Cobalamin inactivation induces formyltetrahydrofolate synthetase

AbstractLoss of cobalamin function produces profound changes in the metabolism of formate. There is impaired synthesis of formyltetrahydropteroylglutamate synthetase (CHO-H4,PteGlu), accumulation of endogenous formate and impaired utilization of [14C]formate. There are contradictory reports on the effect of cobalamin inactivation on CHO-H4PteGlu synthetase. This study confirms a significant increase in synthetase activity following cobalamin inactivation

Ordering folate assays is no longer justified for investigation of anemias, in folic acid fortified countries

<p>Abstract</p> <p>Background</p> <p>Since 1998, in the countries where there is mandatory fortification of grain products with folic acid, folate deficiency has become very rare. Consequently, we decided to find out whether there is any justification for ordering folate assays for investigation of anemias.</p> <p>Methods</p> <p>We reviewed serum folate (SF) and red cell folate (RF) data at two teaching hospitals in Canada. At the Health Sciences Centre (HSC) the folate data for the year 2001 were analyzed and the medical records of those with low SF or low RF were reviewed. At St. Boniface General Hospital(SBGH)all folate data between January 1996 and Dec 31,2004 were analyzed and the medical records of all who had low RF between January 1,1999 and December 31,2004 were reviewed.</p> <p>Results</p> <p>In 2001, at HSC, 11 out of 2154(0.5%)SF were low(<7.0 nmol/L) and 4 out of 560 (0.7%) RF were low (<417 nmol/L). In no subject with low SF or RF could the anemia be attributed to folate deficiency. At SBGH during the 3-year-period of 1999-2001, 19 out of 991(1.9%) had low RF (<225 nmol/L) but in only 2 patients (0.2%) the low RF was in folate deficiency anemia range; but neither of them had anemia.</p> <p>Conclusion</p> <p>In countries where there is mandatory fortification of grain products with folic acid, folate deficiency to the degree that could cause anemia is extremely rare. Ordering folate assays for investigation of anemias, in these countries, is waste of time and money. The result of these tests is more likely to mislead the physicians than to provide any useful information.</p

Association of Blood Lead (Pb) and Plasma Homocysteine: A Cross Sectional Survey in Karachi, Pakistan

Background: High blood lead (Pb) and hyperhomocysteinemia have been found to be associated with cardiovascular disease (CVD). Mean blood Pb and mean plasma homocysteine levels have been reported to be high in Pakistani population. The objective of the present study was to assess the relationship of blood Pb to the risk of hyperhomocysteinemia in a low income urban population of Karachi, Pakistan. Methodology/Principal Findings: In a cross sectional survey, 872 healthy adults (355 males, 517 females, age 18-60 years) were recruited from a low income urban population of Karachi. Fasting venous blood was obtained and assessed for blood Pb and plasma/serum homocysteine, folate, pyridoxal phosphate (PLP, a coenzymic form of vitamin B6) and vitamin B12. The study population had median (IQR) blood Pb of 10.82 microg/dL (8.29-13.60). Prevalence of high blood Pb (levels\u3e10 microg/dL) was higher in males compared to females (62.5% males vs 56% females, p value=0.05). Mean+/-SD/median (IQR) value of plasma homocysteine was significantly higher in the highest quartile of blood Pb compared to the lowest quartile 16.13+/-11.2 micromol/L vs 13.28+/-9.7micromol/L/13.15 (10.33-17.81) micromol/L vs 11.09 (8.65 14.31) micromol/L (p valu

Early onset of Chanarin-Dorfman syndrome with severe liver involvement in a patient with a complex rearrangement of ABHD5 promoter

BACKGROUND: \u3b1/\u3b2-hydrolase domain-containing protein 5 (ABHD5) plays an important role in the triacylglycerols (TAG) hydrolysis. Indeed, ABHD5 is the co-activator of adipose triglyceride lipase (ATGL), that catalyses the initial step of TAG hydrolysis. Mutations in ABHD5 gene are associated with the onset of Chanarin-Dorfman syndrome (CDS), a rare autosomal recessive lipid storage disorder, characterized by non-bullous congenital ichthyosiform erythroderma (NCIE), hepatomegaly and liver steatosis. CASE PRESENTATION: We describe here a 5-years-old Brazilian child who presented with NCIE at birth and diffuse micro and macro-vesicular steatosis on liver biopsy since she was 2 years old. Molecular analysis of coding sequence and putative 5' regulatory region of ABHD5 gene was performed. A homozygous novel deletion, affecting the promoter region and the exon 1, was identified, confirming the suspected diagnosis of CDS for this patient. RT-PCR analysis showed that the genomic rearrangement completely abolished the ABHD5 gene expression in the patient, while only a partial loss of expression was detected in her parents. This is the first report describing the identification of a large deletion encompassing the promoter region of ABHD5 gene. The total loss of ABHD5 expression may explain the early onset of CDS and the severe liver involvement. After molecular diagnosis, the patient started a special diet, poor in fatty acids with medium chain triglycerides (MCT), and showed hepatic and dermatologic improvement in spite of severe molecular defect. CONCLUSIONS: This case report extends the spectrum of disease-causing ABHD5 mutations in CDS providing evidence for a novel pathogenic mechanism for this rare disorder. Moreover, our preliminary data show that early diagnosis and prompt treatment of neutral lipid accumulation might be useful for CD patients

