Trans fatty acids – A risk factor for cardiovascular disease

Trans fatty acids (TFA) are produced either by hydrogenation of unsaturated oils or by biohydrogenation in the stomach of ruminant animals. Vanaspati ghee and margarine have high contents of TFA. A number of studies have shown an association of TFA consumption and increased risk of cardiovascular disease (CVD). This increased risk is because TFA increase the ratio of LDL cholesterol to HDL cholesterol. Food and Agriculture Organization of the United Nations and World Health Organization have come up with the recommendation that the contents of TFA in human dietary fat should be reduced to less than 4%. There is high prevalence of CVD in Pakistan. High consumption of vanaspati ghee which contains 14.2-34.3% of TFA could be one of the factors for this increased burden of CVD in Pakistan. Consumption of dietary fat low in TFA would be helpful in reducing the risk of CVD in South Asia. Denmark by banning the sale of food items with TFA has brought down the number of deaths due to coronary heart disease by nearly 50% over a period of 20 years. Public awareness about the adverse effects of TFA on human health would be extremely important. Media can play a very effective role in educating the masses and advocating the policy for the sale of only low TFA food items. Literature sources: Google and US National Library of Medicine, National Institute of Health were the sources of papers cited in this review article

Smokeless Tobacco Use: A Risk Factor for Hyperhomocysteinemia in a Pakistani Population

Background Smokeless tobacco (ST) use is highly prevalent in the South Asian populations. While there have been a number of reports on association of ST consumption with cancer, very few studies have been conducted to investigate its relationship with cardiovascular disease. Hyperhomocysteinemia is a well-recognized risk factor for cardiovascular disease; however, its association with ST use has never been investigated. The objective of this study was to evaluate the relationship of ST use with hyperhomocysteinemia in an urban Pakistani population. Methodology/Principal Findings In a cross-sectional study for assessment of risks of hyperhomocysteinemia, 872 healthy adults (355 males and 517 females of age range 18–60 years) were recruited from a low-income population in Karachi, Pakistan. A detailed questionnaire was administered which included information about smoking, non-smoking, use of ST alone (chewing as well as sniffing) and use of ST with betel nuts. Fasting serum/plasma levels of homocysteine, folate, vitamin B12 and pyridoxal phosphate (PLP; a coenzymic form of vitamin B6) were analyzed. In this population, 43.4% males and 15.5% females were found to be regular users of ST products. Laborers and vendors were the major ST consumers. Smoking was not found to be associated with plasma/serum concentrations of homocysteine, folate, vitamin B12 and PLP. However, homocysteine concentrations in the group which consumed ST alone and the group which consumed ST along with betel nut were significantly higher compared to the non-user group (17.7±7.5 µmol/L, 25.48 µmol/L vs. 11.95 µmol/L, respectively; p\u3c0.01). Odds ratio for the association of hyperhomocysteinemia (\u3e15 µmol/L) was 11-fold higher in the ST-consumer group compared to the non-user group, [OR (95%CI) =11.34 (7.58–16.96); p\u3c0.001], when the model was adjusted for age, gender, folate and vitamin B12 status. Conclusion This study shows a positive association between ST consumption and hyperhomocysteinemia in a low-income urban Pakistani population

A simple micro method for determination of plasma levels of alpha tocopherol (Vitamin E) in Pakistani normal adults.

A relatively simple spectrophotometeric method has been developed for the determination of alpha tocopherol in human plasma. Method is modification of a previous micromethod base on oxidation of alpha tocopherol by ferric chloride. The complex of ferrous ions (generated in this reaction) with bathophenanthroline is determined spectrophotometrically at 536 nm. The absorbance of this colored complex is directly proportional to concentration of alpha tocopherol. The method involves extraction of alpha tocopherol from human plasma using n-hexane which is relatively less toxic than xylene. The assay is sensitive enough to detect as little as 0.2 mug of vitamin. The recovery of alpha tocopherol from the plasma using n-hexane was in the range of 75% - 100%. The mean values of intra-assay and interassy coefficient of variation were found to be 5.3% and 13%, respectively. The assay was used to monitor alpha tocopherol levels in plasma samples of 81 normal healthy adults. Mean concentration of plasma alpha tocopherol in these normal healthy adults was found to be 9.45+/-2.64 microg/ ml. Sixteen percent of adults had low levels of alpha tocopherol. The method is rapid, convenient, reproduciable and relatively less hazardous compared to methods using xylene for the extraction of vitamin E. It can be routinely used to analyze as many as 20 plasma samples in about 2 hours time

Does vitamin E have a role in treatment and prevention of anemia?

