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Over the past few years, Th17 cells is considered a key player in osteoporosis pathogenesis. Although extensively studied in murine models, comprehensive Th17 cell characterization in osteoporotic women is elusive. We thus aimed to examine peripheral Th17 cells frequency and phenotypes in healthy and osteoporotic women. Our results demonstrated that Th17 cells were primarily CD4

Osteoprotegerin (OPG) and receptor activator of the NF-kB ligand (RANKL) are key players in bone remodelling. Reports show that OPG and RANKL gene polymorphisms are associated with osteoporosis and fracture risk. The aim of this study was to examine the influence of 5 single nucleotide polymorphisms (SNPs) in OPG and RANKL gene on bone mineral density (BMD) in Indian women. The study included 374 healthy Indian women. Kompetitive Allele Specific PCR (KASP) was used for genotyping. There was a significant difference in the BMD at spine between genotypes of OPG rs2073618 (CC: 0.988 ± 0.167 CG: 1.023 ± 0.17 GG: 1.053 ± 0.155; p = 0.039) which was lost upon adjustment for age and BMI (p = 0.087). Multiple linear regression revealed that genotypes of OPG rs2073618 (β = 0.098; p = 0.027) and rs3102735 (β = 0.092; p = 0.038) are predictors of BMD at spine in Indian women. We did not observe any association of SNPs in RANKL gene with BMD. Thus, SNPs rs2073618 and rs3102735 in OPG gene may influence BMD at spine in Indian women.

RANKL and OPG are cytokines involved in bone remodeling that makes them potential bone biomarkers. The reference interval for these cytokines, their ratio, and bone turnover markers CTX and PINP were established in Indian women, which may serve in diagnosis and management of osteoporosis. Purpose The aim of the study was to establish reference interval for RANKL, OPG, RANKL/OPG, and bone turnover markers CTX and PINP in healthy Indian women. Methods This was a cross-sectional study on 374 healthy Indian women in the age group of 20-65 years. Serum levels of total RANKL, OPG, CTX, PINP, and estradiol were determined by commercial ELISA kits. The reference intervals for these cytokines and bone turnover markers were based on the 95% centrally distributed data. Results Median RANKL (245.6 pmol/L vs. 149 pmol/L) and RANKL/OPG (38.7 vs. 20.4) were higher, while sCTX (380 ng/L vs. 551 ng/L) and OPG levels (6.1 pmol/L vs. 7.4 pmol/L) were lower in premenopausal women than those in postmenopausal women. PINP levels were comparable in both groups. Women were classified into 5 groups according to decades of age and the reference intervals for RANKL, OPG, RANKL/OPG ratio, and CTX and PINP in each group were reported. Conclusion We reported menopausal status-based and age-related reference intervals for serum RANKL, OPG, RANKL/OPG ratio, and CTX and PINP in healthy Indian women.

Estrogen regulates bone homeostasis and has a cardio-protective effect. Its physiological functions are mediated through receptors (ER) whose expression can be regulated by presence or absence of polymorphisms. However, the association between ER polymorphisms and BMD as well as lipids are inconsistent. The aim of the study was to investigate whether polymorphisms in ESR are associated with bone mineral density (BMD) and lipids in a cohort of Indian women. We studied PvuII, XbaI polymorphisms in ESR1 and AluI, RsaI polymorphisms in ESR2 genes and their association with bone mineral density (BMD) and lipids in premenopausal (n = 293, mean age: 33.01 ± 5.23 years) and postmenopausal (n = 145, mean age: 56.91 ± 7.1 years) women from Northeast India. AluI and RsaI polymorphisms in ESR2 gene were associated with BMD in postmenopausal women. Logistic regression analysis adjusted for age, BMI, tobacco and alcohol consumption revealed that xx genotype in XbaI polymorphism is associated with osteopenia at spine (OR = 3.3, 95% CI = 1.067–10.204) in postmenopausal women suggesting that allele X is protective (OR = 0.419, 95% CI = 0.177–0.991). Genotype aa in AluI polymorphism, seemed to be protective (OR = 0.092 for osteopenia; OR = 0.152 for osteoporosis) at spine whereas A allele was associated with osteopenia at femur (OR = 2.123, 95% CI = 1.079–4.166) in postmenopausal women. Allele r of RsaI polymorphism, was associated with osteoporosis at spine (OR = 3.222, 95% CI = 1.302–7.96). Thus, AIuI polymorphism of ESR2 gene was associated with spinal and femoral BMD whereas RsaI only with spinal BMD in postmenopausal women and ESR genotypes were not associated with lipids.

Serum Osteocalcin (OC) is a biomarker for evaluating bone turnover in humans. Commercial kits of OC in India are imported, hence the associated high cost prohibits their use in routine screening of osteoporosis. The present study describes the development, validation of human OC ELISA and establishes cut off values for its use in screening and management of women at risk for osteoporosis.A sandwich OC ELISA was developed using immuno-reagents prepared indigenously and validated for analytical sensitivity, specificity, accuracy and compared with commercial kit using Bland-Altman method. The utility of OC assay was evaluated by ROC analysis.The new ELISA was sufficiently precise, accurate, matrix-free, sensitive and cost effective. The levels of OC were significantly different in women with osteopenia and osteoporosis (ANOVA, p .0001) compared to women with normal BMD. ROC analysis demonstrated the cut off values of OC11.9 ng/mL for osteopenia and 14.9 ng/mL for osteoporosis. The OC levels had maximum AUC of 0.831 in osteopenia and 0.932 in osteoporosis. Further, OC levels showed significant changes within 3 months in women monitored on therapy.The developed OC ELISA has great potential to be used as a biomarker for routine screening and management of osteoporosis in Indian women.

