Importance of acetylator phenotype in the identity of Asian populations

The Marma, Tripura, and Chakma are tribal populations of South Asian countries such as Bangladesh. The populations are thought to be immigrants who started moving from their original home in the Far East toward the west and south. We randomly selected 80 Marma, 53 Tripura, and 43 Chakma to determine acetylation capacity and acetylator phenotype. The mean acetylation capacities were 63% in the Marma, 65% in the Tripura, and 70% in the Chakma. The acetylator phenotype was bimodally distributed as fast and slow acetylator. The frequencies of fast acetylator were 83% in the Marma, 89% in the Tripura, and 88% in the Chakma. According to acetylation capacity, the tribes are different from the founder nontribal populations of Bangladesh. They identify themselves as having a separate single population origin. The frequency of fast acetylator predicted served as the acetylator status of the Far East Asian population. The segregation of populations by acetylator phenotype on geographic longitude might be appropriate for geonational identification of Asian populations.     

Association of Body Iron Status with the Risk of Premature Acute Myocardial Infarction in a Pakistani Population

Background

Coronary artery disease is very common in Pakistani population. Some of the studies carried out on Western populations have shown a relationship between body iron status as determined by the ratio of concentrations of serum soluble transferrin receptor (sTfR) to ferritin and the risk of acute myocardial infarction (AMI). In order to investigate whether increased body iron status has any relationship with the risk of premature AMI in Pakistani population, a case-control study was carried out.

Methodology/Principal findings

In this case-control study, 203 consecutive AMI patients [146 males and 57 females; age range 18–45 years] admitted to the National Institute for Cardiovascular Diseases, Karachi, were enrolled with informed consent. In addition, 205 healthy controls whose gender and age (within 3 years) matched the patients, and who had a similar socio-economic background were recruited. Fasting venous blood was obtained and assessed for plasma/serum folate, vitamin B12, homocysteine, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, sTfR and ferritin and blood lead. It was found that serum concentration of ferritin and blood lead levels were significantly higher in AMI patients compared to their age and gender-matched healthy controls (p value <0.05), while the concentrations of vitamin B12 and HDL-cholesterol were significantly lower in AMI patients compared to controls (p value <0.01). The ratio of sTfR to ferritin was significantly lower in AMI patients compared to controls [mean±SD/median (IQR) values 84.7±295/28.9 (38.4) vs 255±836/49.4 (83.8), respectively; p value <0.001]. Compared with the highest quartile of sTfR/ferritin (low body iron status), the OR for the risk of AMI was 3.29(95% CI, 1.54–7.03) for the lowest quartile (quartile 1) when the model was adjusted for vitamin B12 and HDL-cholesterol (p value for trend <0.01).

Conclusions/Significance

This study shows a positive association between total body iron status and risk of premature AMI in a Pakistani population.     

Multi-symptom illnesses, unexplained illness and Gulf War Syndrome

Explanatory models for the increased prevalence of ill health in Gulf veterans compared to those not deployed to the Gulf War 1990-1991 remain elusive. This article addresses whether multi-symptom reporting in Gulf veterans are types of medically unexplained symptoms and whether the alleged Gulf War Syndrome is best understood as a medically unexplained syndrome. A review of the epidemiological studies, overwhelmingly cross-sectional, describing ill health was conducted including those that used factor analysis to search for underlying or latent clinical constructs. The overwhelming evidence was that symptoms in Gulf veterans were either in keeping with currently defined psychiatric disorders such as depression and anxiety or were medically unexplained. The application of factor analysis methods had varied widely with a risk of over interpretation in some studies and limiting the validity of their findings. We concluded that ill health in Gulf veterans and the alleged Gulf War Syndrome is best understood within the medically unexplained symptoms and syndromes constructs. The cause of increased reporting in Gulf veterans are still not clear and requires further inquiry into the interaction between sociological factors and symptomatic distress.     

SIRT4 Regulates Fatty Acid Oxidation and Mitochondrial Gene Expression in Liver and Muscle Cells

SIRT4, a member of the sirtuin family, has been implicated in the regulation of insulin secretion by modulation of glutamate dehydrogenase. However, the role of this enzyme in the regulation of metabolism in other tissues is unknown. In this study we investigated whether depletion of SIRT4 would enhance liver and muscle metabolic functions. To do this SIRT4 was knocked down using an adenoviral shRNA in mouse primary hepatocytes and myotubes. We observed a significant increase in gene expression of mitochondrial and fatty acid metabolism enzymes in hepatocytes with reduced SIRT4 levels. SIRT4 knockdown also increased SIRT1 mRNA and protein levels both in vitro and in vivo. In agreement with the increased fatty acid oxidation (FAO) gene expression, we showed a significant increase in FAO in SIRT4 knockdown primary hepatocytes compared with control, and this effect was dependent on SIRT1. In primary myotubes, knockdown of SIRT4 resulted in increased FAO, cellular respiration, and pAMPK levels. When SIRT4 was knocked down in vivo by tail vein injection of a shRNA adenovirus, we observed a significant increase in hepatic mitochondrial and FAO gene expression consistent with the findings in primary hepatocytes. Taken together these findings demonstrate that SIRT4 inhibition increases fat oxidative capacity in liver and mitochondrial function in muscle, which might provide therapeutic benefits for diseases associated with ectopic lipid storage such as type 2 diabetes.     

