Why Leadership Skills are Essential for the Future of Laboratory Medicine?

A Study on Insulin Levels and the Expression of Glut 4  in Streptozotocin (STZ) Induced Diabetic Rats Treated with Mustard Oil Diet Abstract The study was undertaken to evaluate the therapeutic effect of mustard oil incorporated diet in streptozotocin (STZ)-induced type 1 diabetic rats. Dietary composition has shown to play a significant role in improving insulin sensitivity. Various authors have reported the hypoglycemic effect of mustard oil in experimentally induced diabetic rats. In the present study, reverse transcriptase polymerase chain reaction (RT-PCR) was done to analyze the Glut 4 expression in STZ induced diabetic rats as it is a key player in glucose homeostasis. The effect of mustard oil on serum biochemical parameter and insulin levels was also studied. Twenty-four male Wistar rats were randomly divided into three different groups with each containing eight animals. The first, second and third groups were control, diabetic control and treatment group with mustard oil respectively. All the rats in respective groups were fed for 60 days with iso-caloric mash diet containing 8% lipid. Diabetes was induced by intra-peritoneal administration of STZ (40 mg/kg body weight). A highly significant reduction in blood glucose level, with an increase in insulin activity was observed in mustard oil-treated diabetic rats when compared to control group indicating anti-hyperglycemic activity of mustard oil. Mustard oil-treated diabetic rats showed increased expression of  Glut 4 in muscle tissue when compared to diabetic control. A significant reduction in the levels of triacylglycerols, total cholesterol, VLDL and LDL and raised plasma HDL were noticed in mustard oil-treated diabetic rats when compared to diabetic control rats. Histopathological studies revealed a mild regeneration of β cells of pancreas in mustard oil-treated diabetic rats. The results from our investigation suggest that mustard oil elicits hypoglycemic effect by increased insulin activity and up-regulation of  Glut 4 gene expression in muscle tissue of STZ-induced diabetic rats.

Expression of FOXP3 and GATA3 Transcription Factors Among Bronchial Asthmatics in Northern Population Abstract Asthma is a common chronic airways inflammatory disorder in which the expression of genes for the transcription factors FoxP3 and GATA3 plays crucial roles in activation of specific T cells population and pathogenesis of asthma. Recent data have shown that Hb, Eosinophils, total leucocytes count (TLC), absolute eosinophil count (AEC), and IgE, may be involved in adversely influencing the status of several chronic diseases including asthma. In this communication, we have carried out a case control study in order to evaluate the expression of FoxP3, GATA-3 genes in 80 bronchial asthmatic patients using real time polymerase chain reaction technique, and also to analyse and compare the values of Hb, TLC, AEC, and IgE in asthmatics with 80 control subjects. The numbers of eosinophils and total leucocytes and the level of serum IgE were higher in asthmatics compared to healthy subjects. The relative expressions of FoxP3 and GATA-3 genes in control versus asthmatics were 12.42 ± 1.413 versus 5.79 ± 0.260 (P value = < 0.0001) and 4.731 ± 0.350 versus 8.415 ± 0.359 (P value = 0.0043), respectively. The asthmatics displayed comparatively decreased level of FoxP3 expression and higher level of GATA-3 expression. There was a positive and significant correlation between the level of IgE and expression of GATA-3 in asthmatics. Relatively lower level of FoxP3 mRNA expression in bronchial asthmatics may be linked with the sustained inflammatory process and decreased immune tolerance by asthmatics. A positive correlation of GATA-3 expression with the increase in IgE level shows it to be a characteristic of asthma. However, extensive work is required to delineate the targets involved in the pathogenesis of asthma for adequate therapeutic interventions.

Synergetic Interaction of HLA-DRB1*07 Allele and TNF-Alpha − 863 C/A Single Nucleotide Polymorphism in the Susceptibility to Systemic Lupus Erythematosus Abstract Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease which is characterized by dysregulation of various cytokines propagating the inflammatory processes that is responsible for tissue damage. Tumor necrosis factor alpha (TNF-α) is one of the most important immunoregulatory cytokines that has been implicated in the different autoimmune diseases including SLE. Two hundred and two patients with SLE and 318 controls were included in the study. The TNF-α gene promoter region (from − 250 to − 1000 base pairs) was analyzed by direct Sanger’s DNA sequencing method to find promoter variants associated with South Indian SLE patients. We have analyzed six TNF-α genetic polymorphisms including, − 863C/A (rs1800630), − 857C/T (rs1799724), − 806C/T (rs4248158), − 646G/A (rs4248160), − 572A/C (rs4248161) and − 308G/A (rs1800629) in both SLE patients and controls. We did not find association of TNF-α gene promoter SNPs with SLE patients. However, the − 863A (rs1800630) allele showed association with lupus nephritis phenotype in patients with SLE (OR: 1.62, 95%CI 1.04–2.53, P = 0.034). We found serum TNF-α level was significantly elevated in SLE cases as compared to control and found no association with any of the polymorphisms. The haplotype analysis revealed a significant protective association between the wild TNF-α alleles at positions − 863C, − 857C, − 806C, − 646G, − 572A and − 308G (CCCGAG) haplotype with lupus nephritis phenotype (OR 0.53, 95% CI 0.35–0.82, P = 0.004). Additionally, the TNF-α − 863 C/A (rs1800630) polymorphism and HLA-DRB1*07 haplotype showed significant differences between SLE patients and controls (OR 4.79, 95% CI 1.73–13.29, P = 0.0009). In conclusion, TNF-α − 863A allele (rs1800630) polymorphism is associated with increased risk of nephritis in South Indian SLE patients. We also found an interaction between HLA-DRB1*07 allele with TNF-α − 863 C/A promoter polymorphism giving supportive evidence for the tight linkage disequilibrium between TNF-α promoter SNPs and MHC class II DRB1 alleles.