Background: Vitamin D deficiency is prevalent among Indian women. Subclinical vitamin D deficiency is a significant risk factor for osteopenia and fractures. However, its effect on bone metabolism and bone mineral density (BMD) is still debatable. Objectives: This study aimed to determine relationships of the vitamin D status with bone turnover markers, carboxy-terminal telopeptide of type-I collagen (CTX), N-terminal propeptide of type I procollagen (PINP), and BMD in healthy Indian women. Methods: In this cross-sectional study, we determined serum levels of 25-hydroxy vitamin D (25(OH)D), parathyroid hormone, serum CTX, and PINP using commercial ELISA kits in 310 healthy Indian women aged 25 - 65 years who underwent BMD measurements with DXA scan. Results: The prevalence of vitamin D deficiency was 53.87% and vitamin D insufficiency 31.29%. A direct correlation of BMD with vitamin D levels was not observed. PINP negatively correlated with vitamin D in both premenopausal (Spearman’s r = -0.169, P < 0.05) and postmenopausal (Spearman’s r = -0.241, P < 0.05) women. However, CTX positively correlated with vitamin D in both premenopausal (Spearman’s r = 0.228, P < 0.01) and postmenopausal (Spearman’s r = 0.244, P < 0.05) women. Conclusions: Vitamin D deficiency is more prevalent in premenopausal women than in postmenopausal ones. Although vitamin D does not show any association with BMD, it affects bone remodeling, which is reflected by changes in the bone formation marker PINP and the bone resorption marker CTX.

Osteoporosis a major public health problem of the elderly, is associated with substantial morbidity and socio economic burden. The aim of the study was to screen women with low bone mass using the indigenously developed Osteocalcin (OC) ELISA kit and compare it with commercial ELISA kit and evaluate. The diagnostic potential of the assay was assessed in 359 samples from neighboring tertiary care hospitals over a period of 2 years. OC levels were estimated by the developed indigenous assay in samples, correlated with the Bone Mineral Density (BMD) measurements and compared by a commercial ELISA kit. On the basis of T-scores the women were stratified into Normal and case groups as Osteopenia and Osteoporosis. The serum biochemical parameters calcium and phosphorus were estimated on an auto-analyzer. To compare two different assays Bland–Altman plot and Deming linear regression analysis was performed. The prevalence of Osteopenia was high (56%) and Osteoporosis (13%) in the healthy Indian women aged 21–65 years with significant differences in OC levels in normal and women with low bone mass. Good correlation (p 85%. The cost effective OC prototype can be used in screening and management of Indian women with low bone mass. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12291-019-00841-0) contains supplementary material, which is available to authorized users.

This study investigated association between lipids and homocysteine (Hcy) with bone mineral density (BMD) in young women as opposed to previous studies on elderly women. HDL, triglyceride, and Hcy are significantly associated with BMD in young women and tobacco and alcohol consumption have no effect on this association. The present study investigates whether the association of serum lipids and homocysteine (Hcy) with bone mineral density (BMD) reported mostly in elderly population can be generalized to young or premenopausal women, consequently suggesting screening of young women with low BMD for dyslipidemia or any cardiovascular events and vice versa. Women (n = 293, aged 20–47 years) from Northeast India belonging to Tibeto-Burman origin were enrolled. Information about their physical and clinical attributes were collected by a structured questionnaire. Their BMDs at lumbar spine and femur were measured by dual-energy X-ray absorptiometry (DXA) and sera were profiled for lipid parameters and Hcy by auto-analyzer and ELISA, respectively. Women consuming tobacco and/or alcohol were grouped as consumers and others as non-consumers for the analysis. Positive correlation of BMD with HDL (spine and femur r = 0.38, p

Aim Fracture risk assessment tool® calculations can be performed with or without addition of bone mineral density; however, the impact of this addition on fracture risk assessment tool® scores has not been studied in Indian women. Given the limited availability and high cost of bone mineral density testing in India, it is important to know the influence of bone mineral density on fracture risk assessment tool® scores in Indian women. Therefore, our aim was to assess the contribution of bone mineral density in fracture risk assessment tool® outcome in Indian women. Methods Apparently healthy postmenopausal Indian women (n = 506), aged 40–72 years, without clinical risk factors for bone disease, were retrospectively selected, and their fracture risk assessment tool® scores calculated with and without bone mineral density were compared. Results Based on WHO criteria, 30% women were osteoporotic, 42.9% were osteopenic and 27.1% had normal bone mineral density. Fracture risk assessment tool® scores for risk of both major osteoporotic fracture and hip fracture significantly increased on including bone mineral density ( P 0.05, whereas, for hip fracture risk number of women eligible without bone mineral density was 2 and with bone mineral density was 17, P Conclusion Until the establishment of country-specific medication intervention thresholds, bone mineral density should be included while calculating fracture risk assessment tool® scores in Indian women.