Vitamin E is a highly effective fat-soluble vitamin with a variety of cellular membrane stabilizing-antioxidant and non-antioxidant functions. Vitamin E has been suggested to prevent the oxidation of polyunsaturated fatty acids in red blood cell (RBC) membrane, thus inhibiting the premature erythrocytelysis. Animal studies have shown that treatment with vitamin E results in increased number of colony forming units of erythroid precursors, enhanced erythropoiesis and improved blood hemoglobin levels in these animals. Several clinical trials have indicated that vitamin E might be used therapeutically as a potential erythropoietic agent for decreasing the premature erythrocyte hemolysis by reducing the fragility of erythrocytes. By this way, it improves the post-supplemental blood hemoglobin and hematocrit levels in some of the anemic human subjects, including low birth weight premature infants, Patients suffering from various types of inherited hemolytic anemia, chronic renal failure Patients on hemodialysis and apparently healthy mildly anemic subjects

Admission creatine kinase as a prognostic marker in acute myocardial infarction

OBJECTIVES: To investigate the prognostic significance of creatine kinase (CK) in Pakistani patients suffering from acute myocardial infarction (AMI) and to find out if CK combined with troponin T (TnT) could be a better predictor for long-term adverse cardiac event. METHODS: One hundred and eighty six consecutive patients with AMI who were eligible for streptokinase (SK) treatment were included in this prospective cohort study. The relationship between their serum/plasma CK and TnT levels at the time of admission and clinical outcome was investigated over a mean follow up of 24.12 +/- 3.75 months. RESULTS: Admission CK was found to be associated with subsequent cardiac event and mortality (P \u3c 0.01 and P \u3c 0.04 respectively). Admission CK was also mildly associated with time interval between onset of symptoms to SK treatment (correlation coefficient \u27r\u27 = 0.23). Odds of encountering a cardiac event in AMI patients with above-normal CK levels (adjusted for gender) were 3.46 times higher than the odds in patients with normal CK levels. Similarly, odds of mortality in patients with positive TnT were 4.6 times the odds in patients with negative TnT. The two biochemical markers, CK and TnT, together did not provide any further information about prognosis of the disease. CONCLUSION: Admission CK is a better prognostic marker for a subsequent cardiac event, while TnT is a better predictor of mortality over a mean follow up of nearly 2 years. Together, they do not improve predictability of an adverse cardiac event

Relationship of sociodemographic factors with serum levels of vitamin D in a healthy population of Pakistan

High prevalence of vitamin D deficiency has been reported from Pakistan. Association of sociodemographic factors with vitamin D status has received little attention in this region. Therefore, we embarked on investigating the relationship of sociodemographic factors with vitamin D levels in a healthy Pakistani population. Venous blood from 226 healthy participants (age range 19-69 years) was collected and analyzed for serum concentrations of 25(OH) vitamin D [25(OH)D] and other related biomarkers. Demographic characteristics of the study participants were collected. Vitamin D deficiency (25(OH)D levels less than 20 ng/ml) was found to be 75% in this cohort. Gender, sunlight exposure and monthly household income emerged as predictors of hypovitaminosis D. Mean serum 25(OH)D levels in the groups with monthly household income less than Pakistani Rupees (PKR) 20,000, between PKR 20,000-50,000 and above PKR 50,000 were found to be 11.0±7.5, 13.9±9.6 and16.9±11.7 ng/ml, respectively. Using logistic regression the odds of having vitamin D deficiency was 3.22 (95% CI, 1.65-6.28) in the group with household income less than PKR 50,000 per month compared to the group with household income more than PKR 50,000 per month when the model was adjusted for gender and exposure to sunlight. There is an association between household income and hypovitaminosis D in a healthy Pakistani population

Low doses of colony-stimulating factors lead to resolution of neutropenia in cancer patients through increased levels of dihydrofolate reductase

Low doses of granulocyte- colony stimulating factor (G-CSF) and granulocyte macrophage- colony stimulating factor (GM-CSF) have been shown to be beneficial in reducing duration of systemic antibiotic therapy and in-patient hospitalization by decreasing the period of neutropenia in cancer patients undergoing chemotherapy. Since the underlying mechanism is unclear, the aim of this study was to investigate whether the administration of G-CSF and GM-CSF in two different doses (low dose and standard dose) would result into resolution of neutropenia with concomitant increase in multiple forms of dihydrofolate reductase (DHFR, a pivotal enzyme in the pathway of de novo DNA synthesis). Thirty seven cancer patients (26 males and 11 females; age 14-73 years) having chemotherapy-induced neutropenia (absolute neutrophil counts \u3c 500/mul) were treated with colony stimulating factor (CSF) in the following manner: 11 received GM-CSF (7 received a dose 250 mug/m2 and 4 received a dose of 100 mug/m(2)); 26 received G-CSF (14 received a dose of 5 mug/kg and 12 received a dose of 2.5 mug/kg). CSFs was given every day till the absolute neutrophil count was more than 1,000/mul. Ten ml blood was collected from each patient and analyzed for total leukocyte count (TLC) and active DHFR and immunoreactive nonfunctional form of DHFR (IRE) in the cytoplasm of blood leukocytes by using methotrexate binding assay and enzyme-linked immunosorbent assay (ELISA). A significant increase (p \u3c 0.05) in concentrations of both active DHFR and IRE following stimulation with low as well as standard doses of CSFs was observed along with increase in the TLC. There was no significant difference in number of days to resolution of neutropenia at these two doses, indicating that even low doses of CSFs are clinically effective. Along with an increase in TLC, the levels of DHFR increased even at low doses of CSF suggesting that this might be one of the mechanisms for CSF-induced proliferation of leukocytes in neutropenic cancer patients

