Purine nucleoside phosphorylase: A potential target for the development of drugs to treat T-cell- and apicomplexan parasite-mediated diseases

Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of nucleosides and deoxynucleosides, generating ribose 1-phosphate and the purine base, which is an important step of purine catabolism pathway. The lack of such an activity in humans, owing to a genetic disorder, causes T-cell impairment, and thus drugs that inhibit human PNP activity have the potential of being utilized as modulators of the immunological system to treat leukemia, autoimmune diseases, and rejection in organ transplantation. Besides, the purine salvage pathway is the only possible way for apicomplexan parasites to obtain the building blocks for RNA and DNA synthesis, which makes PNP from these parasites an attractive target for drug development against diseases such as malaria. Hence, a number of research groups have made efforts to elucidate the mechanism of action of PNP based on structural and kinetic studies. It is conceivable that the mechanism may be different for PNPs from diverse sources, and influenced by the oligomeric state of the enzyme in solution. Furthermore, distinct transition state structures can make possible the rational design of specific inhibitors for human and apicomplexan enzymes. Here, we review the current status of these research efforts to elucidate the mechanism of PNP-catalyzed chemical reaction, focusing on the mammalian and Plamodium falciparum enzymes, targets for drug development against, respectively, T-Cell and Apicomplexan parasites-mediated diseases.

Paediatric rheumatology - A global perspective

This chapter aims to give a global perspective to paediatric rheumatology. The main points covered are the incidence, recognition of paediatric autoimmune diseases, and ethnic/geographic distribution. The most prevalent disease is juvenile idiopathic arthritis; robust data are still required for childhood-onset systemic lupus erythematosus, dermatomyositis, and scleroderma. Mimicking or overlapping infections are a major challenge in developing countries, and immunization policies in our patients in these areas need specific attention. The delivery of paediatric rheumatology care is also overviewed. Discrepancies in health-care resources and priorities are found in developing countries. Although most anti-rheumatic treatments are available worldwide, they are prohibitively expensive in many countries. For more traditional antirheumatic drugs there is still an ongoing need for good core outcome data across the world to ensure valid comparisons. Parent/patient education has been implemented worldwide in paediatric rheumatology through the power of the Internet. Physician and undergraduate training goals must be met to facilitate competent musculoskeletal assessment, a proper understanding of age-dependent variations, diagnosis, referral to specialists, and improved standards of care.

Incidência de malformações congênitas em crianças concebidas através de injeção intracitoplasmática de espermatozóides

Purpose: to evaluate the incidence and types of major congenital malformations (MCM) in liveborn children conceived by intracytoplasmic sperm injection (ICSI). Methods: a total of 680 liveborn children resulted from 511 couples submitted to ICSI from January, 1999 to December, 2002. Data collection of the children was performed through standardized questionnaire and clinical examination. Of the 511 couples, 366 had been contacted for a sampling of 371 gestations. Of the 680 liveborn, 520 had been evaluated, 250 of them (48.1%) through questionnaire and 270 (51.9%) through questionnaire and physical examination. Two hundred and fifty children were from singleton pregnancies and 270 from multiple pregnancies. Malformations were classified according to the 10th revision of the International Statistical Classification of Diseases and Related Health. Only MCM were analyzed in this study. The incidence of MCM was compared with that of the general population obtained by the Latin American Collaborative Study of Congenital Malformations. The statistical analysis was performed by the χ 2 test (level of significance p<0.05). Results: of the 520 children, 15 presented MCM, resulting in an incidence of 2.9%. There was no difference in relation to the control group (p>0.05), which showed 2.6% incidence of MCM. The most frequent malformations were of cardiac origin (four isolated and two associated), corresponding to 40% of the total. The other types of MCM were: renal (three), neural tube (two), skull (one), cleft lip (one), genital (one), Down syndrome (associated with cardiac malformations) (two), and musculoskeletal (one). Six MCM occurred in children from singleton pregnancies and nine in children from multiple pregnancies. Conclusion: the liveborn children conceived by ICSI presented incidence of major congenital malformations (2.9%) near to the expected for the general population (2.6%). However, to establish the risks of MCM with precision it is necessary to continue the evaluation of the children conceived by ICSI.