Background & objectives: Phosphorylated heat shock protein 27 (pHSP27) has been implicated in the pathogenesis of osteoporosis. oxidative stress and proinflammatory cytokines, which are known to be involved in aetiology of osteoporosis, can trigger HSP27 phosphorylation. Since pHSP27 is present in circulation, it was hypothesized that serum pHSP27 would be elevated in low bone mineral density (BMD) condition and might serve as an indicator of osteoporosis/osteopenia. Hence, the aim of this study was to examine serum levels of pHSP27 in relation with BMD in pre- and postmenopausal women. Methods: Premenopausal (30 to 40 yr) and postmenopausal (50 to 60 yr) women having either low BMD (osteopenia/osteoporosis) or high BMD were selected (n=80) from a prospective cohort (n=200). Serum levels of pHSP27; along with levels of oestradiol, malondialdehyde, total antioxidant capacity, interleukin (IL)-1, IL-6, tumour necrosis factor - alpha, (TNF-α), c-telopeptide fragments of collagen type I (CTX-1) and osteocalcin were estimated. Results: The serum levels of pHSP27 were significantly elevated in low BMD groups in premenopausal and postmenopausal categories (p

The Indian Society for Pediatric and Adolescent Endocrinology has formulated locally relevant Clinical Practice Guidelines for newborn screening, diagnosis and management of primary congenital hypothyroidism (CH). Recommendations: Screening should be done for every newborn using cord blood, or postnatal blood, ideally at 48 to 72 h of age. On this screen sample, neonates with TSH > 20 mIU/L serum units (or >34 mIU/L for samples taken between 24 to 48 h of age) should be recalled for confirmation. For screen TSH > 40 mIU/L, immediate confirmatory venous T4/FT4 and TSH, and for milder elevation of screen TSH, a second screening TSH at 7 to 10 d of age, should be taken. Preterm and low birth weight infants should undergo screening at 48–72 h postnatal age. Sick babies should be screened at least by 7 d of age. Venous confirmatory TSH >20 mIU/L before age 2 wk and >10 mIU/L after age 2 wk, with low T4 (

The Indian Society for Pediatric and Adolescent Endocrinology has formulated Clinical Practice Guidelines for newborn screening, diagnosis and management of congenital hypothyroidism (CH). This manuscript, part II addresses management and follow-up. Recommendations: Screening should be done for every newborn using cord blood, or postnatal blood ideally at 48 to 72 h of age. Neonates with screen TSH > 20 mIU/L serum units (or >34 mIU/L for samples taken between 24 and 48 h of age) should be recalled for confirmation. For screen TSH > 40 mIU/L, immediate confirmatory venous T4/FT4 and TSH, and for mildly elevated screen TSH, a second screening TSH at 7 to 10 d of age, should be taken. Preterm and low birth weight infants should undergo screening at 48–72 h age. Sick babies should be screened at least by 7 d of age. Venous confirmatory TSH >20 mIU/L before age 2 wk and >10 mIU/L after age 2 wk, with low T4 (

The exponential growth of biological sciences and biotechnology has promoted the development of subspecialties / super specialties in medicine. In developing countries, socioeconomic factors influence and determine competing health priorities, often delaying the development of subspecialties in medicine. Tracing the history of development and progress of Endocrinology in general and Pediatric Endocrinology in particular, provides an overall perspective of the problems and challenges which lie ahead.

To detect growth hormone GH-1 gene deletions (6.7 kb, 7.6 kb, 7 kb) in familial/nonfamilial isolated growth hormone deficiency (IGHD) and note their clinical and investigative profile.Thirty (M16,F14) prepubertal IGHD patients aged 0.25 to 14 y, from 25 families were screened. Duration of growth failure, relevant history, clinical phenotype, and height SDS were recorded. Peak GH response to Clonidine (0.15 mg/m(2)), IGF-1, IGFBP-3 and pituitary/target gland hormones were studied. Genomic DNA of patients and family was analysed by PCR and DNA fragments were visualized on agarose gel electrophoresis.This series was divided into deletion +ve, Group I (n=12,40%) inclusive of six familial/six nonfamilial patients, and deletion -ve Group II (n=18,60%), 5 familial/13 nonfamilial cases; in total 11/30 were familial. Onset of growth failure was earlier in Group I (p0.001) mean 1.1 vs 4.7 y. Mean height SDS was -7 vs. -4.5 in Groups I/II (p0.01), age at presentation 5.1 vs 8.6 y. Overhanging forehead, prominent eyes, hypoplastic facies characterized Group I with FBS50 mg/dl in 50% and very low peak GH0.04 vs 2.04 ng/ml (p0.001) in Group II. In both groups IGF-1 and IGFBP3 were low, other hormones were normal and MRI showed hypoplastic adenohypophysis. 40% had GH-1 gene deletion (6.7 kb deletion in 83%, 7.6 kb and a compound heterozygote in 8% each).In this series of 30 IGHD patients, frequency of GH-1 gene deletions (12/30) was 40%, and 54% among familial patients, and 31% with height SDS-4. 83% had 6.7 kb deletion. Height SDS-4, clinical phenotype, peak GH1 ng/ml and hypoglycemia characterised IGHD Type IA.

Morganella morganii is a gram negative pathogen and may cause lethal disease in patients with immunosuppressive disease. It is commonly found in long term urinary catheter used and immune system deficiency patients as nosocomial disease. Morganella morganii was also involving skin, skeletal system and central nervous system. In this case we present sporadic Morganella morganii infection on sinonasal region with the presence of sinusitis, orbital absess, preseptal cellulitis and lamina propasia defect on 58 year old female diabetic patient. Microbiological assessment from nasal tissue and sinus puss discharge were reported as Morganella morganii. This is the first case of sinonasal Morganella morganii infection with sinonasal, preseptal cellulitis and orbital absess with lamina papyracea bone destruction.