Association of Pseudohypoparathyroidism and Autoimmune Polyglandular Syndrome: Causal or Coincidental? Abstract Pseudohypoparathyroidism (PHP) is a state of parathyroid hormone resistance and is characterised by low serum calcium, and elevated serum phosphate and parathyroid hormone level. Association of PHP with autoimmune disorders is rare and seldom reported in the literature. Here we describe a case of PHP who subsequently developed multiple autoimmune disorders (type 3 polyglandular autoimmune syndrome), which has not been reported so far.

New Horizons in Correction of Mutated ATP7B in Wilson Disease Using Pharmacological Agents: Precise Medicine

A Revisit to a Qualitative Method for the Detection of Organophosphorus Pesticides

CCR5, MCP-1 and VDR Gene Polymorphisms Are Associated with the Susceptibility to HBV Infection Abstract Genetic variants of chemokine and regulatory cytokines play functional roles in chronic HBV infection. The objective of the study, was to evaluate the association between the CCR5D32, CCR5-2459A/G, MCP-1-2518A/G, VDR-APa1A/C, VDR-Taq1T/C SNPs and HBV susceptibility, in samples of Iranian populations. The CCR5D32, CCR5-2459A/G, MCP1-2518A/G, VDR-APa1A/C, VDR-Taq1T/C polymorphisms were analyzed by polymerase chain reaction and PCR-RFLP using 100 chronic HBV infected (HBV) patients, 40 spontaneously recovered HBV (SR) subjects and 100 healthy controls (C). Also, serum levels of protein were monitored. The study showed that the existence of CCR5-2459A, MCP1-2518G and VDR-CC alleles significantly increased risk of chronic HBV infection. In addition, WtAGCC haplotype had a higher frequency in HBV patients than C and SR groups and might relate to the natural history of the infection. Statistical analysis indicated positive correlations between CCR5-2459A/G, MCP1-2518A/G, VDR-APa1A/C, VDR-Taq1T/C genotypes and serum levels of the CCR5, MCP-1 and VDR in HBV patients. According to the statistical analysis, significant associations with susceptibility to chronic HBV infection was observed with CCR5-2459A/G, MCP1-2518A/G, VDR-APa1A/C, VDR-Taq1T/C polymorphisms. In addition, no association of the CCR5D32 SNP with the disease was found.

Comparison of Serum Thyroglobulin Levels in Differentiated Thyroid Cancer Patients Using In-House Developed Radioimmunoassay and Immunoradiometric Procedures Abstract Thyroglobulin (Tg) is a proven tumor marker in the follow-up and post-operative management of patients with differentiated thyroid cancer (DTC). All assays for serum thyroglobulin (s-Tg) are based on immunoassays, however, the assay technique has a bearing on the variations seen in the estimations. We studied this using four in-house developed radioimmunoassays (RIA) and immunoradiometric assays (IRMA). Limit of detection, working range, recovery, dilution test, precision profiles and method comparison were evaluated. All four methods were used for the estimation of s-Tg in DTC patients and also compared for their performance using commercially available Tg IRMA kits from DiaSorin and Izotop. The s-Tg values measured by six different immunoassays showed very significant inter-method correlation (0.84–0.99, p < 0.001). However, among the in-house developed assays; the coated tube IRMA showed a better sensitivity and precision at the lower concentration range and hence, is preferable for the routine measurement of s-Tg in patients negative for Tg autoantibodies (TgAb). Although the second generation IRMAs offer practical benefits of having higher sensitivity, shorter turn-around time and convenience of automation, they, unfortunately, also have higher tendency for interference from both TgAb and heterophilic antibodies, if present in the sample. On the contrary, RIA is less prone to such interference and, hence, can be used in patients with TgAb. In order to effectively use this test, it is important that nuclear medicine physicians and endocrinologists understand these intrinsic technical limitations encountered during s-Tg measurement.

Genotyping and Frequency of PCSK9 Variations Among Hypercholesterolemic and Diabetic Subjects Abstract Non-synonymous single-nucleotide polymorphism (SNPs) in the gene for proprotein convertase subtilisin/kexin type 9 (PCSK9) can influence cholesterol and glucose metabolism, leading to increased risk of cardiovascular disease and diabetes. To determine the frequency of four common PCSK9 SNPs, L10Ins, A56V, I474V, and E670G, in a population sample (n = 98) of the Hail region of Kingdom of Saudi Arabia. Blood was collected from participants; serum cholesterol, blood glucose and glycated hemoglobin were determined; genomic DNA was extracted and PCR amplicons from SNP-containing PCSK9 exons were subjected to Sanger sequencing. Out of 98 participants. 10 (10.20%) carried none of the SNPs, 2 (2.04%) the L10ins/A56V linked SNPs, 35 (35.71%) the I474V SNP, 22 (22.45%) both the I474V and E670G SNPs, and 29 (29.59%) the E670G SNP. Of the 30 eucholesterolemic diabetics patients, 11 (36.66%) carried the I474V SNP, 10 (33.33%) the E679G SNP and 6 (20%) the I474V/E679G. SNPs. Of 63 diabetic patients, 26 (41.26%) carry I474V SNP and 22 (34.92%) carry E670G SNP. Our data demonstrated that the I474V and E670G PCSK9 variants are very frequent in the Hail region of Saudi Arabia and are found at even higher frequency among diabetics. Further investigations are needed to determine whether these variations or another variant segregating with them can explain its apparent association with diabetes in this population.