Inhibiting silence information regulator 2 and glutaminase in the amygdala can improve social behavior in autistic rats / 浙江大学学报·医学版

OBJECTIVE@#To investigate the underlying molecular mechanisms by which silence information regulator (SIRT) 2 and glutaminase (GLS) in the amygdala regulate social behaviors in autistic rats.@*METHODS@#Rat models of autism were established by maternal sodium valproic acid (VPA) exposure in wild-type rats and SIRT2-knockout ( SIRT2 -/-) rats. Glutamate (Glu) content, brain weight, and expression levels of SIRT2, GLS proteins and apoptosis-associated proteins in rat amygdala at different developmental stages were examined, and the social behaviors of VPA rats were assessed by a three-chamber test. Then, lentiviral overexpression or interference vectors of GLS were injected into the amygdala of VPA rats. Brain weight, Glu content and expression level of GLS protein were measured, and the social behaviors assessed.@*RESULTS@#Brain weight, amygdala Glu content and the levels of SIRT2, GLS protein and pro-apoptotic protein caspase-3 in the amygdala were increased in VPA rats, while the level of anti-apoptotic protein Bcl-2 was decreased (all P<0.01). Compared with the wild-type rats, SIRT2 -/- rats displayed decreased expression of SIRT2 and GLS proteins in the amygdala, reduced Glu content, and improved social dysfunction (all P<0.01). Overexpression of GLS increased brain weight and Glu content, and aggravated social dysfunction in VPA rats (all P<0.01). Knockdown of GLS decreased brain weight and Glu content, and improved social dysfunction in VPA rats (all P<0.01).@*CONCLUSIONS@#The glutamate circulatory system in the amygdala of VPA induced autistic rats is abnormal. This is associated with the upregulation of SIRT2 expression and its induced increase of GLS production; knocking out SIRT2 gene or inhibiting the expression of GLS is helpful in maintaining the balanced glutamate cycle and in improving the social behavior disorder of rats.

Enhanced production of glutaminase-free L-asparaginase by marine Bacillus velezensis and cytotoxic activity against breast cancer cell lines

Background: The increasing rate of breast cancer globally requires extraordinary efforts to discover new effective sources of chemotherapy with fewer side effects. Glutaminase-free L-asparaginase is a vital chemotherapeutic agent for various tumor malignancies. Microorganisms from extreme sources, such as marine bacteria, might have high L-asparaginase productivity and efficiency with exceptional antitumor action toward breast cancer cell lines. Results: L-Asparaginase-producing bacteria, Bacillus velezensis isolated from marine sediments, were identified by 16S rRNA sequencing. L-Asparaginase production by immobilized cells was 61.04% higher than that by free cells fermentation. The significant productivity of enzyme occurred at 72 h, pH 6.5, 37°C, 100 rpm. Optimum carbon and nitrogen sources for enzyme production were glucose and NH4Cl, respectively. L-Asparaginase was free from glutaminase activity, which was crucial medically in terms of their severe side effects. The molecular weight of the purified enzyme is 39.7 KDa by SDS-PAGE analysis and was ideally active at pH 7.5 and 37°C. Notwithstanding, the highest stability of the enzyme was found at pH 8.5 and 70°C for 1 h. The enzyme kinetic parameters displayed Vmax at 41.49 µmol/mL/min and a Km of 3.6 × 10−5 M, which serve as a proof of the affinity to its substrate. The anticancer activity of the enzyme against breast adenocarcinoma cell lines demonstrated significant activity toward MDA-MB-231 cells when compared with MCF-7 cells with IC50 values of 12.6 ± 1.2 µg/mL and 17.3 ± 2.8 µg/mL, respectively. Conclusion: This study provides the first potential of glutaminase-free L-asparaginase production from the marine bacterium Bacillus velezensis as a prospect anticancer pharmaceutical agent for two different breast cancer cell lines.

