Quantitative analysis of some important metals and metalloids in tobacco products by inductively coupled plasma-mass spectrometry (ICP-MS)

BACKGROUND: Large scale usage of tobacco causes a lot of health troubles in human. Various formulations of tobacco are extensively used by the people particularly in developing world. Besides several toxic tobacco constituents some metals and metalloids are also believed to pose health risks. This paper describes inductively coupled plasma-mass spectrometric (ICP-MS) quantification of some important metals and metalloids in various brands of smoked, sniffed, dipped and chewed tobacco products. RESULTS: A microwave-assisted digestion method was used for sample preparation. The method was validated by analyzing a certified reference material. Percentage relative standard deviation (% R.S.D.) between recovered and certified values was < 5.8. Linearity value for calibration curve of each metal was 1 > r > 0.999. Improved limits of detection (LODs) were in range of ng/L for all elements. Fe, Al and Mn were found to be in the highest concentration in all types of tobacco products, while Zn, Cu, Ni and Cr were below the average concentration of 40 μg/g, and Pb, Co, As, Se and Cd were below 5 μg/g. All elements, apart from Pb, were high in concentration in dipping tobacco in comparison to other tobacco products. Generally, the order of all elemental concentration can be expressed in different tobacco products as chewing < smoked < sniffing < dipping. However, smoked and sniffing will interchange their position in the case of Mn, Cu, Se and Cd. Multivariate statistical analyses were also performed to evaluate the correlation and variations among tobacco products. CONCLUSIONS: The present study highlights the quantification of some important metals and metalloids in a wide spectrum of tobacco formulations. The outcome of this study would be beneficial for health authorities and individuals

Ionomic profiling of pericardial fluid in ischemic heart disease

Metals are essential cofactors that play a crucial role in heart function at the cell and tissue level. Information regarding the role of metals in the pericardial fluid and its ionome in ischemic heart disease (IHD) is limited. We aimed to determine the association of elements in pericardial fluid and serum samples of IHD patients and their correlation with systolic and diastolic function. IHD patients have been studied with systolic and diastolic dysfunction categorized on the basis of echocardiographic parameters. We measured concentrations of sixteen elements in the pericardial fluid and serum of 46 patients obtained during open heart surgery with IHD by ICP-MS. The levels of chromium and nickel in pericardial fluid were significantly higher as compared with serum samples of IHD patients (p \u3c 0.05). The chromium, nickel and manganese levels in pericardial fluid were lower in patients with ejection fraction (EF) \u3c 45% as compared to EF \u3e 45% (p \u3c 0.05). There was no significant difference in pericardial concentrations of elements in diastolic dysfunction grade 0–1 with 2 in IHD patients. We also found that decreased concentration of these elements in pericardial fluid is associated with decreased systolic function. These results suggest that pericardial fluid concentrations of these metals may reflect the extent of ischemic heart disease. These findings are hypothesis generating with regards to a role in the pathogenesis of the disorder

Understanding of metals dysregulation in patients with systolic and diastolic dysfunction in ischemic heart disease

Ischemic heart disease (IHD) is the leading cause of death and chronic disability in the world. IHD affects both the systolic and diastolic function of the heart which progressively leads to heart failure; a structural and functional impairment of filling or ejection of blood from the heart. In this study, the progression of systolic and diastolic dysfunction characterized according to their echocardiographic parameters including left ventricular ejection fraction (EF), grades of diastolic dysfunction and ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e\u27), were correlated with differential regulation of various metals in patients sera samples (n = 62) using inductive coupled plasma-mass spectrometry (ICP-MS). Chromium, nickel and selenium were found significant (p \u3c 0.05) in patients having EF \u3c 45% compared with EF \u3e 45%. In patients with systolic dysfunction (EF \u3c 45%), the level of selenium was decreased while the level of chromium and nickel was increased compared to patients with EF \u3e 45%. Selenium level was also decreased significantly (p \u3c 0.05) in grade 1A and 2 patients that are considered as higher grades of diastole dysfunction in comparison to grade 0-1. Overall, selenium deficiency was identified in both systolic and diastolic dysfunctions of IHD patients corresponding to the progression of disease that could be related to many metabolic and translational pathways specifically which involve selenoproteins

