Unequal Impact of COL1A1 and COL1A2 Variants on Dentinogenesis Imperfecta.

Dentinogenesis imperfecta (DI) is the main orodental manifestation of osteogenesis imperfecta (OI) caused by COL1A1 or COL1A2 heterozygous pathogenic variants. Its prevalence varies according to the studied population. Here, we report the molecular analysis of 81 patients with OI followed at reference centers in Brazil and France presenting COL1A1 or COL1A2 variants. Patients were submitted to clinical and radiographic dental examinations to diagnose the presence of DI. In addition, a systematic literature search and a descriptive statistical analysis were performed to investigate OI/DI phenotype-genotype correlation in a worldwide sample. In our cohort, 50 patients had COL1A1 pathogenic variants, and 31 patients had COL1A2 variants. A total of 25 novel variants were identified. Overall, data from a total of 906 individuals with OI were assessed. Results show that DI was more frequent in severe and moderate OI cases. DI prevalence was also more often associated with COL1A2 (67.6%) than with COL1A1 variants (45.4%) because COL1A2 variants mainly lead to qualitative defects that predispose to DI more than quantitative defects. For the first time, 4 DI hotspots were identified. In addition, we showed that 1) glycine substitution by branched and charged amino acids in the α2(I) chain and 2) substitutions occurring in major ligand binding regions-MLRB2 in α1(I) and MLBR 3 in α2(I)-could significantly predict DI (P < 0.05). The accumulated variant data analysis in this study provides a further basis for increasing our comprehension to better predict the occurrence and severity of DI and appropriate OI patient management.

Effectiveness of gastrostomy for improving nutritional status and quality of life in patients with epidermolysis bullosa: a systematic review.

Individuals with epidermolysis bullosa (EB) may present with a broad spectrum of growth impairment and multiorgan disorders, with compromised nutritional status and quality of life. The provision of nutrients through a gastrostomy tube may minimize EB-related malnourishment but may also result in skin injuries and infections. In this systematic review we consider the current evidence about the effectiveness of gastrostomy in restoring nutritional status and improving quality of life in patients with EB. Seven studies (n = 146) met selection criteria and patients ranged in age from 6 weeks to 33 years of age. Although it is not a risk-free procedure, the placement of a gastrostomy tube is a feasible and safe alternative to provide nutritional support and to improve the quality of life of patients.

Avaliação da atividade antimicrobiana de extratos de Eugenia anomala e Psidium salutare (Myrtaceae) frente à Escherichia coli e Listeria monocytogenes / Evaluation of the antimicrobial activity of extracts of Eugenia anomala and Psidium salutare (Myrtaceae) against the Escherichia coli and Listeria monocytogenes

RESUMO As doenças transmitidas por alimentos ocorrem principalmente devido à ingestão de alimentos contaminados por microrganismos patogênicos, dentre eles a Escherichia coli e Listeria monocytogenes. Uma das alternativas estudadas para minimizar a contaminação de alimentos é o emprego de plantas, ou seus extratos, como agentes antimicrobianos de origem natural em produtos alimentícios. Desta forma o objetivo do presente estudo é fornecer dados científicos a respeito de duas plantas nativas do RS ainda não estudadas, Eugenia anomala e Psidium salutare, visando potencial emprego como agente antimicrobiano natural em alimentos. Para tanto, avaliou-se a atividade antimicrobiana de extratos de E. anomala e P. salutare contra E. coli e L. monocytogenes através da determinação da concentração inibitória mínima (CIM) pelo método de microdiluição em caldo, a capacidade antioxidante dos extratos por meio do método de redução do radical DPPH e a citotoxicidade in vitro empregando células CHO-K1. Os resultados obtidos mostraram que os extratos de acetato de etila e etanólico de ambas as espécies possuem ação antioxidante muito alta, de 94,08% e 93,86%, respectivamente. Apenas o extrato hexânico de P. salutare apresentou ação antimicrobiana moderada (CIM = 312,5 µg/mL). Todos os extratos apresentaram ação citotóxica sendo que os maiores percentuais foram do extrato clorofórmico de E. anomala (77,05%) e hexânico de P. salutare (76,79%), na concentração de 100 µg/mL. Assim, o presente estudo demonstrou que as espécies vegetais estudadas apresentam potencial para emprego como agente antimicrobiano destes microrganismos.

