Circulating Biomarkers and their Possible Role in Pathogenesis of Chronic Hepatitis B and C Viral Infections

The present study evaluated the plausible role of circulating biomarkers in immune pathogenesis of chronic hepatitis considered a priority in clinical hepatology. Total viral load of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) patients was quantified and correlation studies were performed with circulating levels of Th1/Th2 cytokines; C reactive protein and circulating nucleosomes; glutathione reductase (GR) and superoxide dismutase. To our knowledge, the study is first among its kind that validates strong positive correlation of viral load with IL-4, IL-6, GR in HBV and IL-6, IL-10, GR in HCV infections. Although, multi-centric studies including large cohorts are required for translating our findings to clinical practice, however, role of these biomarkers with potential diagnostic or prognostic significance might be helpful in clinical assessment of high-risk individuals, thereby, designing interventional strategies, towards development of personalized medicare. The results of our study also offer valuable insights of immune signaling mediators engaged in development of hepatocellular carcinoma.     

Adiponectin Gene Polymorphism and its Association with Type 2 Diabetes Mellitus

Mutations in different regions of adiponectin gene have been reported to be associated with obesity, atherosclerosis and type 2 diabetes mellitus. The present study was aimed to investigate the association among SNP 45 T > G of adiponectin gene and type 2 diabetes in South Indian population. 75 clinically diagnosed case of type 2 diabetes were studied and compared with 75 apparently healthy controls. The genotype frequency of SNP45 T > G in exon 2 of adiponectin gene was determined by PCR based restriction enzyme analysis using the restriction enzyme SmaI. (recognition site: CCC↓GGG). Three kind of genotypes: wild type TT (470 bp), heterozygous type TG (470 bp, 336 bp, 134 bp) and homozygote mutant type GG (336 bp, 134 bp) were studied. A positive association has been found between SNP45 T > G and type 2 diabetes in the study population (P = 0.010, OR = 3.797, 95% CI = 1.312–10.983). Therefore, SNP45T > G in adiponectin gene may be one of the risk factors for type 2 diabetes.     

Mechanism of Antidiabetic Action of Compound GII Purified from Fenugreek (<Emphasis Type="Italic">Trigonella foenum graecum</Emphasis>) Seeds

To study the mechanism of action of water soluble compound GII purified from fenugreek (Trigonella foenum graecum) seeds which was shown earlier to have antidiabetic effect in the subdiabetic, moderately and severely diabetic rabbits. In rabbits (1–1.5 kg bw) diabetes was induced by intravenous injection of 80 mg/kg bw of alloxan. They were fed with GII at a dose of 50 mg/kg bw daily once in the morning for 15 days in the subdiabetic and moderately diabetic and 30 days in the severely diabetic rabbits. Serum total cholesterol (TC), triglycerides (TG), LDL + VLDL cholesterol [(LDL + VLDL)C], HDL cholesterol [(HDL)C], total tissue lipids, glycogen and enzymes of carbohydrate metabolism (glycolysis, gluconeogenesis, polyol pathway) hexokinase, glucokinase, pyruvate kinase, malic enzyme, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, aldose reductase and sorbitol dehydrogenase and antioxidant enzymes glutathione peroxidase, glutathione reductase and superoxide dismutase were estimated. Liver and kidney function parameters were also estimated. Treatment with GII for 15 days in the subdiabetic and moderately diabetic rabbits and for 30 days in the severely diabetic rabbits (i) decreased the elevated lipids TC, TG, (LDL + VLDL)C and increased the decreased (HDL)C, (ii) decreased the elevated liver and heart total lipids, TC and TG, (iii) increased the decreased liver and muscle glycogen, (iv) increased the decreased hexokinase, glucokinase, pyruvate kinase, malic enzyme, glucose-6-phosphate dehydrogenase, superoxide dismutase, glutathione peroxidase, (v) decreased the increased glucose-6-phosphatase, sorbitol dehydrogenase, aldose reductase. Results thus show that treatment with GII compound purified from fenugreek seeds for 15 days in the subdiabetic and moderately diabetic and 30 days in the severely diabetic rabbits corrects the altered serum lipids, tissue lipids, glycogen, enzymes of glycolysis, gluconeogenesis, glycogen metabolism, polyol pathway and antioxidant enzymes. Histopathological abnormalities (fatty infiltration and other cellular changes) seen in the pancreas, liver, heart and kidneys were repaired after treatment with GII. In fact partially damaged pancreas was repaired. Liver and kidney function test results were normal in the GII treated animals indicating that GII treatment is safe and free from any side effects.     

Diagnosis of Major Organic Acidurias in Children: Two Years Experience at a Tertiary Care Centre

Organic acid disorders are inherited metabolic disorders in which organic acids accumulate in tissues and biological fluids of affected individuals. Classical organic acidurias include methylmalonic aciduria, propionic aciduria, isovaleric aciduria and maple syrup urine disease (MSUD). They are considered the most frequent metabolic disorders among severely ill children. Patients frequently present with acute symptoms early in life. 420 cases clinically suspected to have organic aciduria, with upper age limit of 12 years for a 2-year period (January 2007–December 2008) were enrolled into this study. Metabolic acidosis and neurological symptoms were the most common signs. Screening tests and thin layer chromatography were done for detection of organic acidurias. Identification and quantitation of organic acids in urine and quantification of amino acids in blood were done by high performance liquid chromatography. Out of 420 patients, 45 patients (10.7%) were found to have organic acidurias. 15 cases of methylmalonic aciduria, 16 cases of propionic aciduria, 13 cases of MSUD, and one case of isovaleric aciduria were diagnosed. Results demonstrate the importance of testing for organic acidurias. Since organic aciduria may cause irreversible brain damage if not treated, we recommend selective screening amongst severely ill children despite implied extra costs.     

