Prenatal diagnosis of fetal lung maturity in high-risk pregnancies

The objective was to evaluate the accuracy of the foam stability test, lecithin/sphingomyelin (LS) ratio, presence of phosphatidylglycerol (PG) and lung profile (L/S ratio > 1.7 and PG present simultaneously) in 121 consecutive high-risk gestations at the São Paulo Hospital from January 1990 to January 1995. Delivery occurred within 3 days of fetal lung maturation testing. This is a prospective study in which the sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of all the tests were determined. Neonatal respiratory outcome and amniocentesis results were stratified by gestational age for comparison. The distribution of the studied population according to maternal pathology was diabetes mellitus (48), hypertensive disorders (41), Rh isoimmunization (14) and miscellaneous (18). Respiratory distress (RD) was present in 33 infants (27.2%), mainly in the diabetic group. There was no false negative using lung profile (all patients) and foam stability tests among hypertensive pregnancies (specificity 100%), but there were about 20% to 50% false positives in the other tests. Overall, all four tests had a low PPV: 23% for foam test, 51% for L/S ratio, 63% for PG, 61% for lung profile, and high NPV: 92% for foam test, 88% for L/S ratio, 89% for PG and 100% for lung profile. All tests had less accuracy in the diabetic pregnant women. This study shows that the presence of PG and L/S ratio > 1.7 in the amniotic fluid of high-risk pregnancies confirms maturity with a very low risk to develop RD and that the foam stability test was useful as a first-line test to predict the absence of surfactant-deficient respiratory distress syndrome, particularly in hypertensive pregnant women.Trata-se de um estudo prospectivo para a avaliação da maturidade fetal em 121 gestações de alto risco realizado no Hospital São Paulo - Universidade Federal de São Paulo (UNIFESP), entre janeiro de 1990 e janeiro de 1995. Em todos os casos, o parto foi realizado em até 3 dias após a obtenção de líquido amniótico por amniocentese. O objetivo principal foi o de analisar a acurácia do teste de Clements (TC), da relação lecitina/esfingomielina (L/E), da presença de fosfatidilglicerol (PG) e do perfil pulmonar (relação L/E >1,7 e PG presente) para antecipar a ocorrência ou não de sindrome de desconforto respiratório neonatal (SDR). Foram calculados a sensibilidade, a especificidade e os valores preditivos positivo (VPP) e negativo (VPN) de todos os testes. O grupo de estudo foi composto por 48 gestações complicadas por diabetes mellitus, 41 por síndromes hipertensivas, 14 por isoimunização Rh e 18 por diversas patologias. O perfil pulmonar apresentou sensibilidade de 100% em todos os casos. O teste de Clements também não apresentou resultados falso-positivos em gestantes hipertensas, apurando-se, contudo, de 20% a 50% de falso-negativos em todos os outros testes. Os quatro testes apresentaram baixos VPP (23% no TC, 51% na relação L/E, 63% na presença de PG, 61% no perfil pulmonar) e elevados VPN (92% no TC, 88% na relação L/E, 89% na presença de PG, 100% no perfil pulmonar). Este estudo demonstrou que a presença de PG e relação L/E >1,7 simultâneos no líquido amniótico comprovam a maturidade pulmonar com muito baixo risco de DR ao nascimento. Concluiu-se também que o teste de Clements deve constituir o rastreamento inicial para predizer a ausência de SDR, particularmente em gestações complicadas por síndromes hipertensivas.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

A structural-dynamical characterization of human Cox17.

Human Cox17 is a key mitochondrial copper chaperone responsible for supplying copper ions, through the assistance of Sco1, Sco2, and Cox11, to cytochrome c oxidase, the terminal enzyme of the mitochondrial energy transducing respiratory chain. A structural and dynamical characterization of human Cox17 in its various functional metallated and redox states is presented here. The NMR solution structure of the partially oxidized Cox17 (Cox17(2S-S)) consists of a coiled coil-helix-coiled coil-helix domain stabilized by two disulfide bonds involving Cys(25)-Cys(54) and Cys(35)-Cys(44), preceded by a flexible and completely unstructured N-terminal tail. In human Cu(I)Cox17(2S-S) the copper(I) ion is coordinated by the sulfurs of Cys(22) and Cys(23), and this is the first example of a Cys-Cys binding motif in copper proteins. Copper(I) binding as well as the formation of a third disulfide involving Cys(22) and Cys(23) cause structural and dynamical changes only restricted to the metal-binding region. Redox properties of the disulfides of human Cox17, here investigated, strongly support the current hypothesis that the unstructured fully reduced Cox17 protein is present in the cytoplasm and enters the intermembrane space (IMS) where is then oxidized by Mia40 to Cox17(2S-S), thus becoming partially structured and trapped into the IMS. Cox17(2S-S) is the functional species in the IMS, it can bind only one copper(I) ion and is then ready to enter the pathway of copper delivery to cytochrome c oxidase. The copper(I) form of Cox17(2S-S) has features specific for copper chaperones

