Cerebral Organoids to Study Central Mechanisms of Pain: The Effect of Stem Cell Secretome on Opioid Receptors and Neuroplasticity.

Over 90% of chronic pain (CP) patients receive opioids-based treatments, which led to a public health crisis with lasting impacts on social and economic wellbeing based on opioid addiction. Opioids act through activation of µ (MOR), δ (DOR), and κ (KOR) opioid receptors, which are broadly and differentially distributed throughout the brain. Chronic opioid consumption leads to brain changes such as alterations on neurotransmission, dendritic branching, and spine density, as well as an increase in apoptosis. To overcome opioid-related issues, extensive efforts have been made to search for an alternative treatment. Bioactive molecules secreted by stem cells, collectively known as secretome, have shown a positive impact in different pain models. However, there is a lack of studies on the role of secretome in modulating opioid receptors. By using cerebral organoids (CeO), a self-organized, functional, and multicellular 3D structure that resemble the brain, we were able to identify MOR, DOR, and KOR at different stages of maturation. Treatment with secretome increased MOR expression highlighting a possible role in pain signaling mechanisms. Opioid treatments did not impact the expression of neuronal maturation markers but together with secretome, they increased astrogliogenesis. Opioid-treated organoids presented higher dopamine secretion recapitulating an important physiological event after opioid exposure. This work demonstrates that CeO is an important model system for the study of opioid signaling with potential implications to the understanding of basic mechanisms related to pain physiology.

Exposure of Free-Ranging Wild Carnivores and Domestic Dogs to Canine Distemper Virus and Parvovirus in the Cerrado of Central Brazil.

Human population growth around protected areas increases the contact between wild and domestic animals, promoting disease transmission between them. This study investigates the exposure of free-ranging wild carnivores and domestic dogs to canine distemper virus (CDV) and parvovirus in Emas National Park (ENP) in the Cerrado savanna of central Brazil. Serum samples were collected from 169 wild carnivores, including the maned wolf (Chrysocyon brachyurus), crab-eating fox (Cerdocyon thous), hoary fox (Pseudalopex vetulus), puma (Puma concolor), ocelot (Leopardus pardalis), pampas cat (Leopardus colocolo), jaguarundi (Herpailurus yagouaroundi), striped hog-nosed skunk (Conepatus semistriatus) and coati (Nasua nasua), and from 35 domestic dogs living on rural properties bordering ENP. Serological tests showed that 10.6% of wild carnivores (maned wolves, crab-eating foxes and ocelots) and 71.4% of domestic dogs were exposed to CDV, and 56.8% of wild carnivores, including all species sampled except coatis, and 57.1% of domestic dogs were exposed to parvovirus. This report is the first to indicate that the free-ranging pampas cat, jaguarundi and striped hog-nosed skunk are exposed to parvovirus. CDV and parvovirus deserve attention in ENP, and it is extremely important to monitor the health of carnivore populations and perform molecular diagnosis of the viruses to determine the possible involvement of the domestic dog in their transmission.

Serosurvey for selected viral infections in free-ranging jaguars (Panthera onca) and domestic carnivores in Brazilian Cerrado, Pantanal, and Amazon.

We investigated the exposure of jaguar (Panthera onca) populations and domestic carnivores to selected viral infections in the Cerrado, Amazon, and Pantanal biomes of Brazil. Between February 2000 and January 2010, we collected serum samples from 31 jaguars, 174 dogs (Canis lupus familiaris), and 35 domestic cats (Felis catus). Serologic analyses for antibodies to rabies virus, canine distemper virus (CDV), feline immunodeficiency virus (FIV), and for feline leukemia virus (FeLV) antigen were conducted. The jaguars from Cerrado and Pantantal were exposed to rabies virus, while the jaguars from the Pantanal and the dogs from all three areas were exposed to CDV. Two cats from the Amazonian site were antigen-positive for FeLV, but no jaguars had FeLV antigen or FIV antibody. Canine distemper and rabies viruses should be carefully monitored and considered potential threats to these jaguar populations. Currently FIV and FeLV do not appear to represent a health threat for jaguar populations in this area. Domestic dogs and cats in these areas should be vaccinated, and the movement of domestic animals around protected areas should be restricted.

An acqueous extract of Bidens pilosa L. protects liver from cholestatic disease: experimental study in young rats.

