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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+CD45RA-CCR7-HALDR+CCR6lowT-cells. Compared to Pre-N, Post-L showed increased proportion of Th17 with concomitant decrease in Th1 cells. The Th17 cells frequency in effector memory CD4+ T cells was significantly elevated in Post-N with a decrease of Th1 cells in effector memory subsets compared to Pre-N and Post-L. Both Post-N and Post-L had decreased frequency of dual positive Th1-Th17 cells and increased HLA-DR expression on Th17 cells compared to Pre-N. Thus, our study demonstrates increased Th17 cells frequency and reduced Th1 cells frequency with effector memory phenotype in postmenopausal women with estrogen insufficiency and correlates with aging process.
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Pós-Menopausa , Células Th17 , Feminino , Animais , Camundongos , Células Th17/metabolismo , Células Th1/metabolismo , Fenótipo , Estrogênios/metabolismoRESUMO
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 (ß = 0.098; p = 0.027) and rs3102735 (ß = 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.
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Densidade Óssea , Osteoprotegerina/genética , Ligante RANK/genética , Densidade Óssea/genética , Feminino , Humanos , Ligantes , Polimorfismo de Nucleotídeo ÚnicoRESUMO
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.
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Osteoporose , Ligante RANK , Adulto , Idoso , Biomarcadores , Densidade Óssea , Remodelação Óssea , Estudos Transversais , Estradiol , Feminino , Humanos , Pessoa de Meia-Idade , Valores de Referência , Adulto JovemRESUMO
Osteoporosis is one of the chronic and often neglected bone diseases in aging postmenopausal women that affect the quality of life. Studies on ovariectomized mice models indicated the reciprocal role of Th17 cells and Treg cells in the aetiology of osteoporosis. While Th17 cells promote osteoclastogenesis, Treg cells exhibit anti-osteoclastogenic activity. This exploratory study aimed to determine the difference in the frequency of these T-cell subtypes in pre-and postmenopausal women and to examine their association with BMD. In our study, the frequency of Treg cells, analyzed by flow cytometry, did not differ between pre-and postmenopausal women. However, plasma levels of IL-10 along with IL-10+CD4+T cells were higher in post- compared to premenopausal women. The frequency of Th17 cells was higher in postmenopausal women irrespective of their BMD, however, only postmenopausal women with low BMD had elevated IL-17 levels and their T-scores were associated with Th17 frequency. Collectively, the results suggest that estrogen insufficiency in postmenopausal women may lead to increased Th17 cell frequency and elevated IL-17 levels which are associated with low BMD. This study highlights, Th17 cells and IL-17 as key players in the pathogenesis of osteoporosis and they can be the potential targets for immunotherapy in the treatment of osteoporosis.
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Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/imunologia , Interleucina-17/sangue , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/imunologia , Pós-Menopausa/sangue , Pós-Menopausa/imunologia , Células Th17/imunologia , Adulto , Idoso , Biomarcadores/sangue , Densidade Óssea/imunologia , Doenças Ósseas Metabólicas/etiologia , Linfócitos T CD4-Positivos/imunologia , Estudos de Coortes , Citocinas/sangue , Estrogênios/deficiência , Feminino , Humanos , Interleucina-10/sangue , Subunidade alfa de Receptor de Interleucina-2/sangue , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/etiologia , Linfócitos T Reguladores/imunologiaRESUMO
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 < 0.0001) in the OC levels by the two assays was observed. Cut off limits established earlier with indigenous assay (11.9 ng/mL and 14.9 ng/mL) for Osteopenia and Osteoporosis were similar to those with the commercial kit (13.2 ng/mL and 16.8 ng/mL) respectively. The diagnostic sensitivity, specificity and accuracy of the OC prototype was > 85%. The cost effective OC prototype can be used in screening and management of Indian women with low bone mass.
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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.
