dolor crónico (CGDC) fue desarrollado como una forma de evaluar y monitorear a estos pacientes, con altos niveles de fiabilidad y validez. Objetivos: Desarrollar una versión española del CGDC, adaptado culturalmente a Chile y determinar su validez y fiabilidad, en el Hospital Clínico de la Universidad de Chile. Material y métodos: El cuestionario fue traducido y adaptado culturalmente de acuerdo a las recomendaciones internacionales. Se aplicó SF-36 v2.0 en 130 pacientes condolor musculoesquelético crónico (más de 6 meses). La fiabilidad se calculó con Alfa de Cronbach y el índice de validez se evaluó mediante la comparación de las respuestas de la CGDC para cada categoría con las subescalas del SF-36 v.2. Resultados: La versión chilena de la CGDC fue válida. Se obtuvieron altos niveles de confiabilidad con alfa de Cronbach> 0,7. Se observaron correlaciones significativas del SF -36,especialmente con las subescalas que tienen alta capacidad de medir el dolor y la salud física (p <0,01). Conclusiones: Los resultados presentados aquí confirman la fiabilidad y validez de la versión chilena del CGDC en la evaluación de pacientes con dolor musculoesquelético crónico.

Introduction: chronic pain is a condition that affectss 1 in every 5 people in the world, compromising different areas of quality of life. The Chronic Pain Graded questionnaire (CPG) was developed as a form to assess and monitor these patients, with high levels of reliability and validity. Objectives: To develop a spanish version of the chronic pain graded questionnaire, culturally adapted to Chile determine its reliability and convergent construct validity , in the University of Chile Clinical Hospital. Materials and Methods: The chronic pain graded questionnaire was translated and culturally adapted accordingt o international recommendations. It was applied with SF -36 v2.0 questionnaire in 130 patients with chronic musculoskeletal pain (more than 6 months). The reliability was calculated with de Alpha the Cronbach Index and de validity was assessed by comparing the responses of the CPG for each category with the subscales of SF-36 v.2. Results: The Chilean version of the CBDC was valid. High levels of reliability was obtained with Cronbach’s alpha > 0.7. Compared with the SF -36 significant correlations were observed, especially with the SF -36 subscales having high ability to measure pain and physical health ( P < 0.01). Conclusions: The results presented here confirm the reliability and validity of the Chilean version of the chronic pain graded questionnaire in the evaluation of patients with chronic musculoskeletal pain.

TIMP-2 gene methylation in cervical precursor and invasive lesions.

OBJECTIVE: To analyze the presence of HPV-DNA and TIMP-2 gene methylation in cervical precursor and invasive lesions, as well as to study the associations among the latter, the presence of HPV-DNA, and the clinical evolution of such lesions. METHODS: Cross-sectional study that includes 49 biopsy or brush smear samples from women with a normal cervix, LSIL, HSIL, microinvasive carcinoma and invasive carcinoma. The presence of HPV-DNA and specific methylation was analyzed using PCR. Thirty-eight biopsy samples for HSIL, microinvasive carcinoma and frank invasive carcinoma as well as 11 brush smear samples for LSIL and normal cervices were analyzed. RESULTS: TIMP-2 gene methylation was detected in 86.8% (33/38) of the samples from the group with lesions and 50% (4/8) of the normal samples (p=0.03). HPV-DNA was detected in 81.6% (31/38) of the samples from the group with lesions and 25% (2/8) of the normal samples (p=0.003). HPV-DNA was more frequent in the methylated samples (50%), and the group with methylation had a higher risk of unfavorable evolution than the group without methylation; however, such observations were not statistically significant (p=0.19). CONCLUSION: TIMP-2 gene methylation and the presence of HPV-DNA were characteristic of the group with cervical lesions. Methylation was not associated with the presence of HPV-DNA or an unfavorable clinical evolution.

HPV DNA genotyping and methylation of gene p16 INK4A in cervical LSIL.