PURPOSE: To test the hepatoprotective effect of water extract from Bidens Pilosa L. (BPE) in cholestatic liver disease induced by ligature and resection of the common bile ducts (LRBD) in young rats. METHODS: We studied four groups of ten 21 days old (P21) Wistar rats, Group SW: sham operation and water; Group SD: sham operation and BPE (160 mg of fresh leaves/100 g of body weight/day); Group LW: LRBD and water and Group LD: LRBD and BPE daily. Pentobarbital sleeping time (PST) and serum activities of aspartate aminotransferase (AST) and of alanine aminotransferase (ALT) were determined after the sacrifice (P70). A Ruwart's score for hepatic fibrosis (RS) was given to each animal. Were employed two way ANOVA and the test of Tukey or a non-parametric test for multiple comparisons. RESULTS: There were statistically significant differences between LW and LD in the measurements of the PST ((means LW=390; LD=173), AST (means LW=8, LD=5), ALT (medians LW=2; LD=1) e RS (medians LW=2; LD=1). CONCLUSION: BPE could be used in the phytotherapy of the hepatic damage induced by chronic obstructive cholestasis, because protects liver function, decreases the rate of necrosis and liver fibrosis in cholestatic liver disease.

An acqueous extract of Bidens pilosa L. protects liver from cholestatic disease: experimental study in young rats / Um extrato aquoso de Bidens pilosa L. protege o fígado da doença colestática: estudo experimental em ratos jovens

PURPOSE: To test the hepatoprotective effect of water extract from Bidens Pilosa L. (BPE) in cholestatic liver disease induced by ligature and resection of the common bile ducts (LRBD) in young rats. METHODS: We studied four groups of ten 21 days old (P21) Wistar rats, Group SW: sham operation and water; Group SD: sham operation and BPE (160 mg of fresh leaves/100 g of body weight/day); Group LW: LRBD and water and Group LD: LRBD and BPE daily. Pentobarbital sleeping time (PST) and serum activities of aspartate aminotransferase (AST) and of alanine aminotransferase (ALT) were determined after the sacrifice (P70). A Ruwart's score for hepatic fibrosis (RS) was given to each animal. Were employed two way ANOVA and the test of Tukey or a non-parametric test for multiple comparisons. RESULTS: There were statistically significant differences between LW and LD in the measurements of the PST ((means LW=390; LD=173), AST (means LW=8, LD=5), ALT (medians LW=2; LD=1) e RS (medians LW=2; LD=1). CONCLUSION: BPE could be used in the phytotherapy of the hepatic damage induced by chronic obstructive cholestasis, because protects liver function, decreases the rate of necrosis and liver fibrosis in cholestatic liver disease.

OBJETIVO: Testar o efeito hepatoprotetor do extrato aquoso de Bidens pilosa L. (EBP) na doença hepática induzida pela ligadura e ressecção do ducto biliar comum (LRDBC) em ratos jovens. MÉTODOS: Estudamos ratos Wistar com 21º. dia de vida (P21) divididos em quatro grupos de 10 animais, Grupo SA: operação simulada e água; Grupo SD: operação simulada e EBP (160mg de folhas frescas/100g de peso corporal/dia); Grupo LA: LRDBC e água e Grupo LD: LRDBC e EBP diariamente. O tempo de sono por pentobarbital (TSP), aspartato (AST) e alanina (ALT) aminotransferase foram determinadas após o sacrifício (P70). O Score de Ruwart (SR) para fibrose hepática foi atribuído para cada animal. Foi realizada análise de variância com dois fatores e pelo teste de Tukey para comparações múltiplas ou por teste não paramétrico. RESULTADOS: Houve diferença estatisticamente significativa entre LA e LD nas variáveis: TSP (médias LA=390; LD=173), AST (médias LA=8, LD=5), ALT (medianas LA=2; LD=1) e SR (medianas LA=2; LD=1). CONCLUSÃO: EBP poderá ser empregado na fitoterapia da doença hepática induzida pela colestase obstrutiva crônica, pois protege a função hepática, diminui a velocidade de necrose e a intensidade da fibrose hepática na obstrução biliar extra-hepática.

Mitochondrial alterations in nonalcoholic fatty liver disease. Pediatric case description of three submitted sequential biopsies.