ABSTRACT The foodborne diseases occur mainly due to the ingestion of food contaminated by pathogenic microorganisms, including Escherichia coli and Listeria monocytogenes. One of the alternatives studied to minimize contamination of food is the use of plants or their extracts as antimicrobial agents naturally occurring in food products. The objective of this study is to provide scientific data on two native plants of RS have not studied Eugenia anomala and Psidium salutare for a potential use as a natural antimicrobial agent in food. To this end, we evaluated the antimicrobial activity of extracts of E. anomala and P. salutare against E. coli and L. monocytogenes by determining the minimum inhibitory concentration (MIC) by the broth microdilution method, the antioxidant capacity of the extract for means DPPH radical reduction method and in vitro cytotoxicity using CHO-K1 cells. The results showed that the ethyl acetate and ethanolic extracts of both species have very high antioxidant activity, of 94.08% and 93.86%, respectively. Only the hexane extract of P. salutare showed a moderate antimicrobial activity (MIC = 312.5 mg/mL). Moreover, all extracts showed cytotoxic action of which the highest percentages were the chloroform extract of E. anomala (77.05%) and hexane P. salutare (76.79%) at a concentration of 100 mg/mL. Thus, the present study showed that plant species have potential for use as an antimicrobial agent against these microorganisms.

Pamidronate affects the mandibular cortex of children with osteogenesis imperfecta.

We hypothesized that mandibular cortical width (MCW) is smaller in children with osteogenesis imperfecta (OI) than in healthy children and that pamidronate can improve the cortical mandibular thickness. The aim of this study was to assess changes in the MCW on dental panoramic radiographs (DPRs) of children with normal bone mineral density (BMD) and with OI. We also compared the MCW of children with different types of OI regarding the number of pamidronate cycles and age at the beginning of treatment. MCW measurements were retrospectively obtained from 197 DPRs of 66 children with OI types I, III, and IV who were in treatment with a comparable dosage of cyclical intravenous pamidronate between 2007 and 2013. The control group had 92 DPRs from normal BMD children. Factorial analysis of variance was used to compare MCW measurements among different age groups and between sexes and also to compare MCW measurements of children with different types of OI among different pamidronate cycles and age at the beginning of treatment. No significant differences in results were found between male and female subjects in both OI and healthy children, so they were evaluated altogether (P > 0.05). There was an increase of MCW values related to aging in all normal BMD and OI children but on a smaller scale in children with OI types I and III. Children with OI presented lower mean MCW values than did children with normal BMD at the beginning of treatment (P < 0.05). A linear model estimated the number of pamidronate cycles necessary to achieve mean MCW values equivalent to those of healthy children. The thinning of the mandibular cortex depended on the number of pamidronate cycles, the type of OI, and the age at the beginning of treatment. DPRs could thus provide a way to identify cyclic pamidronate treatment outcomes in patients with OI.

Avaliação de indicadores biológicos na validação de processos de esterilização de isoladores por peróxidos de hidrogênio / Assessment of biological indicators in the validation of isolator decontamination with hydrogen peroxide

Os isoladores permitem a aplicação de descontaminação por gases, resultando em ambiente estéril. Esta característica, adicionada a possibilidade de não interferência humana no processo, torna o emprego dos isoladores consideravelmente vantajosa quando comparada com a performance dos processos em salas limpas convencionais. A descontaminação empregando peróxido de hidrogênio é vantajosa em relação a outros métodos disponíveis uma vez que é de fácil remoção após aplicação; sendo água e oxigênio seus produtos de degradação, apresenta boa compatibilidade com materiais usualmente empregados nas áreas produtivas; e seu custo é relativamente baixo. O propósito deste estudo foi demonstrar que o Geobacillus stearothermophilus (ATCC 12980) é o microrganismo mais resistente quando comparado com microrganismos isolados presentes em áreas produtivas, assim como avaliar o melhor material a servir de suporte durante a validação do processo de descontaminação das superfícies internas do isolador e externas de materiais presentes. Bacillus sp., Micrococcus luteus, Corynebacterium sp., Staphylococcus sp. e Penicilium sp. foram os microrganismos que apresentaram maior incidência na área produtiva. Aço inoxidável é o material mais adequado a ser usado como suporte para o emprego do peróxido de hidrogênio, por ser inerte e o principal componente dos isoladores e por não demonstrar incompatibilidade com o agente esterilizante. Os resultados obtidos nesta etapa do estudo demonstraram que o Geobacillus stearothermophilus é o microrganismo mais resistente para ser utilizado na avaliação da eficácia do peróxido de hidrogênio quando comparado com aqueles microrganismos encontrados na flora normal. Adicionalmente, o melhor suporte é o aço inoxidável, significando que os indicadores biológicos comercialmente disponíveis neste material são a melhor opção para este propósito.