Due to non-affordability of GnRH analogues (GnRHa), Medroxy Progesterone Acetate (MPA) is still used as a treatment option in girls with CPP in India. The aim here is to study the clinical features of girls with CPP in respect to the age at presentation, etiology and outcome as per the medication used for their treatment (GnRHa vs MPA). Retrospective study of 38 girls with CPP(19 idiopathic) treated with either MPA or GnRHa (Luprorelin or Triptorelin) were followed up for period varying from 1 to 8 years. The progression of growth parameters in relation to their age, etiology and medication used for the treatment was studied. Statistical analysis was done using one way ANOVA, unpaired t-test and Pearson correlation tests. Mean age at onset of puberty in girls with idiopathic ICPP(n=19), neurogenic NCPP(n=12) and hypothalamic hamartoma(HH)(n=7) were 4.68±2.83, 5.32±2.20 and 1.76±1.44 years, respectively(P 0.003). Mean height sds at presentation of all girls was higher (0.51±1.80) with comparison to MPH sds (0.90±1.19)(P=0.0021). 70% of the girls presented with SMR stage 3. Bone age was more advanced as compared to height age in all (P=0.0001) and this trend continued till last follow up. At presentation, girls with ICPP were significantly heavier and taller as compared to NCPP and HH (P=0.002 for weight SDS and 0.022 for height SDS). Mean baseline LH, FSH and estradiol were 3.05±2.49 mIU/ml, 4.75±2.29 mIU/ml and 29.43 pg/ml; respectively. At presentation, bone age was more advanced in HH(BA/CA P=0.0001 with BA/HA P=0.03) and LH levels significantly higher(5.6±2.26; P=0.02). At last follow up, there was no significant difference in weight sds(p=0.285), height sds(p=0.074) and PAH sds(p=0.056) in girls of different age groups and etiologies. After 4 years of follow up, height sds was better with GnRHa(1.80±0.98) as compared to MPA(P=0.01) but height sds with MPA was also good(0.49±0.81). Due to prevalence of CNS infections, the proportion of NCPP(31.57%) is higher in our set up, as compared to industrialized countries. With financial constraints, MPA can be considered as a treatment option for CPP.

Objectives: Osteoporosis is a common condition in postmenopausal women. Bone mineral density (BMD), the major determinant of osteoporotic fracture risk, has a particular genetic background. However, consensus on the association of BMD with specific gene locus has not been reached. The race and ethnicity specific divergence in association studies must be assessed to predict the susceptibility and therapeutic response of associated genes. We investigated the potential association of Vitamin D receptor (VDR) gene polymorphisms ApaI, BsmI, Fok I and TaqI with BMD in 246 postmenopausal Indian women (average age 54.2 ± 3.4 years). Methods: The subjects were genotyped by PCR-RFLP and underwent BMD measurements at spine and hip by dual energy X-ray absorptiometery. Results: The average BMD at spine and hip of women with genotypes aa, bb (presence of restriction sites for ApaI and BsmI), FF and TT (absence of restriction sites for Fok I and TaqI) was more than 10% higher than those with genotypes AA, BB, ff and tt, respectively. The interaction between BsmI, ApaI and TaqI genotypes showed significant effect of BsmI-ApaI genotypes (p = 0.052) in this combination on BMD. However, presence of T allele in combination showed positive influence on BMD. Within the group, genotypes BB, ff and tt were significantly prevalent in women with osteoporotic bone mass, tt and BB had significantly higher adjusted odd ratio (OR) for age more than 55years. Conclusion: Study reveals that VDR gene polymorphisms are associated with BMD in Indian women and perhaps, influence some determinant of bone metabolism. Ethnicity may attribute to frequency variation, however, allele impact remains same. © 2006 Elsevier Ireland Ltd. All rights reserved.

The present study describes the isolation and purification of osteocalcin (OC) from bovine bones and the development of an enzyme-linked immunosorbent assay (ELISA) for OC as a marker of bone formation, for assessing bone health. Bone proteins were extracted from about 90 g of bovine bone powder using 20% formic acid. The protein extract was fractionated by gel permeation chromatography on Sephadex G-50 column followed by fast protein liquid chromatography (FPLC) on a MONO-Q column. The immunoreactive active fraction was then purified by chromatofocusing, using FPLC on a MONO P column and a single homogeneous band of molecular size of about 5.8kDa, as judged by Tricine SDS-PAGE following silver staining of the gel, was obtained. It reacted specifically with its antibodies in an ELISA. About 678 microg of purified OC was yielded from about 90 g of bovine bones. The purified OC was subsequently used for the raising antisera, which was used in the development of an indirect ELISA. The developed ELISA has a sensitivity of 2.5-4.0 ng/mL and was used in estimating levels of OC in women of various age groups.

Peripheral monocytes, precursors of osteoclasts, have emerged as important candidates for identifying proteins relevant to osteoporosis, a condition characterized by low Bone Mineral Density (BMD) and increased susceptibility for fractures. We employed 4-plex iTRAQ (isobaric tags for relative and absolute quantification) coupled with LC-MS/MS (liquid chromatography coupled with tandem mass spectrometry) to identify differentially expressed monocyte proteins from premenopausal and postmenopausal women with low versus high BMD. Of 1801 proteins identified, 45 were differentially abundant in low versus high BMD, with heat shock protein 27 (HSP27) distinctly upregulated in low BMD condition in both premenopausal and postmenopausal categories. Validation in individual samples (n=80) using intracellular ELISA confirmed that total HSP27 (tHSP27) as well as phosphorylated HSP27 (pHSP27) was elevated in low BMD condition in both categories (P<0.05). Further, using transwell assays, pHSP27, when placed in the upper chamber, could increase monocyte migration (P<0.0001) and this was additive in combination with RANKL (receptor activator ofNFkBligand) placed in the lower chamber (P=0.05). Effect of pHSP27 in monocyte migration towards bone milieu can result in increased osteoclast formation and thus contribute to pathogenesis of osteoporosis. Overall, this study reveals for the first time a novel link between monocyte HSP27 and BMD.