Nonalcoholic fatty liver disease (NAFLD) is a clinical-pathological syndrome that encompasses a wide spectrum of morphologic alterations, ranging from simple hepatic steatosis to a more severe stage, known as nonalcoholic steatohepatitis (NASH). The purpose of this clinical report was to contribute to the understanding of mitochondrial alterations in NAFLD. The child (13-month-old) underwent initial biopsy in the year 2000 and was diagnosed with diffuse macro and microvesicular steatosis. Two additional biopsies were performed in 2001 and 2004. A high percentage of microvesicular steatosis was observed in the biopsies performed in 2000 and 2001. Mitochondrial size was slightly increased in the biopsy performed in the year 2000, significantly increased in 2001 and decreased in 2004. The presence of "mitochondrial hypertrophy" in the hepatocytes of an asymptomatic pediatric patient whose disease presentation was typical of NAFLD, excluding other pathological processes, allowed us to suspect that such a defect was considered the primary mitochondrial disorder.

Ascorbic acid supplementation has a cytoprotective effect on secondary biliary cirrhosis: experimental study in young rats.

OBJECTIVE: To test whether ascorbic acid supplementation has any cytoprotective effect on a model of secondary biliary cirrhosis in young rats. METHODS: We studied 40 Wistar rats weaned at the 21st postnatal day. Each group of 10 was subjected to one of the following four treatments, until 49th postnatal day, when they suffered euthanasia: 1) LC-double ligature and resection of the common bile duct and daily administration of ascorbic acid [100 mg/g of body weight (bw)]; 2) LA-double ligature and resection of the common bile duct and daily administration of aqueous vehicle (1 mL/g bw); 3) SC-sham operation and daily administration of ascorbic acid (100 mg/g bw); 4) SA-double ligature and resection of the common bile duct and daily administration of aqueous vehicle (1 mL/g bw). The rats were weighed daily. On the 27th day after the operation they received an intra-peritoneal injection of 1.5 mg/g bw of sodium pentobarbital, and the pentobarbital sleeping time was measured. Blood was collected for serum alanine aminotransferase and aspartate aminotransferase activity measurements, serum albumin and globulin concentrations, and the liver was assessed for liver water and fat content. Data were submitted to two-way ANOVA and paired comparisons between groups were tested using the SNK method. Significance level was set at 0.05. RESULTS: Ascorbic acid supplementation attenuated the effects of cholestasis: decreased the pentobarbital sleeping time, serum globulin, and the liver fat content. CONCLUSIONS: Our results corroborate the hypothesis that ascorbic acid supplementation has a cytoprotective effect in secondary biliary cirrhosis.

Suplementação com ácido ascórbico tem efeito citoprotetor na cirrose biliar secundária: estudo experimental em ratos jovens / Ascorbic acid supplementation has a cytoprotective effect on secondary biliary cirrhosis: experimental study in young rats

OBJETIVO: Testar se a suplementação com ácido ascórbico tem algum afeito citoprotetor em um modelo de cirrose biliar secundária em ratos jovens. MÉTODOS: Foram estudados 40 ratos Wistar desmamados no 21º dia pós-natal. Cada grupo de 10 foi submetido a um dos seguintes quatro tratamentos, até o 49º dia pós-natal, quando foram submetidos a eutanásia: 1) LC - ligadura dupla e ressecção do ducto biliar comum e administração diária de ácido ascórbico [100 mg/g de peso corporal (pc)]; 2) LA - ligadura dupla e ressecção do ducto biliar comum e administração diária de veículo aquoso (1 mL/g pc); 3) SC - operação simulada e administração diária de ácido ascórbico (100 mg/g pc); 4) SA - ligadura dupla e ressecção do ducto biliar comum e administração diária de veículo aquoso (1 mL/g pc). Os ratos eram pesados diariamente. No 27º dia pós-operatório, eles receberam injeção intraperitoneal de 1,5 mg/g pc de pentobarbital sódico, e o tempo de sono induzido pelo pentobarbital foi medido. Coletou-se sangue para determinação de atividade sérica de alanina aminotransferase e de aspartato aminotransferase, níveis de albumina e globulina séricas, e o fígado foi analisado quanto à conteúdo de água e gordura. Os dados foram submetidos à ANOVA two-way, e comparações pareadas entre grupos foram testadas com o método de SNK. O nível de significância foi estabelecido em 0,05. RESULTADOS: A suplementação com ácido ascórbico atenuou os efeitos da colestase: reduziu o tempo de anestesia pelo pentobarbital, globulina sérica e o conteúdo de gordura no fígado. CONCLUSÕES: Nossos resultados corroboram a hipótese de que a suplementação com ácido ascórbico tem um efeito citoprotetor na cirrose biliar secundária.

