Indian Journal of Clinical Biochemistry最新文献

Anti-mullerian hormone (AMH) has been proposed to add significance to diagnosis of PCOS in case of ambiguity. However, variable cutoffs of AHM among PCOS women have been reported. Using case-control design, this study investigated the diagnostic threshold of serum AMH levels among age matched 113 PCOS and 75 normo-ovulatory women and its correlation with clinical, hormonal and ultrasonographic parameters.PCOS was defined as per Rotterdam criteria 2003. Results depicted the mean serum AMH level to be significantly higher in PCOS group (7.84 ± 3.67vs. 3.23 ± 1.56 ng/mL) than controls. The AMH levels were positively(p = 0.001) associated with ovarian volume (r = 0.521) as well as number of ovarian follicles(r = 0.461). Further, serum AMH levels showed a positive correlation with luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (r = 0.206, p = 0.02), but no correlation significant with age, BMI,FG score and testosterone levels. As per receiver operating characteristic (ROC) curve, cut-off was worked out to be 3.76 ng/ml with 86.7% sensitivity and 62.7% specificity. The mean level of AMH were highest among PCOS women with phenotype A (12.67 ± 3.46 ng/ml) with least among PCOS women displaying phenotype B(7.28 ± 1.60 ng/ml) where there is absence of PCOM. In conclusion, serum AMH levels are highly predictive of PCOM and high LH/FSH ratio among PCOS women and may be a potent diagnostic marker of ovarian dysfunction either alone or in conjunction with other tools.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01058-4.

Blood steroid profile is a recently introduced test in India that is commercially available through a few diagnostic laboratories. In adult women, ACTH-stimulated steroid panel helps to differentiate polycystic ovary syndrome (PCOS) from nonclassical forms of CAH. However, the interpretation of ACTH-stimulated steroid panels is often impeded by the limited availability of reference ranges. Here, we report the adrenal steroid levels after stimulation with Acton Prolongatum in Asian Indian women of reproductive age. This prospective study was conducted at a tertiary health care center in the Southern part of India. Apparently healthy women in the reproductive age group with regular menstrual cycles (21-35 days) at least over the last 6 months were included. All participants received intramuscular Acton Prolongatum® (Pfizer) in the morning hours during the follicular phase and the steroid profile was analyzed by liquid chromatography-tandem mass spectrometry in a blood sample collected 60-min later. The study included 32 apparently healthy women. The mean age of the study population was 22.19 ± 4.36 years. None of the participants experienced any adverse events during the procedure. The median (range) serum cortisol, 17α-hydroxyprogesterone, 11-deoxycortisol, and corticosterone were 22.65 (14.3-37.21) μg/dl, 99.72 (47.21-344.71) ng/dl, 287.2 (74.41-530.61) ng/dl and 728.04 (118.74-1708.2) respectively. In conclusion, this is the first report of the response of adrenal steroids measured by LC-MS/MS at 60 min after Acton Prolongatum in Asian Indian women of the reproductive age group. However, further larger studies are warranted to establish more robust ACTH-stimulated reference ranges for steroid profile in Indian women.

Pseudo-Bartter's (PB) syndrome is characterized by hypokalemic metabolic alkalosis and failure to thrive which constitutes a rare but typical presentation of cystic fibrosis (CF) in children. The most common mutation of CF is F508del, due to loss of 3 base pairs, causing deletion of phenylalanine, at position 508. We present a case of CF presenting with failure to thrive, dehydration, PB syndrome associated with urosepsis and primo-colonization with Escherichia coli suggesting the role of epigenetic factors. The heterozygous state for Phe508del mutation in Exon 11 combination with Glu92Ala in Exon 4 resulted in epigenetic effect on atypical phenotype as PBS, a novel mutation identified in our case.

