Carla Maria Ramos Germano

Adrenalectomy enhances endotoxemia-induced hypophagia: higher activation of corticotrophin-releasing-factor and proopiomelanocortin hypothalamic neurons

Inflammatory and infectious processes evoke neuroendocrine and behavioral changes known as acute-phase response that includes activation of the hypothalamo-pituitary-adrenal (HPA) axis and reduction of food intake. Besides its action as the most important ACTH secretagogue, corticotrophin-releasing factor (CRF), synthesized in the paraventricular nucleus (PVN), is also involved in the control of food intake. Alpha-melanocyte stimulating hormone (alpha-MSH) in the arcuate nucleus also plays a role in the energy homeostasis, possessing anorexigenic effects. To investigate the participation of neuropeptides involved in the regulation of food intake during endotoxemia, we administrated lipopolysaccharide (LPS) in sham-operated and adrenalectomized (ADX) male Wistar rats to evaluate food intake, hormone responses and Fos-CRF and Fos-alpha-MSH immunoreactivity in the PVN and arcuate nucleus, as well as CRF and POMC mRNA expression in these hypothalamic nuclei. In sham-operated rats, treatment with LPS (100 microg/kg) showed lower food intake, higher plasma ACTH and corticosterone levels, as well as an increase in Fos-CRF double labeled neurons and CRF mRNA expression in the PVN, with no changes in Fos-alpha-MSH immunoreactivity and POMC mRNA expression in the arcuate nucleus, compared to saline treated rats. After LPS treatment, ADX rats showed further increase in plasma ACTH levels, marked decrease of food intake, higher Fos-CRF immunoreactive neurons in the PVN and CRF mRNA expression, as well as an increase in Fos-alpha-MSH immunoreactivity and POMC mRNA expression in the arcuate nucleus, compared to sham-operated rats treated with LPS. In conclusion, the present data indicate that the marked hypophagia during endotoxemia following ADX is associated with an increased activation of CRF and POMC neurons in the hypothalamus and an increased mRNA expression of these neuropeptides.

Relato de experiência: o uso de simulações no processo de ensino-aprendizagem em medicina

Este trabalho relata a experiencia, construida ao longo de dois anos, com o uso de estacoes de simulacao da pratica profissional no processo de ensino-aprendizagem do curso de graduacao em Medicina da Universidade Federal de Sao Carlos. Seu referencial pedagogico esta ancorado na concepcao construtivista da aprendizagem e parte da premissa de que aprender nao e reproduzir a realidade, mas ser capaz de elaborar uma representacao pessoal sobre esta e seus conteudos. Assim, a partir da vivencia de situacoes simuladas, os estudantes sao estimulados a ressignificar seus conhecimentos construindo novos saberes. Na Unidade Educacional Estacoes de Simulacao da Pratica Profissional, o estudante se defronta com pacientes simulados e tem a oportunidade de aprender fazendo, errando e aprendendo com os proprios erros. Ao refletir sobre o erro, constroi seu aprendizado por meio da identificacao de lacunas de conhecimento e fundamenta cognitivamente suas capacidades. Professores acompanham o desenvolvimento dos estudantes, atuando ora como avaliadores, ora como facilitadores, ora como consultores. Esta estrategia pedagogica pode ser um instrumento poderoso para o desenvolvimento de competencia na area clinica.

Downregulation of Melanocortin-4 Receptor during Refeeding and its Modulation by Adrenalectomy in Rats

Melanocortin system and corticotropin releasing hormone (CRH) are implicated in the control of feeding behavior. Besides its anorexigenic effect on food intake, CRH is one of the most important regulators of hypothalamic-pituitary-adrenal (HPA) axis activity. Therefore, there could be an interplay between HPA axis activity and melanocortin system. We investigated the expression of melanocortin-4 receptor (MC4-R) mRNA in the hypothalamus of rats after 14 days of food restriction or after a fasting-refeeding regimen, in sham or adrenalectomized rats. Male Wistar rats were subjected to free access to food or food ingestion restricted for 2 h a day (8-10 AM) during 14 d, when plasma corticosterone, ACTH, insulin, leptin concentrations, and MC4-R mRNA expression were determined before and after refeeding. Another set of rats was fasted for 48 h, followed by refeeding during 2 or 4 h on the seventh day after adrenalectomy (ADX) or sham surgery. On the day of the experiment, rats were anesthetized and perfused and the brain processed for MC4-R mRNA by in situ hybridization. Long-term reduction of food intake, either secondary to food restriction or adrenalectomy, reduced body weight gain and also leptin and insulin plasma concentrations. Food ingestion reduced MC4-R expression in the paraventricular nucleus in naive rats subjected to food restriction and also in sham rats fasted for 48 h. However, after ADX, MC4-R expression was not changed by refeeding. In conclusion, the present data indicate that MC4-R expression is downregulated by food ingestion and this response could be modulated by glucocorticoid withdrawal.

