Deficiency of the Cytoskeletal Protein SPECC1L Leads to Oblique Facial Clefting

Genetic mutations responsible for oblique facial clefts (ObFC), a unique class of facial malformations, are largely unknown. We show that loss-of-function mutations in SPECC1L. are pathogenic for this human developmental disorder and that SPECC1L is a critical organizer of vertebrate facial morphogenesis. During murine embryogenesis, Speed 1 1 is expressed in cell populations of the developing facial primordial, which proliferate and fuse to form the face. In zebrafish, knockdown of a SPECC1L homolog produces a faceless phenotype with loss of jaw and facial structures, and knockdown in Drosophila phenocopies mutants in the integrin signaling pathway that exhibit cell-migration and -adhesion defects. Furthermore, in mammalian cells, SPECC1L colocalizes with both tubulin and actin, and its deficiency results in defective actin-cytoskeleton reorganization, as well as abnormal cell adhesion and migration. Collectively, these data demonstrate that SPECC1L functions in actin-cytoskeleton reorganization and is required for proper facial morphogenesis.

Multipotent stem cells from umbilical cord: Cord is richer than blood!

The identification of mesenchymal stem cell ( MSC) sources that are easily obtainable is of utmost importance. Several studies have shown that MSCs could be isolated from umbilical cord (UC) units. However, the presence of MSCs in umbilical cord blood (UCB) is controversial. A possible explanation for the low efficiency of MSCs from UCB is the use of different culture conditions by independent studies. Here, we compared the efficiency in obtaining MSCs from unrelated paired UCB and UC samples harvested from the same donors. Samples were processed simultaneously, under the same culture conditions. Although MSCs from blood were obtained from only 1 of the 10 samples, we were able to isolate large amounts of multi-potent MSCs from all UC samples, which were able to originate different cell lineages. Since the routine procedure in UC banks has been to store the blood and discard other tissues, such as the cord and/or placenta, we believe our results are of immediate clinical value. Furthermore, the possibility of originating different cell lines from the UC of neonates born with genetic defects may provide new cellular research models for understanding human malformations and genetic disorders, as well as the possibility of testing the effects of different therapeutic drugs.

Carpenter Syndrome: Extended RAB23 Mutation Spectrum and Analysis of Nonsense-mediated mRNA Decay

Carpenter syndrome, a rare autosomal recessive disorder characterized by a combination of craniosynostosis, polysyndactyly, obesity, and other congenital malformations, is caused by mutations in RAB23, encoding a member of the Rab-family of small GTPases. In 15 out of 16 families previously reported, the disease was caused by homozygosity for truncating mutations, and currently only a single missense mutation has been identified in a compound heterozygote. Here, we describe a further 8 independent families comprising 10 affected individuals with Carpenter syndrome, who were positive for mutations in RAB23. We report the first homozygous missense mutation and in-frame deletion, highlighting key residues for RAB23 function, as well as the first splice-site mutation. Multi-suture craniosynostosis and polysyndactyly have been present in all patients described to date, and abnormal external genitalia have been universal in boys. High birth weight was not evident in the current group of patients, but further evidence for laterality defects is reported. No genotype-phenotype correlations are apparent. We provide experimental evidence that transcripts encoding truncating mutations are subject to nonsense-mediated decay, and that this plays an important role in the pathogenesis of many RAB23 mutations. These observations refine the phenotypic spectrum of Carpenter syndrome and offer new insights into molecular pathogenesis. (C) 2011 Wiley-Liss, Inc.

Stand-alone posterior ressection of lumbar hemivertebrae: case report

Background: In this case report we presented the stand-alone posterior approach for hemivertebra resection with unilateral laminar hooks.Case report: The patient was male and five years old. The coronal and sagital X-Rays images showed a failure of vertebral formation, segmented hemivertebra of third lumbar vertebra. The segmented hemivertebra caused a thoracolumbar scoliosis from T12 to L4 (rightside convexity), of 30 degrees (Cobb angle). The patient was submitted to a hemivertebra resection from posterior approach with two unilateral laminars hooks stabilization (superior lamina in L2 and inferior lamina of L4) in association to a compression system and autologus bone graft. The coronal X-Ray image after surgery showed a partial improvement to 25 degrees (Cobb angle) between L2 and L4. After three years of follow up it was not observed system failure (hook pull-out), maintance of curve (25 degrees of Cobb angle) and correction of trunk inbalance.Conclusion: The hemivertebra resection with posterior approach is safe, with satisfactory correction of scoliosis curve, which means is a good choice for congenital scoliosis surgical treatment.