Myocardial infarction (MI) remains the most common cause of cardiac failure and continuous increasing rate of morbidity and mortality. We aimed to investigate the association of estrogen receptor-α (ESR1) gene polymorphism c454-397T>C with serum estradiol levels and dyslipidemia in 220 patients with MI in the age range of 35-70 years of both the genders. Genotyping study was performed through PCR-RFLP method using PvuII restriction enzyme. Serum estradiol level was estimated using the Access Sensitive Estradiol assay kit. Men patients had 43.2% increased risk for TC heterozygote in co-dominant (OR 10.66) and over-dominant models (OR 8.30), while women patients had 50% increased risk in co-dominant (OR 16.57) and over-dominant (OR 14.04) models. Variant C allele showed 25% increased risk of MI for in men (OR 2.24; CI 1.49-3.36; p = 0.0001), and 24% increased risk in women (OR 3.35; CI 1.95-5.76; p = 0.0001). Men patients had significantly increased serum estradiol levels compared to controls (25.28 ± 5.80 vs 17.04 ± 2.01; p < 0.0001). Significant difference was observed in estradiol levels between men and women patients (25.28 ± 5.80 vs 17.56 ± 3.32; p < 0.0001). Furthermore, significantly increased estradiol level was found in men patients compared to women for TT (25.46 ± 5.91 vs 16.71 ± 4.46; p < 0.0001), and TC genotypes (25.47 ± 5.91 vs 17.70 ± 2.86; p < 0.0001). Significantly increased HDL levels were observed in men patients with TC (43.10 ± 8.18 vs 38.91 ± 7.84; p < 0.01) and CC (47.16 ± 8.09 vs 38.91 ± 7.84; p < 0.001) genotypes compared to TT genotype. These findings suggest that TC heterozygote plays an important role as a genetic risk factor during MI pathogenesis in the South Indian population.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01104-1.

Combination therapy may counter the risk caused by efflux pumps mediated resistance developed by mycobacteria with a concomitant increase of the bactericidal effect of anti-TB drugs. In the present study, combination of two drugs in a nanoformulation was prepared. Clofazimine targets type 2 NADH dehydrogenase of the electron transport chain, and Verapamil inhibits various mycobacterial efflux pumps. The nanotechnology approach was adopted to overcome limitations associated with administration of free form of drugs by using poly (D, L-lactic-co-glycolic acid) as a polymer. Nanoparticles were prepared by oil/water single emulsion solvent evaporation procedure and characterized by various techniques. The results thus highlighted that developed nanoparticles were spherical with nano range size (200-450 nm). Fourier transform infrared spectroscopy revealed successful encapsulation of drugs in developed nanoformulations. Drugs in combination showed higher encapsulation efficiency and percentage drug loading capacity as compared to individual drug nanoformulations. Also, reduced toxicity of nanoformulation was observed in hemolysis assay as compared to free drugs. Ex-vivo analysis demonstrated efficient uptake of rhodamine encapsulated nanoparticles by THP-1 cells, while in-vivo results revealed sustained drug release of nanoformulation as compared to free drugs in combination. Therefore, we were able to achieve development of a single nanoformulation encapsulating Clofazimine and Verapamil in combination. Based on these findings, future studies can be designed to explore the potential of co-encapsulated Clofazimine and Verapamil nanoparticles in management of tuberculosis.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01062-8.

Excessive dietary fat is mainly responsible for metabolic diseases including atherosclerosis and cardiovascular disease. We have evaluated the role of Vitamin C in an experimental hyperlipidemic model of rats (male Wistar rat 12-16 months). The hyperlipidemic model of the rat was created by treatment with an atherogenic suspension: cholesterol, cholic acid, and coconut oil, for 30 days once daily, and supplemented with Vitamin C (Ascorbic acid) doses of 0.5 g/kg body weight (orally) for the 30 days once daily. Bodyweight, fasting glucose, triglyceride, cholesterol, ROS (Reactive oxygen species), MDA (Malondialdehyde), FRAP (Ferric reducing the ability of plasma), GSH (Reduced glutathione), PCO (Protein carbonyl), PON-1(Paraoxonase-1), AGE (Advanced glycation end product), PMRS (Plasma membrane reduced system), and inflammatory cytokines (TNF-α and IL-6) were estimated in blood and plasma. Our result shows that oxidative stress, and inflammatory markers, were increased in the HFD-treated group of rats. Vitamin C supplementation protected against lipidemic and, oxidative stress. We conclude that Vitamin C may be useful in maintaining cellular redox balance and protecting against lipidemic stress.

