Total syntheses and antiproliferative activities of prenostodione and its analogues.

A high-yielding total synthesis of the indole alkaloid prenostodione was completed in 4 steps and 44% overall yield from 1H-indole-3-carboxylic acid. The expedient syntheses of prenostodiones containing distinct substituents at the para position of the phenyl frame underscored the scope of this methodology. The cytotoxic activities of the tert-butyl esters of prenostodione analogues were tested using six tumor cell lines. Preliminary structure-activity studies revealed the importance of the identity of the aromatic substituent at the C-4 position for cytotoxic activity. The IC50 values of these compounds were found to compare satisfactorily with those of the commercially available drugs etoposide and cisplatin. Furthermore, the compounds with, respectively, -OMe (14d) and -NO2 (14f) groups at C-4 were more selective than these control compounds in PC-3, K-562, and MCF-7 cells. Also, computational studies were carried out to determine the ADMET profiles and passive membrane permeabilities of the compounds. The results suggested the promise of 14d and 14f as hit compounds for the development of new anticancer agents.

Synthesis and antituberculosis activity of new acylthiosemicarbazides designed by structural modification.

Acylthiosemicarbazides 8a-n were designed by structural modification of lead Compound 7. The syntheses of 8a-n involve a five-step procedure starting from carboxylic acids. Compounds 8a-n were tested against three Mycobacterium tuberculosis strains to measure their inhibitory antituberculosis activities. These activities could be explained according to the presence or absence of the chlorine substituent in the aromatic ring of the amide joined to the thiosemicarbazide core. Thiosemicarbazide derivative 8n is a candidate for the development of novel antitubercular agents. Ongoing studies are focused on exploring the mechanism by which these compounds inhibit M. tuberculosis cell growth.

5,6-Dihydropyrrolo[2,1-a]isoquinolines as Alternative of New Drugs with Cytotoxic Activity.

In this study, the pyrrolo[2,1-a]isoquinolines 4a-n were synthesized in good yields in a three steps synthesis from the corresponding α,ß-unsaturated esters starting materials. These compounds were tested on six human cancer cells lines to measure the cytotoxic activity as a function of the electronic properties and aromaticity of the substituent at the C-2 position of the pyrroloisoquinoline. Our results reveal that the cytotoxic activity could be explained in terms of the distribution of electronic density across the ring joined to C-2. Also, this study identified 3-hydroxy (4d) and 3-chloro (4j) derivatives with powerful cytotoxic activities. The IC50 values of these compounds were found to be comparable to those of the commercially available Topotecan, Irinotecan, Etoposide, Tamoxifen, and Cisplatin.

Emergency First Responders' Misconceptions about Suicide: A Descriptive Study.

BACKGROUND: In 2022, suicide was the second leading cause of external death in Spain (the first among young people aged 15-29 years). This study aims to analyze the presence of myths among emergency first responders and identify the most prevalent false beliefs among them. METHODS: The research is a observational and descriptive study carried out using a questionnaire composed of a total of 25 myths, with the response options being true or false. A total of 543 professionals took part in the study. All of them could intervene before, during, and after a suicide attempt. RESULTS: The main finding of the study is that more than 50% of the participants accept as true the statement "There are more serious and less serious problems", underlining the idea that caring for patients could be related to the importance the health professional gives to the patients' problem. Myths such as "The suicidal person wants to die" and "The suicidal person is determined to die" are also evident. CONCLUSION: The subjective thought the first responder has about suicide could affect their acts, and there is a need to train first responders in suicidal behavior to be able to create an adequate approach.

Optimization of rifampicin encapsulation in PLGA polymeric reservoirs.