Treatment of Eclampsia: Comparative Study on the Use of Magnesium Sulfate and Phenytoin

Purpose: to compare the efficiency between magnesium sulfate and phenytoin in the control of convulsions in patients with eclampsia and to evaluate the effects of magnesium sulfate and phenytoin on the maternal and perinatal prognosis in patients with eclampsia. Methods: this is a prospective, randomized and controlled study in which the results obtained with the use of anticonvulsive treatment in 77 women with eclampsia, treated with either magnesium sulfate or phenytoin, were analyzed comparatively. The drugs which were used in both therapeutic schemes were distributed in a one to one ratio, in randomly numbered boxes which presented similar characteristics. When a patient was admitted, a box was opened and its contents were given to the patient. Results: in the group whose patients were treated with magnesium sulfate, 19.5% had recurrent convulsions while in the group whose patients used phenytoin, 36.1% had new crises (p 0,05). Conclusion: magnesium sulfate is shown to be more efficient than phenytoin in the control and the prevention of convulsions in patients with eclampsia. However, its utilization showed a higher prevalence of postpartum hemorrhage and respiratory distress. Phenytoin should be used in cases where the use of magnesium sulfate is contraindicated.Objetivos: comparar a eficácia do sulfato de magnésio e da fenitoína no controle das convulsões em pacientes com eclâmpsia e avaliar os efeitos de sulfato de magnésio e da fenitoína sobre o prognóstico materno e perinatal em pacientes com eclâmpsia. Métodos: estudo prospectivo, randômico e controlado no qual foram analisados, de forma comparativa, os resultados obtidos no tratamento anticonvulsivante da eclâmpsia em 77 mulheres tratadas com sulfato de magnésio ou fenitoína. As drogas que constituíram os dois esquemas terapêuticos foram distribuídas, na proporção de um para um, em caixas numeradas aleatoriamente que apresentavam características semelhantes. À medida que cada paciente era admitida, uma caixa era aberta e o esquema nela contido administrado à paciente. Resultados: observou-se que, no grupo tratado com sulfato de magnésio, 19,5% das pacientes apresentaram recidiva de convulsões, ao passo que no grupo que usou fenitoína, 36,1% manifestaram novas crises (p0,05). Conclusões: o sulfato de magnésio mostrou-se mais eficaz que a fenitoína no controle e prevenção da recidiva de convulsões em pacientes com eclâmpsia, embora sua utilização esteja associada a maior prevalência materna de hemorragia pós-parto e desconforto respiratório neonatal. A fenitoína apresenta-se como droga alternativa para o tratamento de eclâmpsia nos casos em que houver contra-indicação ao uso do sulfato de magnésio.Universidade Federal do Piauí Maternidade Dona Evangelina Rosa Disciplina de ObstetríciaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de ObstetríciaUNIFESP, EPM, Disciplina de ObstetríciaSciEL

Fetal reanimation: a case report

A tocolytic treatment is described with the use of terbutaline in a case of cardiotocographic prolonged deceleration of fetal heart rate with successful outcome.Os autores descrevem caso de desaceleração prolongada da freqüência cardíaca fetal, diagnosticada através da cardiotocografia, tratada com sucesso mediante tocólise aguda com terbutalina intravenosa.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Amparo MaternalUNIFESP, EPM, Amparo MaternalSciEL

Transient Expression in Red Beet of a Biopharmaceutical Candidate Vaccine for Type-1 Diabetes

Plant molecular farming is the use of plants to produce molecules of interest. In this perspective, plants may be used both as bioreactors for the production and subsequent purification of the final product and for the direct oral delivery of heterologous proteins when using edible plant species. In this work, we present the development of a candidate oral vaccine against Type 1 Diabetes (T1D) in edible plant systems using deconstructed plant virus-based recombinant DNA technology, delivered with vacuum infiltration. Our results show that a red beet is a suitable host for the transient expression of a human derived autoantigen associated to T1D, considered to be a promising candidate as a T1D vaccine. Leaves producing the autoantigen were thoroughly characterized for their resistance to gastric digestion, for the presence of residual bacterial charge and for their secondary metabolic profile, giving an overview of the process production for the potential use of plants for direct oral delivery of a heterologous protein. Our analysis showed almost complete degradation of the freeze-dried candidate oral vaccine following a simulated gastric digestion, suggesting that an encapsulation strategy in the manufacture of the plant-derived GAD vaccine is required