Isolators allow decontamination gases to be employed to create a sterile processing environment. This feature, added to the potential removal of human interference in the process, makes the use of isolators rather advantageous, compared to performing aseptic processes in conventional clean rooms. Decontamination with vaporized hydrogen peroxide (VHP) offers several advantages over other available methods, as it decomposes to water and oxygen and is thus easy to remove after use, is highly compatible with materials usually employed in production areas and it is relatively cheap. The aims of this study were to prove that Geobacillus stearothermophilus (ATCC 12980) is more resistant than microorganisms isolated from the normal production area flora and to determine the best material to serve as a support during validation of the decontamination of the inner surfaces of isolators and outer surfaces of materials inside them. Bacillus sp., Micrococcus luteus, Corynebacterium, Staphylococcus sp. and Penicillium sp. were the microorganisms of highest incidence among those identified in the production area. Stainless steel is the best material to be used as a support for the VHP treatment of specimens, as it is inert and the main component of isolators and showed no incompatibility with this sterilizing agent. The results obtained in this phase of the experiment proved that Geobacillus stearothermophilus is the most resistant microorganism with which to challenge the effectiveness of hydrogen peroxide, when tested against species of the normal flora. Secondly, the best support material is stainless steel, showing that the commercial bioindicators available on the market with this support material are scientifically proved to be the best choice for this purpose.

Gangliosides on intestinal microcirculation and animal survival during reperfusion.

This study investigated the effect of gangliosides (Gang) on small bowel microcirculation and animal survival after normothermic intestinal ischemia-reperfusion injury. Five adult male EPM-1 Wistar rats in each of three groups received FK506 (0.2 mg/kg), Gang (3 mg/kg), or vehicle (at same volume) either 24 or 12 hours prior to the experiment. The animals were anesthetized intramuscularly with ketamine (60 mg/kg) and xylazine (10 mg/kg) and hydrated with 80 mL/kg of prewarmed saline solution delivered subcutaneously before the ischemic insult and 40 mL/kg at 1 hour after reperfusion. Under anesthesia, they underwent a laparotomy with clamping of the superior mesenteric artery (SMA) at its origin for 75 minutes. Microcirculation was evaluated with a laser Doppler flowmeter, 5 minutes before ischemia (baseline) and reperfusion (ischemia), and 20, 40, and 60 minutes after reperfusion. Animal survival was observed up to 24 hours. Small bowel flow measured before ischemia was considered to be the baseline level (100%). After SMA occlusion a significant reduction in microcirculatory tissue perfusion to about 8% was observed in all groups. At 20, 40, and 60 minutes of reperfusion treatment with Gang (77%, 81%, and 100%) or FK506 (70%, 85%, and 98%) promoted better recovery of the intestinal microcirculation when compared to the control group (45%, 72%, and 75%). Concerning animal survival there was no difference between groups (just one animal from each group, Gang and FK506, survived up to 24 hours). Based on our data we conclude that Gang and FK506 improve intestinal microcirculation in ischemia-reperfusion injury but do not change animal survival after severe ischemia.

Contribuição para melhoria da prática farmacêutica no atendimento de pacientes com queixas referentes a doenças sexualmente transmissíveis, em Campo Grande-MS / Contribution to the improvement of pharmaceutical practice in the attendance of patients with referring complaints to sexually transmissible diseases, in Campo Grande, state of Mato Grosso do Sul

As doenças sexualmente transmissíveis vêm se mantendo como problema de Saúde Pública. Após o surgimento da AIDS, tal situação agravou-se. É sabido que nossa população busca atendimento nas farmácias para seus problemas de saúde. Vários autores já constataram a indicação de medicamentos, ilegal e irracional em farmácias de todo o Brasil. O presente trabalho visa contribuir para a melhora da prática farmacêutica no município de Campo Grande - MS. O universo estudado abrangeu todas as farmácias registradas no CRF/MS no momento da pesquisa. Na primeira fase do estudo, investigou-se a prática dos trabalhadores da farmácia frente a um paciente com sintomas de gonorréia. Na segunda fase do estudo, procedeu-se uma intervenção educativa em pequeno grupo de farmacêuticos e seus balconistas. Após quatro meses foi feita avaliação dessa intervenção. Efetuou-se também a avaliação de uma intervenção educativa de larga escala realizada pelo CFF e dirigida a farmacêuticos, ocorrida concomitantemente a este estudo. Obteve-se resposta de 92,5 por cento das farmácias cadastradas pelo CRF/MS, verificando-se que as mesmas apresentaram um percentual elevado de indicações de medicamentos aos pacientes com queixa de DSTs (72,0 por cento para o sexo masculino e 62,5 por cento para o sexo feminino), principalmente antibióticos. Observou-se que, apesar das intervenções pedagógicas, a venda de medicamentos sem receita médica não se alterou significativamente. Por outro lado, as informações transmitidas modificaram a conduta dos farmacêuticos proprietários e também melhoraram as orientações fornecidas pelos leigos.