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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 (nâ¯=â¯293, mean age: 33.01⯱â¯5.23â¯years) and postmenopausal (nâ¯=â¯145, mean age: 56.91⯱â¯7.1â¯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 (ORâ¯=â¯3.3, 95% CIâ¯=â¯1.067-10.204) in postmenopausal women suggesting that allele X is protective (ORâ¯=â¯0.419, 95% CIâ¯=â¯0.177-0.991). Genotype aa in AluI polymorphism, seemed to be protective (ORâ¯=â¯0.092 for osteopenia; ORâ¯=â¯0.152 for osteoporosis) at spine whereas A allele was associated with osteopenia at femur (ORâ¯=â¯2.123, 95% CIâ¯=â¯1.079-4.166) in postmenopausal women. Allele r of RsaI polymorphism, was associated with osteoporosis at spine (ORâ¯=â¯3.222, 95% CIâ¯=â¯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.
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Doenças Ósseas Metabólicas/genética , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Lipídeos/análise , Polimorfismo de Nucleotídeo Único , Pós-Menopausa/genética , Pré-Menopausa/genética , Absorciometria de Fóton , Adulto , Densidade Óssea , Doenças Ósseas Metabólicas/metabolismo , Feminino , Fêmur/diagnóstico por imagem , Estudos de Associação Genética , Humanos , Índia , Modelos Logísticos , Pessoa de Meia-Idade , Coluna Vertebral/diagnóstico por imagem , População Branca/genéticaRESUMO
BACKGROUND: 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. METHODS: 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. RESULTS: 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, pâ¯<â¯.0001) compared to women with normal BMD. ROC analysis demonstrated the cut off values of OC >11.9â¯ng/mL for osteopenia andâ¯>â¯14.9â¯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 3â¯months in women monitored on therapy. CONCLUSION: The developed OC ELISA has great potential to be used as a biomarker for routine screening and management of osteoporosis in Indian women.
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Ensaio de Imunoadsorção Enzimática/métodos , Osteocalcina/sangue , Osteoporose/sangue , Osteoporose/diagnóstico , Adulto , Análise Custo-Benefício , Ensaio de Imunoadsorção Enzimática/economia , Feminino , Terapia de Reposição Hormonal , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade , Osteoporose/terapia , Valor Preditivo dos Testes , Curva ROC , Fatores de TempoRESUMO
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. PURPOSE: 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. METHODS: 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. RESULTS: Positive correlation of BMD with HDL (spine and femur r = 0.38, p < 0.0001) and triglyceride (spine r = 0.534, p < 0.0001; femur r = 0.423, p < 0.0001) was observed, whereas Hcy correlated negatively with BMD (spine r = - 0.189, p = 0.0026; femur r = - 0.273, p < 0.0001). LDL showed a weak negative correlation with BMD (spine r = - 0.128, p = 0.0283; femur r = - 0.199, p = 0.0006). However, after adjusting for age, BMI, and consumption, HDL, triglyceride, and Hcy continued to show significant correlation with BMD at both the sites. Logistic regression analyses indicated that HDL, triglyceride, and Hcy were significant predictors of osteopenia and osteoporosis in our study cohort; however, consumption did not contribute to its prediction. CONCLUSION: Low levels of HDL and triglyceride and high levels of Hcy are significantly associated with osteopenia and osteoporosis in young Northeast Indian women.
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Absorciometria de Fóton/estatística & dados numéricos , Densidade Óssea , Homocisteína/sangue , Lipoproteínas HDL/sangue , Triglicerídeos/sangue , Adulto , Povo Asiático/estatística & dados numéricos , Doenças Ósseas Metabólicas/epidemiologia , Doenças Ósseas Metabólicas/etnologia , Doenças Ósseas Metabólicas/etiologia , Estudos de Coortes , Feminino , Fêmur/diagnóstico por imagem , Humanos , Índia/etnologia , Vértebras Lombares/diagnóstico por imagem , Programas de Rastreamento , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/etnologia , Osteoporose/etiologia , Grupos Populacionais , Pré-Menopausa/etnologia , Fatores de Risco , Adulto JovemRESUMO
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.
