Indian Journal of Clinical Biochemistry最新文献

Drug-resistant (DR) tuberculosis (TB) is a global threat to health security and TB control programs. Since conventional drug susceptibility testing (DST) takes several weeks, we have developed a molecular method for the rapid identification of DR strains of Mycobacterium Tuberculosis (M.tb) utilizing DNA bio-chips. DNA bio-chips were prepared by immobilizing oligonucleotides (probes) on highly microporous polycarbonate track-etched membranes (PC-TEM) as novel support. Bio-chip was designed to contain 15 specific probes to detect mutations in three genes (rpoB, embB, and inhA). A sensitive and specific chemiluminescence based bio-chip assay was developed based on multiplex PCR followed by hybridization on bio-chip. Fifty culture isolates were used to evaluate the ability of in-house developed bio-chip to detect the mutations. Bio-chip analysis shows that 37.7% of samples show wild type sequences, 53.3% of samples were monoresistance showing resistance to either rifampicin (RMP), isoniazid (INH), or ethambutol (EMB). 4.4% of samples were polydrug resistant showing mutations in both the rpoB gene and embB gene while 4.4% of samples were multidrug-resistant (MDR), harboring mutations in the rpoB and inhA genes. The results were compared with DST and sequencing. Compared to sequencing, bio-chip assay shows a sensitivity of 96.5% and specificity of 100% for RMP resistance. For EMB and INH, the results were in complete agreement with sequencing. This study demonstrates the first-time use of PC-TEMs for developing DNA bio-chip for the detection of mutations associated with drug resistance in M.tb. Developed DNA bio-chip accurately detected different mutations present in culture isolates and thus provides detailed and reliable data for clinical diagnosis.

This was a prospective observational study, conducted at a tertiary care health centre in Rajasthan. A total of 68 women with PCOS (Rotterdam criteria) attending OPD at Department of Obstetrics and Gynecology qualified as per inclusion and exclusion criteria were included in the study. Each participant was examined for anthropometric and biochemical parameters. The largest phenotypic group was phenotype A, (41.17%); followed by B (26.47%); C (20.58%), and D (P + O) phenotypes (11.76%). Hyperandrogenic phenotypes (A, B, C), had significantly higher prevalence of deranged serum glucose (fasting and postprandial), lipid profile and serum TSH than normoandrogenic phenotype D. BMI was strongly correlated with anthropometric (p < 0.001) and biochemical parameters (p < 0.05) in phenotype A among four phenotypes of PCOS. Phenotype A was the most common form of PCOS and a strong correlation of BMI with waist circumference (WC), dyslipidemia and Sub-clinical hypothyroidism (SCH) was observed in women of this phenotype of PCOS. These results indicate that phenotype A is at increased risk of CVD and diabetes and phenotype D has least metabolic risks.

Arthritis is a clinical condition, which mainly affects the structure and function joints. During this condition the joints gets swelled and stiffed resulting into development of pain and morbidity. Corticosteroids are frequently prescribed to manage various clinical conditions including the chronic inflammatory diseases such as arthritis. The steroidal drug also causes certain adverse effects depending on the dose, the route of administration and duration of treatment. However, a systematic investigation on the biochemical consequences of steroids as a therapeutic has not been carried out. In the present study we analyzed certain parameters associated to oxidative stress, liver function and energy metabolism has been done in the blood plasma of the arthritis patients who were using steroidal drugs (methylprednisolone and deflazacort) up to 168 days for the treatment of the disease. The results indicated increase in level of MDA and decrease in the activities of SOD, CAT and LDH. The activities of AST and ALT were found to be significantly enhanced over the increase in the treatment period. These results suggested that corticosteroids may induce lipid peroxidation, oxidative stress and liver toxicity in the arthritis patients in the dose and duration dependent manner. The use of antioxidants as supplements to the anti-arthritis agents could play a role in suppressing the oxidative stress mediated adverse effects. However, extensive research is required to explore for safer medication devoid of steroids to cure arthritis.