Gangliosides in rat femoral injury: early effect on intimal hyperplasia.

Previous studies demonstrated that some immunosuppressive agents inhibit arterial intimal hyperplasia. Our previous studies demonstrated that gangliosides (Gang) have an immunosuppressive effect on as well as an anti-inflammatory role in the wound-healing process. Therefore, we decided to examine the effect of Gang on intimal hyperplasia. Twenty Wistar isogenic rats received a transverse division of the anterior wall of the femoral artery, followed by suturing using mononylon 10-0 under surgical microscopy and were then divided into two groups: Gang group, 3 mg/kg per day of Gang, and control group, vehicle, intramuscularly from surgery to death (1 and 3 weeks, respectively). Concentric intimal hyperplasia was observed in arteries stained by hematoxylin-eosin in control and Gang groups. However, the media layer did not demonstrate any major alterations. After 3 weeks, the Gang group showed more intimal hyperplasia than the control group. Therefore, because intimal hyperplasia worsened in the presence of Gang after 3 weeks, further studies will be necessary to clarify its role in intimal proliferation.

Sequential use of Prepidil and extra-amniotic saline infusion for the induction of labor in nulliparous women with very low Bishop scores.

OBJECTIVE: To evaluate the efficacy of sequential use of Prepidil (prostaglandin E2 gel) and extra-amniotic saline infusion for the induction of labor in nulliparous women with very low Bishop scores. STUDY DESIGN: Nulliparous women with singleton gestations, intact membranes and a cervical Bishop score of < or = 2 who received Prepidil gel and extra-amniotic saline infusion sequentially for the induction of labor between July 1996 and July 1998 were studied. RESULTS: Thirty-one women met the inclusion criteria. Indications for induction included post-dates (six of 31), pre-eclampsia (ten of 31), diabetes (three of 31), oligohydramnios (three of 31), intrauterine growth restriction (two of 31) and non-reactive non-stress test (NST) (seven of 31). The average time from onset of induction to delivery was 38.1 +/- 13.5 h. Vaginal delivery was achieved in 80.6%. Women requiring > 2 doses of Prepidil had a higher risk of delivering abdominally (OR = 3.5). Three of seven (42.9%) women with labor induced for non-reactive NST but only three of 24 (12.5%) with labor induced for other indications had a Cesarean section delivery (p < 0.001). CONCLUSIONS: Nulliparous women with very unfavorable cervices can be counselled that they have an 80% chance of vaginal delivery using sequential Prepidil and extra-amniotic saline infusion as an induction method, with 90% delivering within the first 48 h.

Recognition of melanoma cell antigens with antibodies present in sera from patients with vitiligo.

BACKGROUND: Patients with vitiligo show specific losses of integumentary melanocytes, probably due to autoimmunity against melanocytes. We attempted to determine the presence of antibodies against pigment cell antigens in the sera of vitiligo patients. METHODS: Detergent-solubilized human melanoma cells were submitted to electrophoretic separation and immunoblotted against serum samples obtained from 19 patients with vitiligo and from 20 age- and sex-matched healthy individuals. RESULTS: Eighty-nine per cent of patients with vitiligo had antibodies to one or more pigment cell antigens. Similar antibodies were detected in 20% of healthy individuals. Antigens of 165, 90, and 68 kDa were recognized by the antibodies present in sera from 11%, 26%, and 37% of vitiligo patients, respectively, and in none of the normal sera. All patients with familial vitiligo also had antibodies to these three proteins. CONCLUSIONS: Proteins of 165, 90, and 68 kDa are specifically recognized by antibodies present in the sera of vitiligo patients and in all patients with genetic vitiligo. Whether or not these proteins might be implicated in the destruction of melanocytes by the immune system in vitiligo remains to be evaluated.

Expectant management of severe preterm preeclampsia: is intrauterine growth restriction an indication for immediate delivery?