Rifampicin is one of the most commonly used antibiotics for treating tuberculosis, but shows low bioavailability and requires long-term administration, and hence its use may result in severe side effects. Encapsulation of rifampicin in polymeric reservoirs allows it to be administered locally and improves its pharmacological action. High rifampicin loading is crucial for obtaining an adequate therapeutic effect. Generally, the drug loading is a complex function of reservoir fabrication parameters. In the current work, we systematically varied the drug (rifampicin), polymer (PLGA) and dispersed phase contents as well as the solvent evaporation rate, particle size and number of particle washing cycles to characterize the challenges involved in encapsulating rifampicin. Physical insight into the low encapsulation efficiencies was provided, as well as an optimization of fabrication conditions to achieve higher drug loading levels. The particle solidification stage was found in the current work to be the most crucial step, where a significant amount of rifampicin was lost enhanced by its solubility in the aqueous medium. Increases in polymer concentration, solvent evaporation rate and particle size each significantly improved the drug loading by hindering of solvent-assisted escape of the drug. Based on our observation of the drug loading being extremely sensitive to the particle recovery and washing procedure after the solvent evaporation, most of the encapsulated rifampicin was concluded to be located on or very near the reservoir surface. Encapsulation could be significantly improved by fabricating multiple emulsions, especially double w/o/w emulsions, but the resultant particles were relatively large and porous, which might be a drawback for drug administration.

(2Z)-3-Hydroxy-3-(4-R-Phenyl)-Prop-2-Enedithioic Acids as New Antituberculosis Compounds.

BACKGROUND: Tuberculosis is an infectious disease caused by the bacillus Mycobacterium tuberculosis. Compounds including a sulfur-containing scaffold have been shown to be key scaffolds in various antituberculosis agents. Interestingly, the 3-hydroxy-3-phenyl-prop-2-enedithioic acids 11a-j have, to the best of our knowledge, not been previously described as antituberculosis agents. PURPOSE: In the present study, we investigated the role of substituents attached to the phenyl ring of a 3-hydroxy-3-phenyl-prop-2-enedithioic acid scaffold (compounds 11a-j) in inhibiting the growth of M. tuberculosis strain H37Rv. METHODS: (Z)-3-hydroxy-3-(4-R-phenyl)-prop-2-enedithioic acids 11b-j, with R groups including various electron-donating or electron-withdrawing groups, were designed by structurally modifying the lead compound 11a. The syntheses of 11a-j involved each one-step procedure starting from the corresponding substituted acetophenone. Compounds 11a-j were tested against M. tuberculosis strain H37Rv to evaluate their bacterial growth inhibitory activities. ADMET profiles were predicted by employing three different methods. In addition, molecular docking studies were carried out, based on the molecular similarities of the synthesized compounds with ethionamide (5), on the active site of the M. tuberculosis H37Rv (3R)-hydroxyacyl-ACP (HadAB) dehydratase heterodimer. RESULTS: The antituberculosis activities of compounds 11a-j could be explained in terms of the presence of electron-donating or electron-withdrawing substituents on the aromatic ring of the substituted 3-hydroxy-3-phenyl)-prop-2-enedithioic acid core. The activity and selectivity index (SI) value of (Z)-3-hydroxy-3-(4-nitrophenyl)-prop-2-enedithioic acid 11e suggested that this compound could be used for the design of novel antituberculosis agents. Most of the synthesized molecules showed an acceptable ADME profile and a low probability of being toxic. Docking studies of 11d and 11e showed them forming hydrogen bonds with the ACys61 residue of the HadAB enzyme. CONCLUSION: Our results suggested that the antituberculosis compound 11e could be used for the design of novel antituberculosis agents.

Early neonatal deaths associated with perinatal asphyxia in infants ≥2500g in Brazil.