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MicroRNAs (miRNAs) are small endogenous, non-coding RNA molecules that can modulate the expression of their target genes. Since its discovery, an enormous breakthrough has been established regarding its biogenesis and pathophysiological action, which has revolutionized the field of molecular biology. In addition, recent studies have identified the existence of stable extracellular/circulating miRNAs tissues and in biological fluids like blood where they are safeguarded from endogenous ribonuclease activity. Type 2 diabetes mellitus (T2DM) has emerged as a prime health issue worldwide. Incidence has increased considerably over the past decade. There are various tests that have been employed to diagnose T2DM. But for early detection and development, the establishment of biomarkers are of paramount importance. Contemporary evidence also validates the signature of a set of this epigenetic factor miRNA in the development of various diseases, including T2DM. This article reviews the contemporary corroboration associating miRNAs and T2DM and emphasizes the potential role of miRNA as a circulatory biomarker that could alert the growing prevalence of T2DM. Also, it acknowledges the valuable compendium of information regarding biogenesis and functional role of circulating miRNA in insulin resistance which is intimately linked to T2DM.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01069-1.

Serum hyperviscosity is a rare laboratory finding. Amongst several causes of serum hyperviscosity, malignant disorders are quite common. Monoclonal gammopathy is a family of disorders in which monoclonal gammopathy of unknown significance (MGUS) and smoldering myeloma are the asymptomatic variants whereas multiple myeloma is the malignant variant showing different signs and symptoms related to bone lesions, renal failure and anemia. Initially during sample preparation, pipetting of a serum sample was found to be cumbersome. This sample during routine analysis in the automated analyser flagged repeated alarms for clot detection indicating a possibility of a hyper viscous sample. Serum was subjected to fibrinogen and D- dimer test. The D-Dimer levels were found to be normal and fibrinogen levels were mildly elevated. Routine biochemistry investigations were normal except grossly reversed A/G ratio. Due to gross reversal of A/G ratio, the possibility of Multiple myeloma was entertained. Physician's were alerted on telephone. Serum was sent for electrophoresis which showeda M spike. Bone marrow aspirate showed 13% plasma cells. Considering the above lab results the diagnosis of monoclonal gammopathy of smoldering type was considered. The sample was traced to a 77 years old male, who presented to Medicine OPD with the chief complaints of generalised weakness for two months without any history of fever. On physical examination pallor was evident but there was no icterus, cyanosis, clubbing, lymphadenopathy or edema. On haematological evaluation patient was found to be anemic. Careful tracking of hyperviscous patient's serum followed up by thorough investigation led us to the final conclusion that the case mentioned is a rare case of Smoldering type of multiple myeloma.

Immune dysregulation in COVID-19 is the major causal factor associated with disease progression and mortality. Role of monocyte HLA-DR (mHLA-DR), neutrophil CD64 (nCD64) and Immune dysregulation index (IDI) were studied in COVID-19 patients for assessing severity and outcome. Results were compared with other laboratory parameters. Antibody bound per cell for mHLA-DR, nCD64 and IDI were measured in 100 COVID-19 patients by flow cytometry within 12 h of hospital admission. Thirty healthy controls (HC) were included. Clinical and laboratory parameters like C - reactive protein (CRP), Procalcitonin (PCT), Absolute Lymphocyte count (ALC), Absolute Neutrophil count (ANC) and Neutrophil to Lymphocyte ratio (NLR) were recorded. Patients were followed up until recovery with discharge or death. Parameters from 54 mild (MCOV-19), 46 severe (SCOV-19) and 30 HC were analysed. mHLA-DR revealed significant and graded down regulation in MCOV-19 and SCOV-19 as compared to HC whereas IDI was lowest in HC with increasing values in MCOV-19 and SCOV-19. For diagnostic discrimination of MCOV-19 and SCOV-19, IDI revealed highest AUC (0.99). All three immune parameters revealed significant difference between survivors (n = 78) and non-survivors (n = 22). mHLA-DR < 7010 and IDI > 12 had significant association with mortality. Four best performing parameters to identify patients with SCOV-19 at higher risk of mortality were IDI, NLR, ALC and PCT. mHLA-DR and IDI, in addition to NLR and ALC at admission and during hospital stay can be utilized for patient triaging, monitoring, early intervention, and mortality prediction. IDI reported for the first time in this study, appears most promising. Immune monitoring of 'in hospital' cases may provide optimized treatment options.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01087-z.