At our Institute, a panel of reproductive hormones, viz., estrone glucuronide (E1G), pregnanediol glucuronide (PdG), luteinising hormone (LH), and follicle stimulating hormone (FSH) are estimated by ELISA for the assessment of fertility from a single urine sample collected from a subject. In order to make the estimates less cumbersome, the selection and mode of presentation of immunoreagents of the assay were modified in such a way that, either on reconstitution or single dilution, would result in ready-to-use reagents in the assay. Retrospective analysis on the performance of these ELISAs with uniform protocols (n = 86) was compared with assays having individual assay protocols (n = 116). The performance of the assay, based on the standard curve characteristics and quality control pools, was better and the rate of acceptance of these assays improved from 87.9 to 97.6%. The simplification of assay protocols, thus, had better impact on the quality and reproducibility of immunoassay of the four analytes.

Baseline data available on the excretory profiles of estrone giucuronide (E(1)G), pregnanediol glucuronide (PdG) and luteinising hormone (LH) on human menstrual cycles (n=104) was retrospectively analysed for identifying the limits of fertile period (FP) to be used as natural method of family planning. The limits of fertile period are suggested based on centile distribution of E(1)G and PdG levels during defined phase of menstrual cycle. Two approaches, which do not involve any mathematical calculation are suggested. In approach A, fertile period is said to have started when E(1)G value of 35 ng/ml is reached and is said to have ended when the PdG value of 2 μg/ml on two consecutive days is obtained. The criteria were applied to 30 test cycles in whom authentic fertile period was identified based on excretory profiles of E(1)G, PdG and LH throughout the menstrual cycles. When approach A was followed the authentic fertile period was covered in 27 cycles giving an accuracy of 90% with a mean fertile period length of 9.11+1.9 days. In approach B, the cut off limit of E(1)G value was increased to 55 ng/ml in order to reduce the days of abstinence. Though the length of the fertile period was reduced to 7.2+1.5 days the accuracy of the approach was 66.6%. Thus the approach A which has accuracy of 90% may appeal to determined couples who wish to practice family planning by periodic abstinence or restrict the use of barrier methods.

Horse radish peroxidase, alkaline phaosphatase and beta-D-galactosidase are widely used as labels in the development of enzyme immunoassays (EIAs). Enzyme beta-lactamase, though introduced as a label in late seventies has not yet become very popular inspite of having the necessary features of an enzyme to be used in EIAs. The present article reviews assays developed with this enzyme, highlights its salient features and brings out an argument in favour of its wide spread use in EIAs.

Background The serum PSA (sPSA) test has low specificity for prostate cancer (PCa), since sPSA also rises in benign prostatic hyperplasia (BPH). Serum PSP94 (sPSP94), a major secreted prostate protein, is indicated as a PCa marker. The potential of sPSP94 and sPSA in conjunction with each other to improve specificity of diagnostic test for PCa needs to be evaluated. Methods PCa patients (n = 33), BPH patients (n = 44) and healthy controls (n = 50) were recruited. A serum-based sandwich ELISA was developed to measure sPSP94 concentrations. Utility of sPSP94 in improving specificity of sPSA test was evaluated by studying sPSP94/sPSA ratios of study participants. Results Considerable decrease in overlap among sPSP94/sPSA ratio values of BPH and PCa patients was observed, as compared to sPSP94 or sPSA alone. For differentiating between BPH and PCa patients, this ratio had a maximum area under the curve (AUC) of 0.859 (P = 0.0132) and had a comparable sensitivity (90.91%) to sPSA with an increased specificity of 70.45%. Further, decision curve analysis (DCA) showed that sPSP94/sPSA ratio had a superior net benefit in identifying PCa, in patients opting for biopsy. Conclusion The sPSP94/sPSA ratio can be a better differentiating marker between BPH and PCa, than sPSP94 or sPSA alone.

To screen Isolated Growth Hormone Deficiency (IGHD) patients with congenital Familial Isolated (FIGHD) and Nonfamilial Isolated Growth Hormone Deficiency (NFIGHD) for GH1gene deletions (6.7 kb,7.6 kb,7 kb) and Growth hormone releasing hormone receptor GHRHR(E72X) gene mutation and study genotype/phenotype correlation in this multicentre study. Clinical, auxologic (Ht.SDS ≤ −2.5), hormonal and MRI evaluation of hypothalamic/pituitary (HP) axis, IGF1, IGFBP3 estimation and GH stimulation test confirmed IGHD in 107 patients. Of these 107 patients, 97 consented for molecular genetic studies. Height, weight and Bone Age (BA) were obtained. PCR based restriction digestion method was used for molecular genetic analysis of patients and families. Ethics committee approval was obtained. Based on the genotype, these 97 patients (M60,F37;1.62:1) age 3 mo to 17 y belonging to 80 families (consanguinity, 15/80), were categorized into Group I with GH1 gene deletion, n = 17 (17.5 %) from 14 families, Group II with GHRHR (E72X) mutation n = 34 (35 %) from 24 families, Group III, n = 46 (47 %) from 42 families having neither of these deletions/mutations (but with sibling involvement). In Group I, homozygous 6.7 kb and 7.6 kb deletions involved 76 % and 18 %. 6.7 kb deletion with characteristic IGHD phenotype predominated in nonconsanguineous community from Rajasthan having lowest mean FBS (55.6 mg/dl, p

A sensitive and specific, enzyme labelled immunosorbent assay (ELISA) for 6 beta-hydroxycortisol in diluted urine using penicillinase was developed. 6 beta-Hydroxycortisol-21-hemisuccinate was conjugated with enzyme penicillinase. Antibody immobilized on a polyvinylchloride ELISA plate (Dynatech) was used for separation of bound from free ligand. The sensitivity of the assay was between 2.0-3.0 pg per well and recovery of 6 beta-hydroxycortisol from urine ranged between 85.0-108.0%. The assay is simple, rapid and precise.