Diagnosis of Smith-Lemli-Opitz syndrome by ultraviolet spectrophotometry

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder due to an inborn error of cholesterol metabolism, characterized by congenital malformations, dysmorphism of multiple organs, mental retardation and delayed neuropsychomotor development resulting from cholesterol biosynthesis deficiency. A defect in 3ß-hydroxysteroid-delta7-reductase (delta7-sterol-reductase), responsible for the conversion of 7-dehydrocholesterol (7-DHC) to cholesterol, causes an increase in 7-DHC and frequently reduces plasma cholesterol levels. The clinical diagnosis of SLOS cannot always be conclusive because of the remarkable variability of clinical expression of the disorder. Thus, confirmation by the measurement of plasma 7-DHC levels is needed. In the present study, we used a simple, fast, and selective method based on ultraviolet spectrophotometry to measure 7-DHC in order to diagnose SLOS. 7-DHC was extracted serially from 200 µl plasma with ethanol and n-hexane and the absorbance at 234 and 282 nm was determined. The method was applied to negative control plasma samples from 23 normal individuals and from 6 cases of suspected SLOS. The method was adequate and reliable and 2 SLOS cases were diagnosed.

Glargine vs. NPH insulin therapy in pregnancies complicated by diabetes: An observational cohort study

Aims: The effects of glargine insulin therapy in pregnancies are not well established. We compared maternal and neonatal outcomes of women with pregestational and gestational diabetes treated with glargine or NPH insulin.Methods: A prospective cohort study was conducted analyzing outcomes from 56 women with pregestational and 82 with gestational diabetes treated with either insulin regimen.Results: Comparisons were performed among 138 women: 56 with pregestational and 82 with gestational diabetes. In relation to maternal complications, worsening of retinopathy and nephropathy, preeclampsia, micro and macroalbuminuria, and all kinds of hypoglycemia were found higher in women with pregestational diabetes NPH-treated vs. glargine-treated. In women with gestational diabetes NPH-treated, it was observed increased incidence of prepregnancy and new-onset pregnancy hypertension, micro and macroalbuminuria, as well as mild and frequent hypoglycemia, compared to glargine-treated. Among the neonatal outcomes, 1-min Apgar score <7, necessity of intensive care unit and fetal death in pregestational, while jaundice and congenital malformations in gestational diabetes, respectively, were more frequently observed in infants born to NPH-treated, compared to glargine-treated.Conclusions: Glargine use during pregnancy from preconception through delivery, showed to be safe since it is associated with decreased maternal and neonatal adverse outcomes compared with NPH insulin-treated patients. (C) 2010 Elsevier B.V. All rights reserved.

Expressão imunoistoquímica de Glut-1 e marcadores de proliferação e apoptose em anomalias vasculares orais

Vascular anomalies constitute a distinct group of lesions, but they may present similar clinical and histopatological characteristics, which can lead to diagnostic mistakes. This study aimed by histopathology and immunohistochemical expression of human glucose transporter protein (GLUT-1), correctly identify and classify oral vascular anomalies, besides analyzing the immunoexpression of markers proliferation and apoptosis (Ki-67 and Bcl-2). All cases diagnosed as "oral hemangiomas" belonging to the archives of the Service of Pathological Anatomy from the subject of Oral Pathology of the Department of Dentistry (DOD), of the Federal University of Rio Grande do Norte (UFRN) were reviewed, totalizing 77 cases. Immunohistochemical analysis for GLUT-1 showed that only 26 (33.8%) of the specimens were true infantile hemangiomas (IHs). The 51 (66.2%%) GLUT-1 negative specimens were then reclassified as pyogenic granulomas (PGs) and vascular malformations (VMs) from their histopathologic characteristics,totalizing 26 (33.8%) cases of IHs, 20 (26.0%) of PGs and 31 (40.2) cases of oral VMs. The cases analyzed by the marker Ki-67 showed different median IH (13,85), PG (33,70) and VM (4.55) with statistically significant differences between them (p <0.001). In relation to the protein Bcl-2, the groups also showed different median of the established scores IH (1.00), PG (1.50), VMs (0.0) demonstrating statistically significant differences between them (p<0,001). No statistically significant correlation between the indexes of positivity for Ki-67 and the scores of immunoexpression of Bcl-2 were observed in any group. Thus, we can conclude that it is necessary a careful and parameterized review of cases of vascular anomalies making use of auxiliary tools such as GLUT-1, since the histopathological findings alone, sometimes, are not sufficient to differentiate some anomalies. Furthermore, analysis of the expressions of markers involved in the levels of proliferation of lesions is important for a better understanding of its biological behavior aspect