OBJECTIVE: To test whether ascorbic acid supplementation has any cytoprotective effect on a model of secondary biliary cirrhosis in young rats. METHODS: We studied 40 Wistar rats weaned at the 21st postnatal day. Each group of 10 was subjected to one of the following four treatments, until 49th postnatal day, when they suffered euthanasia: 1) LC-double ligature and resection of the common bile duct and daily administration of ascorbic acid [100 mg/g of body weight (bw)]; 2) LA-double ligature and resection of the common bile duct and daily administration of aqueous vehicle (1 mL/g bw); 3) SC-sham operation and daily administration of ascorbic acid (100 mg/g bw); 4) SA-double ligature and resection of the common bile duct and daily administration of aqueous vehicle (1 mL/g bw). The rats were weighed daily. On the 27th day after the operation they received an intra-peritoneal injection of 1.5 mg/g bw of sodium pentobarbital, and the pentobarbital sleeping time was measured. Blood was collected for serum alanine aminotransferase and aspartate aminotransferase activity measurements, serum albumin and globulin concentrations, and the liver was assessed for liver water and fat content. Data were submitted to two-way ANOVA and paired comparisons between groups were tested using the SNK method. Significance level was set at 0.05. RESULTS: Ascorbic acid supplementation attenuated the effects of cholestasis: decreased the pentobarbital sleeping time, serum globulin, and the liver fat content. CONCLUSIONS: Our results corroborate the hypothesis that ascorbic acid supplementation has a cytoprotective effect in secondary biliary cirrhosis.

Hepatoprotective effect of water soluble extract of Coleus barbatus on cholestasis on young rats.

PURPOSE: To test the effects of water extract of Coleus barbatus (WEB) on liver damage in biliary obstruction in young rats. METHODS: Forty 21 day-old male Wistar rats were divided into four groups of ten 21 day old (P21) submitted to sham or actual operation (S or L) combined with WEB or Water (B or A). At P48 pentobarbital sleeping time (ST) was measured. At P49 they were submitted to euthanasia to determine of serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), liver wet weight (PFF) and, on hepatic histological slides, the frequency of mitoses (FM), the number of necrotic areas (NN), intensity of fibrosis (IF) and intensity of ductal proliferation (IPD). Two Way ANOVA, the S.N.K. test and the Wilcoxon test for paired multiple comparisons were employed to study the effects of cholestasis and those of EAB and their interactions. The Pearson's coefficient of linear correlation of between paired histological variables separately for the groups LA and LD was determined. The test results were considered statistically significant when the p of alpha error <0.05. RESULTS: Cholestasis increased the TS, ALT, AST, PFF, MI, NN, IF and IPD. The EAB decreased the TS and IM in the animals without cholestasis (sham operated animals). The EAB decreased the TS, ALT, AST, PFF, MI, NN and IF of the cholestatic animals. In the LA group there was a positive correlation between the IPD and the IF, a negative correlation between the IPD and the FM and a negative correlation between the IF and the FM. In the LD group there was a negative correlation between the NN and the IPD. CONCLUSIONS: In the absence of cholestasis the EAB reduces the pentobarbital sleeping time and decreases the frequency of mitoses. The EAB has a hepatoprotective effect on the biliary cirrhosis secondary to extra-hepatic biliary obstruction.