To determine the variables affecting serum 17 hydroxyprogesterone (17OHP) in neonates born at a tertiary hospital in Mumbai, India. Serum 17OHP was measured in peripheral venous blood between 3rd to 5th day of life by competitive radioimmunoassay and on follow up at 3 mo of age. Serum 17OHP was compared among four groups [full term healthy(FT), full term stressed(FS), preterm healthy(PT), preterm stressed(PS)] by non-parametric tests (Kruskal Wallis (KW) test and Mann- Whitney (MW) test). Pearson’s test was used to correlate natural log of serum 17OHP (ln17OHP) with variables like gestational age, birth weight, stress factor, sex, antenatal administration of glucocorticoids to mothers, Apgar score at 5 min and mode of delivery. Linear regression analysis was done using significant variables in Pearson’s test to determine best predictors of ln17OHP. The initial median (number of cases, inter-quartile range) serum 17OHP (ng/ml) for the four groups was as follows; FT 8.4 (33, 6–13); PT 20 (36, 11–29.5); FS 34 (29, 26–45) and PS 58 (24, 40.75–76.5) [total N = 122 newborns, p = 0.001]. Pearson’s test showed that gestational age, birth weight, stress factor, Apgar score were negatively correlated with 17OHP whereas stress factor, mode of delivery, use of antenatal steroids in mothers were significantly positively correlated. However, stress factor emerged as the most important significant positive predictor (multiple R = 0.643, P =

Hypersensitivity Pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease is characterized by alveolitis, granuloma formation and in some patients' fibrosis. IFNγ plays a critical role in HP; in the absence of IFNγ granuloma formation does not occur. However, recent studies using animal models of HP have suggested that HP is a Th17 disease calling into question the role of IFNγ. In this study, we report that initially IFNγ production is dependent on IL-18 and the transcription factor T-bet, however as the disease continues IFNγ production is IL-18-independent and partially T-bet dependent. Although IFNγ production is required for granuloma formation its role is distinct from that of T-bet. Mice that are deficient in T-bet and exposed to S. rectivirgula develop more severe disease characterized by an exacerbated Th17 cell response, decreased Th1 cell response, and increased collagen production in the lung. T-bet-mediated protection does not appear to be due to the development of a protective Th1 response; shifting the balance from a Th17 predominant response to a Th1 response by inhibition of IL-6 also results in lung pathology. The results from this study suggest that both Th1 and Th17 cells can be pathogenic in this model and that IFNγ and T-bet play divergent roles in the disease process.

Ten children, five boys and five girls with true precocious puberty at an early age were found to have hypothalamic hamartomas on brain imaging. Very early onset of puberty, varying from a few weeks to three years of age, and rapid progression were characteristic. Accelerated growth velocity and markedly advanced bone age were evident in all. Gonadotropin and gonadal hormone levels were elevated above the prepubertal range. Six children had associated developmental delay or hyperactivity.

Sixteen specimens of heart with persistent truncus arteriosus were studied to evaluate the anatomic features. Using the Collet and Edwards classification, type I truncus arteriosus was the most frequent (62.5%). Using Van Praagh's classification type A1 was the most common (43.7%). There were two cases which could not be classified according to the Collet and Edwards classification. The truncal valve was tricuspid in 75% of the cases and bicuspid in the remaining 25%. In all 6 cases with interruption of the aorta, the truncal valve was committed to the right ventricle. The ventricular septal defect was subtruncal in all except 1 case. There was variation in the thickness of the posterior limb of the septal band and the ventriculo-infundibular fold. Absence of the ventriculo-infundibular fold in 3 cases led to truncal tricuspid continuity. Right-sided aortic arch and interruption of the aorta were frequently associated arch anomalies.

Aprototype kit for the detection of occurrence of ovulation based on urinary pregnanediol glucuronide estimations by ELISA was developed in our laboratory. This kit was sent for evaluation at 4 centres in Bombay and Pune, India. The diagnosis of ovulation/anovulation based on the results of the kit is comparable with that based on reference parameters commonly used (ultrasonography of ovarian follicles and serum progesterone estimations). The accuracy of the test was 93.5%, specificity was 87.5% and sensitivity was 95.7%. This rapid indigenous test can be very useful in assessing ovulatory status of the woman by the clinicians in their offices.

Background. 5a-Reductase deficiency (5RD) is uncommon autosomal recessive disorder of sexual differentiation. It results from impaired conversion of testosterone to dihydrotestosterone due to mutations in the steroid 5a-reductase type 2 gene (SRD5A2). Mutations in SRD5A2 have not been previously reported in Indian patients with 5RD. Aim: To delineate the clinical features and mutations in the SRD5A2 gene in Indian patients with 5RD. Patients and Methods: The SRD5A2 gene was sequenced in two unrelated patients with elevated testosterone/dihydrotestosterone ratio and in one patient with classical clinical features and virilization at puberty (in whom the ratio could not be measured due to prior gonadectomy). The prevalence of SRD5A2 mutations was also studied in 52 healthy ethnic control subjects by PCR-RFLP. Results: Two patients, both from the north Indian state of Uttar Pradesh, carried the homozygous missense mutation p.R246Q in exon 5. Parents of both probands were heterozygous for the mutation. The mutation was absent in 52 control subjects. The third patient, with severe perineoscrotal hypospadias and micropenis, was detected to have a novel heterozygous missense mutation p.Q56H, as well as the homozygous polymbrohism, p.V89L, both in exon 1. The p.Q56H, mutation was absent in 52 control subjects. Conclusion: p.R246Q is a common SRD5A2 mutation in 5RD patients from the Indian subcontinent. © Freund Publishing House Ltd.