OBJECTIVE: To assess the annual burden of early neonatal deaths associated with perinatal asphyxia in infants weighing ≥2500g in Brazil from 2005 to 2010. METHODS: The population study enrolled all live births of infants with birth weight ≥2500g and without malformations who died up to six days after birth with perinatal asphyxia, defined as intrauterine hypoxia, asphyxia at birth, or meconium aspiration syndrome. The cause of death was written in any field of the death certificate, according to International Classification of Diseases, 10th Revision (P20.0, P21.0, and P24.0). An active search was performed in 27 Brazilian federative units. The chi-squared test for trend was applied to analyze early neonatal mortality ratios associated with perinatal asphyxia by study year. RESULTS: A total of 10,675 infants weighing ≥2500g without malformations died within six days after birth with perinatal asphyxia. Deaths occurred in the first 24h after birth in 71% of the infants. Meconium aspiration syndrome was reported in 4076 (38%) of these deaths. The asphyxia-specific early neonatal mortality ratio decreased from 0.81 in 2005 to 0.65 per 1000 live births in 2010 in Brazil (p<0.001); the meconium aspiration syndrome-specific early neonatal mortality ratio remained between 0.20 and 0.29 per 1000 live births during the study period. CONCLUSIONS: Despite the decreasing rates in Brazil from 2005 to 2010, early neonatal mortality rates associated with perinatal asphyxia in infants in the better spectrum of birth weight and without congenital malformations are still high, and meconium aspiration syndrome plays a major role.

Toward hemodynamic diagnosis of carotid artery stenosis based on ultrasound image data and computational modeling.

The ability of using non-expensive ultrasound (US) image data together with computer fluid simulation to access various severities of carotid stenosis was inquired in this study. Subject-specific hemodynamic conditions were simulated using a developed finite element solver. Individual structured meshing of the common carotid artery (CCA) bifurcation was built from segmented longitudinal and cross-sectional US images; imposed boundary velocities were based on Doppler US measurements. Simulated hemodynamic parameters such as velocities, wall shear stress (WSS) and derived descriptors were able to predict disturbed flow conditions which play an important role in the development of local atherosclerotic plaques. Hemodynamic features from six individual CCA bifurcations were analyzed. High values of time-averaged WSS (TAWSS) were found at stenosis site. Low values of TAWSS were found at the bulb and at the carotid internal and external branches depending on the particular features of each patient. High oscillating shear index and relative residence time values assigned highly disturbed flows at the same artery surface regions that correlate only moderately with low TAWSS results. Based on clinic US examinations, results provide estimates of flow changes and forces at the carotid artery wall toward the link between hemodynamic behavior and stenosis pathophysiology.

Perfil sociodemográfico de idosos com a Síndrome da Imunodeficiência Adquirida no Brasil: revisão integrativa / Sociodemographic profile of elderly people with immunodeficiency syndrome Acquired in Brazil: integrative review / Perfil sociodemográfico de las personas mayores portadoras del Síndrome de Inmunodeficiencia Adquirida em Brasil: revisión integrativa

Este estudo objetiva determinar o perfil sociodemográfico dos idosos com HIV/AIDS, no Brasil, a partir de uma revisão bibliográfica na base de dados SciELO. Foram analisados 12 artigos publicados em português no período de 2012 a 2018. A infecção apresenta predominância de indivíduos do sexo masculino a partir de 60 anos, de cor branca e com menos de oito anos de escolaridade, sem diferenciação quanto ao estado civil, o que torna imprescindível o cuidado em saúde relacionado à vida sexual desses indivíduos.

This study, aims to determine the sociodemographic profile of elderly people living with HIV/AIDS in Brazil from a integrative review in the SciELO database. Analyzing 12 articles, published in Portuguese in the period from 2012 to 2018. The infection has a predominance of white men aged 60 years and older and less than 8 years of schooling, with no difference in marital status. Essential health care related to the sexual life of these individuals.

Este estudio tiene por objetivo, determinar el perfil sociodemográfico de las personas mayores con del VIH/Sida en el Brasil, desde una revisión integrativa en las bases de datos SciELO. Fueron analizados 12 artículos publicados en portugués en los años de 2012 a 2018. La infección presenta dominancia en las personas del sexo masculino a partir de los 60 años, blancos y con menos de 8 años de escolaridad, sin diferencia en el estado civil, lo que resulta imprescindible em el cuidado de la salud relacionada a la vida sexual de estos individuos.