Prova de Trabalho de Parto Após uma Cesárea Anterior

Objetivo: estudar a validade da prova de trabalho de parto (PTP) em gestantes com uma cesárea anterior. Métodos: estudo retrospectivo, tipo coorte, incluindo 438 gestantes com uma cesárea anterior ao parto em estudo e seus 450 recém-nascidos (RN), divididas em dois grupos - com e sem PTP. O tamanho amostral mínimo foi de 121 gestantes/grupo. Considerou-se variável independente a PTP e as dependentes relacionaram-se à ocorrência de parto vaginal e à freqüência de complicações maternas e perinatais. Foram efetuadas análises uni e multivariada, respectivamente. A comparação entre as freqüências (%) foi analisada pelo teste do qui-quadrado (chi²) com significância de 5% e regressão logística com cálculo do odds ratio (OR) e do intervalo de confiança a 95% (IC95%). Resultados: a PTP associou-se a 59,2% de partos vaginais. Foi menos indicada nas gestantes com mais de 40 anos (2,7% vs 6,5%) e nas portadoras de doenças associadas e complicações da gravidez: síndromes hipertensivas (7,0%) e hemorragias de 3º trimestre (0,3%). A PTP não se relacionou às complicações maternas e perinatais. As gestantes que tiveram o parto por cesárea, independente da PTP, apresentaram maior risco de complicações puerperais (OR = 3,53; IC95% = 1,57-7,93). A taxa de mortalidade perinatal foi dependente do peso do RN e das malformações fetais e não se relacionou à PTP. Ao contrário, as complicações respiratórias foram mais freqüentes nos RN de mães não testadas quanto à PTP (OR = 1,92; IC95% = 1,20-3,07). Conclusões: os resultados comprovaram que a PTP em gestantes com uma cesárea anterior é estratégia segura - favoreceu o parto vaginal em 59,2% dos casos e não interferiu com a morbimortalidade materna e perinatal. Portanto, é recurso que deve ser estimulado.

Genotoxicity and Fetal Abnormality in Streptozotocin-Induced Diabetic Rats Exposed to Cigarette Smoke Prior to and during Pregnancy

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

Resultado perinatal de fetos com malformações do trato urinário

PURPOSE: to evaluate the perinatal outcome of fetuses with congenital anomalies of the urinary tract. METHODS: we reviewed the perinatal outcome of 35 fetuses with congenital anomalies of the urinary tract. The following characteristics related to the uropathy were analyzed: type (hydronephrosis, dysplasia and renal agenesis), side of lesion (bilateral or unilateral), and level of the obstruction (high or low, in hydronephrosis). The perinatal outcome was evaluated according to these characteristics. The data were analyzed by the c² test and by the exact Fisher test. The level of significance was 0.05. RESULTS: the incidence of hydronephrosis was 68.6%. Half of the fetuses had unilateral hydronephrosis. Renal dysplasia occurred in 17.1% of the cases; 83.3% of these were bilateral and 16.7%, unilateral. The incidence of renal agenesis was 14.3%, all bilateral. The fetuses with dysplasia/agenesis had a 91% incidence of oligohydramnios, preterm birth, low birth weight, and death. In the group with bilateral disease the presence of oligohydramnios, preterm birth, low birth weight, death, urinary tract infections, and the need of hospitalization for a period greater than 7 days was significant when compared to the group with unilateral disease. The need of hospitalization for a period greater than 7 days in patients with low obstruction was significantly higher when compared to the patients with high obstruction. CONCLUSIONS: hydronephrosis, bilateral disease, and lower obstruction were the most frequent uropathies. The dysplasia/agenesis group had a worse prognosis when compared with the hydronephrosis group. Bilateral disease had a worse prognosis when compared with the unilateral disease group. In the low obstruction group, the need for a period of hospitalization greater than seven days was higher than in the high obstruction group.

Malformação arteriovenosa uterina após doença trofoblástica gestacional

OBJETIVO: investigar a presença e resultados de malformações vasculares uterinas (MAVU) após doença trofoblástica gestacional (DTG). MÉTODOS: estudo retrospectivo com inclusão de casos diagnosticados entre 1987 e 2004; 2764 pacientes após DTG foram acompanhadas anualmente com ultra-sonografia transvaginal e Doppler colorido no Centro de Neoplasia Trofoblástica Gestacional da Santa Casa da Misericórdia (Rio de Janeiro, RJ, Brasil). Sete pacientes tiveram diagnóstico final de MAVU baseado em análise ultra-sonográfica - índice de pulsatilidade (IP), índice de resistência (IR) e velocidade sistólica máxima (VSM) - e achados de imagens de ressonância nuclear magnética (RNM). Dosagens negativas de beta-hCG foram decisivas para estabelecer o diagnóstico diferencial com DTG recidivante. RESULTADOS: a incidência de MAVU após DTG foi 0,2% (7/2764). Achados ultra-sonográficos de MAVU: IP médio de 0,44±0,058 (extremos: 0,38-0,52); IR médio de 0,36±0,072 (extremos: 0,29-0,50); VSM média de 64,6±23,99 cm/s (extremos: 37-96). A imagem de RNM revelou útero aumentado, miométrio heterogêneo, espaços vasculares tortuosos e vasos parametriais com ectasia. A apresentação clínica mais comum foi hemorragia transvaginal, presente em 52,7% (4/7) dos casos. Tratamento farmacológico com 150 mg de acetato de medroxiprogesterona foi empregado para controlar a hemorragia, após a estabilização hemodinâmica. Permanecem as pacientes em seguimento, assintomáticas até hoje. Duas pacientes engravidaram com MAVU, com gestações e partos exitosos. CONCLUSÃO: presente sangramento transvaginal em pacientes com beta-hCG negativo e história de DTG, deve-se considerar a possibilidade de MAVU e solicitar avaliação ultra-sonográfica com dopplervelocimetria. O tratamento conservador é a melhor opção na maioria dos casos de MAVU pós-DTG.

