Fructose-1,6-bisphosphate preserves glucose metabolism integrity and reduces reactive oxygen species in the brain during experimental sepsis.

Sepsis is one of the main causes of hospitalization and mortality in Intensive Care Units. One of the first manifestations of sepsis is encephalopathy, reported in up to 70% of patients, being associated with higher mortality and morbidity. The factors that cause sepsis-associated encephalopathy (SAE) are still not well known, and may be multifactorial, as perfusion changes, neuroinflammation, oxidative stress and glycolytic metabolism alterations. Fructose-1,6-bisphosphate (FBP), a metabolite of the glycolytic route, has been reported as neuroprotective agent. The present study used an experimental sepsis model in C57BL/6 mice. We used in vivo brain imaging to evaluate glycolytic metabolism through microPET scans and the radiopharmaceutical 18F-fluoro-2-deoxy-D-glucose (18F-FDG). Brain images were obtained before and 12 h after the induction of sepsis in animals with and without FBP treatment. We also evaluated the treatment effects in the brain oxidative stress by measuring the production of reactive oxygen species (ROS), the activity of catalase (CAT) and glutathione peroxidase (GPx), and the levels of fluorescent marker 2'7'-dichlorofluorescein diacetate (DCF). There was a significant decrease in brain glucose metabolism due to experimental sepsis. A significant protective effect of FBP treatment was observed in the cerebral metabolic outcomes. FBP also modulated the production of ROS, evidenced by reduced CAT activity and lower levels of DCF. Our results suggest that FBP may be a possible candidate in the treatment of SAE.

A certificate program in health informatics: Brazil/USA experience.

Considering the continued demand for a large number of trained professionals we decided to offer a certificate program in health informatics. The objective is to prepare professionals to conduct research and implement the curriculum content in their original institutions. We selected 14 candidates from several national institutes. The disciplines are taught by Brazilian and US faculty. Researches conducted by the certificate students were relevant to Brazil's health needs. The goal is to promote better health informatics education, regardless of geographic distribution of students.

Experimental Lung Injury Promotes Changes in Oxidative/Nitrative Status and Inflammatory Markers in Cerebral Cortex of Rats.

In the present study, we investigate the effect of lung injury on parameters of oxidative/nitrative stress [reactive oxygen species production, nitrite levels, thiobarbituric acid-reactive substances (TBARS), carbonyl content, sulfhydryl content, activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), total radical-trapping antioxidant potential, glutathione content, and glucose-6-phosphate dehydrogenase], as well as on inflammation mediators [immunocontent of nuclear factor-kappaB (NF-κB) total (p65), NF-κB phosphorylated (pp65) subunit (cytosolic and nuclear), TNF-α, IL-1ß, IL-6, and IL-10] in the cerebral cortex. Cytokine levels in serum were also evaluated. Adult Wistar rats were submitted to lung injury induced by intratracheal instillation of lipopolysaccharide in a dose of 100 µg/100 g body weight. Sham group (control) received isotonic saline instillation. Twelve hours after the injury, rats were decapitated and blood samples were collected and the cerebral cortex dissected out. Results showed an increase in reactive oxygen species production, TBARS, and nitrite and carbonyl levels in the cerebral cortex of rats submitted to lung injury. Antioxidant enzymatic defenses were altered, superoxide dismutase and glutathione peroxidase activities decreased, and catalase activity increased. Non-enzymatic antioxidant capacity, glutathione content, and glucose-6-phosphate dehydrogenase were decreased. Inflammatory parameters were also altered in the cerebral cortex of rats subjected to lung injury; it was observed an increase in the immunocontent of NF-κB/p65 (nuclear fraction) and NF-κB/pp65 (cytosolic and nuclear faction), as well as an increase in TNF-α, IL-1ß, IL-6, and IL-10 levels. The levels of IL-10 also increased in the serum. Our findings show that the lung injury alters oxidative/nitrative status and induces inflammation in the cerebral cortex of rats, which might be associated with cognitive impairments present in patients with lung injury.

International training in health informatics: a Brazilian experience.

Technology is transforming not only the practice of health-care but also professional training and educational models. Developing countries, such as Brazil, are increasingly suffering from a severe shortage of health informatics specialists. Training of professionals in this field is expensive, and there is a limited supply of high-quality teaching resources available. We envision that training in health informatics can be better achieved if cultural and technological barriers are anticipated and the training program is prepared accordingly. We describe our four-year experience of a Brazil/USA training program and discuss lessons learned during its implementation. Eleven onsite courses, one seminar, and two conferences were developed under this unique initiative, which made possible the collaboration among different countries and distinguished leaders in the field of medical informatics.

Training in health informatics in Brazil.