Previous studies on the influence of alcohol intake and smoking on bone mineral density (BMD) in men are inconsistent and the effect of these variables on BMD in physically active men is yet to be explored.To investigate the influence of alcohol intake and smoking on BMD in a cohort of males with well-defined lifestyle conditions.Men from the armed forces (n=400) having uniform and defined routines were enrolled. BMD was measured by DXA and participants were grouped according to lifestyle variables. Hormonal parameters were measured by immunoassays.Participants with intake of24 g/wk of alcohol had significantly higher BMD at femur compared to non-alcohol consumers (p=0.0001) and a linear increase in mean femoral BMD over increasing categories of alcohol intake (p(trend)0.0001) was observed. Smoking was negatively associated with femoral BMD. In multiple regression analysis, age, BMI, alcohol consumption and smoking were independent predictors of femoral BMD, explaining 10.6% variance. At lumbar spine, age, height and BMI were independent predictors, explaining 9.4% variance in BMD. The concentrations of total testosterone, free testosterone, bioavailable testosterone and PTH were low (p0.0001) whereas estradiol (p=0.02), free and bioavailable estradiol (p0.001) were high in alcohol consumers compared to non-consumers. In multiple regression analysis alcohol intake and height explained 5.5% variance in estradiol(.)In physically active men with well-defined lifestyle conditions, alcohol consumption was associated with higher femoral BMD, the effect of alcohol is complex and is probably partly mediated by influencing the sex steroid levels.

Age-related changes in sex steroid levels and its contribution to variations in rate of bone loss among men is unclear. Although, Bio-T and Bio-E2 levels declined with age and depicted an association with BMD in healthy Indian men, Bio-E2 was found to be an independent predictor of BMD. Ethnicity influences sex steroid levels, therefore, their role in pathogenesis of low bone mass needs to be established in various populations. We assessed the extent of changes in sex steroid levels with age and related these to bone mineral density (BMD) in healthy Indian men. Total testosterone (TT), estradiol (E2), sex hormone-binding globulin (SHBG), PTH, osteocalcin (OC), and c-terminal telopeptide (CTX) were measured in 330 men aged 20–55 years and correlated with BMD measured by DXA. Both Bio-T (1% per year) and Bio-E2 (0.8% per year) levels decreased significantly in ageing men, whereas TT (0.4% per year) and E2 (0.3% per year) levels decreased only marginally with age. In contrast, SHBG (1.4% per year) and PTH (1% per year) levels increased significantly with age. Serum TT (r = 0.19, p = 0.01) and Bio-T (r = 0.2, p = 0.01) levels were associated positively with BMD at spine, whereas E2 and Bio-E2 levels were associated with BMD at spine [E 2 (r = 0.31, p

To determine Vitamin D status of mother-newborn diads at birth and of their exclusively breastfed (EBF) infants at 3 months.Longitudinal study.Exclusively breastfed infants born at term with birth weight2.5 kg to normal, healthy mothers followed till 3 months. Serum calcium, phosphorous, heat labile alkaline phosphatase (HLAP) and 25(OH)D estimated in 42 mother / cord blood diads and in 35 (EBF) infants followed up at 3 months. Twenty five (OH)D15 ng/mL was considered low and 15 to 25 ng/mL low to normal.Ca, P, HLAP were significantly higher in cord blood (P0.001) but mean 25 (OH)D, 19.36 ng/mL was comparable to maternal level of 22.9 ng/mL (r = 0.82, P0.001). At 3 months only HLAP was significantly higher compared to cord blood. Higher 25 (OH)D at 3 months correlated with higher 25 (OH)D values in cord blood (r = +0.616, P0.001) as well as higher antenatal maternal levels (r = + 0.552, P0.001). Serum 25 (OH)D values25 ng/mL was observed in 50 % mothers, 62 % cord blood specimens and 80 % infants at 3 months.Subnormal maternal vitamin D status is associated with vitamin D deficiency in newborns and persists in exclusively breastfed infants.

Epithelial-myoepithelial carcinoma is a rare salivary gland tumor. It comprises less than 1% of all salivary gland tumors. It generally arises from the parotid gland. Unusual sites of occurrence include sinonasal tract, lung, trachea, lacrimal gland and breast. Histopathologically epithelial-myoepithelial carcinoma comprises a dual population of ductal and myoepithelial cells. We report an extremely rare case of epithelial-myoepithelial carcinoma occurring in the sinonasal tract of young man.