Non invasive evaluation of cardiomechanics in patients undergoing MitrClip procedure

Abstract BACKGROUND: In the last recent years a new percutaneous procedure, the MitraClip, has been validated for the treatment of mitral regurgitation. MitraClip procedure is a promising alternative for patients unsuitable for surgery as it reduces the risk of death related to surgery ensuring a similar result. Few data are present in literature about the variation of hemodynamic parameters and ventricular coupling after Mitraclip implantation. METHODS: Hemodynamic data of 18 patients enrolled for MitraClip procedure were retrospectively reviewed and analyzed. Echocardiographic measurements were obtained the day before the procedure (T0) and 21 ± 3 days after the procedure (T1), including evaluation of Ejection Fraction, mitral valve regurgitation severity and mechanism, forward Stroke Volume, left atrial volume, estimated systolic pulmonary pressure, non invasive echocardiographic estimation of single beat ventricular elastance (Es(sb)), arterial elastance (Ea) measured as systolic pressure • 0.9/ Stroke Volume, ventricular arterial coupling (Ea/Es(sb) ratio). Data were expressed as median and interquartile range. Measures obtained before and after the procedure were compared using Wilcoxon non parametric test for paired samples. RESULTS: Mitraclip procedure was effective in reducing regurgitation. We observed an amelioration of echocardiographic parameters with a reduction of estimated systolic pulmonary pressure (45 to 37,5 p = 0,0002) and left atrial volume (110 to 93 p = 0,0001). Despite a few cases decreasing in ejection fraction (37 to 35 p = 0,035), the maintained ventricular arterial coupling after the procedure (P = 0,67) was associated with an increasing in forward stroke volume (60,3 to 78 p = 0,05). CONCLUSION: MitraClip is effective in reducing mitral valve regurgitation and determines an amelioration of hemodynamic parameters with preservation of ventricular arterial couplin

Factors related to the presence of large for gestational age newborns in pregnant women with gestational diabetes mellitus

PURPOSE: to evaluate factors related to the presence of neonatal macrosomia in pregnant women with gestational diabetes mellitus. METHODS: 157 pregnant women presenting gestational diabetes mellitus in follow-up were retrospectively selected from January 2004 to July 2006. This group has been divided into two subgroups: one with newborns with weight in accordance with the gestational age (n=136) and another with macrosomic newborns (n=21). Maternal characteristics have been compared between the groups. The t-Student test was used for the analysis of equality hypothesis between the averages of the two groups, and chi-square test, to check the groups' homogeneity concerning ratios. RESULTS: the groups did not show any significant difference concerning the gestational age, body mass index, weight gain along the gestation, number of previous pregnancies, fast glycemia in the oral glucose tolerance test after the ingestion of 75 g (TOTG 75 g), gestational age at delivery, glycemic values during the treatment, and the type of treatment used (p>0.05). In the group with neonatal macrosomia, there was a higher two-hour-glycemia in the TOTG 75 g (p=0.02), higher gestational age at the treatment onset (p=0.02), and a lower number of appointments at the health service (p0,05). No grupo com recém-nascidos grandes para a idade gestacional, observou-se valor de glicemia de duas horas no TOTG 75 g maior (p=0,02), a idade gestacional de início de tratamento maior (p=0,02), e um número menor de consultas realizadas no serviço (p<0,01). Ajustando-se a um modelo de regressão logística, foi encontrado, no valor da glicemia de duas horas do TOTG 75 g, o fator de maior importância (p<0,01) na predição de recém-nascidos grandes para a idade gestacional. CONCLUSÕES: os fatores que se relacionam melhor com a ocorrência de recém-nascidos grandes para a idade gestacional foram o início tardio do tratamento e, consequentemente, o menor número de consultas e, principalmente, o maior valor da glicemia de duas horas no TOTG 75 g.Universidade da Região de JoinvilleHospital Dona HelenaUniversidade Federal de São Paulo (UNIFESP) Hospital da Universidade Federal de São Paulo (UNIFESP) Departamento de ObstetríciaHospital Dona Helena Hospital da Universidade Federal de São Paulo (UNIFESP)UNIFESP, Hospital da UNIFESP, Depto. de ObstetríciaHospital Dona Helena Hospital da UNIFESPSciEL