Hepatoprotective effect of water soluble extract of Coleus barbatus on cholestasis on young rats / Efeito hepatoprotetor do extrato aquoso de Coleus barbatus na colestase em ratos jovens

PURPOSE: To test the effects of water extract of Coleus barbatus (WEB) on liver damage in biliary obstruction in young rats. METHODS: Forty 21 day-old male Wistar rats were divided into four groups of ten 21 day old (P21) submitted to sham or actual operation (S or L) combined with WEB or Water (B or A). At P48 pentobarbital sleeping time (ST) was measured. At P49 they were submitted to euthanasia to determine of serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), liver wet weight (PFF) and, on hepatic histological slides, the frequency of mitoses (FM), the number of necrotic areas (NN), intensity of fibrosis (IF) and intensity of ductal proliferation (IPD). Two Way ANOVA, the S.N.K. test and the Wilcoxon test for paired multiple comparisons were employed to study the effects of cholestasis and those of EAB and their interactions. The Pearson's coefficient of linear correlation of between paired histological variables separately for the groups LA and LD was determined. The test results were considered statistically significant when the p of alpha error <0.05. RESULTS: Cholestasis increased the TS, ALT, AST, PFF, MI, NN, IF and IPD. The EAB decreased the TS and IM in the animals without cholestasis (sham operated animals). The EAB decreased the TS, ALT, AST, PFF, MI, NN and IF of the cholestatic animals. In the LA group there was a positive correlation between the IPD and the IF, a negative correlation between the IPD and the FM and a negative correlation between the IF and the FM. In the LD group there was a negative correlation between the NN and the IPD. CONCLUSIONS: In the absence of cholestasis the EAB reduces the pentobarbital sleeping time and decreases the frequency of mitoses. The EAB has a hepatoprotective effect on the biliary cirrhosis secondary to extra-hepatic biliary obstruction.

OBJETIVO: Testar os efeitos do extrato aquoso de Coleus barbatus (EAB) na cirrose biliar secundária por obstrução das vias biliares extra-hepáticas em ratos jovens. MÉTODOS: Quarenta ratos Wistar machos com 21 dias de vida (P21), foram distribuídos em quatro grupos de 10 animais, submetidos a operação simulada ou dupla ligadura e ressecção do ducto biliar (S ou L) combinados EAB e a Água (B ou A). No P48, foi medido o tempo de sono com o pentobarbital (TS). No P49, foram submetidos a eutanásia para a determinação das atividades séricas do aspartato aminotransferase (AST) e da alanina aminotransferases (ALT); após a eutanásia foram avaliados o peso fresco do fígado (PFF) e, em cortes histológicos do fígado, a freqüência de mitoses (FM), o número de áreas de necrose (NN), a intensidade da fibrose (IF) e da proliferação ductal (IPD). Os efeitos da colestase, os do EAB e suas interações foram testados pela ANOVA com dois fatores, e as comparações múltiplas pareadas foram realizadas pelo teste de S.N.K ou teste de Wilcoxon. Também foi determinada a correlação linear de Pearson entre as variáveis histológicas duas a duas separadamente para os grupos LA e LD. O nível de significância estatística para os vários testes foi de p do erro alfa <0,05. RESULTADOS: A colestase aumentou significativamente o TS, a ALT, a AST, o PFF, a MI, o NN, a IF e a IPD. O EAB diminuiu o TS e a IM nos animais sem colestase (operação simulada). O EAB diminuiu o TS, a ALT, a AST, o PFF, a MI, o NN e IF na colestase. No grupo LA houve correlação positiva entre a IPD e a IF, correlação negativa entre a IPD e a FM e correlação negativa entre a IF a FM. No grupo LD houve correlação negativa entre o NN e a IPD. CONCLUSÕES: Na ausência de colestase o EAB encurta o tempo de sono e diminui a freqüência de mitoses. O EAB apresenta efeito hepatoprotetor no modelo de cirrose biliar secundária a obstrução biliar extra-hepática.

Effects of low fat and babassu fat diets on nutritional status in obstructive cholestasis in young rats.

PURPOSE: To test the effects of a low fat diet compared with a babassu fat diet on nutritional status in obstructive cholestasis in young rats. METHODS: We submitted 40 rats in 4 groups of 10 animals each from P21 (21st postnatal day) to P49 to two of the following treatments: bile duct ligation or sham operation and low fat diet (corn oil supplying 4.5% of the total amount of energy) or babassu fat diet (this fat supplying 32.7% and corn oil supplying 1.7% of the total amount of energy). Weight gain from P25 to P49 every 4 days was measured. The Verhulst's growth function was fitted to these values of weight gain. Growth velocity and acceleration at each moment were estimated using the same equation. Total food and energy intake from P21 to P49, energy utilization rate (EUR) from P25 to P49 and fat absorption rate (FAR) and nitrogen balance (NB) from P42 to P49 were measured. Two Way ANOVA and the S.N.K. test for multiple paired comparisons were employed to study the effects of cholestasis and those of the diets and their interaction (p<0.05) on those variables. RESULTS: In cholestatic animals, a higher growth velocity at P45, a higher growth acceleration at P41 and P45, a greater EUR, a greater FAR and a greater NB, were found with the low fat diet as compared with the babassu fat diet. CONCLUSION: A low fat diet lessens the growth restriction brought about by cholestasis and allows for an improved dietary energy utilization and a better protein balance than the babassu fat diet.