This study characterizes age‐related changes in bone turnover markers in relation to ovarian hormones. The data (N = 236) were divided into 5‐year age bands and three groups: premenopausal (Group I, N = 139), perimenopausal (Group II, N = 30), and postmenopausal (Group III, N = 67). Age‐related increases in mean parathyroid hormone (PTH), osteocalcin (OC), and collagen telopeptide (CTx) levels were observed. Women in Group II (N = 37) with osteopenia had lower levels of E(1)G (P

Obesity and decreased final height are described in children with CAH 21OHD. Of 119 children (50 M, 69F;79 Salt Wasters(SW), 40 Simple Virilizers (SV)) diagnosed over 24 years, various growth parameters were studied in 43 children with regular follow up for 5 years or more. Clinical data, anthropometry, genotype, hormonal and biochemical profile were evaluated at presentation. On follow up, growth and clinical characteristics, metabolic control (8am 17OH-Progesterone), bone age and replacement doses of gluco-corticoid (GC) and mineralo-corticoid (MC) were studied. Growth parameters were expressed as SDS. Obesity, defined as BMI SDS >/= 2 and short stature, defined as Ht SDS /=2 found in 32.6% cases (N=14/43: 2M, 12F; 8SW, 6SV) correlated positively with 17 OHP values (p=0.013). Girls were heavier than boys (p=0.006). Adiposity rebound occurred at 4 years for both the genders. At the time of study analysis, Ht SDS showed a distinct shift to the left and BMI SDS, a distinct shift to the right of mean of the reference population as cited [1]. In the present series, there was a higher incidence of obesity (32.6%) but short stature was noted in 27.9% only. Aggressive lifestyle management, dietary control, optimizing dose of therapy (GC) and regular monitoring should be an integral part of long term management of patients with CAH 21OHD.

BACKGROUND Various mutations of the growth hormone releasing hormone receptor (GHRH-R) gene have been recently described to cause familial isolated growth hormone (GH) deficiency (FIGHD), with the GHRH-R nonsense mutation E72X reported in patients with FIGHD from South Asia. The molecular genetic basis of FIGHD in Indian children is not known. OBJECTIVE To look for the GHRH-R E72X non-sense mutation in our patients with FIGHD and describe its clinical phenotype. PATIENTS AND METHOD A total of 31 patients from 22 families diagnosed 4-20 years previously, 20 patients with familial IGHD-IB from 11 families and 11 patients with non-familial isolated GH deficiency (NFIGHD) (phenotypes IGHD-IB in eight patients and -IA in three) were included. Twenty-eight of 31 patients with IGHD-IB came from two states of Western India, 27 of them Hindus from 18 families (three consanguineous) and one from an inbred Moslem kindred. RESULTS Twenty-two of the patients (71%) (18 FIGHD and four NFIGHD) had a homozygous G-->T transversion in exon 3, with this GHRH-R gene mutation E72X in 90% (18/20) of patients with FIGHD, 36% (4/11) of NFIGHD, altogether 78% (22/28) with phenotype IB. One parent pair with IGHD had homozygous E72X mutation, the rest were heterozygous carriers. Two siblings with IGHD due to homozygous E72X mutation were also heterozygous carriers for GH-1 gene 6.7 kb deletion, inherited from their mother, heterozygous for both GH-1 and GHRH-R mutations. Initial chronological age was 10.89 +/- 3.69 years, bone age 6.4 +/- 3.4 years, and mean height SDS was -5.83 +/- 1.41. The clinical phenotype, with sharp features, lean habitus, lack of frontal bossing or hypoglycemia, was characteristic. The mean peak GH was 1.25 +/- 0.75 ng/ml, IGF-I and IGFBP-3 below -2 SDS with no response to GHRH in those tested. MRI (n = 10) showed pituitary hypoplasia, mean vertical height 2.61 +/- 0.76 mm. Among the other 7/11 NFIGHD patients, four with phenotype IB were negative for genotypes tested in this study; of three patients with phenotype IA, two had the GH-1 gene 6.7 kb deletion, and one was a compound heterozygote with 6.7 and 7.6 kb deletions. CONCLUSIONS The majority of patients with FIGHD from different communities belonged to non-consanguineous Hindu families from Western India. The GHRH-R gene E72X mutation was found in 71% of this series, in 90% of FIGHD, 36% of NFIGHD, and in 78% with phenotype IB. The characteristic phenotype helped in suspecting this mutation. GHRH-R gene mutations may be the most reasonable candidate for IGHD-IB with the E72X mutation predominating in the Indian subcontinent. More extensive studies need to be undertaken.

Bone mineral density (BMD) is the major determinant of osteoporotic fracture risk with a particular genetic background. However, consensus on the association of BMD with specific gene locus has not been reached. In the present study, we investigated the potential association of estrogen receptor alpha (ER alpha) gene intron I polymorphisms with BMD in 246 postmenopausal Indian women (average age 54.2+/-3.4 years). All the subjects were genotyped for XbaI and PvuII polymorphisms and underwent BMD measurements at spine and hip by dual energy X-ray absorptiometery. The average BMD of subjects with the genotypes XX and PP (absence of restriction sites for XbaI and PvuII, respectively) was 12.7 and 5.4% higher at the spine and 13.1 and 4.6% higher at the hip, respectively, than those with genotypes xx and pp. In age vs. BMD scatterplot, the intercept and slope of regression lines for genotypes xx and pp at spine and hip demonstrated comparatively rapid decrease in BMD across the age. The genotype XX was significantly prevalent (p

An identical nonsense mutation (E72X) in growth hormone releasing hormone receptor (GHRHR) gene was identified in 17 patients with isolated GH deficiency belonging to one Muslim and four Hindu families residing in the Western part of India. Analysis of two dinucleotide repeat polymorphism, one at 6 kb downstream and the other at 13 kb downstream of GHRHR gene, revealed that all the patients shared the same homozygotic alleles at both loci. These results strongly indicate that the nonsense mutation occurred in a single ancestor and was subsequently transmitted to the descendants. This GHRHR mutation may be an important cause of familial IGHD in Western India and Sindh area of Pakistan as previous studies have also reported the same mutation.