Bases neurofisiológicas da dependência do tabaco

A maioria dos estudos pré-clínicos e clínicos aponta a nicotina como o principal agente responsável pelo desenvolvimento da dependência ao tabaco. Muitos trabalhos têm demonstrado que as bases neurais da dependência à nicotina são semelhantes àquelas das outras drogas de abuso. A nicotina induz preferência condicionada por lugar e auto-administração e, portanto, atua como reforçador positivo, esse efeito parece ser mediado pelo sistema dopaminérgico mesolímbico. A nicotina também induz à sensibilização comportamental que é provavelmente resultante de alterações da expressão gênica do núcleo acumbens induzidas pela exposição prolongada a essa substância. A suspensão do uso de nicotina resulta em síndrome de abstinência. As evidências indicam que esses sinais e sintomas sejam mediados por receptores colinérgicos nicotínicos centrais e periféricos. Outros neurotransmissores, como por exemplo a serotonina e os peptídeos opióides, também podem estar envolvidos na mediação da dependência e síndrome de abstinência à nicotina. A revisão da literatura mostra a complexidade dos efeitos da nicotina no organismo. A integração entre as abordagens comportamental, neuroquímica e molecular possibilitará a compreensão dos mecanismos neurais da dependência ao tabaco e fornecerá as bases para o desenvolvimento racional de agentes terapêuticos que possam ser utilizados para o tratamento da dependência e síndrome de abstinência ao tabaco.

Partial HELLP Syndrome: maternal and perinatal outcome

CONTEXTO: A síndrome HELLP é uma grave complicação da gestação caracterizada por hemólise, elevação das enzimas hepáticas e plaquetopenia. Algumas gestantes desenvolvem somente uma ou duas dessas características da síndrome HELLP. Esse quadro é denominado de síndrome HELLP parcial (SHP). OBJETIVO: O objetivo deste estudo foi avaliar as repercussões maternas e perinatais das mulheres que desenvolveram SHP e comparar os resultados com mulheres que tiveram hipertensão gestacional ou pré-eclâmpsia sem alterações dos exames laboratoriais para síndrome HELLP. TIPO DE ESTUDO: Observacional, retrospectivo e analítico. LOCAL: Maternidade do Hospital das Clínicas da Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu, São Paulo, Brasil. AMOSTRA: Foram selecionadas gestantes ou puérperas que tiveram elevação dos níveis pressóricos detectada pela primeira vez após a primeira metade da gestação com ou sem proteinúria entre janeiro/1990 a dezembro/1995. As mulheres foram divididas em dois grupos: Grupo SHP quando as mulheres com hipertensão arterial tinham pelo menos uma, mas não todas as alterações de exames que demonstravam hemólise, elevação das enzimas hepáticas ou plaquetopenia e Grupo Hipertensas pacientes com hipertensão sem alterações nos exames laboratoriais para síndrome HELLP. PRINCIPAIS VARIÁVEIS: Analisamos idade materna, raça, paridade, classificação da hipertensão, idade gestacional no diagnóstico da SHP, alterações nos exames laboratoriais para síndrome HELLP, tempo de permanência no hospital, complicações maternas, via de parto, incidência de prematuridade, restrição de crescimento intra-uterino, natimortos e neomortos. RESULTADOS: 318 mulheres foram selecionadas, das quais 41 (12,9%) tiveram SHP e 277 (87,1%) não desenvolveram alterações dos exames laboratoriais que compõem o diagnóstico da síndrome HELLP. A pré-eclâmpsia foi um tipo de hipertensão mais freqüente no grupo SHP que no grupo hipertensas. Não houve pacientes com hipertensão crônica isolada que desenvolveram SHP. A taxa de cesárea, eclâmpsia e de partos prematuros foi significativamente mais freqüente no grupo SHP que no grupo hipertensas. CONCLUSÃO: Observamos uma conduta agressiva nas pacientes com SHP, que resultou na interrupção imediata da gestação, com elevada taxa de cesárea e de recém-nascido pré-termo. Esta conduta deve ser revista para a redução desses índices.

Perinatal factors associated with early deaths of preterm infants born in Brazilian Network on Neonatal Research centers

Objective: To evaluate perinatal factors associated with early neonatal death in preterm infants with birth weights (BW) of 400-1,500 g.Methods: A multicenter prospective cohort study of all infants with BW of 400-1,500 g and 23-33 weeks of gestational age (GA), without malformations, who were born alive at eight public university tertiary hospitals in Brazil between June of 2004 and May of 2005. Infants who died within their first 6 days of life were compared with those who did not regarding maternal and neonatal characteristics and morbidity during the first 72 hours of life. Variables associated with the early deaths were identified by stepwise logistic regression.Results: A total of 579 live births met the inclusion criteria. Early deaths occurred in 92 (16%) cases, varying between centers from 5 to 31%, and these differences persisted after controlling for newborn illness severity and mortality risk score (SNAPPE-II). According to the multivariate analysis, the following factors were associated with early intrahospital neonatal deaths: gestational age of 23-27 weeks (odds ratio - OR = 5.0; 95%CI 2.7-9.4), absence of maternal hypertension (OR = 1.9; 95%CI 1.0-3.7), 5th minute Apgar 0-6 (OR = 2.8; 95%CI 1.4-5.4), presence of respiratory distress syndrome (OR = 3.1; 95%CI 1.4-6.6), and network center of birth.Conclusion: Important perinatal factors that are associated with early neonatal deaths in very low birth weight preterm infants can be modified by interventions such as improving fetal vitality at birth and reducing the incidence and severity of respiratory distress syndrome. The heterogeneity of early neonatal rates across the different centers studied indicates that best clinical practices should be identified and disseminated throughout the country.