Myeloperoxidase in Chronic Kidney Disease

Numerous lines of evidence implicate a role of myeloperoxidase (MPO) in the pathogenesis of cardiovascular disease (CVD). It is a well accepted fact that patients with chronic kidney disease (CKD) are at an increased risk for CVD. MPO is a pro-oxidant enzyme which could be involved in the increased susceptibility of these patients to CVD. Hence, the levels of plasma MPO was determined in healthy controls as well as in patients with CKD [stratified with the level of their kidney failure as CKD stages II–V (end stage renal disease)]. Plasma MPO was assayed by a spectrophotometric method. Serum urea and creatinine were estimated on a clinical chemistry analyzer using standard laboratory procedures. The mean plasma MPO levels were significantly lower with advancing stages of renal failure (P < 0.001). There was a positive correlation between MPO and GFR (r = +0.89, P < 0.001) and a negative correlation with urea (r = −0.85, P < 0.001) and creatinine (r = −0.82, P < 0.001). While an inverse association was observed between plasma MPO and urea in CKD patients, such an association was not observed in control subjects (P = 0.43). In conclusion, the decline in plasma MPO levels may be due to the inhibitory effect of uraemic toxins on the enzyme.     

Diagnostic Dilemma of HbA1c Detection in Presence of a Hemoglobinopathy: A Case Report

We report a case of a diabetic, heterozygote with near normal hematology, marginally low level of hemoglobin A₂(HbA₂) having an increased level of hemoglobin F(HbF) that was pancellularly distributed among the red cells. BioRad DiaSTAT measurements gave a high glycated hemoglobin A1c(HbA1c) of 31.5% and the BioRad Variant analyzer recorded an HbA1c value which was very low, in discordance with the detected blood glucose levels. Flow cytometry and polymerization chain reaction (PCR) based studies were carried out which revealed the case to be that of the common hereditary persistence of fetal hemoglobin (HPFH)-3, an Asian Indian mutation. Fructosamine estimation and HbA1c by Boronate affinity chromatography were able to resolve the discordant value detected and was able to confirm the diabetes status. The case would have been a diagnostic dilemma, if reported without correlation.     

BMD and Serum Intact Osteocalcin in Postmenopausal Osteoporosis Women

India seems to have the highest prevalence of osteoporosis. With growing awareness of osteoporosis and its impact on life span especially in India, special attention is being paid to early detection, management and treatment of postmenopausal osteoporosis in women. Measurement of BMD and osteocalcin are of value in estimating bone turnover rates. The aim of this study is (1) to measure the specific, sensitive bone formation marker such as osteocalcin and BMD in postmenopausal osteoporosis women and postmenopausal non-osteoporosis women; (2) the follow up study to evaluate the impact of specific antiresorptive therapy (alendronate + calcium + vitamin D) regimen in postmenopausal osteoporosis by assaying osteocalcin and BMD. Sixty clinically diagnosed postmenopausal osteoporosis patients and 60 normal subjects (postmenopausal non-osteoporosis women) were recruited as control. Mean bone mineral density T score and Z score was significantly decreased (P < 0.001) in postmenopausal osteoporosis patients as compared to controls. Highly significant increase in the mean score of BMD—T score and Z score from baseline to post therapy of 3 months was observed in postmenopausal osteoporosis women. Serum osteocalcin levels were significantly increased (P < 0.001) as compared to control group. Serum osteocalcin levels were decreased significantly (P < 0.001) from baseline to post therapy of 3 months in postmenopausal osteoporosis women. BMD is the best quantifiable predictor of osteoporotic fracture and osteocalcin is specific, sensitive, promising, currently used marker for better prognosis of osteoporosis and for monitoring responses to antiresorptive therapy.     

A Review on Salivary Genomics and Proteomics Biomarkers in Oral Cancer

Oral cancer has emerged as an alarming public health problem with increasing incidence and mortality rates all over the world. Therefore, the implementation of newer screening and early detection approaches are of utmost importance which could reduce the morbidity and mortality associated with this disease. Sensitive and specific biomarkers for oral cancer are likely to be most effective for screening, diagnosis, staging and follow-up for this dreaded malignancy. Unlike other deep cancers, oral cancer is located in oral cavity. Hence, the direct contact between saliva and oral cancer lesion makes the measurement of tumor markers in saliva an attractive alternative to serum and tissue testing. The DNA, RNA and protein molecules derived from the living cancer cells can be conveniently obtained from saliva. Thus, salivary biomarkers, a non-invasive alternative to serum and tissue-based biomarkers may be an effective modality for early diagnosis, prognostication and monitoring post therapy status. In the current post-genomic era, various technologies provide opportunities for high-throughput approaches to genomics and proteomics; which have been used to evaluate altered expressions of gene and protein targets in saliva of oral cancer patients. The emerging field of salivary biomarkers has great potentials to prove its clinical significance to combat oral cancer. Hence, we have reviewed importance of several salivary genomics and proteomics biomarkers for oral cancer.     

Exact analysis for the identification of non-minimum phase processes

Analytical expressions are derived from a single symmetrical relay feedback test for the identification of open loop stable and unstable non-minimum phase processes. The second derivative of the limit cycle output helps in finding the time delay of the process. The derived expressions can be used to identify the process models with up to five unknowns. The effectiveness of the proposed identification method is verified through different simulation results.