Developing countries, such as Brazil, are increasingly suffering from a severe shortage of health informatics specialists. Training of professionals in this field is expensive, and there is a limited supply of high-quality teaching resources available. We report on five initiatives of the Brazil/USA training program in health informatics. The main goal of this program is to train professionals in establishing medical informatics programs in Brazilian universities and major healthcare facilities.

Guanidinoacetate Methyltransferase Deficiency: A Review of Guanidinoacetate Neurotoxicity

Abstract Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessively inherited disorder of the metabolism of creatine that leads to depleted levels of creatine and excessive concentrations of guanidinoacetate (GAA). Patients affected develop neurological symptoms during childhood, such as muscular hypotonia, involuntary extrapyramidal movements, convulsions, slurred speech, and even autism. Although the pathophysiology of GAMT deficiency is unclear, neurological dysfunction is commonly found in this disease, and it has been mainly attributed to a reduction in creatine or/and an increase in GAA levels. Reports from literature suggest that GAA may interfere with neuronal γ-aminobutyric acid (GABA) receptors type A and cause epilepsy in human. Preclinical studies show that GAA increases free radical formation and decreases brain antioxidant defenses, inducing alteration in oxidative status. Guanidinoacetate also impairs energy metabolism in brain. The discussion of this review focuses on various and latest studies addressing GAMT deficiency and creatine metabolism, as well as addresses the question of neurotoxicity GAA.

Training health informatics professionals in Brazil: rationale for the development of a new certificate program.

Current graduate degree programs in Brazil cannot fulfill the demand for highly trained health informatics practitioners. We have developed an intensive six-month program to train 20 students per year. They will receive partial subsidy from our bilateral training program and receive the title of Specialist in Health Informatics. They will benefit from a curriculum involving coursework and collaborative research designed by Brazilian and US-based faculty.

Perfil de pacientes diabéticos internados em Hospital Universitário do Rio de Janeiro / Profile of diabetic inpatients in an Universitary Hospital in Rio de Janeiro

Com o objetivo de delinear o perfil de pacientes diabéticos internados no Hospital Universitário Pedro Ernesto - UERJ, foram revistos 233 prontuários de diabéticos correspondendo a 7,9 por cento de um total de 2.929 pacientes hospitalizados, cujas altas ocorreram em tres meses de 1990. Do grupo estudado 135 (58 por cento) eram mulheres e 98 (42 por cento) homens. As médías (variaçoes) de idade, tempo de diagnóstico da doença e tempo de internaçao foram respectivamente: 58,6 + l5,5 anos (2-90), 7,7 + 8,6 anos (O-40) e 21,2 ñ 21,6 dias (l-l70). O diabetes mellitus (DM) foi a causa primária de internaçao em 107 (46 por cento) dos casos, dos quais 26 (ll,2 por cento) com complicaçoes agudas: descompensaçao metabólica hiperglicêmica (n=25) e coma bipoglicêmico (n=l) e 81(34,8 por cento) com complicaçoes crônicas: doença coronariana (n=46), doença arterial periférica (n= 18, sendo que destes 12 apresentaram gangrena), acidente vascular cerebral (n=7), nefropatia (n=7), neuropatia (n=2) e retinopatia (n= 1). Entre os pacientes de vasculopatia periférica, nove evoluíram para algum tipo de amputaçao. Os pacientes internados com DM como causa secundária representaram 126 (54 por cento), dos quais as neoplasias malígnas foram responsáveis por 28 (l2 por cento), outras doenças contribuíram com percentuais variando de 1,3 por cento a 7,7 por cento. Houve 37 (l5,9 por cento) óbitos entre todos os pacientes diabéticos, sendo 22 homens e 15 mulheres (p

Estudo de auto-anticorpos para ilhotas pancreáticas (ICA e ICA-CF) e evoluçäo para o diabetes insulino-dependente (DM ID) / Progression to IDDM and islet cell antibodies (ICA; ICA-CF)

Foram acompanhados, por três anos, oito familiares em 1§ grau de pacientes com Diabetes insulino-dependentes (DMID) regularmente atendidos no ambulatório de Diabetes da Disciplina de Diabetes e Metodologia do HUPE-UERJ, todos ICA e/ou ICA-CF positivos. Dois oito casos, três casos, todos com idade inferior a 15 anos, evoluíram para o DMID respectivamente 12, 21 e 8 meses após a primeira detecçäo dos auto-anticorpos. Quatro casos persistiram ICA e/ou ICA-CF positivos e em um caso houve negativaçäo da reaçäo no período de observaçäo. A evoluçäo para o DMID foi correlacionada à titulaçäo dos ICA e/ou ICA-CF (ò1/16). Pelo tamanho da amostra concluímos que, em três anos de observaçäo, 37,5 por cento dos familiares em 1§ grau com títulos de ICA elevados e positividade aos ICA-CF evoluíram para o DMID, enfatizando a importância de ambos como marcadores de previsäo para o DMID.