Effects of betel nut on cardiovascular risk factors in a rat model

Background: Areca nut (commonly known as betel nut) chewing has been shown to be associated with metabolic syndrome and cardiovascular disease (CVD). The mechanism by which betel nut ingestion could lead to development of CVD is not precisely known; however, dyslipidemia, hyperhomocysteinemia, hypertriglyceridemia and inflammation could be some of the potential risk factors. This study was undertaken to investigate the effects of two dosages of betel nut on homocysteinemia, inflammation and some of the components of metabolic syndrome, such as hypertriglyceridemia, low HDL-cholesterol, obesity and fasting hyperglycemia in a rat model.Methods: Thirty-six adult female Sprague Dawley rats, aged 10–12 weeks were divided into three equal groups. Group-1 served as the control group (n = 12) and received water, whereas groups 2 and 3 were given water suspension of betel nut orally in two dosages, 30 mg and 60 mg, respectively for a period of 5 weeks. At the end of the fifth week, the animals were weighed and sacrificed, blood was collected and liver, kidney, spleen and stomach were removed for histological examination. Plasma/serum was analyzed for glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, homocysteine, folate, vitamin B12 and N-acetyl-β-D-glucosaminidase (NAG) – a marker of inflammation.Results: When the mean concentration values of 3 groups were compared using one way ANOVA followed by Tukey’s HSD-test, there was a significant increase in the concentration of total cholesterol (p = 0.04) in the group receiving 30 mg/day betel nut compared to the control group. However, administration of a higher dose of betel nut (60 mg/day) had no significant effect on the serum concentrations of glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, and NAG. Histological examination of spleen revealed a dose-dependent extramedullary hematopoiesis. No other remarkable change in the tissues (liver, kidney and stomach) was observed. Mean serum/plasma levels of folate, vitamin B12 and homocysteine were not found to be significantly different in all the groups. Betel nut ingestion had no effect on the mean body weights of rats.Conclusions: Low dosage of betel nut is found to be associated with hypercholesterolemia. However, betel nut ingestion is not associated with hyperhomocysteinemia, hypertriglyceridemia, hyperglycemia, inflammation and increase in body weight in a rat model

Micronutrient malnutrition and wasting in adults with pulmonary tuberculosis with and without HIV co-infection in Malawi

BACKGROUND: Wasting and micronutrient malnutrition have not been well characterized in adults with pulmonary tuberculosis. We hypothesized that micronutrient malnutrition is associated with wasting and higher plasma human immunodeficiency virus (HIV) load in adults with pulmonary tuberculosis. METHODS: In a cross-sectional study involving 579 HIV-positive and 222 HIV-negative adults with pulmonary tuberculosis in Zomba, Malawi, anthropometry, plasma HIV load and plasma micronutrient concentrations (retinol, α-tocopherol, carotenoids, zinc, and selenium) were measured. The risk of micronutrient deficiencies was examined at different severity levels of wasting. RESULTS: Body mass index (BMI), plasma retinol, carotenoid and selenium concentrations significantly decreased by increasing tertile of plasma HIV load. There were no significant differences in plasma micronutrient concentrations between HIV-negative individuals and HIV-positive individuals who were in the lowest tertile of plasma HIV load. Plasma vitamin A concentrations <0.70 μmol/L occurred in 61%, and zinc and selenium deficiency occurred in 85% and 87% respectively. Wasting, defined as BMI<18.5 was present in 59% of study participants and was independently associated with a higher risk of low carotenoids, and vitamin A and selenium deficiency. Severe wasting, defined as BMI<16.0 showed the strongest associations with deficiencies in vitamin A, selenium and plasma carotenoids. CONCLUSIONS: These data demonstrate that wasting and higher HIV load in pulmonary tuberculosis are associated with micronutrient malnutrition