OBJECTIVE: Expectant management of severe preterm preeclampsia is gaining widespread acceptance in clinical practice. The objective of our study was 2-fold-to determine the frequency of fetal deterioration with expectant management of severe preterm preeclampsia and to evaluate whether the presence of intrauterine growth restriction on admission is associated with a shorter admission-to-delivery interval or more deliveries resulting from nonreassuring fetal status in comparison with pregnancies with preeclampsia but without intrauterine growth restriction. STUDY DESIGN: This was an observational study of women with singleton pregnancies at <34 completed weeks' gestation who were admitted to the hospital with the diagnosis of severe preeclampsia and managed expectantly. Fetal status on admission, admission-to-delivery interval, indication for delivery, and neonatal outcome were examined. RESULTS: Forty-seven women were studied during a 3-year period (1996-1999). Gestational age at admission was 29.8 +/- 2.6 weeks. The mean admission-to-delivery interval for the entire group was 6.0 +/- 5.1 days; in 42.5% delivery was for fetal indications. In comparison with the absence of intrauterine growth restriction, the presence of intrauterine growth restriction at admission resulted in a significantly shorter admission-to-delivery interval (3.1 +/- 2.1 vs 6.6 +/- 6.1 days; P <.05). Most fetuses with intrauterine growth restriction (85.7%) were delivered before 1 week. Although 57% of fetuses with intrauterine growth restriction were delivered for fetal indications, versus 39% of fetuses without intrauterine growth restriction, these rates were not found to be significantly different. Neonatal outcomes, as reflected by Apgar scores, number of admissions to and duration of stay in the neonatal intensive care unit, and neonatal mortality rates, were similar. CONCLUSION: Pregnancies complicated by severe preterm preeclampsia and the presence of intrauterine growth restriction at admission may not benefit from expectant management beyond the 48 hours needed for betamethasone to act. Furthermore, all patients may benefit from close fetal monitoring before delivery because of the high rate of intervention for deteriorating fetal status.

Inhibition of mouse and rat lymphoproliferation by gangliosides

Our previous study have demonstrated that Glycosphingolipids (GSLs) have an immunosuppressive effect on murine lymphoproliferation and IL-2 production. In the present study we examined the effect of a pool of Gangliosides (Gang) on spleen lymphocyte proliferation from either isogeneic strains of Wistar rats or BALB/c mice. Two hundred-fifty grams adult female isogeneic Wistar rats and 8-week-old BALB/c mice were used. The animals were sacrificed and the spleen harvested aseptically for cellular assays. Spleen cells suspensions were obtained by homogenization in RPMI 1640 with a loose tissue grinder. After washing, the cells were suspended in RPMI 1640 supplemented. Cell viability was measured by Trypan blue exclusion. Cells were cultured in triplicate using increasing concentrations of Gang (1; 2; 5; 10; 15; 20 mg/well) and in the presence of Concanavalin A. The cells were incubated for 48 hours and were pulsed with [3H] thymidine 18 hours prior to harvesting on glass fiber paper for counting in a beta-counter. Data were presented as rate of inhibition, as previously described. At concentrations 1 and 2 mug/well, Gang stimulated lymphoproliferation (30 percent and 50 percent, rats and mice respectively), while at concentration from 5 to 20 mg/well an increasing inhibition was observed for spleen cells from both mouse and rat (from 40 percent up to 80 percent). In preliminary studies we observed inhibition of mixed lymphocyte reaction on spleen cells from rats treated with Gang for 10 days (data not shown). Our data suggest that Gang may be investigated as a immunosuppressive drug in organ transplantation.

Gangliosideos e a resposta de hipersensibilidade retardada em camundongos / Gangliosides and the delayed hypersensitivity response in mice