BACKGROUND: DNA methylation is the most important epigenetic change involved in the control of gene expression in human cells. Methylation of the p16(INK4a) gene occurs early in the development of cervical cancer. Low-grade squamous intraepithelial lesions (LSILs) are prevalent, and their behavior is variable. OBJECTIVE: To identify the HPV DNA type, detect the methylation status of the p16(INK4A) gene, and analyze their association with the cytological evolution of LSIL over a period of two years. METHODS: We conducted a cohort study with 40 participants. Cervical scrapings were collected for cytological and molecular analysis. HPV DNA detection and typing were performed by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Methylation-specific PCR was performed to detect methylation. RESULTS: HPV DNA was detected in 87% of the cases, and type 16 was the most frequent type. Methylation was detected in 11% of the cases and did not exhibit a significant correlation with the HPV type. Unfavorable cytological evolution exhibited a significant association with the presence of methylation. CONCLUSION: HPV 16 was the most frequently detected type of HPV in LSIL. Methylation of the p16(INK4A) gene was infrequent and occurred independent of the presence of HPV DNA. Methylation of the p16(INK4a) gene exhibited a significant correlation with persistence/progression of LSIL.

Alterations in the extracellular catabolism of nucleotides and platelet aggregation induced by high-fat diet in rats: effects of α-tocopherol.

The aim of this study was to assess whether α-tocopherol administration prevented alterations in the ectonucleotidase activities and platelet aggregation induced by high-fat diet in rats. Thus, we examined four groups of male rats which received standard diet, high-fat diet (HFD), α-tocopherol (α-Toc), and high-fat diet plus α-tocopherol. HFD was administered ad libitum and α-Toc by gavage using a dose of 50 mg/kg. After 3 months of treatment, animals were submitted to euthanasia, and blood samples were collected for biochemical assays. Results demonstrate that NTPDase, ectonucleotide pyrophosphatase/phosphodiesterase, and 5'-nucleotidase activities were significantly decreased in platelets of HFD group, while that adenosine deaminase (ADA) activity was significantly increased in this group in comparison to the other groups (P < 0.05). When rats that received HFD were treated with α-Toc, the activities of these enzymes were similar to the control, but ADA activity was significantly increased in relation to the control and α-Toc group (P < 0.05). HFD group showed an increased in platelet aggregation in comparison to the other groups, and treatment with α-Toc significantly reduced platelet aggregation in this group. These findings demonstrated that HFD alters platelet aggregation and purinergic signaling in the platelets and that treatment with α-Toc was capable of modulating the adenine nucleotide hydrolysis in this experimental condition.

Worldwide human papillomavirus genotype attribution in over 2000 cases of intraepithelial and invasive lesions of the vulva.

BACKGROUND: Human papillomavirus (HPV) contribution in vulvar intraepithelial lesions (VIN) and invasive vulvar cancer (IVC) is not clearly established. This study provides novel data on HPV markers in a large series of VIN and IVC lesions. METHODS: Histologically confirmed VIN and IVC from 39 countries were assembled at the Catalan Institute of Oncology (ICO). HPV-DNA detection was done by polymerase chain reaction using SPF-10 broad-spectrum primers and genotyping by reverse hybridisation line probe assay (LiPA25) (version 1). IVC cases were tested for p16(INK4a) by immunohistochemistry (CINtec histology kit, ROCHE). An IVC was considered HPV driven if both HPV-DNA and p16(INK4a) overexpression were observed simultaneously. Data analyses included algorithms allocating multiple infections to calculate type-specific contribution and logistic regression models to estimate adjusted prevalence (AP) and its 95% confidence intervals (CI). RESULTS: Of 2296 cases, 587 were VIN and 1709 IVC. HPV-DNA was detected in 86.7% and 28.6% of the cases respectively. Amongst IVC cases, 25.1% were both HPV-DNA and p16(INK4a) positive. IVC cases were largely keratinising squamous cell carcinoma (KSCC) (N=1234). Overall prevalence of HPV related IVC cases was highest in younger women for any histological subtype. SCC with warty or basaloid features (SCC_WB) (N=326) were more likely to be HPV and p16(INK4a) positive (AP=69.5%, CI=63.6-74.8) versus KSCC (AP=11.5%, CI=9.7-13.5). HPV 16 was the commonest type (72.5%) followed by HPV 33 (6.5%) and HPV 18 (4.6%). Enrichment from VIN to IVC was significantly high for HPV 45 (8.5-fold). CONCLUSION: Combined data from HPV-DNA and p16(INK4a) testing are likely to represent a closer estimate of the real fraction of IVC induced by HPV. Our results indicate that HPV contribution in invasive vulvar cancer has probably been overestimated. HPV 16 remains the major player worldwide.