Quality of Life in Adults with Neurofibromatosis 1 in Brazil

Neurofibromatosis type 1 (NF1) is a neurocutaneous genetic disorder that can be associated with severe complications, and it may shorten patients’ lifespan and affect their quality of life negatively. This study aimed to examine quality of life constructs among adults with NF1 in Brazil. It is an exploratory, descriptive and cross-sectional study consisting of two stages, involving thirteen adult patients with NF1. The first stage was developed using a quantitative methodology, namely the WHOQOL-100 questionnaire; responses for the 13 patients were compared to a matched control group. The second stage comprised clinical-qualitative research whereby participants took part in a semi-structured interview; these data were analyzed using the categorical thematic analysis technique. There were no statistically significant differences in the questionnaire domains between the NF1 patients and the control subjects. Eighteen main themes were extracted from the interviews, showing interference of the NF1 visibility principally in psychological aspects and social relationships. Patients mentioned curiosity about NF1 and confusion about the distinctions between NF1 and contagious diseases, which lead to prejudice. They were concerned about the future and how the disease would develop in themselves and their offspring, and emphasized difficulties acquiring proper healthcare. These findings may help in planning healthcare for Brazilian NF1 patients and improving their quality of life.

Possíveis novos determinantes da qualidade de vida de pacientes com câncer de tireoide tratado: um estudo qualitativo.

The aim of this study was to develop a qualitative approach of determinant factors of the quality of life of treated patients with papillary thyroid carcinoma. Sixteen in-depth interviews were conducted with individuals 18 to 45 years old regarding their disease representations and experiences, followed by statements content analysis. The results show issues already provided in structured questionnaires about quality of life, although others were only partially assumed in these surveys (management of the concept of disease etiology; the “forced” patient introduction into the medical conceptual universe; the fear of the prognosis and positive changes in lifestyle). The results interpretation were benefited from recently developed theoretical elaborations: the anxieties related to illness experience seem to be configured as a “modern risk”, in the context of a “risk society”. The development of structured questionnaires on quality of life requires frequent qualitative studies to capture changes in subjective aspects of the construct, given the dynamic changes of historical, cultural and psychological meanings of the health disease process, constantly influenced by technological innovations and continuing epidemiological interpretations.

Maternal and perinatal aspects of birth defects: a case-control study

Objective: To assess the prevalence of congenital defects and to investigate their maternal and perinatal associated aspects by reviewing Birth Certificates. Methods: Among all born alive infants from January 2003 to December 2007 in Maternidade da Santa Casa de Misericórdia of São Carlos, Southeast Brazil (12,199 infants), cases were identified as the newborns whose Birth Certificates registered any congenital defect. The same sex neonate born immediately after the case was chosen as a control. In total, 13 variables were analyzed: six were maternal related, three represented labor and delivery conditions and four were linked to fetal status. The chi-square and Fishers exact tests were used to compare the variables, being significant p<0.05. Results: The prevalence of congenital defects was 0.38% and the association of two or more defects represented 32% of all cases. The number of mothers whose education level was equal or less than eight years was significantly higher among the group with birth defects (p=0.047). A higher frequency of prematurity (p<0.001) and cesarean delivery (p=0.004) was observed among children with birth defects. This group also showed lower birth weight and Apgar scores in the 1st and the 5th minute (p<0.001). Conclusions: The prevalence of congenital defect of 0.38% is possibly due to underreporting. The defects notified in the Birth Certificates were only the most visible ones, regardless of their severity. There is a need of adequate epidemiological monitoring of birth defects in order to create and expand prevention and treatment programs.Objetivo: Avaliar a prevalencia de defeitos congenitos e investigar aspectos maternos e perinatais associados pela analise da Declaracao de Nascido Vivo. Metodos: Estudo do tipo caso-controle, considerando-se todos os nascidos vivos de janeiro de 2003 a dezembro de 2007 na Maternidade da Santa Casa de Misericordia de Sao Carlos, o que totalizou 12.199 criancas. Identificaram-se como casos os recem-nascidos cuja Declaracao de Nascido Vivo apontava algum defeito congenito. Para o grupo controle, escolheu-se a crianca do mesmo sexo, nascida imediatamente apos o caso. No total, analisaram-se 13 variaveis, sendo seis maternas, tres relacionadas as condicoes de parto e quatro fetais. Os testes do qui-quadrado e exato de Fisher foram usados para comparar as variaveis, considerando-se nivel de significância de 5%. Resultados: A prevalencia de defeitos congenitos foi de 0,38%, sendo que a associacao de dois ou mais defeitos representou 32% dos casos. No grupo com defeito congenito, houve um numero maior de maes com escolaridade igual ou inferior a oito anos (p=0,047). Entre as criancas com defeitos congenitos, observou-se maior frequencia de prematuridade (p<0,001) e de parto cesareo (p=0,004), assim como peso e valores de Apgar no 1o e 5o minutos significativamente mais baixos (p<0,001). Conclusoes: A prevalencia de defeito congenito de 0,38% deve-se, possivelmente, a subnotificacao das anomalias, tendo sido registrados os defeitos congenitos mais visiveis, independentemente da gravidade. Os dados deste trabalho reforcam a importância do monitoramento epidemiologico adequado, alem da necessidade de criar e expandir programas de prevencao e tratamento de defeitos congenitos.