Em trabalhos anteriores mostrou-se que os gangliosídeos (GSLs) têm um efeito inibitório sobre a proliferação linfocitária e a síntese de IL-2, assim como sobre a reação mista de linfócitos. Neste estudo objetivou-se avaliar o efeito dos GSLs sobre a resposta de hipersensibilidade retardada. Foram utilizados 12 camundongos BALB/c, machos, pesando em média 30 gramas, provenientes do biotério setorial da Disciplina de Parasitologia e mantidos por 5 dias para adaptação no biotério setorial da Disciplina de Técnica Operatória e Cirurgia Experimental da UNIFESP-EPM, recebendo água e ração própria para a espécie. Os animais foram distribuídos em três grupos, de acordo com as doses de GSLs, da seguinte forma: grupo 3mg. kg-1, grupo 9mg. kg-1 e grupo simulado (veículo). Os animais foram tratados, por via intramuscular, nos dias 0 e 4. O parâmetro avaliado foi o edema da pata traseira esquerda no local da inoculação do antígeno. Os animais foram anestesiados com Cetamina (60mg.kg-1) e Xilazina (10mg.kg-1), por via intramuscular, sendo em seguida submetidos à dissecção da veia jugular direita, por onde foram inoculadas 10(6) hemácias de Carneiro no dia 0, para sensibilização. No dia 4 subsequente, os animais foram novamente anestesiados e receberam, por via subcutânea, 10(8) hemácias de Carneiro, num volume de 0,02ml. Foram realizadas medidas do edema da pata traseira com paquímetro 24, 48, 72 e 96 horas após o desafio. Os dados mostraram que após 48h houve um aumento do edema em animais dos grupos simulado e 3mg (médias=2,3 and 2,1mm, respectivamente), e os camundongos do grupo 9mg não apresentaram aumento importante (média=0,1mm). Entretanto, após 72h, o grupo 9mg apresentou aumento de 1,7mm enquanto, os outros grupos não apresentaram mudança significativa no edema da pata (médias=0,2 e 0,8mm), grupos simulado e 3mg, respectivamente) comparados aos dados do dia antecedente. Após 96h, todos os grupos apresentaram desaparecimento do edema. Com base nos dados obtidos pode-se concluir que a resposta de hipersensibilidade retardada alterou-se na vigência de alta dose de GSLs.

Efeito imunossupressor dos gangliosídeos: estudo in vivo / Immunosupressive effect of gangliosides: in vivo study

Imunomodulação mais específica e eficaz é uma meta importante a ser atingida na área de órgão. Neste sentido, foi estudado previamente o papel imunomodulador dos gangliosídeos "in vitro". No presente trabalho objetivou-se avaliar este efeito agora "in vivo", mimetizando a situação do transplante alogênico. Foram utilizados 26 ratos Wistar 1 EPM, machos, com 3 meses de idade, pesando cerca de 250g, procedentes do Centro de Desenvolvimento de Pesquisa Experimental em Medicina e Biologia. Os animais fora mantidos por 5 dias, para adaptação, no biotério setorial da Disciplina de Técnica Operatória e Cirurgia Experimental da UNIFESP-EPM, recebendo água e ração própria para a espécie. Os animais foram distribuídos em grupos conforme segue: grupos experimento (que receberam 1, 3 e 6 mg/kg/dia de gangliosídeos) e um grupo controle que recebeu veículo, todos por via intramuscular durante 7 dias consecutivos. No 8º dia, com os animais anestesiados com éter etílico foi feita a remoção cirúrgica do baço de todos os animais, os quais foram sacrificados por exsanguinação, ainda sob efeito anestésico. Os baços removidos foram processados para a obtenção de linfócitos os quais foram cultivados em placa de cultura com 96 poços, distribuídos da seguinte forma: 1,5x10(5) linfócitos viáveis de cada animal dos grupos experimento e controle foram cultivados com 1,5x10(5) linfócitos viáveis de um rato não tratado, sendo assim realizada a reação mista de linfócitos. Os linfócitos provenientes dos animais dos grupos controle e 1 mg apresentaram aumento da proliferação sem nenhuma alteração. Por outro lado, foi observada uma taxa de inibição ao redor de 70 por cento sobre a proliferação linfocitária dos animais dos grupos 3 e 6 mg comparados aos animais dos grupos controle e 1 mg. O resultado desta investigação estimula a utilização dos gangliosídeos no tratamento da rejeição alogênica.

Gangliosideos: estudo do colágeno e da resposta inflamatória no processo cicatricial / Gangliosides: study of colagem and the inflamatory response in cicatricial process