Transplant tolerance: new insights and strategies for long-term allograft acceptance.

One of the greatest advances in medicine during the past century is the introduction of organ transplantation. This therapeutic strategy designed to treat organ failure and organ dysfunction allows to prolong the survival of many patients that are faced with no other treatment option. Today, organ transplantation between genetically dissimilar individuals (allogeneic grafting) is a procedure widely used as a therapeutic alternative in cases of organ failure, hematological disease treatment, and some malignancies. Despite the potential of organ transplantation, the administration of immunosuppressive drugs required for allograft acceptance induces severe immunosuppression in transplanted patients, which leads to serious side effects such as infection with opportunistic pathogens and the occurrence of neoplasias, in addition to the known intrinsic toxicity of these drugs. To solve this setback in allotransplantation, researchers have focused on manipulating the immune response in order to create a state of tolerance rather than unspecific immunosuppression. Here, we describe the different treatments and some of the novel immunotherapeutic strategies undertaken to induce transplantation tolerance.

Ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) activities in prostate cancer patients: influence of Gleason score, treatment and bone metastasis.

The relation between adenine nucleotides and cancer has already been described in literature. Considering that the enzymes ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) act together to control nucleotide levels, we aimed to investigate the role of these enzymes in prostate cancer (PCa). E-NPP and ADA activities were determined in serum and platelets of PCa patients and controls. We also verified the influence of the Gleason score, bone metastasis and treatment in the enzyme activities. Platelets and serum E-NPP activity increased, whereas ADA activity in serum decreased in PCa patients. In addition, Gleason score, metastasis and treatment influenced E-NPP and ADA activities. We may propose that E-NPP and ADA are involved in the development of PCa. Moreover, E-NPP and ADA activities are modified in PCa patients with distinct Gleason score, with bone metastasis, as well as in patients under treatment.

T helper type 17 cells contribute to anti-tumour immunity and promote the recruitment of T helper type 1 cells to the tumour.

T helper type 17 (Th17) lymphocytes are found in high frequency in tumour-burdened animals and cancer patients. These lymphocytes, characterized by the production of interleukin-17 and other pro-inflammatory cytokines, have a well-defined role in the development of inflammatory and autoimmune pathologies; however, their function in tumour immunity is less clear. We explored possible opposing anti-tumour and tumour-promoting functions of Th17 cells by evaluating tumour growth and the ability to promote tumour infiltration of myeloid-derived suppressor cells (MDSC), regulatory T cells and CD4(+)  interferon-γ(+) cells in a retinoic acid-like orphan receptor γt (RORγt) -deficient mouse model. A reduced percentage of Th17 cells in the tumour microenvironment in RORγt-deficient mice led to enhanced tumour growth, that could be reverted by adoptive transfer of Th17 cells. Differences in tumour growth were not associated with changes in the accumulation or suppressive function of MDSC and regulatory T cells but were related to a decrease in the proportion of CD4(+) T cells in the tumour. Our results suggest that Th17 cells do not affect the recruitment of immunosuppressive populations but favour the recruitment of effector Th1 cells to the tumour, thereby promoting anti-tumour responses.

Role of the purinergic system in patients with cervical intraepithelial neoplasia and uterine cancer.