Muscle protein metabolism in neonatal alloxan-administered rats: effects of continuous and intermittent swimming training

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Demographic of short gut syndrome: Increasing demand is not followed by referral of potential candidates for small bowel transplantation

Background. Despite improvements in small bowel transplantation (SBTx), early referral of patients with irreversible intestinal failure (IF) remains a major obstacle. In this study we evaluated the demand for SBTx among seven surgical pediatric centers located at least 200 km from our center.Methods. From 1997 to 2001, 640 patients have been treated for neonatal diseases, including 248 who underwent a minor or major intestinal resection. Twenty-four patients with major resections presented with short gut syndrome, requiring total parenteral nutrition (TPN). The greatest demand was in postsurgical neonates with necrotizing enterocolitis, gastroschiesis, onphalocoeles, or midgut volvulus, and in three adults with postradiotherapy arteritis (n = 2) and mesenteric vein thromboses (n = 1). The median length of residual bowel after resection was 20 to 30 cm, without an ileocecal valve. Four patients were referred for SBTx evaluation; three died while awaiting a donor; 20 were not referred, among whom 14 died of TPN complications.Results. Approximately 62 children per year require nutritional support for IF, most of whom develop complications related to TPN. Because many patients who are TPN-dependent develop complications, we believe that early referral would reduce mortality.Conclusions. Greater medical awareness about the feasibility of SBTx procedures and earlier referral may improve results and quality of life after transplant.

Acute and sustained effects of early administration of inhaled nitric oxide to children with acute respiratory distress syndrome

OBJECTIVE: To determine the acute and sustained effects of early inhaled nitric oxide on some oxygenation indexes and ventilator settings and to compare inhaled nitric oxide administration and conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation in children with acute respiratory distress syndrome. DESIGN: Observational study. SETTING: Pediatric intensive care unit at a university-affiliated hospital. PATIENTS: Children with acute respiratory distress syndrome, aged between 1 month and 12 yrs. INTERVENTIONS: Two groups were studied: an inhaled nitric oxide group (iNOG, n = 18) composed of patients prospectively enrolled from November 2000 to November 2002, and a conventional therapy group (CTG, n = 21) consisting of historical control patients admitted from August 1998 to August 2000. MEASUREMENTS AND MAIN RESULTS: Therapy with inhaled nitric oxide was introduced as early as 1.5 hrs after acute respiratory distress syndrome diagnosis with acute improvements in Pao(2)/Fio(2) ratio (83.7%) and oxygenation index (46.7%). Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. Pao(2)/Fio(2) ratio was lower (CTG, 116.9 +/- 34.5; iNOG, 62.5 +/- 12.8, p <.0001) and oxygenation index higher (CTG, 15.2 [range, 7.2-32.2]; iNOG, 24.3 [range, 16.3-70.4], p <.0001) in the iNOG. Prolonged treatment was associated with improved oxygenation, so that Fio(2) and peak inspiratory pressure could be quickly and significantly reduced. Mortality rate for inhaled nitric oxide-patients was lower (CTG, ten of 21, 47.6%; iNOG, three of 18, 16.6%, p <.001). There was no difference in intensive care stay (CTG, 10 days [range, 2-49]; iNOG, 12 [range, 6-26], p >.05) or duration of mechanical ventilation (TCG, 9 days [range, 2-47]; iNOG, 10 [range, 4-25], p >.05). CONCLUSIONS: Early treatment with inhaled nitric oxide causes acute and sustained improvement in oxygenation, with earlier reduction of ventilator settings, which might contribute to reduce the mortality rate in children with acute respiratory distress syndrome. Length of stay in intensive care and duration of mechanical ventilation are not changed. Prospective trials of inhaled nitric oxide early in the setting of acute lung injury in children are needed.

Clinical and molecular phenotype of Aicardi-Goutières syndrome

Aicardi-Goutières syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3′→5′ exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P = .001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified. © 2007 by The American Society of Human Genetics. All rights reserved.

Preeclampsia: Early and late neonatal outcomes

Newborn infants exposed to preeclampsia (PE) present increased short-term morbidity, mainly respiratory diseases such as respiratory distress syndrome and bronchopulmonary dysplasia. Gastrointestinal problems are also frequent, although a higher risk of necrotizing enterocolitis has not been confirmed. These problems could be related not just to PE itself but also to prematurity or intrauterine growth restriction, which frequently occur in this maternal disease. Other findings, however, seem to be due to the direct effect of the maternal disease; these findings include an increased frequency of neutropenia and thrombocytopenia and a lower incidence of cerebral disorders, such as periventricularintraventricular hemorrhage and cerebral palsy. The evaluation of long-term outcome shows increasing evidence that PE has important implications for the future health of the mother and her child, suggesting that PE is not a simple gestational disorder but a clinical syndrome with an unclear etiology, a genetic component, and a complex pathophysiology. This syndrome involves important maternal and fetal vascular alterations that can persist and cause diseases in later life. The divergence in results on outcomes for children exposed to PE could, in part, be due to methodological differences in the studies, most of which are retrospective case-control studies. Better evidence on prognosis is obtained from cohort studies. Even in the cohort studies, differences in patient characteristics and severity of maternal disease, as well as sample size, follow-up time, and main outcome measures certainly contribute to the variability in results reported in the literature. © 2012 by the American Academy of Pediatrics. All rights reserved.

Effects of therapeutic approach on the neonatal evolution of very low birth weight infants with patent ductus arteriosus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)