Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Vitamin D deficiency.

Phytoremediation of heavy metals—Concepts and applications

Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide. Discovered 30 years ago, it is produced as a consequence of alternative RNA processing of the calcitonin gene. CGRP has two major forms (α and β). It belongs to a group of peptides that all act on an unusual receptor family. These receptors consist of calcitonin receptor-like receptor (CLR) linked to an essential receptor activity modifying protein (RAMP) that is necessary for full functionality. CGRP is a highly potent vasodilator and, partly as a consequence, possesses protective mechanisms that are important for physiological and pathological conditions involving the cardiovascular system and wound healing. CGRP is primarily released from sensory nerves and thus is implicated in pain pathways. The proven ability of CGRP antagonists to alleviate migraine has been of most interest in terms of drug development, and knowledge to date concerning this potential therapeutic area is discussed. Other areas covered, where there is less information known on CGRP, include arthritis, skin conditions, diabetes, and obesity. It is concluded that CGRP is an important peptide in mammalian biology, but it is too early at present to know if new medicines for disease treatment will emerge from our knowledge concerning this molecule.

Calcitonin Gene-Related Peptide: Physiology and Pathophysiology

Phytoremediation of heavy metals assisted by plant growth promoting (PGP) bacteria: A review

Background 
Hyperhomocysteinemia (>15 µmol/L) is highly prevalent in South Asian populations including Pakistan. In order to investigate the genetic determinants of this condition, we studied 6 polymorphisms in genes of 3 enzymes - methylenetetrahydrofolate reductase (MTHFR; C677T; A1298C), methionine synthase (MS; A2756G), cystathionine-β-synthase (CBS; T833C/844ins68, G919A) involved in homocysteine metabolism and investigated their interactions with nutritional and environmental factors in a Pakistani population.


Methodology/Principal Findings 
In a cross-sectional survey, 872 healthy adults (355 males and 517 females; age 18–60 years) were recruited from a low-income urban population in Karachi. Fasting venous blood was obtained and assessed for plasma/serum homocysteine; folate, vitamin B12, pyridoxal phosphate and blood lead. DNA was isolated and genotyping was performed by PCR-RFLP (restriction-fragment-length- polymorphism) based assays. The average changes in homocysteine levels for MTHFR 677CT and TT genotypes were positive [β(SE β), 2.01(0.63) and 16.19(1.8) µmol/L, respectively]. Contrary to MTHFR C677T polymorphism, the average changes in plasma homocysteine levels for MS 2756AG and GG variants were negative [β(SE β), −0.56(0.58) and −0.83(0.99) µmol/L, respectively]. The average change occurring for CBS 844ins68 heterozygous genotype (ancestral/insertion) was −1.88(0.81) µmol/L. The combined effect of MTHFR C677T, MS A2756G and CBS 844ins68 genotypes for plasma homocysteine levels was additive (p value <0.001). Odds of having hyperhomocysteinemia with MTHFR 677TT genotype was 10-fold compared to MTHFR 677CC genotype [OR (95%CI); 10.17(3.6–28.67)]. Protective effect towards hyperhomocysteinemia was observed with heterozygous (ancestral/insertion) genotype of CBS 844ins68 compared to homozygous ancestral type [OR (95% CI); 0.58 (0.34–0.99)]. Individuals with MTHFR 677CT or TT genotypes were at a greater risk of hyperhomocysteinemia in folate and vitamin B12 deficiencies and high blood lead (p value <0.05) level.


Conclusions 
Gene polymorphism (especially MTHFR C677T transition), folate and vitamin B12 deficiencies, male gender and high blood lead level appear to be contributing towards the development of hyperhomocysteinemia in a Pakistani population.

/pdf/polymorphisms-in-mthfr-ms-and-cbs-genes-and-homocysteine-1l5oigou9c.pdf

Polymorphisms in MTHFR, MS and CBS genes and homocysteine levels in a Pakistani population.

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.

/pdf/trans-fatty-acids-a-risk-factor-for-cardiovascular-disease-1y7s03i6aq.pdf

Trans fatty acids - A risk factor for cardiovascular disease.