Síndrome de crouzon: fatores envolvidos no desenvolvimento neuropsicologico e na qualidade de vida

A síndrome de Crouzon é caracterizada por deformidade craniana, alterações faciais e exoftalmia. O retardo no desenvolvimento neuropsicomotor é observado em alguns casos. Este estudo tem como objetivo analisar a influência do momento da cirurgia, da classe sócio-econômica associada ao nível educacional dos pais e da ocorrência de malformações do sistema nervoso central no desenvolvimento cognitivo destes pacientes correlacionando estes achados à qualidade de vida deles e de suas famílias. Foram estudados 11 pacientes com diagnóstico de síndrome de Crouzon com idade entre um ano e quatro meses e treze anos. A avaliação multidisciplinar dos pacientes incluiu, avaliação social, avaliação cognitiva, estudo do encéfalo por ressonância magnética e avaliação da qualidade de vida. O quociente de inteligência variou de 46 a 102 (m=84,2) e foi correlacionado de forma inversa com o Fator 4 do Questionário de Recursos e Estresse Simplificado (incapacidade da criança); não se correlacionou com as alterações encefálicas, com a condição sócio-econômica dos pais e nem com o momento do tratamento neurocirúrgico.

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.

Síndrome do incisivo central superior solitário: relato de caso

INTRODUÇÃO: a presença de um incisivo central superior solitário é um evento bastante incomum na população. A prevalência da chamada Síndrome do Incisivo Central Superior Solitário (SICSS) é verificada em 1:50.000 nascimentos, sendo registrado um maior acometimento no sexo feminino. Essa alteração no desenvolvimento da oclusão dentária é caracterizada por más formações estruturais, sobretudo na região de linha média do paciente. O diagnóstico precoce e o tratamento adequado dessa síndrome são de grande importância, pois essa condição talvez seja um indicativo de que o paciente pode apresentar outras más formações congênitas severas, não devendo ser a SICSS considerada uma simples anomalia dentária. Os procedimentos ortodônticos, nesses casos, variam dependendo do grau de comprometimento das estruturas ósseas da maxila, da oclusão em si, e principalmente da sutura palatina mediana. OBJETIVO: discutir, baseado em evidências científicas, aspectos importantes relacionados à SICSS, bem como apresentar um caso clínico de paciente do sexo feminino com SICSS, que foi submetida a tratamento ortodôntico na Clínica Odontológica Integrada Infantil da Universidade Federal de Santa Maria (UFSM) / RS. CONCLUSÃO: pela análise crítica da literatura, verifica-se ser muito importante o diagnóstico correto e precoce acerca dessa síndrome, visto que há possibilidade da mesma estar associada a outros problemas de desenvolvimento. Além disso, o paciente acometido pela SICSS deve ser assistido por uma equipe multidisciplinar de saúde, de forma a otimizar os resultados clínicos e devolver-lhe qualidade de vida.

Fetotoxicity caused by the interaction between zinc and arsenic in mice

Arsenic is an environmental pollutant that induces congenital malformations in experimental models and can contribute to human birth defects. The environmental exposure to arsenic is relatively small when compared with the doses required to cause teratogenicity in mice and other laboratory animals. In order to study the action of zinc in the arsenic-induced teratogenicity, in the present work mice were either pretreated with zinc and later with arsenic or were treated simultaneously with zinc and arsenic in vivo and in vitro. Following administration of arsenate on gestation day 8, pregnant females were killed on the 17th day of gestation; maternal and fetal data were collected by laparotomy and used to calculate reproductive parameters. Fetuses were analyzed for the presence of external malformation and, after the appropriate processing, visceral and skeletal analyses were accomplished. Conceptuses were exposed in whole embryo culture to arsenicals on gestation day 8 (3-6 somite stage). After a 26 h culture period, morphological development was assessed. Neither pretreatment with zinc nor simultaneous administration of zinc prevented arsenic teratogenicity in these experimental models. (C) 2002 Wiley-Liss, Inc.