Auditory hallucinations in tinnitus patients: Emotional relationships and depression.

INTRODUCTION: Over the last few years, our Tinnitus Research Group has identified an increasing number of patients with tinnitus who also complained of repeated perception of complex sounds, such as music and voices. Such hallucinatory phenomena motivated us to study their possible relation to the patients' psyches. AIMS: To assess whether hallucinatory phenomena were related to the patients' psychosis and/or depression, and clarify their content and function in the patients' psyches. METHOD: Ten subjects (8 women; mean age = 65.7 years) were selected by otolaryngologists and evaluated by the same psychologists through semi-structured interviews, the Hamilton Depression Rating Scale, and psychoanalysis interviews. RESULTS: We found no association between auditory hallucinations and psychosis; instead, this phenomenon was associated with depressive aspects. The patients' discourse revealed that hallucinatory phenomena played unconscious roles in their emotional life. In all cases, there was a remarkable and strong tendency to recall/repeat unpleasant facts/situations, which tended to exacerbate the distress caused by the tinnitus and hallucinatory phenomena and worsen depressive aspects. CONCLUSIONS: There is an important relationship between tinnitus, hallucinatory phenomena, and depression based on persistent recall of facts/situations leading to psychic distress. The knowledge of such findings represents a further step towards the need to adapt the treatment of this particular subgroup of tinnitus patients through interdisciplinary teamwork. Prospective.

Early neonatal deaths associated with perinatal asphyxia in infants ≥2500g in Brazil / Óbitos neonatais precoces associados à asfixia perinatal em neonatos ≥2500g no Brasil

Abstract Objective: To assess the annual burden of early neonatal deaths associated with perinatal asphyxia in infants weighing ≥2500 g in Brazil from 2005 to 2010. Methods: The population study enrolled all live births of infants with birth weight ≥2500 g and without malformations who died up to six days after birth with perinatal asphyxia, defined as intrauterine hypoxia, asphyxia at birth, or meconium aspiration syndrome. The cause of death was written in any field of the death certificate, according to International Classification of Diseases,10th Revision (P20.0, P21.0, and P24.0). An active search was performed in 27 Brazilian federative units. The chi-squared test for trend was applied to analyze early neonatal mortality ratios associated with perinatal asphyxia by study year. Results: A total of 10,675 infants weighing ≥2500 g without malformations died within six days after birth with perinatal asphyxia. Deaths occurred in the first 24 h after birth in 71% of the infants. Meconium aspiration syndrome was reported in 4076 (38%) of these deaths. The asphyxia-specific early neonatal mortality ratio decreased from 0.81 in 2005 to 0.65 per 1000 live births in 2010 in Brazil (p < 0.001); the meconium aspiration syndrome-specific early neonatal mortality ratio remained between 0.20 and 0.29 per 1000 live births during the study period. Conclusions: Despite the decreasing rates in Brazil from 2005 to 2010, early neonatal mortality rates associated with perinatal asphyxia in infants in the better spectrum of birth weight and without congenital malformations are still high, and meconium aspiration syndrome plays a major role.