Effects of low fat and babassu fat diets on nutritional status in obstructive cholestasis in young rats

PURPOSE: To test the effects of a low fat diet compared with a babassu fat diet on nutritional status in obstructive cholestasis in young rats. METHODS: We submitted 40 rats in 4 groups of 10 animals each from P21 (21st postnatal day) to P49 to two of the following treatments: bile duct ligation or sham operation and low fat diet (corn oil supplying 4.5 percent of the total amount of energy) or babassu fat diet (this fat supplying 32.7 percent and corn oil supplying 1.7 percent of the total amount of energy). Weight gain from P25 to P49 every 4 days was measured. The Verhulst's growth function was fitted to these values of weight gain. Growth velocity and acceleration at each moment were estimated using the same equation. Total food and energy intake from P21 to P49, energy utilization rate (EUR) from P25 to P49 and fat absorption rate (FAR) and nitrogen balance (NB) from P42 to P49 were measured. Two Way ANOVA and the S.N.K. test for multiple paired comparisons were employed to study the effects of cholestasis and those of the diets and their interaction (p<0.05) on those variables. RESULTS: In cholestatic animals, a higher growth velocity at P45, a higher growth acceleration at P41 and P45, a greater EUR, a greater FAR and a greater NB, were found with the low fat diet as compared with the babassu fat diet. CONCLUSION: A low fat diet lessens the growth restriction brought about by cholestasis and allows for an improved dietary energy utilization and a better protein balance than the babassu fat diet.

OBJETIVO: Testar os efeitos de uma dieta com baixo teor de gordura comparada a uma dieta com gordura de babaçu sobre o estado nutricional em ratos jovens com colestase obstrutiva. MÉTODOS: Submetemos 40 ratos divididos em quatro grupos de 10 animais a partir do P21 (21º dia pós-natal) até o P49 a dois dos seguintes tratamentos: ligadura e ressecção do ducto biliar comum ou operação simulada e dieta com baixo teor de gordura (óleo de milho fornecendo 4,5 por cento da quantidade total de calorias) ou dieta com gordura de babaçu (essa gordura fornecendo 32,7 por cento e óleo de milho fornecendo 1,7 por cento da quantidade total de calorias). Foi mensurado o ganho de peso a cada 4 dias do P25 ao P49. A função de crescimento de Verhulst foi ajustada aos valores de ganho de peso. A velocidade e a aceleração de crescimento nos mesmos momentos foram estimadas usando a mesma equação. Foram mensurados: quantidade de ração ingerida e ingestão energética total do P21 ao P49, utilização de energia do P25 ao P49, gordura absorvida e balanço de nitrogênio (BN) do P42 ao P49. A ANOVA com dois fatores e o método de S.N.K para comparações pareadas foram utilizados para estudar os efeitos, sobre as variáveis, da colestase e das dietas e sua interação (p<0,05). RESULTADOS: Em ratos com colestase e dieta com baixo teor de gordura, houve maior velocidade de crescimento no P45, maior aceleração de crescimento no P41 e P45, maior utilização de energia, maior percentual de gordura absorvida e maior BN do que em ratos com colestase e dieta com gordura de babaçu. CONCLUSÃO: A dieta com baixo teor de gordura atenua a restrição de crescimento provocada pela colestase e proporciona melhor aproveitamento da dieta e maior incorporação da proteína ingerida do que a dieta com gordura de babaçu.

Hiperplasia nodular focal do fígado: apresentação de um caso e revisão da literatura / Focal nodular hyperplasia of the liver: a case report and review of the literature

Neste trabalho apresentamos um caso de hiperplasia nodular focal que foi diagnosticado aos seis anos de idade e que está sendo acompanhado até o momento presente. Para o diagnóstico foram imprescindíveis as técnicas de imagem, tendo importância de realce a cintilografia hepatoesplênica e a tomografia computadorizada. Apresentamos, também, revisão da literatura sobre o assunto.