Effects of intrauterine latent iron deficiency on auditory neural maturation in full-term newborns

OBJECTIVE This study analyzed the relationship between latent iron deficiency evaluated by ferritin, and the myelination of the central nervous system evaluated through the brainstem evoked response audiometry test. METHOD A total of 109 full-term newborns, born without anemia and risk factor for hearing deficiency, were enrolled. After delivery, umbilical cord blood was collected to determine ferritin and hematocrit levels. The brainstem evoked response audiometry test was carried out in the first 28 days of life. Analysis was performed between the control group (n=71) with ferritin greater than 75ng/mL, and the latent iron deficiency group (n=38) with ferritin between 11 and 75ng/mL. Results were presented as mean±standard deviation. Statistical analysis was performed using GraphPad prism7 and SPSS with a significance level of 5%. RESULTS A significant higher V-wave (p=0.02) and interpeak intervals I-III (p=0.014), I-V (p=0.0003), and III-V (p=0.0002) latencies were found in the latent iron deficiency group, as well as a significant inversely proportional correlation between ferritin and the same wave and intervals (p=0.003, p=0.0013, p=0.0002, p=0.009, respectively). Multiple correlation analysis showed a significant correlation of latent iron deficiency with all interpeak intervals, even taking into account newborn gestational age. CONCLUSION Iron deficiency anemia is a prevalent pathology; this study showed auditory delayed maturation associated to intrauterine iron deficiency, even in its latent form. This reinforces the importance of adopting effective measures, on a global scale, to prevent and treat this pathology in different life periods, especially in the most vulnerable population.

Prevalence and factors associated with alcohol consumption during pregnancy

Objetivos: investigar a prevalencia de consumo de alcool na gravidez e fatores sociodemograficos, reprodutivos e dos recem-nascidos associados. Metodos: estudo transversal e exploratorio, desenvolvido sobre amostra sequencial de puerperas, recrutadas diariamente durante seis meses. Foram coletadas informacoes sociodemograficas e reprodutivas das mulheres, e dados dos recem-nascidos. O questionario T-ACE foi aplicado para identificar o padrao de consumo alcoolico das mulheres, dividindo-as em dois grupos: consumidoras (pontuacao T-ACE ≥ 2) e nao consumidoras de alcool. As comparacoes entre os dois grupos foram realizadas utilizando-se os testes t nao pareado, qui-quadrado ou exato de Fisher, conforme o tipo de variavel analisada. O nivel de significância adotado foi de 5%. Resultados: 925 puerperas foram convidadas e 818 (88,4%) concordaram em participar da pesquisa. Das participantes, 60 (7,3%) foram T-ACE positivas, ou seja, identificadas como consumidoras de alcool. Com relacao as informacoes sociodemograficas, o consumo de alcool foi mais frequente entre mulheres sem companheiro fixo (p=0,010). Nenhuma variavel reprodutiva apresentou diferenca significativa entre os grupos. Observou-se menor peso entre filhos de maes T-ACE positivas (3.045g±71,0 vs 3.192g±19,2; p=0,040). Conclusoes: identificar e caracterizar as mulheres mais susceptiveis ao consumo de alcool na gravidez pode colaborar no desenvolvimento de estrategias de intervencao em saude publica mais eficazes.