Resumo Objetivo: Avaliar a taxa anual de óbitos neonatais precoces associados à asfixia perinatal em neonatos de peso ≥ 2.500 g no Brasil de 2005 a 2010. Métodos: A população do estudo envolveu todos os nascidos vivos de neonatos com peso ao nascer ≥ 2.500 g e sem malformações que morreram até seis dias após o nascimento por asfixia perinatal, definida como hipóxia intrauterina, asfixia no nascimento ou síndrome de aspiração de mecônio. A causa do óbito foi escrita em qualquer linha do atestado de óbito, de acordo com a Classificação Internacional de Doenças, 10a Revisão (P20.0, P21.0 e P24.0). Foi feita uma pesquisa ativa em 27 unidades federativas brasileiras. O teste qui-quadrado de tendência foi aplicado para analisar os índices de mortalidade neonatal associados a asfixia perinatal até o ano do estudo. Resultados: Morreram 10.675 neonatos com peso ≥ 2.500 g sem malformações até 0-6 dias após o nascimento por asfixia perinatal. Os óbitos ocorreram nas primeiras 24 horas após o nascimento em 71% dos neonatos. A síndrome de aspiração de mecônio foi relatada em 4.076 (38%) dos óbitos. O índice de mortalidade neonatal precoce relacionada à asfixia caiu de 0,81 em 2005 para 0,65 por 1.000 nascidos vivos em 2010 no Brasil (p < 0,001); o índice de mortalidade neonatal precoce relacionada a síndrome de aspiração de mecônio permaneceu entre 0,20-0,29 por 1.000 nascidos vivos durante o período do estudo. Conclusões: Apesar da redução nas taxas no Brasil de 2005 a 2010, as taxas de mortalidade neonatal precoce associadas à asfixia perinatal em neonatos no melhor espectro de peso ao nascer e sem malformações congênitas ainda são altas e a síndrome de aspiração de mecônio desempenha um importante papel.

Musical hallucination associated with hearing loss.

In spite of the fact that musical hallucination have a significant impact on patients' lives, they have received very little attention of experts. Some researchers agree on a combination of peripheral and central dysfunctions as the mechanism that causes hallucination. The most accepted physiopathology of musical hallucination associated to hearing loss (caused by cochlear lesion, cochlear nerve lesion or by interruption of mesencephalon or pontine auditory information) is the disinhibition of auditory memory circuits due to sensory deprivation. Concerning the cortical area involved in musical hallucination, there is evidence that the excitatory mechanism of the superior temporal gyrus, as in epilepsies, is responsible for musical hallucination. In musical release hallucination there is also activation of the auditory association cortex. Finally, considering the laterality, functional studies with musical perception and imagery in normal individuals showed that songs with words cause bilateral temporal activation and melodies activate only the right lobe. The effect of hearing aids on the improvement of musical hallucination as a result of the hearing loss improvement is well documented. It happens because auditory hallucination may be influenced by the external acoustical environment. Neuroleptics, antidepressants and anticonvulsants have been used in the treatment of musical hallucination. Cases of improvement with the administration of carbamazepine, meclobemide and donepezil were reported, but the results obtained were not consistent.

Group psychotherapy: an additional approach to burning mouth syndrome.

INTRODUCTION: Glossodynia or burning mouth syndrome (BMS) is a common and poorly understood disorder. Its treatment is uncertain. Otherwise, there is some evidence of the importance of psychological factors in the genesis of this disease. OBJECTIVES: Verify the usefulness of group psychotherapy as an adjuvant therapeutic method in the treatment of BMS. CASUISTICS AND METHODS: The study group consisted of 64 consecutive patients with a clinical diagnosis of BMS seen at the Stomatology Outpatient Clinic, ENT Department, Sao Paulo University Medical School, between May 2002 and May 2007. All the patients were submitted to physical examination, laboratorial screening tests, psychological assessment (Crown-Crisp Experimental Inventory), and answered a short form of the McGill Pain Questionnaire. Only 44 patients who did not show any abnormality in the protocol exams entered the study. Twenty-four of them underwent group psychotherapy. Twenty patients received placebo. Chi-square test was applied to compare the results of treatment with or without psychotherapy. RESULTS: There were 15 men and 29 women in the study group. Tongue burning was the main complaint of the patients. Improvement of symptoms was reported by 17 (70.8%) of the patients undergoing psychotherapy, while among those who did not eight (40%) had improvement of symptoms (P=.04). CONCLUSION: Psychological assessment demonstrated a close correlation between symptoms and psychological factors, suggesting that group psychotherapy is an important alternative to conventional treatment methods.

A stress-inducible resveratrol O-methyltransferase involved in the biosynthesis of pterostilbene in grapevine.