In this case report we discuss a focal nodular hyperplasia diagnosed in a female, six-year old patient, as well as her follow-up from the diagnosis to the present time. Imaging techniques, particularly hepatosplenic scintigraphy and computed tomography, are essential for the diagnosis. Also, a literature review is presented.

Investigação diagnóstica de erros inatos do metabolismo em um hospital universitário / Diagnostic investigation of inborn errors of metabolism in a university hospital

OBJETIVOS: Estabelecer a freqüência de erros inatos do metabolismo (EIMs) em uma amostra de pacientes com hipótese diagnóstica de EIM proveniente do Hospital das Clínicas da Faculdade de Medicina de Botucatu da Universidade Estadual Paulista (UNESP) e analisar a metodologia empregada nessa investigação. AMOSTRA E MÉTODOS: Foram triadas para EIM, por testes químicos e técnicas cromatográficas, 1.233 amostras de urina de 905 pacientes. RESULTADOS: O diagnóstico de EIM foi estabelecido em 18 (1,98 por cento) pacientes; 12 deles apresentaram triagem (testes químicos e cromatografias) alterada para EIM. Todos os pacientes foram diagnosticados por análises enzimáticas. CONCLUSÃO: A freqüência de EIMs diagnosticados neste estudo (1,98 por cento), quando comparada com a literatura, foi satisfatória, uma vez que este grupo de pacientes foi proveniente de um único hospital. A metodologia provou ser eficaz, indicando 12 casos de EIM entre os 18 diagnosticados. O estudo mostra a importância de laboratórios especializados na detecção deste tipo de patologia.

OBJECTIVE: To establish the frequency of inborn errors of metabolism (IEM) in a cohort of patients with a diagnostic hypothesis of IEM, deriving from the Hospital das Clínicas da Faculdade de Medicina de Botucatu of UNESP and to analyse the methodology used for this investigation. METHODS: 1,233 urine samples from 905 patients were screened for IEM by chemical tests and chromatographic techniques. RESULTS: IEM were diagnosed in 18 patients; twelve of these showed alterations in the IEM screening procedures (chemical tests and chromatography). All the 18 patients were diagnosed by enzymatic analyses. CONCLUSION: The IEM frequency diagnosed in this study (1.98 percent) was reasonable, since this group of patients came from a single hospital. The methodology proved to be efficient, indicating 12 IEM cases among the 18 diagnosed. The study shows the importance of specialized laboratories for the detection of this kind of pathology.

Water-soluble extract of Coleus barbatus modulates weight gain, energy utilization and lipid metabolism in secondary biliary cirrhosis: an experimental study in young rats.

PURPOSE: To test if a water extract of Coleus barbatus (WEB) has any effect on weight gain, food energy utilization and lipid metabolism in young rats with obstructive cholestasis. METHODS: Forty 21 day old (P21) Wistar rats, in groups of 10, were submitted to one of the following treatments: a sham operation with daily water or WEB administration, double ligature and resection of the bile duct with daily water or WEB administration. At P49 they were submitted for euthanasia when the following were determined: ingested feed (IF), energy utilization (EU) and weight gain (WG) from P29 to P49, together with total serum cholesterol (TC) and triacylglycerol (TG) concentrations, liver wet weight (LWW) and fat content (LFC). Two Way ANOVA and the S.N.K. test for paired comparisons were employed to study the effects of cholestasis and those of WEB and their interactions (p < or = 0.05). RESULTS: Cholestasis, independently of WEB, and WEB, independently of cholestasis both reduced IF, EU, and WG but there was no significant interaction between the two factors. Cholestasis, independently of WEB, increased LWW, LFC, the TC and TG The WEB, independently of cholestasis, reduced these values, and there was a significant interaction between the two factors; such that these effects were more accentuated in animals with cholestasis. CONCLUSION: The WEB reduced IF, WG, and EU, both in the presence and absence of cholestasis in the same proportion. It also partially inhibited the increase in LWW, LFC, TC and TG caused by cholestasis.