Qualificação e provimento de médicos no contexto da Política Nacional de Atenção Integral às Pessoas com Doenças Raras no Sistema Único de Saúde (SUS)

Este ensaio teorico reflete sobre a qualificacao e o provimento de medicos no contexto da Politica Nacional de Atencao Integral as Pessoas com Doencas Raras no SUS. Para isso, apresentamos a Politica e suas diretrizes, e situamos a discussao em torno de duas estrategias integradas: o provimento e a fixacao de medicos geneticistas; e a capacitacao de profissionais da Atencao Primaria a Saude em relacao as doencas geneticas e aos defeitos congenitos. Finalmente, considerando as Diretrizes Curriculares Nacionais do Curso de Graduacao em Medicina, apresentamos uma proposta de perfil de competencia minimo em Genetica, elaborada para instrumentalizar os cursos de graduacao da area da Saude, em particular os cursos de Medicina. Assim, oferecemos um referencial teorico para apoiar o delineamento de programas de educacao e formacao em Saude, contribuindo para inclusao do cuidado em Genetica no SUS.Este ensaio teorico reflete sobre a qualificacao e o provimento de medicos no contexto da Politica Nacional de Atencao Integral as Pessoas com Doencas Raras no SUS. Para isso, apresentamos a Politica e suas diretrizes, e situamos a discussao em torno de duas estrategias integradas: o provimento e a fixacao de medicos geneticistas; e a capacitacao de profissionais da Atencao Primaria a Saude em relacao as doencas geneticas e aos defeitos congenitos. Finalmente, considerando as Diretrizes Curriculares Nacionais do Curso de Graduacao em Medicina, apresentamos uma proposta de perfil de competencia minimo em Genetica, elaborada para instrumentalizar os cursos de graduacao da area da Saude, em particular os cursos de Medicina. Assim, oferecemos um referencial teorico para apoiar o delineamento de programas de educacao e formacao em Saude, contribuindo para inclusao do cuidado em Genetica no SUS.

Aspectos maternos e perinatais dos defeitos congênitos: um estudo caso-controle

Objective: To assess the prevalence of congenital defects and to investigate their maternal and perinatal associated aspects by reviewing Birth Certificates. Methods: Among all born alive infants from January 2003 to December 2007 in Maternidade da Santa Casa de Misericórdia of São Carlos, Southeast Brazil (12,199 infants), cases were identified as the newborns whose Birth Certificates registered any congenital defect. The same sex neonate born immediately after the case was chosen as a control. In total, 13 variables were analyzed: six were maternal related, three represented labor and delivery conditions and four were linked to fetal status. The chi-square and Fishers exact tests were used to compare the variables, being significant p<0.05. Results: The prevalence of congenital defects was 0.38% and the association of two or more defects represented 32% of all cases. The number of mothers whose education level was equal or less than eight years was significantly higher among the group with birth defects (p=0.047). A higher frequency of prematurity (p<0.001) and cesarean delivery (p=0.004) was observed among children with birth defects. This group also showed lower birth weight and Apgar scores in the 1st and the 5th minute (p<0.001). Conclusions: The prevalence of congenital defect of 0.38% is possibly due to underreporting. The defects notified in the Birth Certificates were only the most visible ones, regardless of their severity. There is a need of adequate epidemiological monitoring of birth defects in order to create and expand prevention and treatment programs.Objetivo: Avaliar a prevalencia de defeitos congenitos e investigar aspectos maternos e perinatais associados pela analise da Declaracao de Nascido Vivo. Metodos: Estudo do tipo caso-controle, considerando-se todos os nascidos vivos de janeiro de 2003 a dezembro de 2007 na Maternidade da Santa Casa de Misericordia de Sao Carlos, o que totalizou 12.199 criancas. Identificaram-se como casos os recem-nascidos cuja Declaracao de Nascido Vivo apontava algum defeito congenito. Para o grupo controle, escolheu-se a crianca do mesmo sexo, nascida imediatamente apos o caso. No total, analisaram-se 13 variaveis, sendo seis maternas, tres relacionadas as condicoes de parto e quatro fetais. Os testes do qui-quadrado e exato de Fisher foram usados para comparar as variaveis, considerando-se nivel de significância de 5%. Resultados: A prevalencia de defeitos congenitos foi de 0,38%, sendo que a associacao de dois ou mais defeitos representou 32% dos casos. No grupo com defeito congenito, houve um numero maior de maes com escolaridade igual ou inferior a oito anos (p=0,047). Entre as criancas com defeitos congenitos, observou-se maior frequencia de prematuridade (p<0,001) e de parto cesareo (p=0,004), assim como peso e valores de Apgar no 1o e 5o minutos significativamente mais baixos (p<0,001). Conclusoes: A prevalencia de defeito congenito de 0,38% deve-se, possivelmente, a subnotificacao das anomalias, tendo sido registrados os defeitos congenitos mais visiveis, independentemente da gravidade. Os dados deste trabalho reforcam a importância do monitoramento epidemiologico adequado, alem da necessidade de criar e expandir programas de prevencao e tratamento de defeitos congenitos.