Stilbenes are considered the most important phytoalexin group in grapevine (Vitis vinifera) and they are known to contribute to the protection against various pathogens. The main stilbenes in grapevine are resveratrol and its derivatives and, among these, pterostilbene has recently attracted much attention due both to its antifungal and pharmacological properties. Indeed, pterostilbene is 5 to 10 times more fungitoxic than resveratrol in vitro and recent studies have shown that pterostilbene exhibits anticancer, hypolipidemic, and antidiabetic properties. A candidate gene approach was used to identify a grapevine resveratrol O-methyltransferase (ROMT) cDNA and the activity of the corresponding protein was characterized after expression in Escherichia coli. Transient coexpression of ROMT and grapevine stilbene synthase in tobacco (Nicotiana benthamiana) using the agroinfiltration technique resulted in the accumulation of pterostilbene in tobacco tissues. Taken together, these results showed that ROMT was able to catalyze the biosynthesis of pterostilbene from resveratrol both in vitro and in planta. ROMT gene expression in grapevine leaves was induced by different stresses, including downy mildew (Plasmopara viticola) infection, ultraviolet light, and AlCl(3) treatment.

Auditory hallucinations in tinnitus patients: Emotional relationships and depression

Introduction: Over the last few years, our Tinnitus Research Group has identified an increasing number of patients with tinnitus who also complained of repeated perception of complex sounds, such as music and voices. Such hallucinatory phenomena motivated us to study their possible relation to the patients' psyches. Aims: To assess whether hallucinatory phenomena were related to the patients' psychosis and/or depression, and clarify their content and function in the patients' psyches. Method: Ten subjects (8 women; mean age = 65.7 years) were selected by otolaryngologists and evaluated by the same psychologists through semi-structured interviews, the Hamilton Depression Rating Scale, and psychoanalysis interviews. Results: We found no association between auditory hallucinations and psychosis; instead, this phenomenon was associated with depressive aspects. The patients' discourse revealed that hallucinatory phenomena played unconscious roles in their emotional life. In all cases, there was a remarkable and strong tendency to recall/repeat unpleasant facts/situations, which tended to exacerbate the distress caused by the tinnitus and hallucinatory phenomena and worsen depressive aspects. Conclusions: There is an important relationship between tinnitus, hallucinatory phenomena, and depression based on persistent recall of facts/situations leading to psychic distress. The knowledge of such findings represents a further step towards the need to adapt the treatment of this particular subgroup of tinnitus patients through interdisciplinary teamwork. Prospective...

A implantação do Programa de Saúde da Família (PSF) no Estado de São Paulo (1995-2002) / The implementation of the Family Health Program (PSF) in the State of São Paulo (1995-2002)

Este artigo relata a implantação do Programa de Saúde da Família no Estado de São Paulo desde seu início até o ano de 2002. São mencionados como antecedentes importantes outros programas do Ministério da Saúde, como o PIASS (1976-1979), o PACS (1991) e o Projeto do Vale do Ribeira da SES-SP (1980-1987). Destaca-se também a importância do Programa metropolitano de Saúde na década de 1980 e do Movimento Popular de Saúde na Cidade de São Paulo desde a década de 1970. São descritas as principais características do modelo, a composição inicial da equipe mínima e a incorporação de novos atores no programa. São destacados três mecanismos de ação do Governo Estadual em relação ao desenvolvimento do PSF, sendo um de apoio técnico, outro de apoio técnico e financeiro e o terceiro de contratação direta de entidades filantrópicas para a implantação do programa no Município de São Paulo. A avaliação de todas as equipes de saúde da família implantadas no Estado de São Paulo, realizada em 2002, demonstrou grande aceitação da população em relação à atenção desenvolvida e identificou os problemas nos mecanismos de contratação dos profissionais da equipe. Este artigo descreve a preparação das equipes de trabalho e o papel dos Polos de Capacitação e todo o movimento envolvendo Cosems e gestores municipais, universidades e entidades da comunidade.(AU)