Summary Background and aim Pakistani people belong to an ethnic group which has the highest rate of coronary artery disease (CAD). We investigated the possible correlation between deficiency of vitamins B6, B12 or folic acid and hyperhomocysteinemia in Pakistani patients with acute myocardial infarction (AMI). A case-control study was carried out involving 224 AMI patients (age 30–70 years; 55 females and 169 males) and 126 normal healthy subjects (age 31–70 years; 35 females and 91 males). Methods and results Fasting venous blood was obtained from cases and controls. Serum was analyzed for folic acid and B12 using radioassays. Plasma was analyzed for pyridoxal phosphate (PLP; coenzymic form of B6) using a radioenzymatic assay and for total homocysteine using a fluorescence polarization immunoassay. Mean serum B12 concentration in AMI patients was found to be significantly lower than the mean for controls (241±185 pg/ml vs 608±341 pg/ml; p Conclusions Substantial nutritional deficiencies of these three vitamins along with mild hyperhomocysteinemia, perhaps through an interplay with the classical cardiovascular risk factors (highly prevalent in this population), could be further aggravating the risk of CAD in the Pakistani population.

Role of vitamins B6, B12 and folic acid on hyperhomocysteinemia in a Pakistani population of patients with acute myocardial infarction.

Lead (Pb) pollution is a serious problem in the developing countries, especially in South Asia. No levels of blood Pb can be considered safe for human health. While hypertensive effects of Pb have been well studies, there are only a few studies on the relationship of Pb exposure to the development of cardiovascular disease (CVD) in the Asian developing countries. The underlying mechanism is still unclear; however, oxidative stress and hyperhomocysteinemia appear to be most plausible hypotheses for the development of atherosclerosis leading to CVD. Enforcement of regulations for control of Pb pollution, increased public awareness about the harmful effects of Pb, cessation of smoking, frequent use of fruit juices and avoidance from iron and folate deficiencies would be required to protect masses from the deleterious effects of Pb.

Lead pollution - a risk factor for cardiovascular disease in Asian developing countries.

Little attention has been given to the association of dietary patterns with plasma homocysteine. Our objective in this study was to identify major dietary patterns and investigate their association with plasma homocysteine. In a cross-sectional survey, 872 healthy adults (355 males, 517 females; aged 18-60 y) were enrolled from an urban population in Karachi. Dietary intake was assessed by a FFQ. We used factor analysis to define major dietary patterns. Fasting concentrations of plasma or serum homocysteine, folate, pyridoxal-phosphate (PLP; coenzyme form of vitamin B-6), and vitamin B-12 were measured. Three major dietary patterns were identified and labeled as "prudent diet," "high animal-protein diet," and "high plant-protein diet." We observed a protective effect of the prudent dietary pattern for the highest quartile of intake compared with the lowest quartile of hyperhomocysteinemia when the model was adjusted for age, gender, household income, BMI, tobacco chewing, and smoking [OR = 0.52 (95% CI = 0.30-0.90); P = 0.01]. The high plant-protein diet pattern was inversely related to hyperhomocysteinemia, with a higher intake being protective. Compared with the 1st quartile, the adjusted OR was 0.42 (95% CI = 0.25-0.69; P = 0.001) for the 4th quartile. The high animal-protein diet was positively associated with hyperhomocysteinemia, with participants in the highest quartile of intake having the greatest increase in risk [OR = 2.10 (95% CI = 1.22-3.60); P = 0.007]. Plasma homocysteine concentrations appeared to be correlated more with circulating folate (r = -0.25; P < 0.001) than with PLP (r = -0.02; P = 0.663) or vitamin B-12 (r = -0.16; P < 0.001). A diet rich in fruits and uncooked vegetables decreased the risk of hyperhomocysteinemia, whereas diets rich in red meat, chicken, and tea with milk were positively associated with hyperhomocysteinemia.

Mohammad Perwaiz Iqbal

Papers

Polymorphisms in MTHFR, MS and CBS genes and homocysteine levels in a Pakistani population.

Trans fatty acids - A risk factor for cardiovascular disease.

Role of vitamins B6, B12 and folic acid on hyperhomocysteinemia in a Pakistani population of patients with acute myocardial infarction.

Lead pollution - a risk factor for cardiovascular disease in Asian developing countries.

Dietary patterns are associated with hyperhomocysteinemia in an urban Pakistani population