Cerebroplacental ratio and acidemia to the birth in placental insufficiency detected before 34th week's gestation

OBJETIVO: avaliar a hipótese de que a relação cerebroplacentária (RCP) fetal relaciona-se com acidemia no nascimento, em gestações complicadas pela insuficiência placentária detectada antes da 34ª semana de gestação. MÉTODOS: trata-se de coorte prospectiva de 55 pacientes entre a 26ª e a 34ª semanas de gestação, com diagnóstico de insuficiência placentária caracterizada pelo Doppler de artéria umbilical alterado (índice de pulsatilidade &gt;p95). Para cada paciente foi realizada avaliação da vitalidade fetal pela doplervelocimetria de artéria umbilical, artéria cerebral média e ducto venoso, e pelo perfil biofísico fetal. Foi calculada a RCP pela razão entre os valores do índice de pulsatilidade da artéria umbilical e da artéria cerebral média, bem como o cálculo de seu z-score (número de desvios padrão que se afasta da média para a idade gestacional). A acidemia no nascimento foi caracterizada quando pH<7,2. RESULTADOS: das 55 pacientes, 29 (52,7%) apresentaram acidemia no nascimento. O grupo com acidemia, comparado ao grupo com pH&gt;7,2, apresentou associação significativa com os valores da RCP (mediana 0,47 versus 0,58; p=0,009), índice de pulsatilidade da artéria umbilical (mediana 2,45 versus 1,93; p=0,003), índice de pulsatilidade para veias (IPV) do ducto venoso (mediana 1,08 versus 0,85; p=0,034) e perfil biofísico fetal suspeito ou alterado (37 versus 8%; p=0,031). A análise da RCP pelo seu z-score demonstrou tendência de maior afastamento negativo da média, mas sem atingir valor significativo (p=0,08). Foi constatada correlação significativa entre o pH no nascimento e a RCP (r=0,45; p<0,01), o z-score da RCP (r=0,27; p<0,05) e o IPV do ducto venoso (r=-0,35 p<0,01). CONCLUSÃO: A RCP associa-se à presença de acidemia no nascimento nas gestações com insuficiência placentária antes da 34ª semana, e esse parâmetro pode configurar potencial fator para avaliação da gravidade do comprometimento fetal.PURPOSE: to evaluate the hypothesis that the fetal cerebroplacental ratio (CPR) is related to acidemia at birth in pregnancies complicated by placental insufficiency detected before 34 weeks of gestation. METHODS: this is a prospective cohort study of 55 patients between 26 and 34 weeks of gestation with a diagnosis of placental insufficiency characterized by abnormal umbilical artery Doppler (pulsatility index&gt;95p). Fetal assessment was performed for each patient by dopplervelocimetry of the umbilical artery, middle cerebral artery and ductus venosus, and by the fetal biophysical profile. CPR was calculated using the ratio between middle cerebral artery pulsatility index and umbilical artery pulsatility index, and the z-score was obtained (number of standard deviations of the mean value at each gestational age). Acidemia at birth was characterized when pH<7.2. RESULTS: of 55 patients, 29 (52.7%) presented acidemia at birth. In the group of fetal acidemia, when compared with the group with pH&gt;7.2, a significant association was observed with CPR values (median 0.47 versus 0.58; p=0.009), pulsatility index of the umbilical artery (median 2.45 versus 1.93; p=0.003), ductus venosus pulsatility index for veins (PIV) (median 1.08 versus 0.85; p=0.034) and suspected or abnormal fetal biophysical profile (37 versus 8%; p=0.031). CPR analysis by z-score showed a negative tendency, but was not statistically significant (p=0.080). Significant correlations were found between pH at birth and CPR (r=0.45; p<0.01), z-score of CPR (r=0.27; p<0.05) and ductus venosus PIV (r=-0.35 p<0.01). CONCLUSION: CPR is associated with the presence of acidemia at birth in pregnancies with placental insufficiency detected before 34 weeks of gestation and this parameter could potentially represent a factor for assessing the severity of fetal involvement

Cannabidiol exhibits anxiolytic but not antipsychotic property evaluated in the social interaction test

Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa, has been reported to have central therapeutic actions, such as antipsychotic and anxiolytic effects. We have recently reported that Spontaneously Hypertensive Rats (SHRs) present a deficit in social interaction that is ameliorated by atypical antipsychotics. in addition, SHRs present a hyperlocomotion that is reverted by typical and atypical antipsychotics, suggesting that this strain could be useful to study negative symptoms (modeled by a decrease in social interaction) and positive symptoms (modeled by hyperlocomotion) of schizophrenia as well as the effects of potential antipsychotics drugs. At the same time, an increase in social interaction in control animals similar to that induced by benzodiazepines is used to screen potential anxiolytic drugs. the aim of this study was to investigate the effects of CBD on social interaction presented by control animals (Wistar) and SHRs. the lowest dose of CBD (1 mg/kg) increased passive and total social interaction of Wistar rats. However, the hyperlocomotion and the deficit in social interaction displayed by SHRs were not altered by any dose of CBD. Our results do not support an antipsychotic property of cannabidiol on symptoms-like behaviors in SHRs but reinforce the anxiolytic profile of this compound in control rats. (C) 2012 Elsevier Inc. All rights reserved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Farmacol, UNIFESP, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Lab Interdisciplinar Neurociencias Clin, São Paulo, BrazilUniv São Paulo, Dept Neurociencias & Ciencias Comportamento, BR-14049 Ribeirao Preto, BrazilInst Nacl Ciencia & Tecnol Translac Med, INCT TM, CNPq, Ribeirao Preto, BrazilUniversidade Federal de São Paulo, Dept Farmacol, UNIFESP, São Paulo, BrazilUniversidade Federal de São Paulo, UNIFESP, Lab Interdisciplinar Neurociencias Clin, São Paulo, BrazilFAPESP: FAPESP - 2010/07994-3Web of Scienc

Fetal middle cerebral artery Doppler in the prediction of acidemia at birth in pregnancies with placental insufficiency

Objetivo: Avaliar a relação das alterações de fluxo na artéria cerebral média (ACM) com a ocorrência de acidemia no nascimento, em gestações com insuficiência placentária. Métodos: estudo transversal prospectivo com 91 gestações com diagnóstico de insuficiência placentária pelo Doppler de artéria umbilical (AU) alterado (índice de pulsatilidade [IP] > p95). Os critérios de inclusão foram: gestações únicas com idade gestacional (IG) superior a 26 semanas completas, membranas ovulares íntegras, ausência de anomalias cromossômicas ou congênitas. Os parâmetros da dopplervelocimetria analisados foram: IP da AU, IP da ACM, pico de velocidade sistólica (PVS) da ACM, relação cerebroplacentária (RCP) e índice de pulsatilidade para veias (IPV) do ducto venoso (DV). Foi analisada a última avaliação fetal realizada imediatamente antes do parto ou anterior à corticoterapia. Todos os parâmetros foram analisados por meio do escore zeta ou múltiplos da mediana (MoM), baseados nas médias, desvio-padrão e valores de referência para cada IG. Imediatamente após o parto, uma amostra de sangue da artéria umbilical foi obtida para a medida do pH, e os casos classificados de acordo com a presença (pH p95). Inclusion criteria were: singleton pregnancy, intact membranes, abscence of fetal congenital or chromosomal abnormalities. The Doppler parameters analyzed were: UA PI, MCA PI, MCA peak systolic velocity (PSV), cerebroplacental ratio (CPR) and pulsatilility index for veins (PIV) of ductus venosus (DV). It was analyzed the last assessment obtained right before birth or the antenatal steroids. Umbical artey blood samples were collected at birth, and acidemia was defined as pH below 7.20. Results: Forty seven (51.6%) newborns had acidemia at birth. Those who developed acidemia showed a UA PI z-score significantly higher (median 2.1 vs 1.7, p = 0.014), as well as a higher proportion of cases with absent or reverse end diastolic flow (51.0% vs 31.8%, p = 0.006). Regarding the MAC, the PI z-score was significantly lower in cases with pH < 7.20 (median -2.7 vs. -2.1, p = 0.042), but concerning PSV z-score, no significant relation between the groups could be established (p = 0.051).The acidemia at birth was associated with lower values of CPR (median 0.5 vs 0.7, p = 0.006), but not with its z-score (p = 0.055). In relation to the venous territory, greater values of DV PIV z-score were associated with acidemia (median 2.4 vs 0.6, p = 0.015).The correlation analysis between the pH values at birth and the Doppler measurements, a significant correlation was observed between the pH at birth and UA PI z-score (rho = -0.31, p = 0.003 ), MCA PI z-score (rho = 0.26, p = 0.012), CPR z-score (rho 0.25, p = 0.015), PIV DV zscore (rho = -0.32, p = 0.002), and PSV MCA MoM (rho = -0.21, p = 0.042). Logistic regression identified the UA PI z-score and the MCA PI z-score as independent predictors for acidemia at birth, correctly classifying 67.03% of cases. Conclusion: In pregnancies with placental insufficiency, the UA PI and the MCA PI are independent predictors associated with acidemia at birth. This study reinforces that the degree of placental insufficiency and the fetal adaptation capacity are directly related to acidemia at birt