Water-soluble extract of Coleus barbatus modulates weight gain, energy utilization and lipid metabolism in secondary biliary cirrhosis: an experimental study in young rats

OBJETIVO:Testar os efeitos do extrato aquoso de Coleus barbatus (WEB) sobre o aproveitamento nutricional e o metabolismo lipídico em ratos jovens com colestase obstrutiva. MÉTODOS: Quarenta ratos machos Wistar com 21 dias de vida (P21), em grupos de 10, foram submetidos a um dos seguintes tratamentos: operação simulada e administração diária de água ou WEB e dupla ligadura e ressecção do ducto biliar com administração diária de água ou WEB. No P49, foram sacrificados e medidos: a ração ingerida (IF), o aproveitamento nutricional (EU) e o ganho de peso (WG) desde o P29 ao P49, as concentrações séricas do colesterol total (TC) e dos triacilgliceróis (TG), o peso fresco (LWW) e o teor de gordura do fígado (LFC). A ANOVA com dois fatores e o método de S.N.K para comparações pareadas (p<0,05) foram utilizados para estudar os efeitos, sobre as variáveis, da colestase e do EAB e suas interações. RESULTADOS: A colestase, independentemente do WEB, e o WEB independentemente da colestase diminuíram o WG, a IF e o EU, mas não houve interação significativa entre os dois fatores. A colestase, independentemente do WEB elevou o LWW, o LFC, o TC e os TG. O WEB, independentemente da colestase, diminuiu esses valores, havendo interação significativa entre os dois fatores, sendo estes efeitos mais acentuados nos animais com colestase. CONCLUSÃO: O EAB diminui a IF, o EU e o WG, tanto na presença quanto na ausência de colestase, na mesma proporção. O WEB inibi parcialmente o aumento do LWW, do LFC, do TC e dos TG causados pela colestase.

Avaliação da contratilidade da vesícula biliar com leite materno e leite de vaca em lactentes / Gallbladder contractility after breast milk and cow's milk meals in infants

As múltiplas características distintas do leite materno e do leite de vaca fazem com que o esvaziamento gástrico seja mais rápido após ingestão do primeiro. Esta rapidez do esvaziamento gástrico pode estar associada ao esvaziamento da vesícula biliar, também mais rápido. O objetivo do trabalho foi determinar se há diferença na velocidade de esvaziamento da vesícula biliar, por método ultra-sonográfico, após ingestão de leite materno e leite de vaca. Estudamos 47 crianças menores de dois anos, 22 após uma refeição com leite materno e 25 após uma refeição com leite de vaca. A vesícula biliar foi medida após um período de quatro a seis horas de jejum e uma hora após uma refeição (leite materno ou leite de vaca), e a contração da vesícula biliar foi avaliada, em porcentagem, pela diferença de volume da vesícula biliar entre as duas medidas e expressa em porcentagem do volume inicial. As medianas das porcentagens do volume inicial para as crianças alimentadas com leite materno e leite de vaca foram, respectivamente, 92,25 por cento e 53,8 por cento, diferença estatisticamente significativa. Portanto, a contração da vesícula biliar após uma refeição com leite de vaca é muito mais lenta do que aquela após uma refeição com leite materno.

Adaptação do modelo experimental de colestase extra-hepática em ratos jovens / Adaptation of experimental model of extra-hepatic cholestasis in young rats

Os autores descrevem a adaptação da técnica de ligadura e ressecção do ducto biliar comum descrita na literatura, enfatizando suas vantagens na recuperação pós-cirúrgica. Este trabalho foi realizado no Laboratório Experimental do Departamento de Pediatria da FMB-UNESP.

Crescimento fetal e pós-natal: conceitos e principais aspectos de avaliação / Fetal and postnatal growth

O artigo de revisão foi desenvolvido tomando como base as publicações que discutem conceitos clássicos de crescimento, os fatores que podem interferir neste processo bem como os diferentes métodos de avaliação de crescimento fetal e pós-natal. A avaliação do crescimento é um instrumento importante para o acompanhamento das condições de saúde e nutrição, tanto de indivíduos quanto de populações, devido ao fato de o crescimento representar o estado geral da saúde de uma criança.

Repercussoes tardias dos disturbios nutricionais intra-uterinos e neonatais / Late repercussions of intra-uterus and postnatal nutritional disturbances

O objetivo deste ensaio foi avaliar as repercussoes tardias dos disturbios...