INTRODUCTION: Cervical cancer remains the second leading cause of death among women. Intraepithelial neoplasias and uterine invasive cancer are frequently associated with disturbances in coagulation and changes in the concentrations of adenine nucleotides. This work intended to analyze changes in extracellular adenine nucleotide hydrolysis and blood platelet aggregation in patients diagnosed for cervical intraepithelial neoplasia in different stages as well as uterine invasive cancer. PATIENTS AND METHODS: NTPDase, E-NPP, 5'-nucleotidase, total ADA and its isoforms (ADA1 and ADA2), as well as the platelet aggregation from patients with different stages of cervical intraepithelial neoplasia (NICs I, NIC II, NIC III) and uterine invasive cancer were verified. RESULTS: Neither ATP hydrolysis nor E-NPP activity was changed by the neoplasia stage. On the other hand, ADP and AMP hydrolysis as well as ADA activity were enhanced in NIC I group. AMP hydrolysis was also increased in the cancer group. ADA 1 was the ADA isoform found in platelets from both control and patient groups. CONCLUSION: Our results showed for the first time that NTPDase, 5'-nucleotidase, E-NPP and ADA are not sensible regarding the grade of neoplasia development, since no significant difference was found between the groups studied. Only ADP hydrolysis and ADA activity showed a significant enhancement in NIC I group related to the other stages possibly as a result of the beginning of the neoplasic transformation. This increase could be reflecting a body's reaction against the probable high adenosine levels. We propose for the first time that the ADA isoform present in platelets is ADA 1.

Lung cancer alters the hydrolysis of nucleotides and nucleosides in platelets.

BACKGROUND: The nucleotides and nucleosides of adenine are signaling molecules related to thromboregulation and modulation of immune responses in patients with malignancies. Thus, this study aims to determine NTPDase, 5'-nucleotidase, ectonucleotide pyrophosphatase/phosphodiesterase (E-NPP) and adenosine deaminase (ADA) activities in the platelets of patients with lung cancer. METHODS: We collected blood samples from patients (n=33) previously treated for lung cancer with chemotherapy. Patients were classified as stage IIIb and IV according to the Union for International Cancer Control (UICC). RESULTS: Patients showed a significant decrease in the hydrolysis of adenosine diphosphate (ADP) and adenosine, whereas the adenosine monophosphate (AMP) hydrolysis and platelet aggregation were significantly increased in this group. Adenosine triphosphate (ATP) hydrolysis did not show significant results between the group of patients and the control group. CONCLUSIONS: We may suggest that ectonucleotidases as well as ADA are enzymes involved in thromboembolic events but especially here we may see that they are also directly involved in the generation of adenosine formation in the cancer patient circulation.

Microinvasive squamous carcinoma (FIGO stage IA1) of the cervix: are there colposcopic criteria for the diagnosis?

OBJECTIVE: The purpose of this study was to evaluate colposcopic sensitivity in the diagnosis of microinvasive squamous carcinoma of the cervix. STUDY DESIGN: We conducted a cross-sectional study in 151 patients from 1991-2008. The colposcopic findings of microinvasion suspicion were described by the International Federation for Cervical Pathology and Colposcopy in 2003. RESULTS: There has been colposcopic suspicion of invasion in 35 patients, which represents a sensitivity of 23%. The major colposcopic findings that were observed in the transformation zone included acetowhite epithelium in 21% (32/151 patients), coarse punctuation in 19% (29/151 patients), coarse mosaic in 17% (26/151 patients), and atypical vessels in 3.9% (6/151 patients). Suspicion of microinvasion was found in 14.5% of unsatisfactory colposcopy and in 8.6% of satisfactory colposcopy. CONCLUSION: The sensitivity of colposcopy in the diagnosis of microinvasive carcinoma of the cervix was low. Colposcopy plays an important role in directing the biopsy to the most suspicious area. The definitive diagnosis of microinvasive squamous carcinoma is established only by histologic study.

Nucleotide degrading enzymes in platelets from uterine cervical neoplasia patients treated with conization or radiotherapy.