Objetivo: Investigar o efeito dos gangliosídeos sobre a infiltração seqüencial de leucócitos e fibroblastos durante o processo de cicatrização usando um modelo de cicatrização da pele em ratos. Método: Foram utilizados 12 ratas EPM - 1 Wistar, com peso médio de 200 gramas e 4 meses de idade. Os animais procederam do Centro de Desenvolvimento de Pesquisa Experimental em Medicina e Biologia e foram mantidos por 5 dias para adaptação no biotério setorial da disciplina de Técnica Operatória e Cirurgia Experimental da UNIFESP-EPM, recebendo água e ração própria para a espécie. O protocolo anestésico utilizado foi uma associação de Cetamina (60mg.kg-1) e Xilazina (10mg.kg-1), por via intramuscular. Em seguida, realizava-se uma incisão longitudinal com 7 cm de extensão, na região dorsal paravertebral, interessando pele e tela subcutânea que foi fechada com pontos separados, com fio de prolene 7-0 e agulha triangular. As ratas foram distribuídas em dois grupos a saber: grupo experimento, que recebeu 3mg.kg-1.dia-1 de gangliosídeos, e um grupo controle, que recebeu veículo, ambos por via intramuscular durante 14 dias consecutivos. No 7º e 14º dias de pós-operatório foram ressecados fragmentos da pele e tela subcutânea para análise histológica, com a coloração de Tricrômio de Masson e Hematoxilina - Eosina. Resultados: As amostras apresentaram a mesma quantidade de colágeno em ambos os grupos mostrando que não houve inibição dos fibroblastos. Entretanto, a infiltração leucocitária foi retardada no grupo experimento quando comparado ao grupo controle. Conclusão: A alteração encontrada no processo cicatricial foi devida a um retardo na resposta inflamatória e não a uma inibição fibroblastos.

Maternal plasma corticotropin-releasing hormone associated with stress at 20 weeks' gestation in pregnancies ending in preterm delivery.

OBJECTIVE: This study tested the hypothesis that maternal stress is associated with elevated maternal levels of corticotropin releasing hormone and activation of the placental-adrenal axis before preterm birth. STUDY DESIGN: In a behavior in pregnancy study, 524 ethnically and socioeconomically diverse women were followed up prospectively and evaluated at 3 gestational ages: 18 to 20 weeks, 28 to 30 weeks, and 35 to 36 weeks. Maternal variables included demographic data, medical conditions, perceived stress level, and state anxiety. Maternal plasma samples were collected at each gestational age. Eighteen case patients with spontaneous onset of preterm labor were matched against 18 control subjects who were delivered at term, and their samples were assayed for corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol by means of radioimmunoassay. Statistical tests were used to examine mean differences in these hormones. In addition, the relationship between stress level and each hormone was tested with a Pearson correlation coefficient and hierarchic multiple regressions in each group. RESULTS: Patients who had preterm delivery had significantly higher plasma corticotropin-releasing hormone levels than did control subjects at all 3 gestational ages (P <.0001). Analyses did not find any differences in reported levels of stress between 18 to 20 weeks' gestation and 28 to 30 weeks' gestation. A hierarchic multiple regression indicated that maternal stress level at 18 to 20 weeks' gestation and maternal age accounted for a significant amount of variance in corticotropin-releasing hormone at 28 to 30 weeks' gestation, after controlling for corticotropin-releasing hormone at 18 to 20 weeks' gestation (P <. 001). In addition, patients who were delivered preterm had significantly elevated plasma levels of adrenocorticotropic hormone at all 3 gestational ages (P <.001) and significantly elevated cortisol levels at 18 to 20 weeks' gestation and 28 to 30 weeks' gestation (P <.001). CONCLUSION: Maternal plasma levels of corticotropin-releasing hormone are significantly elevated at as early as 18 to 20 weeks' gestation in women who are subsequently delivered preterm. Changes in corticotropin-releasing hormone between 18 to 20 weeks' gestation and 28 to 30 weeks' gestation are associated with maternal age and stress level at 18 to 20 weeks' gestation. Maternal stress and corticotropin-releasing hormone levels may be potential markers for the patient at risk for preterm birth. Activation of the placental maternal pituitary-adrenal axis is consistent with the classic endocrine response to stress.

Open clinical study of the efficacy and safety of terbinafine cream 1% in children with tinea corporis and tinea cruris.

BACKGROUND: Topical application of antifungal agents is considered the treatment of choice for dermatomycoses. Most of the available drugs are fungistatic, requiring long term treatment to prevent relapses. Terbinafine is a synthetic antifungal agent that, because of its fungicidal action, provides high cure rates and low relapse rates after short periods of treatment. METHODS: Ninety-seven children ages 2 to 15 years with a suspected diagnosis of tinea corporis and/or tinea cruris were enrolled in this open trial. After mycologic assessment to confirm diagnosis (culture and direct microscopy) terbinafine 1% cream was applied once daily during 1 week. Clinical and mycologic assessments were made at the baseline visit and on Days 7, 14 and 21. Efficacy assessment was based on 88 children (9 patients excluded by protocol violation). RESULTS: Therapy was considered effective in 92.0% (81 of 88) of patients (complete clinical and mycologic cure or mycologic cure with minimum signs and symptoms or clinical improvement, > or = 50%). Tolerability was assessed in 97 patients on an intention-to-treat basis. Adverse reactions were itching 3% (3 of 97), itching associated with erythema exacerbation 1% (1 of 97) and contact dermatitis 1% (1 of 97). CONCLUSION: Terbinafine 1% cream appears to be an effective and well-tolerated treatment for tinea corporis and tinea cruris in children.