Glutaric aciduria type II, also known as Multiple acyl-CoA Dehydrogenase Deficiency, results from a defect in the mitochondrial electron transport chain resulting in an inability to break down fatty-acids and amino acids. There are three phenotypes- type 1 and 2 are of neonatal onset and severe form, with and without congenital anomalies, respectively, and presents with acidosis, severe hypotonia, cardiomyopathy, hepatomegaly, and non-ketotic hypoglycemia. Type 3 or late-onset Multiple acyl-CoA Dehydrogenase Deficiency usually presents in the adolescent or adult age group with phenotype ranging from mild forms of myopathy and exercise intolerance to severe forms of acute metabolic decompensation on its chronic course. Type 3 Multiple acyl-CoA Dehydrogenase Deficiency rarely presents in infancy and in liver failure. We present a five-month-old developmentally normal female child with acute encephalopathy, hypotonia, non-ketotic hypoglycemia, metabolic acidosis, and liver failure, with a history of sibling death of suspected inborn error of metabolism. The blood acyl-carnitine levels in Tandem Mass Spectrometry and urinary organic acid analysis through Gas Chromatography-Mass Spectrometry were unremarkable. The patient initially responded to riboflavin, CoQ, and supportive management but ultimately succumbed to sepsis with shock and multi-organ dysfunction. The clinical exome sequencing reported a homozygous missense variation in exon 11 of the ETFDH gene (chr4:g.158706270C > T) that resulted in the amino acid substitution of Leucine for Proline at codon 456 (p.Pro456Leu) suggestive of Glutaric aciduria type IIc (OMIM#231,680).

Various evidences have unveiled the significance of Vitamin D in diverse processes which include its action in prevention of immune dysfunction, cancer and cardiometabolic disorders. Studies have confirmed the function of VD in controlling the expression of approximately nine hundred genes including gene expression of insulin. VD insufficiency may be linked with the pathogenesis of diseases that are associated with insulin resistance (IR) including diabetes as well as obesity. Thus, VD lowers IR-related disorders such as inflammation and oxidative stress. This review provides an insight regarding the molecular mechanism manifesting, how insufficiency of VD may be connected with the IR and diabetes. It also discusses the effect of VD in maintaining the Ca²⁺ levels in beta cells of the pancreas and in the tissues that are responsive to insulin.

Coronary artery disease (CAD) is the third foremost reason of death worldwide in both men and women of different age groups, and is associated with 17.8 million mortalities annually due to unknown specific genetic background. Hence, we elucidated the age- and gender-based predisposition of MMP-9 -1562 C > T (rs3918242) genotype and allele frequencies along with serum MMP-9 levels as probable risk factors in the development of CAD. This case-control study comprised 150 CAD patients and 150 controls from the South Indian Population. PCR-RFLP was performed to determine different genotypes of MMP-9 gene and serum levels of MMP-9 were measured using ELISA. Age- and gender-based subgroup analysis was performed to assess the probable risk of genotype-based serum MMP-9 levels. CT heterozygote showed 25.4% increased frequency in overall CAD patients compared to controls (OR, 4.48; p < 0.0001); while it was 29.2% in men patients (OR, 6.68; p < 0.0001). The CT heterozygote incurred 25.2% increased risk of CAD in younger patients (p = 0.0033), and 25.6% in older patients (p = 0.001). Allele frequency analysis revealed 20% increased risk of minor T allele in younger patients (p = 0.001), and was 13% higher compared to older patients (p = 0.04). Patients with CC homozygote and CT heterozygote showed significantly increased serum MMP-9 levels. Further, comparative analysis showed significantly increased MMP-9 serum levels in women with CT heterozygote compared to men with the same genotype. Our findings clearly demonstrated that rs3918242 of MMP-9 gene and high serum levels of MMP-9 are associated with CAD in South Indian population specifically in older women.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01073-5.