The morphological changes of exocrine pancreas in chronic pancreatitis

The following changes were found by either light or electron microscopic observation of the pancreas in spontaneously developed chronic pancreatitis models (WBNIKob rats, spontaneously hypertensive rats, and rats with common bile-pancreatic duct stones) and in experimental models of chronic pancreatitis (alcoholic pancreatitis, ischemic pancreatitis, and obstructive pancreatitis): 1) the units of lobules, which were constituted by acinar cell deletion, ductular proliferation, and fibrosis; and 2) tortuous or helical ductal channels of pancreatic ducts with periductal fibrosis, which had many crater-like depressions and very long cilia in their inner surface. These are considered to be the results of obstructive pancreatitis, which are caused by the reactions of defensive factors against the increase of pancreatic duct pressure, including the apoptosis of acinar cells, the hyperplasia and hypertrophy of duct cells, a tighter junctional complex of duct cells, and periductal fibrosis

Efeitos da cocaina sobre a memoria de camundongos avaliada pelo modelo de esquiva discriminativa em labirinto em cruz elevado

BV UNIFESP: Teses e dissertaçõe

Investigação de sinais prodrômicos e possíveis tratamentos preventivos em um modelo animal de esquizofrenia: a linhagem de ratos shr

Schizophrenia is a severe mental disease which begins after puberty and early adulthood. The pharmacotherapy, characterized by the antipsychotic drugs, even being a useful treatment tool, still remains unsatisfactory. In this way the study of prodromic signs as well as the search for preventive treatments has become very relevant in the attempt to delay or even prevent the onset of the disease. In this context, we have recently proposed the Spontaneously Hypertensive Rats (SHR) as an animal model of Schizophrenia, as long as this strain presented (I) hyperlocomotion; (II) deficits in social behavior (SI); (III) deficits in the prepulse inhibition of startle (PPI) and (IV) contextual fear conditioning (CFC) deficits; furthermore, all these deficits seem to be specifically reverted by antipsychotics drugs and potentiated by proschizophrenic manipulations. In the first part of the project, we analyze these behavioral characteristics in juvenile SHR in order to compare possible prodromal signs in this strain. As a result, we have found that juvenile SHR presents deficits in SI, CFC and latent inhibition; but not in PPI, nor presents hyperlocomotion. These results are in line with the presence of social and cognitive deficits in prodromal phase of the schizophrenia as well as the absence of positive symptoms (here assigned to the hyperlocomotion) in this period. In the sequence, we evaluated the SHR throughout their development to the adult phase, revealing that these deficits persisted in the adulthood. In the second part of the project, we evaluated the effects of a preventive antipsychotic treatment and it results that each drug was able to prevent some behavioral deficits in adult SHR, but also impaired the control strain. In this way, clozapine altered PPI and CFC; quetiapine altered SI and PPI; risperidona altered PPI; while haloperidol altered PPI and promoted hyperlocomotion in both strain. None of the treatment produced extra-pyramidal collateral effects, nor altered sensibilization to methylphenidate. Finally, we evaluated the effects of an atypical antipsychotics combination treatment in two different designs: in the first treatment, we used the same dosage tested before, but in a shorter time interval (TTO A); on the other hand, in the second treatment we used lower doses with the same time interval (TTO B). As a result, both drug combination treatments attenuated the adult SHR hyperlocomotion. Moreover, TTO B reversed CFC deficits, but, as well as TTO A, deteriorated the control performance in CFC task. In this way, we suggest that early interventions may be useful to attenuate schizophrenia-like deficits in the adulthood; but it also may be harmful if administrated to individuals which may not convert to schizophrenic later on. Thus, more studies are needed in order to elaborate a preventive and safe treatment which can be feasible in clinical practice.A esquizofrenia é um grave transtorno mental que tem início no fim da adolescência e início da idade adulta. Seu tratamento é realizado pelo uso de antipsicóticos, que além de