BACKGROUND: Uterine cervical neoplasia is an important worldwide malignancy sometimes associated with thrombosis. Ectonucleotidases are membrane-bound enzymes which participate in thromboregulation by hydrolyzing adenine nucleotides in the extracellular medium. In this sense, we aimed to investigate their activity in patients with uterine cervical neoplasia. METHODS: We evaluated NTPDase and 5'-nucleotidase activities from patients previously treated for uterine cervical neoplasia with either conization or radiotherapy (RTX). These patients were divided into four groups: two conization groups (I and II) and two RTX groups (III and IV), which were further divided based on the amount of time that had passed since the conclusion of their treatment, where groups I and III were extended-remission-period groups (patients with 1 to 5 years elapsed after the conclusion of treatment), and groups II and IV were recently treated patients (treated up to three months before). RESULTS: For both conization and RTX groups, ATP and ADP hydrolysis decreased in the extended-remission groups when compared to the control and recently treated groups. On the other hand, AMP hydrolysis was decreased in all the treated groups (both conization and RTX) compared to the control. CD39 expression was decreased in extended-remission groups (I and III) when compared to the other groups. CONCLUSIONS: NTPDase protects against platelet aggregation and 5'-nucleotidase is more involved in the control of adenosine formation.

The presence of methylation of the p16INK4A gene and human papillomavirus in high-grade cervical squamous intraepithelial lesions.

Methylation is a chemical modification in which a methyl group (CH3) is added to the cytosine in the promoter region of the gene. It involves a very frequent epigenetic event that is found in many human cancers. Currently, there is no consensus on whether methylation of the p16 gene could be used as a biomarker in cervical intraepithelial neoplasia. The authors studied the presence of methylation of the p16 gene and human papillomavirus (HPV) DNA, and a possible relationship between them in high-grade squamous intraepithelial lesions of the cervix. This case-control study analyzed 27 high-grade squamous intraepithelial lesion samples and 20 normal cytology samples. To detect p16 methylation, methylation-specific polymerase chain reaction was used, and for HPV DNA detection the polymerase chain reaction was performed by using MY09/MY11 and GP5+/GP6+ consensus primers. The presence of methylation of the promoter region of the p16INK4a gene was detected in 55.6% of the samples from the case group, whereas it was detected only in 20% of the samples from the control group (P=0.005). HPV DNA was found in 66.7% of the samples from the case group, whereas only 15% from the control group (P=0.0001). The relationship between the presence of methylation of the p16 gene and HPV DNA did not prove statistically significant in the case group (P=0.67) or the control group (P=0.51). In conclusion, the presence of methylation of the p16 gene constituted an occurrence that was early but independent of the presence of HPV DNA.

Ectonucleotidase and acetylcholinesterase activities in synaptosomes from the cerebral cortex of streptozotocin-induced diabetic rats and treated with resveratrol.

The aim of the present study was to investigate the effects of resveratrol (RV), an important neuroprotective compound on NTPDase, 5'-nucleotidase and acetylcholinesterase (AChE) activities in cerebral cortex synaptosomes of streptozotocin (STZ)-induced diabetic rats. The animals were divided into six groups (n=8): control/saline; control/RV 10mg/kg; control/RV 20mg/kg; diabetic/saline; diabetic/RV 10mg/kg; diabetic/RV 20mg/kg. After 30 days of treatment with resveratrol the animals were sacrificed and the cerebral cortex was removed for synaptosomes preparation and enzymatic assays. The results demonstrated that NTPDase and 5'-nucleotidase activities were significantly increased in the diabetic/saline group (p<0.05) compared to control/saline group. Treatment with resveratrol significantly increased NTPDase, 5'-nucleotidase activities in the diabetic/RV10 and diabetic/RV20 groups (p<0.05) compared to diabetic/saline group. When resveratrol was administered per se there was also an increase in the activities of these enzymes in the control/RV10 and control/RV20 groups (p<0.05) compared to control/saline group. AChE activity was significantly increased in the diabetic/saline group (p<0.05) compared to control/saline group. The treatment with resveratrol prevented this increase in the diabetic/RV10 and diabetic/RV20 groups. In conclusion, this study demonstrated that the resveratrol interfere with the purinergic and cholinergic neurotransmission by altering NTPDase, 5'-nucleotidase and AChE activities in cerebral cortex synaptosomes of diabetic rats. In this context, we can suggest that resveratrol should be considered potential therapeutics and scientific tools to be investigated in brain disorders associated with the diabetes.

Effect of different vasodilators on NTPDase activity in healthy and hypertensive patients.