Polymeric hydrophilic interaction liquid chromatography coupled with Orbitrap mass spectrometry and chemometric analysis for untargeted metabolite profiling of natural rice variants

GC-MS based metabolomics of genetically modified rice varieties are widely reported but involves tedious derivatization processes. Broad-scale LC-MS-based metabolomics are lacking or limited to targeted analyses. In this study, metabolite diversity in natural rice variants including basmati and non-basmati rice varieties was investigated using polymeric hydrophilic interaction chromatography coupled to an Orbitrap mass analyzer. Identification was performed using exact mass and standard retention times. A total of 329 metabolites were selected using IDEOM (Identification of metabolites) software. Statistical tests were used to filter out top 50 rice varieties discriminating metabolites. Several up- or down-regulated metabolites were observed in rice varieties and can be used as biomarker compounds to differentiate between rice varieties. The developed method and generated data can be used for the comparison of genetically modified rice varieties with natural ones, an important requirement for the implementation of comparator-based GMO risk assessment procedures demanded by national and international regulations

BOR-Syndrome-Associated Eya1 Mutations Lead to Enhanced Proteasomal Degradation of Eya1 Protein

Mutations in the human EYA1 gene have been associated with several human diseases including branchio-oto (BO) and branchio-oto-renal (BOR) syndrome, as well as congenital cataracts and ocular anterior segment anomalies. BOR patients suffer from severe malformations of the ears, branchial arches and kidneys. The phenotype of Eya1-heterozygous mice resembles the symptoms of human patients suffering from BOR syndrome. The Eya1 gene encodes a multifunctional protein that acts as a protein tyrosine phosphatase and a transcriptional coactivator. It has been shown that Eya1 interacts with Six transcription factors, which are also required for nuclear translocation of the Eya1 protein. We investigated the effects of seven disease-causing Eya1 missense mutations on Eya1 protein function, in particular cellular localization, ability to interact with Six proteins, and protein stability. We show here that the BOR-associated Eya1 missense mutations S454P, L472R, and L550P lead to enhanced proteasomal degradation of the Eya1 protein in mammalian cells. Moreover, Six proteins lead to a significant stabilization of Eya1, which is caused by Six-mediated protection from proteasomal degradation. In case of the mutant L550P, loss of interaction with Six proteins leads to rapid protein degradation. Our observations suggest that protein destabilization constitutes a novel disease causing mechanism for Eya1

Metabolomics Study of Serum Samples of &beta;-YAC Transgenic Mice Treated with Tenofovir Disoproxil Fumarate

&beta;-thalassemia is one of the most common monogenic disorders and a life-threatening health issue in children. A cost-effective and safe therapeutic approach to treat this disease is to reactivate the &gamma;-globin gene for fetal hemoglobin (HbF) production that has been silenced during infancy. Hydroxyurea (HU) is the only FDA approved HbF inducer. However, its cytotoxicity and inability to respond significantly in all patients pose a need for an HbF inducer with better efficacy. The study describes the serum metabolic alteration in &beta;-YAC transgenic mice treated with Tenofovir disoproxil fumarate (TDF) (n = 5), a newly identified HbF inducer, and compared to the mice groups treated with HU (n = 5) and untreated control (n = 5) using gas chromatography-mass spectrometry. Various univariate and multivariate statistical analyses were performed to identify discriminant metabolites that altered the biological pathways encompassing galactose metabolism, lactose degradation, and inositol. Furthermore, the decreased concentrations of L-fucose and geraniol in TDF-treated mice help in recovering towards normal, decreasing oxidative stress even much better than the HU-treated mice. The proposed study suggested that TDF can reduce the deficiency of blood required for &beta;-thalassemia and can be used for the preclinical study at phase I/II for fetal hemoglobin production