Polymorphisms in MTHFR, MS and CBS genes and premature acute myocardial infarction in a Pakistani population

High prevalence of premature coronary heart disease in Pakistanis compared to other populations points towards the genetic predisposition of this population to develop this disease. Since no investigations have been carried out in Pakistan to study the relationship of polymorphisms in genes involved in homocysteine cycle, the objective of the present study was to find out if there is any association of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C; methionine synthase (MS) A2756G; cystathionine-beta-synthase (CBS) 844ins68, G919A polymorphisms with premature acute myocardial infarction (AMI) in a population of Pakistani patients with this disease. In a cross-sectional study, DNA samples of 143 AMI patients (age \u3c 45 years) and 153 healthy controls were genotyped for the above mentioned polymorphisms using PCR-RFLP methods. Plasma/serum samples of both patients and healthy controls were screened for homocysteine, folate and vitamin B12. One way ANOVA and chi-squared test were used for analysis of data. Mean plasma homocysteine levels in premature AMI patients and healthy controls were found to be 23±17.2 and 23±13.4 mumol/l, respectively which are higher than the upper normal limit of this biomarker (15mumol/l). MTHFR 677 CT genotype in healthy controls and MTHFR 677 TT genotype in AMI patients were found to have significantly increased levels of plasma homocysteine (p value \u3c 0.05), while all other polymorphisms did not show any significant difference in mean levels of homocysteine between AMI patients and healthy controls. Moreover, no association was observed between MTHFR C677T, A1298C; MS A2756C; CBS844ins68 polymorphisms and premature AMI in this population. This indicates that common polymorphisms in MTHFR, MS and CBS genes have no role in premature AMI in Pakistani population

Short Communication: Lack of association between MTHFR gene polymorphisms and response to methotrexate treatment in Pakistani patients with rheumatoid arthritis

Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to be associated with response to methotrexate (MTX) in certain populations of patients with rheumatoid arthritis (RA). This study aims at investigating any relationship of two single nucleotide polymorphisms (SNPs) in MTHFR gene, C677T and A1298C with response to therapy with MTX in Pakistani RA patients. Allelic frequencies of the two polymorphisms (C677T and A1298C) were determined in 67 RA patients (9 males and 58 females; mean age 42.87 ± 13.5 years) who had previously participated in a prospective clinical trial. Fifty-one patients had received MTX and were followed up for response up to 6 months. Genotyping of the two MTHFR polymorphisms was carried out using PCR-RFLP, while fasting concentration of plasma homocysteine was determined using a kit method. Twenty-eight patients were found to be good responders , while twenty-three were poor responders . MTHFR 1298C and MTHFR 677T alleles\u27 frequencies in good responders were not different from frequencies in poor responders (0.574 vs. 0.521; p=0.6 and 0.197 vs. 0.196; p=0.75, respectively). Plasma homocysteine levels in female RA patients were significantly higher compared to general population in Karachi (13.1 ± 6.7 mol/l vs. 11.4 ± 5.3 mol/l; p \u3c 0.001). MTHFR C677T and A1298C polymorphisms are not associated with response to MTX in a population of Pakistani RA patients

Lack of association of statin use with vitamin D levels in a hospital based population of type 2 diabetes mellitus patients

Objective: To investigate the relationship of statins (drug given to reduce serum levels of LDL-cholesterol) on vitamin D levels of Pakistani type 2 diabetes mellitus (DM) patients in a hospital in Karachi.Methods: In a cross-sectional survey, 312 consecutive patients with type 2 DM (219 males and 93 females, age 22-70 years) were recruited with informed consent. A questionnaire was administered to find out whether they were statin users or non-users. Serum was analyzed for concentrations of 25(OH) vitamin D [25(OH)D] and other related biomarkers such as serum cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, phosphate and calcium using kit methods. Multiple Linear Regression was used to evaluate association of statin use with serum levels of vitamin D while adjusting for related covariates including duration of statin use, duration of type 2 DM and smoking.Results: Mean concentrations of serum cholesterol, and LDL-cholesterol were lower among statin users compared to statin non-users (P \u3c 0.01), while HDL-cholesterol levels were higher (P\u3c0.01). No relationship was observed between statin use and serum levels of vitamin D (P=0.768), when adjusted for age, gender, BMI, duration of type 2 DM, smoking, serum cholesterol and LDL-cholesterol. The adjusted regression coefficient (β) and standard error [SE(β)] for statin use duration were 0.012 (0.042), when serum levels of vitamin D was taken as an outcome.Conclusion: Lack of association was found between statin use and vitamin D levels in a hospital-based population of Pakistani patients with type 2 DM