INTRODUCTION: The thrombogenic process that affects the hypertensive patient is associated with regulatory mechanisms present in the vascular endothelium. These mechanisms involve release of an endothelium-derived relaxing factor, ectonucleotidase activity and calcium ion concentration. METHODS: Interference with ENTPDase activity in platelets of hypertensive patients and healthy donors was evaluated for arginine, sodium nitroprusside, and hydralazine. In addition, the kinetic behavior of NTPDase was determined in the presence of the vasodilator that showed the greatest inhibitory influence. RESULTS: Vasodilators decreased NTPDase activity with ATP and ADP as substrates. In controls, hydrolysis was increased in the presence of arginine. Captopril did not affect enzyme activities. The dose response for increasing sodium nitroprusside was biphasic. Kinetic behavior studies were estimated in the presence of sodium nitroprusside, which caused a mixed inhibition. The K(m) values increased and V(max) decreased with increasing sodium nitroprusside concentrations. The IC(50) and K(i) values indicated that the vasodilator was a strong NTPDase inhibitor when tested for the control and hypertensive group, using ATP and ADP as substrate, respectively. CONCLUSION: It is postulated that there was an interaction between vasodilators, NO donors and inhibition of NTPDase.

Effects of resveratrol on nucleotide degrading enzymes in streptozotocin-induced diabetic rats.

AIMS: Diabetes mellitus is associated with platelet alterations that may contribute to the development of cardiovascular complications. The present study investigates the effects of resveratrol (RSV), an important compound with cardioprotective activities, on NTPDase, ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP), 5'-nucleotidase and adenosine deaminase (ADA) activities in platelets from streptozotocin (STZ)-induced diabetic rats. MAIN METHODS: The animals were divided into six groups (n=8): control/saline; control/RSV 10 mg/kg; control/RSV 20 mg/kg; diabetic/saline; diabetic/RSV 10 mg/kg; diabetic/RSV 20 mg/kg. RSV was administered during 30 days and after this period the blood was collected for enzymatic assay. KEY FINDINGS: The results demonstrated that NTPDase, E-NPP and 5'-nucleotidase activities were significantly higher in the diabetic/saline group (P<0.05) compared to control/saline group. Treatment with RSV significantly increased NTPDase, 5'-nucleotidase and E-NPP activities in the diabetic/RSV10 and diabetic/RSV20 groups (P<0.05) compared to diabetic/saline group. When RSV was administered per se there was also an increase in the activities of these enzymes in the control/RSV10 and control/RSV20 groups (P<0.05) compared to control/saline group. ADA activity was significantly increased in the diabetic/saline group (P<0.05) compared to control/saline group. The treatment with RSV prevented this increase in the diabetic/RSV10 and diabetic/RSV20 groups. No significant differences in ADA activity were observed in the control/RSV10 and control/RSV20 compared to control/saline group. SIGNIFICANCE: The present findings demonstrate alterations in nucleotide hydrolysis in platelets of STZ-induced diabetic rats and treatment with RSV was able to modulate adenine nucleotide hydrolysis, which may be important in the control of the platelet coagulant status in diabetes.

Measurement of oxidative stress and antioxidant status in acute lymphoblastic leukemia patients.

OBJECTIVES: To evaluate the oxidative status and antioxidant defense in patients with acute lymphoblastic leukemia (ALL). DESIGN AND METHODS: We measured concentrations of plasmatic thiobarbituric acid reactive substances (TBARS), serum protein carbonylation, whole blood catalase (CAT) and superoxide dismutase (SOD) activities, as well as the plasmatic and erythrocyte thiol levels and serum vitamin E concentration. This study was performed on 80 children with ALL divided into 4 groups: just diagnosed, remission induction, remission maintenance and out-of-treatment. RESULTS: TBARS levels and serum protein carbonylation were higher in ALL patients than in controls and reduced levels of antioxidants were found in these patients. CONCLUSION: These findings may indicate a possible link between decreased antioxidants and increased levels of cells alterations due to oxidative damage, supporting the idea that there is a persistence of oxidative stress in acute lymphoblastic leukemia.