A implantação do Programa de Saúde da Família (PSF) no Estado de São Paulo (1995-2002) / The implementation of the Family Health Program (PSF) in the State of São Paulo (1995-2002)

Este artigo relata a implantação do Programa de Saúde da Família no Estado de São Paulo desde seu início até o ano de 2002. São mencionados como antecedentes importantes outros programas do Ministério da Saúde, como o PIASS (1976-1979), o PACS (1991) e o Projeto do Vale do Ribeira da SES-SP (1980-1987). Destaca-se também a importância do Programa metropolitano de Saúde na década de 1980 e do Movimento Popular de Saúde na Cidade de São Paulo desde a década de 1970. São descritas as principais características do modelo, a composição inicial da equipe mínima e a incorporação de novos atores no programa. São destacados três mecanismos de ação do Governo Estadual em relação ao desenvolvimento do PSF, sendo um de apoio técnico, outro de apoio técnico e financeiro e o terceiro de contratação direta de entidades filantrópicas para a implantação do programa no Município de São Paulo. A avaliação de todas as equipes de saúde da família implantadas no Estado de São Paulo, realizada em 2002, demonstrou grande aceitação da população em relação à atenção desenvolvida e identificou os problemas nos mecanismos de contratação dos profissionais da equipe. Este artigo descreve a preparação das equipes de trabalho e o papel dos Polos de Capacitação e todo o movimento envolvendo Cosems e gestores municipais, universidades e entidades da comunidade.

Erythrocyte glucose-6-phosphate dehydrogenase deficiency in male newborn babies and its relationship with neonatal jaundice / Deficiência de glicose-6-fosfato desidrogenase eritrocitária em recém-nascidos do sexo masculino e sua relação com a icterícia neonatal

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the commonest red cell enzymopathy in humans, has an X-linked inheritance. The major clinical manifestations are drug induced hemolytic anemia, neonatal jaundice and chronic nonspherocytic hemolytic anemia. The incidence of neonatal hyperbilirubinemia is much greater in G6PD-deficient neonates than babies without this deficiency. The aim of this study was to ascertain the presence of neonatal jaundice in erythrocyte G6PD-deficient male newborns. Samples of umbilical cord blood from a total of 204 male newborns of the Januário Cicco School Maternity located in Natal, Rio Grande do Norte, Brazil were analyzed. The G6PD deficiency was identified by the methemoglobin reduction test (Brewer's test). The deficiency was confirmed by quantitative spectrophotometric assay for enzyme activity and cellulose acetate electrophoresis was used to identify the G6PD variant. Eight newborns were found to be G6PD deficient with four of them exhibiting jaundice during the first 48 hours after birth with bilirubin levels higher than 10 mg/dL. All deficient individuals presented the G6PD A- variant at electrophoresis. Our findings confirmed the association between G6PD deficiency and neonatal jaundice. Hence, early diagnosis of the deficiency at birth is essential to control the appearance of jaundice and to prevent the exposure of these newborns to known hemolytic agents.

A deficiência de glicose-6-fosfato desidrogenase (G6PD) é a anormalidade enzimática hereditária mais frequente. É transmitida como caráter recessivo ligado ao cromossomo X e as principais manifestações clínicas são hemólise induzida por fármacos, icterícia neonatal e anemia hemolítica não esferocítica. O objetivo do estudo foi determinar a presença de icterícia neonatal em recém-nascidos do sexo masculino deficientes de glicose-6-fosfato desidrogenase. Foram analisadas 204 amostras de sangue umbilical de recém-nascidos do sexo masculino provenientes da Maternidade Escola Januário Cicco em Natal, Rio Grande do Norte. A deficiência da glicose-6-fosfato desidrogenase foi determinada através do método qualitativo da redução da metahemoglobina (teste de Brewer) e confirmada mediante determinação espectrofotométrica quantitativa da atividade da G6PD e pela eletroforese da enzima em acetato de celulose. Oito recém-nascidos apresentaram deficiência da G6PD, e quatro deles exibiram icterícia nas primeiras 48 horas depois do nascimento, com valores de bilirrubina maiores de 10 mg/dL. Todos os deficientes apresentaram a variante A-. Os dados encontrados confirmam a associação da deficiência da G6PD e a icterícia neonatal. Assim sendo, o diagnóstico precoce da deficiência logo após o nascimento é essencial ao controle do aparecimento da icterícia e para evitar o contato destes recém-nascidos com conhecidos agentes hemolíticos.