Long-term nitric oxide blockade in the pregnant rat: effects on blood pressure and plasma levels of endothelin-1.

OBJECTIVE: Abnormalities in the production of nitric oxide and endothelin-1 have been implicated in the development of preeclampsia. We postulated that long-term nitric oxide synthase inhibition with L-nitro-arginine methyl ester would induce sustained hypertension, a rise in plasma levels of endothelin-1, and fetal growth restriction. STUDY DESIGN: Conscious virgin and pregnant Sprague-Dawley rats received infusions of vehicle or L-nitro-arginine methyl ester (2.5 mg/kg/hr) for 11 days. Mean arterial pressure was assessed serially. On day 21 of gestation (or equivalent in virgin rats) plasma was collected for endothelin-1 levels; pup weight and litter size were determined. Data were analyzed with analysis of variance and regression techniques. RESULTS: Mean arterial pressure was constant in virgin control rats (n = 7) but declined in pregnant control rats (n = 11) as gestation advanced. Nitric oxide synthase inhibition in virgin (n = 10) and pregnant (n = 11) rats caused sustained elevations in mean arterial pressure (165 +/- 7 vs 100 +/- 3 mm Hg, L-nitro-arginine methyl ester vs control virgin rats, p < 0.0001; 149 +/- 5 vs 91 +/- 2 mm Hg, L-nitro-arginine methyl ester vs control pregnant rats, p < 0.0001). L-nitro-arginine methyl ester induced a rise in plasma endothelin-1 levels in virgin (4.4 +/- 0.1 vs 3.5 +/- 0.1 pg/ml, L-nitro-arginine methyl ester vs control, p < 0.0001) and pregnant rats (3.0 +/- 0.1 vs 2.6 +/- 0.1 pg/ml, L-nitro-arginine methyl ester vs control, p < 0.0001). Pregnant rats had lower endothelin-1 levels than did virgin rats (p < 0.0001). Mean arterial pressure and endothelin-1 were significantly correlated in pregnant rats. L-nitro-arginine methyl ester decreased pup weight (2.4 +/- 0.4 vs 3.7 +/- 0.2 gm/pup/litter, L-nitro-arginine methyl ester vs control, p < 0.01) and litter size (6.6 +/- 1.3 vs 10.2 +/- 0.9 pups/litter, L-nitro-arginine methyl ester vs control, p < 0.05). CONCLUSIONS: Long-term nitric oxide synthase blockade causes sustained hypertension, elevated levels of endothelin-1, and fetal growth restriction. Although the endocrine and pressor effects are not unique to pregnancy, this model clearly induces some of the changes seen in preeclampsia and may be useful for studying specific interventions.

Adenosine modulates hypoxia-induced atrial natriuretic peptide release in fetal sheep.

The effects of adenosine on atrial natriuretic peptide (ANP) secretion were determined in chronically catheterized fetal sheep (> 0.8 term). Adenosine was infused into the the right jugular vein for 1 h at 8 +/- 0.4 (5 fetuses), 160 +/- 8 (6 fetuses), and 344 +/- 18 micrograms.min-1.kg estimated fetal wt-1. Fetal arterial blood gases and pH were generally unaffected by adenosine, although mean arterial CO2 tension increased transiently by 2-5 Torr and pH fell progressively during the highest rate of infusion. During the intermediate and high infusion rates, fetal hemoglobin concentrations increased by 11-13% and mean fetal heart rate rose by 18% from a control value of approximately 167 beats/min. Mean arterial pressure was not affected during adenosine infusion. Adenosine significantly increased fetal plasma ANP levels, with maximum concentrations 1.80, 2.36, and 2.51 times greater than control means (142-166 pg/ml) for the respective infusion rates of 8, 160, and 344 micrograms.min-1.kg estimated fetal wt-1. In seven fetuses, reducing fetal arterial O2 tension by approximately 9-10 Torr from a control of 23 +/- 1.3 Torr increased plasma ANP concentrations approximately 2.4 times the control mean of 176 pg/min. Adenosine-receptor blockade with 8-(p-sulfophenyl)-theophylline reduced by 50% the maximum hypoxia-induced rise in plasma ANP concentrations. It is concluded that adenosine causes a dose-dependent rise in fetal plasma ANP concentrations and modulates fetal ANP release during hypoxia.