gerar efeitos colaterais graves, não necessariamente beneficia todos os pacientes. Nesse contexto, há um crescente interesse no estudo de sinais prodrômicos e possíveis tratamentos preventivos na tentativa de atrasar ou mesmo evitar o aparecimento da doença em indivíduos com alto risco para o seu desenvolvimento. Nosso grupo recentemente sugeriu a linhagem de ratos SHR (Spontaneously Hypertensive Rats) como um modelo animal de esquizofrenia baseado em alterações comportamentais que essa linhagem apresenta, tais como: (I) hiperlocomoção (modela os sintomas positivos da doença); (II) déficit de interação social (IS) (modela os sintomas negativos); (III) déficit de medo condicionado ao contexto (MCC) e de inibição pré-pulso (PPI) (prejuízos cognitivos); sendo que todas essas alterações são revertidas especificamente por antipsicóticos e agravadas por manipulações pró-esquizofrênicas. Na primeira parte do projeto, analisamos o comportamento dos animais SHR jovens e verificamos que eles já apresentam déficits de IS, de MCC e de inibição latente, mas não apresentam hiperlocomoção ou déficits de PPI. Esses resultados estão de acordo com o aparecimento de sinais prodrômicos (como inibição social e déficits cognitivos) em crianças e adolescentes em alto risco para desenvolver esquizofrenia, mas que ainda não apresentaram o primeiro surto psicótico em si (relacionado, em animais, à hiperlocomoção). Em seguida, avaliamos a linhagem SHR ao longo de seu desenvolvimento até a idade adulta e verificamos que esses déficits permaneceram até a idade adulta, quando também foi detectada a hiperlocomoção desses animais. Na segunda parte do projeto, avaliamos os efeitos de um tratamento preventivo com antipsicóticos nos animais jovens e verificamos que cada droga foi efetiva em prevenir determinadas alterações comportamentais no SHR adulto, mas esse tratamento também prejudicou o desempenho dos animais controle. Assim, a clozapina alterou o desempenho de PPI e MCC; a quetiapina alterou a IS e PPI; a risperidona alterou a PPI enquanto o haloperidol alterou a PPI e promoveu hiperlocomoção em ambas as linhagens. Nenhum tratamento promoveu efeitos colaterais extrapiramidais ou alterou a sensibilização comportamental ao metilfenidato. Na terceira e última parte do projeto avaliamos o efeito de um tratamento combinado de antipsicóticos atípicos com as mesmas doses testadas anteriormente, mas em menor tempo; bem como com doses cinco vezes mais baixas e mesmo tempo de tratamento. Ambas as combinações atenuaram a hiperlocomoção da linhagem SHR adulta. Além disso, o tratamento com doses baixas atenuou déficits de MCC, mas ambos os tratamentos combinados pioraram o desempenho de animais controle na tarefa de MCC. Nesse sentido, podemos sugerir que o tratamento precoce em jovens pode ser benéfico em atenuar alterações comportamentais relacionadas à esquizofrenia na idade adulta, mas ele também pode promover efeitos deletérios em indivíduos saudáveis que não venham a desenvolver a doença posteriormente, portanto muitas considerações ainda devem ser realizadas antes de aplicar um tratamento preventivo seguro na prática clínica.Dados abertos - Sucupira - Teses e dissertações (2013 a 2016

Fine reconstruction of the pancreatic ductular system at the onset of pancreatitis

The three-dimensional structure of the pancreatic ductular system (from the intercalated duct to the intercellular secretory canaliculus) is controversial and unclear. The aim of this study is to reveal the threedimensional structure of the pancreatic ductular sysytem at the onset of pancreatitis. One day following rat pancreatic duct ligation, dilated lumina from the pancreatic ductular system were reconstructed by light microscopic and scanning electron microscopic examination of pancreatic tissue serial sections. The existence of the intra-acinar duct, which is formed only by centroacinar cells and interconnects the adjacent central lumina in an acinus, was demonstrated. The intercellular secretory canaliculi, which are the terminal parts of the pancreatic ductular system, anastomose and end blindly in the intercellular space located between adjacent lateral surfaces of the acinar cells. The intercalated ducts, the intra-acinar ducts, the central lumina, and the intercellular secretory canaliculi are arranged together in a complex connecting and branching system. However, there were no anastomoses found among the central lumina or acini