Tele-education environment and didactic iconography in sexual transmitted diseases

The field of advertising has developed techniques of mass communication and rapid transmission of information. Among these techniques are slogans and iconographies. This work used such tools for educational purposes and was divided into three modules. Module 1 evaluated the use of simplified textual communication (slogans) about the subject Sexually Transmitted Diseases. It was applied to third-year medical students, which had not taken the course on this theme. To evaluate the impact of the textual communication form (slogans), long phrases were elaborated in scientific language containing 15 topics. From these long phrases, compact phrases were developed using techniques of the advertising area for elaboration of slogans. Three forms of didactic material about that theme were developed. The first form consisted of long phrases in descriptive topics, using scientific language. The second was constituted exclusively of compact phrases in the form of slogans, and the third was composed of the combination of the two previous forms. Then, 10 multiple-choice questions were elaborated and applied in two phases. In the first phase, application occurred immediately after the reading of didactic texts; in the second phase, it happened 60 days after the reading. For statistical analysis, Snedcor's F test was used for analysis of variance, at 5% significance level. There was an increase in memorization by students who read the material containing the association between long phrases and slogans, which indicates that the latter, when used as an auxiliary model of learning, can bring significant benefits for education. Module 2 consisted of analyzing the elaboration of educational videos produced in graphic computing (called iconographies) for development of dynamic communication means. The theme Hair Cycle was utilized. Viability of high quantities of information in few minutes of animation could be demonstrated together with the advantage of presenting the process in a dynamic form without wasting scientific details. Module 3 presented the inclusion of slogans in educational videos produced in graphic computing about the Hair Cycle, showing a new tool for rapid and efficient transference of data. Slogans and iconographies, when utilized in educational material, can bring significant benefits for the student's learning.

Chorismate synthase: An attractive target for drug development against orphan diseases

The increase in incidence of infectious diseases worldwide, particularly in developing countries, is worrying. Each year, 14 million people are killed by infectious diseases, mainly HIV/AIDS, respiratory infections, malaria and tuberculosis. Despite the great burden in the poor countries, drug discovery to treat tropical diseases has come to a standstill. There is no interest by the pharmaceutical industry in drug development against the major diseases of the poor countries, since the financial return cannot be guaranteed. This has created an urgent need for new therapeutics to neglected diseases. A possible approach has been the exploitation of the inhibition of unique targets, vital to the pathogen such as the shikimate pathway enzymes, which are present in bacteria, fungi and apicomplexan parasites but are absent in mammals. The chorismate synthase (CS) catalyses the seventh step in this pathway, the conversion of 5-enolpyruvylshikimate-3-phosphate to chorismate. The strict requirement for a reduced flavin mononucleotide and the anti 1,4 elimination are both unusual aspects which make CS reaction unique among flavin-dependent enzymes, representing an important target for the chemotherapeutic agents development. In this review we present the main biochemical features of CS from bacterial and fungal sources and their difference from the apicomplexan CS. The CS mechanisms proposed are discussed and compared with structural data. The CS structures of some organisms are compared and their distinct features analyzed. Some known CS inhibitors are presented and the main characteristics are discussed. The structural and kinetics data reviewed here can be useful for the design of inhibitors. © 2007 Bentham Science Publishers Ltd.

A clinical decision support system for cancer diseases

The second main cause of death in Brazil is cancer, and according to statistics disclosed by National Cancer Institute from Brazil (INCA) 466,730 new cases of cancer are forecast for 2008. The analysis of tumour tissues of various types and patients' clinical data, genetic profiles, characteristics of diseases and epidemiological data may lead to more precise diagnoses, providing more effective treatments. In this work we present a clinical decision support system for cancer diseases, which manages a relational database containing information relating to the tumour tissue and their location in freezers, patients and medical forms. Furthermore, it is also discussed some problems encountered, as database integration and the adoption of a standard to describe topography and morphology. It is also discussed the dynamic report generation functionality, that shows data in table and graph format, according to the user's configuration. © ACM 2008.