Twin-arginine signal peptide of Bacillus licheniformis GlmU efficiently mediated secretory expression of protein glutaminase

Background: Protein glutaminase specifically deamidates glutamine residue in protein and therefore significantly improves protein solubility and colloidal stability of protein solution. In order to improve its preparation efficiency, we exploited the possibility for its secretory expression mediated by twin-arginine translocation (Tat) pathway in Bacillus licheniformis. Results: The B. licheniformis genome-wide twin-arginine signal peptides were analyzed. Of which, eleven candidates were cloned for construction of expression vectors to mediate the expression of Chryseobacterium proteolyticum protein glutaminase (PGA). The signal peptide of GlmU was confirmed that it significantly mediated PGA secretion into media with the maximum activity of 0.16 U/ml in Bacillus subtilis WB600. A mutant GlmU-R, being replaced the third residue aspartic acid of GlmU twin-arginine signal peptide with arginine by site-directed mutagenesis, mediated the improved secretion of PGA with about 40% increased (0.23 U/ml). In B. licheniformis CBBD302, GlmU-R mediated PGA expression in active form with the maximum yield of 6.8 U/ml in a 25-l bioreactor. Conclusions: PGA can be produced and secreted efficiently in active form via Tat pathway of B. licheniformis, an alternative expression system for the industrial-scale production of PGA.

The Association of Glutaminase (glut) P3 Different Alleles of Trichomonas vaginalis with Infertility in a sample of Iraqi women

Trichomonas vaginalis (T. vaginalis), the etiologic agent of human trichomoniasis, is a flagellated protozoan parasite, has been associated sith advese pregnancy outcomes, HIV transmission, and infertilityh. A total of one hundred and fifty-seven (157) women at childbearing age (14-49 years), were included in the presnt study, eighty six (86) symptomatic fertile while the other seventy-one (71) were infertile with or without sumptoms attending the Gynecology outpatient Department in Al-Emamayn Al-Kadhimayn Medical City, the High Institute of Infertility Diagnosis and Assisted Reproductive Technoligies at Al-Nahrain University in Baghdad, the maternity Teaching hospital, and Dr. Khawer center for infertility and IVF in Erbil province in Iraq. Two vaginal swab specimens were obtained from each of them:; one swab was immediately examined by wet mount microscopy, the other swab for molecular study (DNA extraction and p3 nested PCR). One hundred (100) samples positive in one or more test were identified: 20 (12.7%) infecions were detected by wet mount microscopy, while nested PCR was positive in 100 (63.7%) samples. These positive samples were seguenced and phylogenetic tree were done and, there was no association between the variations in glut (p3) gene of T. vaginalis isolated from infected women (fertile and infertile)

Kinetic properties of Streptomyces canarius L- Glutaminase and its anticancer efficiency

Abstract L-glutaminase was produced by Streptomyces canarius FR (KC460654) with an apparent molecular mass of 44 kDa. It has 17.9 purification fold with a final specific activity 132.2 U/mg proteins and 28% yield recovery. The purified L-glutaminase showed a maximal activity against L-glutamine when incubated at pH 8.0 at 40 °C for 30 min. It maintained its stability at wide range of pH from 5.0 11.0 and thermal stable up to 60 °C with Tm value 57.5 °C. It has high affinity and catalytic activity for L-glutamine (Km 0.129 mM, Vmax 2.02 U/mg/min), followed by L-asparagine and L-aspartic acid. In vivo, L-glutaminase showed no observed changes in liver; kidney functions; hematological parameters and slight effect on RBCs and level of platelets after 10 days of rabbit's injection. The anticancer activity of L-glutaminase was also tested against five types of human cancer cell lines using MTT assay in vitro. L-glutaminase has a significant efficiency against Hep-G2 cell (IC50, 6.8 μg/mL) and HeLa cells (IC50, 8.3 μg/mL), while the growth of MCF-7 cells was not affected. L-glutaminase has a moderate cytotoxic effect against HCT-116 cell (IC50, 64.7 μg/mL) and RAW 264.7 cell (IC50, 59.3 μg/mL).

Caracterização bioquímica e celular da glutaminase isoforma Kidney-type com seus parceiros de interação / Biochemical and cellular characterization of Kidney-type glutaminase with their interaction partners

Células tumorais apresentam uma autonomia metabólica aumentada em comparação a células não-transformadas, incorporando nutrientes e metabolizando-os através de vias que suportam o seu crescimento e proliferação. O foco deste trabalho foi a enzima glutaminase, a qual processa glutamina em glutamato para posterior produção de alfa-cetoglutarato pela enzima glutamato desidrogenase, reabastecendo o ciclo do TCA e suportando seu funcionamento e geração de metabólitos essenciais para a síntese de macromoléculas. O gene GLS1 codifica para as isoformas glutaminase kidney-type (KGA) e glutaminase C (GAC). Estas proteínas apresentam outros domínios além do catalítico, e, no caso da KGA, repetições do tipo ankirin, sabidamente envolvidas em contatos proteínas-proteínas. Os objetivos deste projeto foram de encontrar parceiros de interação para a glutaminase kidney-type (KGA) e avaliar o impacto desta interação para o metabolismo tumoral. Um candidato inicialmente avaliado, a Aldolase A, não foi confirmado como parceiro de interação. Outro candidato, a BNIP-H, apesar de ter sido mostrado interagir com a KGA em células nervosas, não mostrou indícios de interação com a KGA em linhagem de células de câncer de mama. Por fim, estudos de duplo-híbrido em levedura revelaram o receptor nuclear PPARγ (Peroxisome proliferator-activated receptor gamma) como forte candidato a parceiro de interação. Realizou-se um mapeamento dos domínios responsáveis pela interação entre estas duas proteínas, também por duplo híbrido, tendo sido identificado o domínio LBD da proteína PPARγ como envolvido na interação. Mesmo estudos realizados com fragmento da KGA, apesar de incompletos, mostraram que a interação não ocorre pelo domínio carboxi-terminal da enzima. Ensaios de anisotropia de fluorescência com as proteínas KGA e PPARγ purificadas indicaram que a interação é favorecida pela presença do produto da reação glutaminolítica, glutamato, e apresenta um Kd de 4,6 ± 0,5 μM...

Tumor cells have an increased metabolic autonomy compared to non-transformed cells, metabolizing nutrients and incorporating them through pathways that support cell growth and proliferation. The focus of this study was the glutaminase enzyme, which processes glutamine to glutamate for subsequent production of alpha-ketoglutarate, by the glutamate dehydrogenase enzyme, replenishing TCA cycle and bearing its function and the generation of metabolites essential for the synthesis of macromolecules. The gene GLS1 codes for the isoforms kidney-type glutaminase (KGA) and glutaminase C (GAC). These proteins exhibit other domains besides the catalytic, and in the case of KGA, ankirin repeats, known to be involved in protein-protein contacts. The goal of this project was to investigate potential interacting partners of KGA and contextualize the interaction within the metabolic demands of tumor cells. A candidate initially evaluated, the Aldolase A, was not confirmed as a partner of interaction. Another candidate, the BNIP-H, despite having been shown to interact with the KGA in nervous cells, showed no evidence of interaction with KGA in one tested breast cancer cell lines. Finally, yeast two-hybrid studies revealed the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) as a strong interaction partner candidate. We mapped the domains responsible for the interaction between these two proteins, also by two-hybrid and identified the LBD domain of PPARγ as involved in the interaction. The same studies with KGA fragments, although incomplete, showed that the interaction did not involve the carboxy-terminal domain of the enzyme. KGA and PPARγ proteins were expressed in E. coli, purified and their interaction was analyzed by pull-down, fluorescence anisotropy, electrophoresis under native conditions, gel filtration chromatography and crosslinking...

Triagem sorológica para doença celíaca em adolescentes e adultos jovens, estudantes universitários / Serological triage for celiac disease in adolescents and young adults attending university

Avaliar a positividade sorológica para doença celíaca em um grupo de adolescentes e adultos jovens da cidade do Recife, Nordeste do Brasil. MÉTODOS: a amostra foi composta por estudantes matriculados nos cursos de graduação do Centro de Ciências da Saúde da Universidade Federal de Pernambuco. Os estudantes foram submetidos à coleta de sangue para pesquisa sorológica do anticorpo antitransglutaminase tecidual humana e responderam a questionário sobre sintomas e condições mórbidas associadas à doença celíaca. O anticorpo antitrans-glutaminase foi pesquisado por técnica de Elisa, considerando-se positivos valores acima de 10 U/mL, conforme estabelecido pelo fabricante. Nos pacientes que tiveram sorologia positiva para o anticorpo antitransglutaminase realizou-se a sorologia para o anticorpo antiendomíseo, por imunofluorescência indireta, utilizando kit comercialmente disponível. RESULTADOS: seiscentos e oitenta e três universitários participaram da pesquisa. Os estudantes tinham entre 18 e 30 anos e mediana de idade de 21 anos. O anticorpo antitransglutaminase foi positivo em 12/683, soroprevalência de 1,76 por cento(IC95 por cento: 0,95-3,13 por cento). O anticorpo antiendomíseo foi realizado em 11 amostras e reagente em quatro. Oito estudantes com sorologia positiva tinham sintomas e/ou condições mórbidas associadas à doença celíaca. CONCLUSÕES: a elevada presença de anticorpos anti-transglutaminase encontrada neste estudo é semelhante a da Europa e Estados Unidos da América, sugere a possibilidade da triagem sorológica mesmo em populações consideradas de baixo risco...

To evaluate serum for celiac disease in a group of adolescents and young adults in the city of Recife, in the Northeast region of Brazil. METHODS: the sample was made up of students enrolled on undergraduate courses at the Center for Health Sciences of the Federal University of Pernambuco. A blood sample was taken from the students to test their serum for the human tissue antitransglutaminase antibody and they were asked to complete a questionnaire on the symptoms and morbid conditions associated with celiac disease. THE antitransglutaminase was identified using the Elisa technique, taking positive values to be those above 10 U/mL, as recommended by the manufacturer. Patients who tested positive for the antitransglutaminase antibody were subsequently tested for the antiendomysial antibody, by indirect immunofluorescence, using the commercially available kit. RESULTS: six hundred and eight-three university students took part in the study. They were aged between 18 and 30 years, with a mean age of 21 years. The antitransglutaminase antibody was found in 12/683, a prevalence of 1.76 percent (CI95 percent: 0.95-3.13 percent). The antiendomysial antibody test was carried out in eleven these samples and the reagent in four. Eight students tested positive and/or had morbid conditions associated with celiac disease. CONCLUSIONS: the high levels of anti-transglutaminase antibodies found in this study were similar to those found in Europe and the United States suggesting that serological triage can be carried out even in populations considered to be low risk...

Metabolism and brain cancer

Cellular energy metabolism is one of the main processes affected during the transition from normal to cancer cells, and it is a crucial determinant of cell proliferation or cell death. As a support for rapid proliferation, cancer cells choose to use glycolysis even in the presence of oxygen (Warburg effect) to fuel macromolecules for the synthesis of nucleotides, fatty acids, and amino acids for the accelerated mitosis, rather than fuel the tricarboxylic acid cycle and oxidative phosphorylation. Mitochondria biogenesis is also reprogrammed in cancer cells, and the destiny of those cells is determined by the balance between energy and macromolecule supplies, and the efficiency of buffering of the cumulative radical oxygen species. In glioblastoma, the most frequent and malignant adult brain tumor, a metabolic shift toward aerobic glycolysis is observed, with regulation by well known genes as integrants of oncogenic pathways such as phosphoinositide 3-kinase/protein kinase, MYC, and hypoxia regulated gene as hypoxia induced factor 1. The expression profile of a set of genes coding for glycolysis and the tricarboxylic acid cycle in glioblastoma cases confirms this metabolic switch. An understanding of how the main metabolic pathways are modified by cancer cells and the interactions between oncogenes and tumor suppressor genes with these pathways may enlighten new strategies in cancer therapy. In the present review, the main metabolic pathways are compared in normal and cancer cells, and key regulations by the main oncogenes and tumor suppressor genes are discussed. Potential therapeutic targets of the cancer energetic metabolism are enumerated, highlighting the astrocytomas, the most common brain cancer.

Detección de anticuerpos antigliadina y antitransglutaminasa en pacientes con clínica sugestiva de enfermedad celíaca / Detection of anti-gliadin and anti-transglutaminase antibodies in patients with possible celiac disease

La enfermedad celíaca es una enfermedad autoinmune que cursa con procesos inflamatorios en la mucosa del intestino delgado. Se produce por la ingesta de una fracción proteica del gluten de la dieta en individuos genéticamente predispuestos. Tiene diferentes formas de presentación que van desde la sintomática, típica o atípica, hasta la silente. La detección de autoanticuerpos con diversas especificidades debe ser considerada como indispensable en todos aquellos enfermos donde predominan síntomas digestivos y afectaciones nutricionales, aunque no deben descartarse otras sintomatologías atípicas como son el retraso en el crecimiento y desarrollo. En nuestro trabajo se estudió la presencia de anticuerpos antigliadina y antitransglutaminasa en el suero de 110 enfermos con clínica sugestiva de enfermedad celíaca, y se detectaron anticuerpos en 23 enfermos: 11 con antigliadina, antitransglutaminasa y biopsia positiva; 6 con antigliadina positiva, antitransglutaminasa negativa y biopsia positiva y 6 con antigliadina positiva, antitransglutaminasa negativa y biopsia negativa.

Celiac disease is an autoimmune entity with inflammatory processes in small intestine. It is caused by ingesta of gluten protein fraction in the diet of subjects with genetic predisposition subjects and has different ways of presentation including the symptomatic, typical or atypical and silent type. The detection of autoantibodies with diverse specificities must to be considered as essential in all those patients where there is predominance of digestive symptoms and nutritional affections without to rule out other atypical symptomatologies including the growth and development retard. The objective of present paper was to study the presence of anti-gliadin and anti-transglutaminase in serum of 110 patients presenting with celiac disease and it was possible to detect antibodies in 23 patients: 11 with anti-gliadin and anti-transglutaminase and a positive biopsy; 6 with positive anti-gliadin, negative anti-transglutaminase and a positive biopsy, negative anti-transglutaminase and also a negative biopsy.

Acivicin with glutaminase regulates proliferation and invasion of human MCF-7 and OAW-42 cells--an in vitro study.

Tumor cells intensely utilize glutamine as the major source of respiratory fuel. Glutamine-analogue acivicin inhibits tumor growth and tumor-induced angiogenesis in Ehrlich ascites carcinoma. In the present study, antitumor properties of acivicin in combination with glutaminase enzyme is reported. Acivicin along with E. coli glutaminase synergistically reduced in vitro proliferation and matrigel invasion of human MCF-7 and OAW-42 cells. Effects of single and combined treatments with acivicin and glutaminase on angiogenic factors were also analyzed in these cell lines. Co-administration of the treatment agents inhibits the release of VEGF and MMP-9 by cells in culture supernatant significantly than single agent treatments. The result suggests that combination of acivicin with glutaminase may provide a better therapeutic option than either of them given separately for treating human breast and ovarian cancer. However, further studies are required to be conducted in vivo for its confirmation.

Modulation of metastatic potential of B16F10 melanoma cells by acivicin: synergistic action of glutaminase and potentiation of cisplatin cytotoxicity.

Treatment for metastatic melanoma has mostly been unsatisfactory despite advances in ongoing medical research. Here we investigated the role of acivicin, a glutamine analogue, singly and in combination with either E. coli glutaminase or cisplatin, on the growth, angiogenic activity and invasiveness of B16F10 cells in vitro and after allografting in C57BL/6 mice. B16F10 melanoma colonization in the lungs of mice was measured by monitoring colony counts. Host toxicity was assessed with reference to tumor bearing host's weight and survivability. Acivicin promoted melanoma dormancy and reduced melanoma associated angiogenic factors like VEGF level and vessel diameter. Acivicin in combination with glutaminase significantly suppressed tumor growth by 66.7% and increased life-span by 43.5% without host toxicity. Tumor VEGF content was significantly lowered by combination therapy as assessed by ELISA. Accelerated cytotoxicity, reduced invasion and enhanced apoptosis of melanoma cells were exhibited in vitro by combined than by single agent treatment. Moreover, invasion of melanoma cells through matrigel chambers was reduced in presence of acivicin and glutaminase combination. These findings support future studies of acivicin in combination with other anticancer agents for prevention of melanoma metastasis.

Optimum conditions for L-glutaminase production by actinomycete strain isolated from estuarine fish, Chanos chanos (Forskal, 1775).

Actinomycetes were isolated from skin, gills and gut contents of estuarine fish. Chanos chanos using Kuster's agar medium. Out of 20 strains tested, the strain LG-10 which was tentatively identified as Streptomyces rimosus showed L-glutaminase activity. Optimum production of L-glutaminase enzyme (17.51 IU/ml) was observed after 96 h of incubation at 27 degrees C, pH 9 and glucose and malt extract as carbon and nitrogen sources, respectively. The present study indicated scope for the use of S. rimosus as an ideal organism for the industrial production of extracellular L-glutaminase.

The cDNA microarray study for the effect of FGF-5 administration on fibroblast

Atividade da glutaminase dependente de prognóstico e estudo comparativo com a pele circunvizinha / Phosphate-dependent glutaminse in cutaneous melanoma of poor prognostic and comparative study with surrounding skin

O melanoma cutâneo, como as neoplasias em geral, deve consumir quantidade elevada de substrato energético, como glicose e glutamina. A glutamina é um aminoácido que participa ativamente da síntese de proteínas e, através de sua principal enzima, a glutaminase dependente de fosfato, da formação de ATP e da síntese de DNA e RNA. A infiltração das células neoplásicas nos planos mais profundos da pele, a ulceração e a supressão de linfócitos reacionais, são consideradas fatores de mau prognóstico no melanoma cutâneo. Também o aumento da neovascularização tem sido considerado um importante facilitador para o crescimento celular e progressão metastática. Como o metabolismo da glutamina, através da atividade da glutaminase dependente de fosfato, em pacientes portadores de melanoma cutâneo, ainda não foi investigado, foi proposta do presente trabalho determinar e comparar, através de metodologia original de coleta de fragmento não fixado, a atividade e o tipo dessa enzima na lesão pigmentada do melanoma cutâneo e pele circunvizinha. Verificou-se um aumento significativo do conteúdo proteínico e diminuição da atividade da glutaminase dependente de fosfato (nmol/min por mg de proteinas) no melanoma cutâneo de mau prognóstico, em relação à pele circunvizinha não pigmentada. O método comparativo entre a região pigmentada e a pele circunvizinha permite sugerir que, à partir da célula transformada, deve ocorrer alterações metabólicas gradativas com aumento do conteúdo proteínico no melanoma cutâneo sem a necessidade de se alterar a síntese de glutamina, conforme foi demonstrado na pele circunvizinha, onde a atividade da glutaminase foi significativamente maior em relação ao melanoma. A identificação da glutaminase do tipo renal demonstra a sensibilidade elevada do melanoma em responder às oscilações plasmáticas de glutamina, mesmo quando está em pequenas concentrações, reafirmando a hipótese de que a glutamina não seja o substrato energético preferencial para as células do melanoma cutâneo. Além disso, a intensa neovascularização observada, contribuindo para o alto potencial de agressividade do melanoma na fase de crescimento vertical, onde as células neoplásicas se proliferam rapidamente, sugere também que a glutamina esteja sendo utilizada preferencialmente no fornecimento de nitrogênio para a síntese das bases púricas e pirimídicas do DNA e RNA

Neovascularisation offers a new perspective to glutamine related therapy.

Angiogenesis or the generation of new blood vessel, is an important factor in the growth of a solid tumor. Hence, it becomes a necessary parameter of any kind of therapeutic study. Glutamine is an essential nutrient of tumor tissue and glutamine related therapy involves clearance of circulatory glutamine by glutaminase. Therefore, using different murine solid tumor models, the present study was undertaken to find out whether the S-180 cell glutaminase has any effect on angiogenesis of solid tumor, or not. Result indicates that the purified S-180 cell glutaminase reduces tumor volume and restrict the generation of neo blood vessels. Therefore, it can be concluded that this enzyme may be an effective device against the cancer metastasis.

Effect of protein malnutrition on the glycolytic and glutaminolytic enzyme activity of rat thymus and mesenteric lymph nodes

The activity of important glycolytic enzymes (hexokinase, phosphofructokinase, aldolase, phosphohexoseisomerase, pyruvate kinase and lactate dehydrogenase) and glutaminolytic enzymes (phosphate-dependent glutaminase) was determined in the thymus and mesenteric lymph nodes of wistar rats submited to protein malnutrition (6 percent protein in the diet rather than 20 percent) from conception to 12 weeks after birth. The wet weight (g) of the thymus and mesenteric lymph nodes decreased due to protein malnutrition by 87 percent (from 0.30 + 0.05 to 0.04 + 0.01) and 75 percent (0.40 + 0.04 to 0.10 + 0.02), respectively. The protein content was reduced only in the thymus from 102.3 + 4.4 (control rats) to 72.6 + 6.6 (malnourished rats). The glycolytic enzymes were not affected by protein malnutrition, but the glutaminase activity of the thymus and lymph nodes was reduced by halfing in protein-malnourished rats as compared to controls. This fact may lead to a decrease in the cellularity of the organ and thus in its size, weight and protein content.

Effect of dietary-turmeric on ammonia metabolism.

Male Sprague-Dawley rats were fed a control diet or the control diet supplemented with 1% turmeric for 10 weeks. Changes in ammonia and urea were investigated as potential marker products of free radical damage to protein and subsequent metabolism of those damaged proteins in vivo. The data suggested that the concentrations of ammonia and urea, major by- products of nitrogen metabolism are unchanged by the oxidant damage and lipid peroxidation and that their control in vivo is a dynamic equilibrium of various metabolic pathways

Effect of lactose induced diarrhea on intestinal glutaminase and muscle glutamine synthetase activities in rats

O objetivo deste estudo foi avaliar o efeito da diarréia induzida por lactose na senzimas chaves do metabolismo de glutamina no músculo esqulético e no intestino delgado, em ratos. Comparados com os controles de peso pareado, os animais com diarréia apresentaram atividade maior de glutamina sintetase do músculo, concomitante com uma reduçäo na concentraçäo de glutamina nesse tecido, e uma queda na concentraçäo de glutamina arterial. Essas alteraçöes säo semelhantes àquelas relatadas por outros investigadores em condiçöes em que ocorre a proteólise muscular tais como, durante a fase pós-operatória e septicemia. Além dos dados que sugerem alteraçöes gerais no metabolismo da glutamina, um achado importante deste estudo foi a verificaçäo de aumento na atividade específica de glutaminase intestinal dependente de fosfato em ratos com diarréia. A alteraçäo da atividade dessa enzima näo tem sido demonstrada em diveresas condiçöes tais como, acidose, alcalose, aumento na ingestäo de gluamina através de água ou dieta, situaçöes que supostamente, poderiam interferir na sua atividade