Anatomical and physiological characteristics relating to ionic relations in some salt tolerant grasses from the Salt Range,Pakistan

Populations of three salt tolerant forage grasses (Cynodon dactylon, Imperata cylindrica, and Sporobolus arabicus) were collected from the salt-affected soils of the Salt Range and normal non-saline soils of the Faisalabad region to assess their mechanism of adaptation to saline stress by determining ion relations and some specific anatomical modifications. The population of S. arabicus from the Salt Range showed increased growth (root and shoot length, and root and shoot dry weights) under saline conditions. Salt tolerance in this species was related to structural modifications such as increased area of root, stem, leaf blade, and leaf sheath for toxic ion accumulation, increased vesicular hair density in leaves and aerenchyma formation in leaf sheath for ion exclusion. Uptake of toxic ions was high in the Salt Range population of C. dactylon and salt tolerance was related to ion exclusion through specific leaf structural modifications such as vesicular hairs. Salt tolerance in the Salt Range population of I. cylindrica was mainly associated with restricted uptake of toxic Na⁺ and Cl⁻ at root level, and accumulation of toxic ions via increased succulence in leaf blades and leaf sheaths in addition to some excretion of toxic ions through leaf sheath aerenchyma.     

Autophagy dysfunction and regulatory cystatin C in macrophage death of atherosclerosis

Autophagy dysfunction in mouse atherosclerosis models has been associated with increased lipid accumulation, apoptosis and inflammation. Expression of cystatin C (CysC) is decreased in human atheroma, and CysC deficiency enhances atherosclerosis in mice. Here, we first investigated the association of autophagy and CysC expression levels with atheroma plaque severity in human atherosclerotic lesions. We found that autophagy proteins Atg5 and LC3β in advanced human carotid atherosclerotic lesions are decreased, while markers of dysfunctional autophagy p62/SQSTM1 and ubiquitin are increased together with elevated levels of lipid accumulation and apoptosis. The expressions of LC3β and Atg5 were positively associated with CysC expression. Second, we investigated whether CysC expression is involved in autophagy in atherosclerotic apoE‐deficient mice, demonstrating that CysC deficiency (CysC^?/?) in these mice results in reduction of Atg5 and LC3β levels and induction of apoptosis. Third, macrophages isolated from CysC^?/? mice displayed increased levels of p62/SQSTM1 and higher sensitivity to 7‐oxysterol‐mediated lysosomal membrane destabilization and apoptosis. Finally, CysC treatment minimized oxysterol‐mediated cellular lipid accumulation. We conclude that autophagy dysfunction is a characteristic of advanced human atherosclerotic lesions and is associated with reduced levels of CysC. The deficiency of CysC causes autophagy dysfunction and apoptosis in macrophages and apoE‐deficient mice. The results indicate that CysC plays an important regulatory role in combating cell death via the autophagic pathway in atherosclerosis.     

Morpho-anatomical and physiological attributes for salt tolerance in sewan grass (Lasiurus scindicus Henr.) from Cholistan Desert,Pakistan

Three differently adapted populations of sewan grass (Lasiurus scindicus Henr.) were evaluated for structural and functional adaptations to high salinity. The habitats were Derawar Fort (DF, least saline, ECe 15.21), Bailahwala Dahar (BD, moderately saline, ECe 27.56 dS m^?1) and Ladam Sir (LS, highly saline, ECe 39.18 dS m^?1) from within the Cholistan Desert. The adaptive components of salt tolerance in sewan grass were assessed by determining various morpho–anatomical and physiological attributes. The degree of salt tolerance of all three ecotypes of L. scindicus from the saline habitats was compared in a controlled hydroponic system to evaluate the adaptive components that are expected to be genetically fixed during a long evolutionary process. Salinity tolerance in the most tolerant LS population relied on increased root length and total leaf area, restricted uptake of toxic Cl^?, increased uptake of Ca²⁺, high excretion of Na⁺, accumulation of organic osmolytes, high water use efficiency, increased root, thicker leaf and cortical region, intensive sclerification, large metaxylem vessels, and dense pubescence on abaxial leaf surface. The BD population (from moderately saline soil) relied on high Ca²⁺ uptake, Na⁺ excretion, epidermal thickness, large cortical cells, thick endodermis and large vascular tissue. The DF population (from less saline soil) showed a significant decrease in all morphological characteristics; however, it accumulated organic osmolytes for its survival under high salinities. Structural modifications in all three populations were crucial for checking undue water loss under physiological stress that is caused by high amounts of soluble salts in the soil.     

Depressed placental prostaglandin E1 metabolism in toxemia of pregnancy

³H-Prostaglandin E₁ metabolism has been assessed in 15,000 × g supernatant preparations from human placentas of normal and toxemic pregnancies. The ability of the toxemic tissue to metabolize ³H-PGE₁ is depressed in direct relationship to the severity of the disease. This impaired metabolism of prostaglandin E₁ appears to be a biochemical characteristic of the toxemia of pregnancy.