The interrelationship between matrix degradation, oxidative stress, inflammation and trace elements can be speculated in COVID-19. The objective of the study was to evaluate the oxidative stress, inflammation and matrix degradation markers and trace elements in COVID-19 positive patients. A group of confirmed severe COVID-19 positive patients (n = 30) along with COVID-19 negative patients (n = 30) with similar symptoms were included. Both group of patients were assessed for oxidative stress markers, inflammatory cytokines, matrix metalloproteinase (MMP)s and their inhibitors along with trace elements in blood. All the data were subjected to univariate as well as multivariate analysis including PCA, PLS-DA, OPLS-DA. Diagnostic accuracy was tested by ROC curve analysis. Further relationship with Neutrophil/ lymphocyte (N/L) ratio was established if any. Increased oxidative stress, inflammation and matrix degradation is evidenced by significant rise in oxidative markers, inflammatory cytokines and MMP9/TIMP-1 ratio. Decreased Cu/Zn ratio is also observed in COVID-19 positive patients. Multivariate analysis identified SOD, Cu/Zn ratio, IL-6 and TOS, as effective discriminant among the two groups of patients. Further, accuracy was confirmed by ROC curves. Neutrophil/ lymphocyte (N/L) ratio, shows significant negative association with SOD (r= -0.75, p < 0.005) and Cu/Zn ratio (r = -0.88, p < 0.005). These data suggest the attributes of these biomarkers in disease severity. The potential use of these blood-based laboratory markers in disease prognosis seems promising and warrants further attention. Given by the symptoms and severity of the disease, it will be promising to monitor Cu/Zn ratio along with other prognostic indicators.

COVID-19, a global pandemic that led to increased morbidity and mortality worldwide since its outcome at the end of the year 2019. A newly discovered variant of severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) was the arbitrator for spreading the syndrome by droplet transmission causing multi-organ failure in many occasions. A post-infection-pro-diabetic disposition was found evident in this study with the persistence of hepato-pancreatic aberrations in respect of reference range of tissue specific bio-markers in hospital admitted COVID-19 cases. The results of this study show that hyperglycemia is a risk factor in precipitating disease oriented complications to the patients with COVID-19 disease. A post-infection follow- up on glycemic-index and related complexities is a vital need to the COVID-19 infected convalescent subjects. Implementation of guidelines on social measure and awareness of anti-viral interventions may be the only way to prevent COVID-19 transmission.

The presence of dyskinesia is the most common side effect of chronic administration of levodopa in Parkinson's disease (PD) subjects. Genetic polymorphisms in levodopa metabolizing gene, catechol-O-methyl transferase (COMT), is shown to influence the inter-individual variability in drug response and adverse events. In the present study, the association of COMT rs6269, rs4633, rs4818, and rs4680 polymorphisms and haplotypes on pharmacokinetics and adverse events with levodopa was investigated in 150 PD patients. The age of onset of PD was 58.00 ± 10 yrs. The most common side effect faced by 78% of the subjects was dyskinesia. The AUC of levodopa was found to be significantly higher in subjects with dyskinesia (1695 ± 113 ng/ml/hr, p < 0.0001) than those without dyskinesia (1550 ± 122 ng/ml/hr). We found that the frequency of subjects presenting dyskinesia was significantly higher in subjects carrying variant genotype of COMT rs6269, rs4633, and rs4680 than that with wild genotype and these subjects presented higher AUC of levodopa. In addition, in subjects with dyskinesia, the AUC of levodopa was found to be significantly higher with low COMT (ACCG) haplotype. The association of COMT rs6269, COMT rs4633, COMT rs4818, and COMT rs4680 variant genotypes with the risk of dyskinesia due to levodopa therapy showed an ROC AUC of 0.67 indicating the moderate prediction of dyskinesia (p = 0.0021) with these COMT variants. In conclusion, PD subjects carrying the variant genotypes of COMT strongly influence high levodopa-induced dyskinesia. Hence the genotyping of COMT before the levodopa therapy will be useful to reduce the adverse events associated with the chronic levodopa treatment.