A criação de Saúde em Debate, revista do CEBES: narrando a própria história / The creation of Saúde em Debate, journal of CEBES: telling its own story

Este artigo trata de memórias da criaráo da revista Saúde em Debate no contexto das origens da Reforma Sanitária e foi elaborado com base em história oral sobre o surgimento do CEBES em São Paulo. O propósito é divulgar detalhes da mobilização que deu origem ao CEBES e à revista e a participaçao de sanitaristas de São Paulo nesse processo. Observou-se a influência de Virchow sobre David Capistrano da Costa Filho na criação da revista e a importância do curso de sanitaristas, criado por Walter Leser, que conceberam o CEBES e contribuíram na divulgacão de idéias sobre a Reforma Sanitária

This paper discusses details of the Sanitary Reform concerning the creation of Saúde em Debate, a journal of the Brazilian Center of Health Studies (CEBES) in the state of São Paulo. The study was based on oral history with key informants involved in the o foundation of both the magazine and the institution. The purpose is to show details of the mobilization, which gave life to CEBES, and the participation of public health doctors in this process. It is stated the influence of Virchow ideas over David Capistrano da Costa Filho in the creation of Saúde em Debate, and of a short course of public health doctors, created by Walter Leser, people who idealized CEBES and contributed to the Sanitary Reform.

A expressão de genes reparadores do DNA nos tumores sincrônicos de câncer colorretal esporádico / DNA repair gene expression in synchronic tumors of sporadic colorectal cancer

RACIONAL: Um dos mecanismos genéticos presentes em aproximadamente 80% dos pacientes com síndrome hereditária não-polipóide do câncer colorretal (HNPCC) são os defeitos nos genes reparadores de DNA, como o MSH2, MSH6 e MLH1, onde os tumores sincrônicos são relativamente freqüentes. Já no câncer colorretal esporádico as lesões sincrônicas são raras. OBJETIVO: Verificar se o mesmo mecanismo genético presente no HNPCC está presente no câncer colorretal esporádico que apresentam com lesões sincrônicas. MÉTODOS: Foram incluídos no estudo todos os pacientes com câncer colorretal sincrônico não HNPCC. Imunoistoquímica com anticorpos para MSH2,MSH6, e MLH1 foi realizada para cada tumor. RESULTADOS: Todos os pacientes apresentaram expressão normal de MSH2 e MLH1. O único gene com imunoexpressão alterada foi o MSH6. CONCLUSÃO: Possivelmente outro mecanismo genético seja responsável pelo surgimento de dois tumores sincrônicos no câncer colorretal esporádico.

BACKGROUND: Mismatch repair genes (such as MSH2, MLH1 and MSH6) mutations are present in over 80% of hereditary non-polyposis colorectal cancer (HNPCC) tumors, which frequently exhibit synchronous lesions. Sporadic colorectal cancer is rarely associated with synchronous lesions. AIM: To investigate the role of mismatch repair gene mutation in synchronous sporadic colorectal cancer. METHODS: Patients with sporadic synchronous colorectal adenocarcinomas were included in the study. Immunohistochemistry was performed using MSH2, MLH1 and MSH6 antibodies. RESULTS: All patients had two synchoronous lesions. None of them had altered MSH2 or MLH1 expression. One patient had altered MSH6 expression in both tumors. CONCLUSION: Possibly, other molecular mechanisms are involved in carcinogenesis of sporadic synchronous colorectal cancer.