Inflammation-Independent Antinociceptive Effects of DF2755A, a CXCR1/2 Selective Inhibitor: A New Potential Therapeutic Treatment for Peripheral Neuropathy Associated to Non-Ulcerative Interstitial Cystitis/Bladder Pain Syndrome

Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic bladder disease of unknown etiology characterized by urinary frequency and episodic and chronic pain. Analgesic treatments for IC/BPS are limited, especially for patients with non-Hunner (non-ulcerative) type IC who usually have poor overall outcomes. Here, we demonstrate that oral treatment with DF2755A, a potent and selective inhibitor of chemokine receptors CXCR1/2, can prevent and reverse peripheral neuropathy associated to non-Hunner IC/BPS by directly inhibiting chemokine-induced excitation of sensory neurons. We tested DF2755A antinociceptive effects in a cyclophosphamide (CYP)-induced non-ulcerative IC rat model characterized by severe peripheral neuropathy in the absence of bladder inflammatory infiltrate, urothelial hyperplasia, and hemorrhage. Treatment with DF2755A prevented the onset of peripheral neuropathy and reversed its development in CYP-induced IC rats, showing a strong and long-lasting anti-hyperalgesic effect. Ex vivo and in vitro studies showed that DF2755A treatment strongly inhibited the expression of CXCR2 agonists, CXCL1/KC, and CXCL5 and of transient receptor potential vanilloid 1 (TRPV1) compared to vehicle, suggesting that its effects can be due to the inhibition of the nociceptive signaling passing through the CXCL1/CXCR1-2 axis and TRPV1. In conclusion, our results highlight the key pathophysiological role played by the CXCL1/CXCR1-2 axis and TRPV1 in the onset and development of peripheral neuropathy in non-Hunner IC and propose DF2755A as a potential therapeutic approach for the treatment of not only inflammatory painful conditions but also neuropathic ones and in particular non-Hunner IC/BPS

Glibenclamide in the treatment for gestational diabetes mellitus in a compared study to insulin

OBJECTIVES: To study glibenclamide as a treatment for gestational diabetes mellitus (GDM) and its impact on newborn birth weight and neonatal glycemia as compared to insulin. METHODS: A randomized and open-label clinical trial, conducted from October 1st, 2003 to March 8, 2005. Seventy-two pregnant women with gestational diabetes mellitus requiring drug therapy were randomized and allocated into two groups - insulin and glibenclamide. RESULTS: The general characteristics in both groups were similar, except for the results of the 75 g OGTT, which were higher in the glibenclamide group (p= 0.02). Maternal fasting and postprandial glucose levels presented no difference. Six (18.75%) pregnant women received the maximum dose of glibenclamide with no glycemic control. The birth weight was higher in the group treated with glibenclamide (p= 0.01), and the incidence of macrosomic newborns statistically different (p= 0.01). Neonatal hypoglycemia was more frequent (p= 0.01) in newborns of glibenclamide group, with one single case of persistent hypoglycemia. CONCLUSION: Glibenclamide can be the first line drug for glycemic control in most GDM patients. The birth weight and incidence of hypoglycemia were higher in the glibenclamide group, but with one single case of persistent hypoglycemia that required intravenous infusion of glucose.OBJETIVOS: Estudar a glibenclamida no tratamento do diabete melito gestacional (DMG) e sua repercussão no peso e na glicemia do recém-nascido (RN), em comparação com a insulina. MÉTODOS: Ensaio clínico randomizado e aberto, realizado entre 1º de outubro de 2003 e 8 de março de 2005. Foram sujeitas 72 gestantes com DMG que necessitaram de terapêutica complementar, sendo randomizadas em dois grupos: insulina e glibenclamida. RESULTADOS: As características gerais nos grupos não apresentaram diferença estatística, com exceção dos resultados do TTOG 75 g, que apresentaram valores maiores no grupo da glibenclamida (p= 0,02). As glicemias médias maternas não apresentaram diferença. Seis (18,75%) gestantes atingiram a dose máxima de glibenclamida sem o controle glicêmico. O peso dos RNs foi maior no grupo tratado com glibenclamida (p= 0,01), com diferença na incidência de macrossômico (p= 0,01). A hipoglicemia neonatal estava mais presente (p= 0,01) nos RNs do grupo da glibenclamida, porém com apenas um caso de hipoglicemia persistente. CONCLUSÃO: A glibenclamida pode ser a droga de escolha para tratamento do DMG na maioria das pacientes.Universidade Federal de São Paulo (UNIFESP) EPM Departamento de ObstetríciaMaternidade Darcy VargasUniversidade da Região de JoinvilleUNIFESP, EPM, Depto. de ObstetríciaSciEL