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Endocrinologia/tendências , Pediatria/tendências , Criança , Países em Desenvolvimento , Humanos , ÍndiaRESUMO
Procedures in class B ambulatory facilities are performed exclusively with oral or IV sedative-hypnotics and/or analgesics. These facilities typically do not stock dantrolene because no known triggers of malignant hyperthermia (ie, inhaled anesthetics and succinylcholine) are available. This article argues that, in the absence of succinylcholine, the morbidity and mortality from laryngospasm can be significant, indeed, higher than the unlikely scenario of succinylcholine-triggered malignant hyperthermia. The Society for Ambulatory Anesthesia (SAMBA) position statement for the use of succinylcholine for emergency airway management is presented.
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Manuseio das Vias Aéreas/métodos , Assistência Ambulatorial/estatística & dados numéricos , Anestesia , Laringismo/mortalidade , Hipertermia Maligna/mortalidade , Fármacos Neuromusculares Despolarizantes/efeitos adversos , Succinilcolina/efeitos adversos , Manuseio das Vias Aéreas/efeitos adversos , Instituições de Assistência Ambulatorial , Dantroleno/efeitos adversos , Dantroleno/uso terapêutico , Serviços Médicos de Emergência , Humanos , Laringismo/tratamento farmacológico , Relaxantes Musculares Centrais/efeitos adversos , Relaxantes Musculares Centrais/uso terapêutico , Assistência Perioperatória , PrevalênciaRESUMO
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<0.05). It also exhibited a significant odds ratio (OR) to differentiate between low and high BMD in both premenopausal (OR=1.734, p=0.013) and postmenopausal (OR=1.463, p=0.042) categories. Additionally, area under the curve to predict low BMD was non-significantly higher for pHSP27 than CTX-1 in premenopausal and postmenopausal categories. INTERPRETATION & CONCLUSIONS: This study highlights a novel relation between serum pHSP27 and BMD in Indian women however, these findings need to be confirmed in larger studies.
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Densidade Óssea/genética , Proteínas de Choque Térmico HSP27/sangue , Osteoporose/sangue , Adulto , Feminino , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico , Humanos , Interleucina-6/sangue , Pessoa de Meia-Idade , Chaperonas Moleculares , Osteocalcina/sangue , Osteoporose/genética , Osteoporose/patologia , Estresse Oxidativo/genética , Fosforilação , Projetos Piloto , Pós-Menopausa/sangue , Pré-Menopausa/sangueRESUMO
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 < 0.0001). When criteria of National Osteoporosis Foundation, US was applied number of participants eligible for medical therapy increased upon inclusion of bone mineral density, (for major osteoporotic fracture risk number of women eligible without bone mineral density was 0 and with bone mineral density was 1, 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 < 0.0001). 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.
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Densidade Óssea , Fraturas do Quadril/prevenção & controle , Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/prevenção & controle , Absorciometria de Fóton , Adulto , Idoso , Feminino , Colo do Fêmur/diagnóstico por imagem , Humanos , Índia , Vértebras Lombares/diagnóstico por imagem , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Pós-Menopausa , Estudos Retrospectivos , Medição de Risco/métodosRESUMO
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 of NFkB ligand) 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.
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Densidade Óssea/genética , Proteínas de Choque Térmico HSP27/metabolismo , Monócitos/metabolismo , Osteoporose/genética , Processamento de Proteína Pós-Traducional , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Movimento Celular , Feminino , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico , Humanos , Pessoa de Meia-Idade , Chaperonas Moleculares , Monócitos/fisiologia , Osteoporose/metabolismo , Osteoporose/patologia , Fosforilação , Pós-Menopausa/metabolismo , Ligante RANK/metabolismoRESUMO
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.
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Ensaio de Imunoadsorção Enzimática/métodos , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Proteínas Secretadas pela Próstata/sangue , Adulto , Biomarcadores/sangue , Análise Química do Sangue , Estudos de Casos e Controles , Estudos de Coortes , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
BACKGROUND: Sustained-release GH formulations may provide a strategy for improving treatment compliance and persistence in GH-deficient patients. OBJECTIVE: The aim of the study was to examine efficacy and safety of LB03002, a sustained-release GH formulation for once-weekly administration. DESIGN: We conducted a phase III, 12-month, multinational, randomized, open-label, comparator-controlled trial with a 12-month uncontrolled extension. PATIENTS: Prepubertal GH treatment-naive GH-deficient children (mean age, 7.8 y) participated in the study. INTERVENTION: We administered once-weekly LB03002 (n=91) or daily GH (n=87) for 1 year, followed by once-weekly LB03002 for all patients for another year (LB03002 throughout, n=87; switched to LB03002, n=80). OUTCOME MEASURES: Height, height velocity (HV), IGF-1, GH antibodies, and adverse events were determined throughout. Primary analysis was noninferiority of LB03002 vs daily GH at 1 year by analysis of covariance. RESULTS: Mean±SD HV during year 1 was 11.63±2.60 cm/y with LB03002, and 11.97±3.09 cm/y with daily GH, with increases from baseline of 8.94±2.91 and 9.04±3.19 cm/y, respectively. The least square mean HV difference for LB03002 - daily GH was -0.43 cm/y (99% confidence interval, -1.45 to 0.60 cm/y). Mean HV also remained above baseline in year 2 (8.33±1.92 cm/y in the LB03002 throughout group, and 7.28±2.34 cm/y in the switched to LB03002 group). Injection site reactions occurred more frequently in LB03002-treated patients but were considered mild to moderate in >90% of cases. CONCLUSIONS: Growth response with once-weekly LB03002 in GH-deficient children is comparable to that with daily GH, achieving expected growth rates for 24 months. Once-weekly LB03002 is a strong candidate for long-term GH replacement in GH-deficient children.
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Transtornos do Crescimento/tratamento farmacológico , Hormônio do Crescimento Humano/administração & dosagem , Anticorpos/sangue , Estatura/efeitos dos fármacos , Criança , Pré-Escolar , Preparações de Ação Retardada , Esquema de Medicação , Feminino , Transtornos do Crescimento/sangue , Hormônio do Crescimento Humano/efeitos adversos , Hormônio do Crescimento Humano/deficiência , Humanos , Masculino , Puberdade , Fatores de TempoRESUMO
OBJECTIVE: 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. METHODS: 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. RESULTS: 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 < 0.001) and peak GH (0.03 ng/dl, p < 0.01). In Group II phenotype was IB. Twenty one of the 23 FIGHD had homozygous GHRHR(E72X) mutation and four with IGHD had heterozygous GHRHR(E72X) mutation. IGF1 and IGFBP3 were low. MRI showed hypoplastic anterior pituitary (APH) in all. Group III is not discussed in detail. CONCLUSIONS: Genetic background is more likely in congenital Growth Hormone Deficiency (GHD). GH1gene deletions and GHRHR(E72X) mutation with characteristic phenotypes are encountered in North Western region of India. Regional studies are essential.
Assuntos
Nanismo Hipofisário/genética , Adolescente , Criança , Pré-Escolar , Consanguinidade , Eletroforese em Gel de Ágar , Feminino , Deleção de Genes , Genótipo , Hormônio do Crescimento/genética , Hormônio Liberador de Hormônio do Crescimento/genética , Humanos , Lactente , Masculino , FenótipoRESUMO
OBJECTIVES: To determine the variables affecting serum 17 hydroxyprogesterone (17OHP) in neonates born at a tertiary hospital in Mumbai, India. METHODS: 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. RESULTS: 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 = <0.0001). On follow up at 3 mo age, the median 17OHP (N = 73 newborns) had significantly decreased to normal level. CONCLUSION: Stress due to neonatal illnesses like meconium aspiration, sepsis, birth asphyxia, etc. significantly elevate serum 17OHP and may lead to false positives in newborn screening for congenital adrenal hyperplasia.
Assuntos
17-alfa-Hidroxiprogesterona/sangue , Hiperplasia Suprarrenal Congênita/sangue , Recém-Nascido Prematuro/sangue , