981 resultados para acid maltase deficiency


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Background & aims: Pregnancy is a period characterized by high metabolic requirements and physiological changes in the female organism. During this period, Low body stores of vitamins and minerals including antioxidants can have adverse effects on the mother and foetus. This cross-sectional. study assessed plasma concentrations of ascorbic acid (AA) in 117 parturients admitted into a university hospital in S (a) over tildeo Paulo city, Brazil. Methods: The concentrations of AA were determined by the high performance liquid chromatographic method. Data concerning socioeconomic, demographic, obstetric and nutritional characteristics of the parturients were collected by a standardized questionnaire. Results: The prevalence of AA deficiency (< 22.7 mu mol/L) among the parturients was 30.8%. Mean plasma AA concentrations were lower in single/divorced women (27.84 +/- 3.48 mu mol./L) compared with married/single with partner women (34.78 +/- 1.85 mu mol/L) (p = 0.047). Blood AA concentrations were significantly correlated with per capita income (r = 0.36, p < 0.001) and vitamin C-rich food intake score (r = 0.42, p < 0.001). Conclusion: The high prevalence of hypovitaminosis C detected in this study is probably due to an inadequate intake of foods rich in vitamin C and tow income. We alert to the need for increasing the intake of vitamin C-rich foods through educational. programs, especially for tow income populations. (c) 2007 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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Aims: In the present work we investigated the in vitro effect of cis-4-decenoic acid, the pathognomonic metabolite of medium-chain acyl-CoA dehydrogenase deficiency, on various parameters of bioenergetic homeostasis in rat brain mitochondria. Main methods: Respiratory parameters determined by oxygen consumption were evaluated, as well as membrane potential, NAD(P)H content, swelling and cytochrome c release in mitochondrial preparations from rat brain, using glutamate plus malate or succinate as substrates. The activities of citric acid cycle enzymes were also assessed. Key findings: cis-4-decenoic acid markedly increased state 4 respiration, whereas state 3 respiration and the respiratory control ratio were decreased. The ADP/O ratio, the mitochondrial membrane potential, the matrix NAD(P)H levels and aconitase activity were also diminished by cis-4-decenoic acid. These data indicate that this fatty acid acts as an uncoupler of oxidative phosphorylation and as a metabolic inhibitor. cis-4-decenoic acid also provoked a marked mitochondrial swelling when either KCl or sucrose was used in the incubation medium and also induced cytochrome c release from mitochondria, suggesting a non-selective permeabilization of the inner mitochondria! membrane. Significance: It is therefore presumed that impairment of mitochondrial homeostasis provoked by cis-4-decenoic acid may be involved in the brain dysfunction observed in medium-chain acyl-CoA dehydrogenase deficient patients. (C) 2010 Elsevier Inc. All rights reserved.

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OBJECTIVES: To study the effect of short-chain fatty-acids on atrophy and inflammation of excluded colonic segments before and after the development of diversion colitis. INTRODUCTION: Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, possibly evolving with mucous and blood discharge. The most favored hypotheses to explain its development is short-chain fatty-acid deficiency in the colon lumen. METHODS: Wistar rats were submitted to colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short-chain fatty-acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after post-operative day 40). The mucosal thickness of the excluded colon was measured histologically. The inflammatory reaction of the mucosal lamina propria and the lymphoid tissue response were quantified through established scores. RESULTS: There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 showed no mucosal thickness recovery and significant increases in the numbers of lymphocytes (p = 0.0006) and eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022). CONCLUSION: Therapeutic use of short-chain fatty-acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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A vitamina C é essencial para dietas de peixe porque muitas espécies não conseguem sintetizá-la. Esta vitamina é necessária par a formação de cartilagem e matriz óssea. Além disso, age como antioxidante e melhora as resposta do sistema imunológico. O presente trabalho investigou os efeitos da suplementação de vitamina C em dietas para alevinos de pintado (Pseudoplatystoma corruscans) pela incidência de deformidades na estrutura óssea e cartilaginosa. O ascorbil polifosfato (AP) foi utilizado como fonte de vitamina C em dietas para alevinos de pintado durante o período de três meses. Seis dietas foram formuladas: uma dieta controle (0 mg de vitamina C / kg) e cinco dietas 500, 1.000, 1.500, 2.000 e 2.500 mg de AP / kg. Os peixes alimentados sem suplementação de vitamina C apresentaram deformidades óssea na cabeça e mandíbula e fragilidade de nadadeiras. Assim, a dieta de 500 mg de AP/kg foi suficiente para prevenir a ocorrência de deformidades, e a ausência desta vitamina prejudica o desenvolvimento ósseo de juvenis de pintados.

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We studied glucose homeostasis in rat pups from darns fed on a normal-protein (170 g/kg) (NP) diet or a diet containing 60 g protein/kg (LP) during fetal life and the suckling period. At birth, total serum protein, serum albumin and serum insulin levels were similar in both groups. However, body weight and serum glucose levels in LP rats were lower than those in NP rats. At the end of the suckling period (28 d of age), total serum protein, serum albumin and serum insulin were significantly lower and the liver glycogen and serum free fatty acid levels were significantly higher in LP rats compared with NP rats. Although the fasting serum glucose level was similar in both groups, the area under the blood glucose concentration curve after a glucose load was higher for NP rats (859 (SEM 58) mmol/l per 120 min for NP rats v. 607 (SEM 52) mmol/l per 120 min for LP rats; P < 0.005). The mean post-glucose increase in insulin was higher for NP rats (30 (SEM 4.7) nmol/l per 120 min for NP rats v. 17 (SEM 3.9) nnol/l per 120 min for LP rats; P < 0.05). The glucose disappearance rate for NP rats(0.7 (SEM 0.1) %/min) was lower than that for LP rats (1.6 (SEM 0.2) %/min; P < 0.001). Insulin secretion from isolated islets (1 h incubation) in response to 16.7 mmol glucose/l was augmented 14-fold in NP rats but only 2.6-fold in LP rats compared with the respective basal secretion (2.8 mmol/l; P <0.001). These results indicate that in vivo as well as in vitro insulin secretion in pups from dams maintained on a LP diet is reduced. This defect may be counteracted by an increase in the sensitivity of target tissues to insulin.

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In order to investigate the effect of folate depletion, lymphocyte sister-chromatid exchange (SCE) rates were compared among homozygous β-thalassaemic patients with low folic acid levels, heterozygous β-thalassaemic patients with normal folate levels and healthy persons with normal haemoglobin, in cultures with both normal and depleted folate conditions. Significantly higher SCE rates were found in homozygous patients in all assays, but the in vitro folate depletion did not induce an increase in SCE frequency in any group.

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Background. Iron-deficiency anemia currently is the most frequently occurring nutritional disorder worldwide. Previous Brazilian studies have demonstrated that drinking water fortified with iron and ascorbic acid is an adequate vehicle for improving the iron supply for children frequenting day-care centers. Objective. The objective of this study was to clarify the role of ascorbic acid as a vehicle for improving iron intake in children in day-care centers in Brazil. Methods. A six-month study was conducted on 150 children frequenting six day-care centers divided into two groups of three day-care centers by drawing lots: the iron-C group (3 day-care centers, n = 74), which used water fortified with 10 mg elemental iron and 100 mg ascorbic acid per liter, and the comparison group (3 day-care centers, n = 76), which used water containing only 100 mg ascorbic acid per liter. Anthropometric measurements and determinations of capillary hemoglobin were performed at the beginning of the study and after six months of intervention. The food offered at the day-care centers was also analyzed. Results. The fo od offered at the day-care center was found to be deficient in ascorbic acid, poor in heme iron, and adequate in non-heme iron. Supplementation with fortified drinking water resulted in a decrease in the prevalence of anemia and an increase in mean hemoglobin levels associated with height gain in both groups. Conclusions. Fortification of drinking water with iron has previously demonstrated effectiveness in increasing iron supplies. This simple strategy was confirmed in the present study. The present study also demonstrated that for populations receiving an abundant supply of non-heme iron, it is possible to control anemia in a simple, safe, and inexpensive manner by adding ascorbic acid to drinking water. © 2005, The United Nations University.

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The development of fast, inexpensive, and reliable tests to identify nontuberculous mycobacteria (NTM) is needed. Studies have indicated that the conventional identification procedures, including biochemical assays, are imprecise. This study evaluated a proposed alternative identification method in which 83 NTM isolates, previously identified by conventional biochemical testing and in-house M. avium IS1245-PCR amplification, were submitted to the following tests: thin-layer chromatography (TLC) of mycolic acids and PCR-restriction enzyme analysis of hsp65 (PRA). High-performance liquid chromatography (HPLC) analysis of mycolic acids and Southern blot analysis for M. avium IS1245 were performed on the strains that evidenced discrepancies on either of the above tests. Sixty-eight out of 83 (82%) isolates were concordantly identified by the presence of IS1245 and PRA and by TLC mycolic acid analysis. Discrepant results were found between the phenotypic and molecular tests in 12/83 (14.4%) isolates. Most of these strains were isolated from non-sterile body sites and were most probably colonizing in the host tissue. While TLC patterns suggested the presence of polymycobacterial infection in 3/83 (3.6%) cultures, this was the case in only one HPLC-tested culture and in none of those tested by PRA. The results of this study indicated that, as a phenotypic identification procedure, TLC mycolic acid determination could be considered a relatively simple and cost-effective method for routine screening of NTM isolates in mycobacteriology laboratory practice with a potential for use in developing countries. Further positive evidence was that this method demonstrated general agreement on MAC and M. simiae identification, including in the mixed cultures that predominated in the isolates of the disseminated infections in the AIDS patients under study. In view of the fact that the same treatment regimen is recommended for infections caused by these two species, TLC mycolic acid analysis may be a useful identification tool wherever molecular methods are unaffordable.

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Effects of dietary α-lipoic acid (LA) and ascorbic acid (AA) on the growth, tissue vitamin C and tocopherol (vitamin E) levels, and malondialdehyde levels were examined in the tropical fish pacu, Piaractus mesopotamicus. Pacu juveniles were fed one of four casein-gelatin-based diets for 8 weeks: with 0.05% AA and 0.1% LA (+AA+LA), with AA and without LA (+AA-LA), without AA and with LA (-AA+LA), and without AA and LA (-AA-LA). When the fish received quantities of feed equal to 1.9-2.5% of its body weight, growth was not influenced, regardless of the presence of AA or LA throughout most of the experimental period. Growth was, however, slightly but significantly lower at week 8 in the AA-deficient/LA-supplemented group. An AA-deficient diet caused a highly significant reduction in both total AA and dehydroascorbic acid content in the liver and gill tissues. This reduction of tissue AA concentrations was reversed in a significant manner by LA (antioxidant-sparing effect). The 8-week-long vitamin C deprivation was sufficient to initiate the reduction in tissue ascorbic acid; however, total ascorbate in the liver of fish in the (-)AA/(+)LA group was 127.7±54.3 nmol g-1 tissue, whereas it was 28.6±26.3 nmol g-1 in the (-)AA/(-)LA group, a 4.4-fold difference. This mitigating effect of the addition of the endogenous antioxidant LA to the diet indicates that LA exerts a vitamin C-sparing effect in teleost fish that by far exceeds the phenomena demonstrated in non-scurvy-prone mammals. There was no difference among the different diet groups for vitamin E and malondialdehyde levels in the liver. These results suggest that LA is a potent substance for the prevention of AA deficiency in cultured fishes. The optimal dietary level of LA needs to be determined in the light of the slight reduction in body weight gain after 8 weeks of feeding in the absence of AA. © Springer Science+Business Media, Inc. 2006.

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Magnesium (Mg2+) deficiency is a frequently occurring disorder that leads to loss of bone mass, abnormal bone growth and skeletal weakness. It is not clear whether Mg2+ deficiency affects the formation and/or activity of osteoclasts. We evaluated the effect of Mg2+ restriction on these parameters. Bone marrow cells from long bone and jaw of mice were seeded on plastic and on bone in medium containing different concentrations of Mg2+ (0.8 mM which is 100% of the normal value, 0.4, 0.08 and 0 mM). The effect of Mg2+ deficiency was evaluated on osteoclast precursors for their viability after 3 days and proliferation rate after 3 and 6 days, as was mRNA expression of osteoclastogenesis-related genes and Mg2+-related genes. After 6 days of incubation, the number of tartrate resistant acid phosphatase-positive (TRACP+) multinucleated cells was determined, and the TRACP activity of the medium was measured. Osteoclastic activity was assessed at 8 days by resorption pit analysis. Mg2+ deficiency resulted in increased numbers of osteoclast-like cells, a phenomenon found for both types of marrow. Mg2+ deficiency had no effect on cell viability and proliferation. Increased osteoclastogenesis due to Mg2+ deficiency was reflected in higher expression of osteoclast-related genes. However, resorption per osteoclast and TRACP activity were lower in the absence of Mg2+. In conclusion, Mg2+ deficiency augmented osteoclastogenesis but appeared to inhibit the activity of these cells. Together, our in vitro data suggest that altered osteoclast numbers and activity may contribute to the skeletal phenotype as seen in Mg2+ deficient patients. © 2012 Elsevier Inc. All rights reserved.

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

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Factor H (FH) is one of the most important regulatory proteins of the alternative pathway of the complement system. Patients with FH deficiency have a higher risk for development of infections and kidney diseases because of the uncontrolled activation and subsequent depletion of the central regulatory component C3 of the complement system. In this study, we investigated the consequences of the Arg(127)His mutation in FH (FHR127H) previously described in an FH-deficient patient, on the secretion of this protein by skin fibroblasts in vitro. We observed that, although the patient cells stimulated with IFN-gamma were able to synthesize FHR127H, the mutant protein was largely retained within the endoplasmic reticulum (ER), whereas normal human fibroblasts stimulated with IFN-gamma secrete FH without retention in the ER. Moreover, the retention of FHR127H provoked enlargement of ER cisterns after treatment with IFN-gamma. A similar ER retention was observed in Cos-7 cells expressing the mutant FHR127H protein. Despite this deficiency in secretion, we show that the FHR127H mutant is capable of functioning as a cofactor in the Factor I-mediated cleavage of C3. We then evaluated whether a treatment could increase the secretion of FH, and observed that the patient's fibroblasts treated with the chemical chaperones 4-phenylbutiric acid or curcumin increased the secretion rate of FH. We propose that these chemical chaperones could be used as alternative therapeutic agents to increase FH plasma levels in FH-deficient patients caused by secretion delay of this regulatory protein. The Journal of Immunology, 2012, 189: 3242-3248.

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The mechanisms underlying immune deficiency in diabetes are largely unknown. In the present study, we demonstrate that diabetic mice are highly susceptible to polymicrobial sepsis due to reduction in rolling, adhesion, and migration of leukocytes to the focus of infection. In addition, after sepsis induction, CXCR2 was strongly downregulated in neutrophils from diabetic mice compared with nondiabetic mice. Furthermore, CXCR2 downregulation was associated with increased G-protein coupled receptor kinase 2 (GRK2) expression in these cells. Different from nondiabetic mice, diabetic animals submitted to mild sepsis displayed a significant augment in alpha 1-acid glycoprotein (AGP) hepatic mRNA expression and serum protein levels. Administration of AGP in nondiabetic mice subjected to mild sepsis inhibited the neutrophil migration to the focus of infection, as well as induced t-selectin shedding and rise in CD11b of blood neutrophils. Insulin treatment of diabetic mice reduced mortality rate, prevented the failure of neutrophil migration, impaired GRK2-mediated CXCR2 downregulation, and decreased the generation of AGP. Finally, administration of AGP abolished the effect of insulin treatment in diabetic mice. Together, these data suggest that AGP may be involved in reduction of neutrophil migration and increased susceptibility to sepsis in diabetic mice. Diabetes 61:1584-1591, 2012