Absence motivated by illness: A non-concurrent prospective study of physical education teachers in the municipal education system of the city of Campinas, São Paulo, Brazil

The object of this investigation was to identify and analize aspects of the health status related to absenteism in physical education teachers in the municipal education system of the city of Campinas, Brazil, as related to the medical leave program. The non-concurrent prospective study was accomplished by means of a comparison with teachers who work only in the classroom, refering to a three year period. In the variables of greatest interest, the Pearson non-parametric chi-square (X2) statistical test was adopted. Calculations of relative risk and level of confidence were made using the Epi-info computer program. Significant differences were observed in the following diagnostic groups favoring the not exposed group: i) Supplementary Classification of factors that exercise influence over the health status and access to health services and ii) Digestive system illness; while the physical education teachers showed a significant difference in: i) diseases of the musculoskeletal and connective tissue system and ii) Injuries and poisoing. Possible explications for some of the adverse effects as well as the protective ones that were observed include physical activity as a way of life along with being a physical education teacher and on the other side, peculiar behavior of epidemiological descriptive characteristics, like sex and age, within the socio-economic context of the country. © Copyright Moreira Jr. Editora.

Identification of foliar diseases in cotton crop

The pathogens manifestation in plantations are the largest cause of damage in several cultivars, which may cause increase of prices and loss of crop quality. This paper presents a method for automatic classification of cotton diseases through feature extraction of leaf symptoms from digital images. Wavelet transform energy has been used for feature extraction while Support Vector Machine has been used for classification. Five situations have been diagnosed, namely: Healthy crop, Ramularia disease, Bacterial Blight, Ascochyta Blight, and unspecified disease. © 2012 Taylor & Francis Group.

Advances in drug design based on the amino acid approach: Taurine analogues for the treatment of CNS diseases

Amino acids are well known to be an important class of compounds for the maintenance of body homeostasis and their deficit, even for the polar neuroactive aminoacids, can be controlled by supplementation. However, for the amino acid taurine (2-aminoethanesulfonic acid) this is not true. Due its special physicochemical properties, taurine is unable to cross the blood-brain barrier. In addition of injured taurine transport systems under pathological conditions, CNS supplementation of taurine is almost null. Taurine is a potent antioxidant and anti-inflammatory semi-essential amino acid extensively involved in neurological activities, acting as neurotrophic factor, binding to GABA A/glycine receptors and blocking the excitotoxicity glutamate-induced pathway leading to be a neuroprotective effect and neuromodulation. Taurine deficits have been implicated in several CNS diseases, such as Alzheimer's, Parkinson's, epilepsy and in the damage of retinal neurons. This review describes the CNS physiological functions of taurine and the development of new derivatives based on its structure useful in CNS disease treatment.&; 2012 by the authors; licensee MDPI, Basel, Switzerland.

Fatores de risco de desordens osteomusculares presentes no posto de trabalho de estudantes de odontologia

Objective: To identify the perception of undergraduate dental students with respect of the risk factors present at the study/work place that could contribute to the development of musculoskeletal disorders. Method: A total of 348 undergraduate dental students from Araraquara Dental School - UNESP were evaluated. The Portuguese version of the Work-related activities that may contribute to job-related pain and/or injury questionnaire was used. Data were analyzed by descriptive statistics. Results: The mean perception of the undergraduates was 5.68 (SD=1.92). The factors with highest mean values were continue working with some kind of pain or lesion (7.49, SD=2.55), bending or twisting the back in an uncomfortable manner (7.39, SD=2.59), working in uncomfortable/inadequate positions (7.27. SD=2.60) and working in the same position for long periods (7.02. SD=2.53). Overall, female students presented higher mean scores of perception than male students. The body parts with highest prevalence of pain were the neck (67.0%) and lower back (65.8%). Conclusion: The students showed perception in relation to the risk factors for musculoskeletal disorders present at the study/work place.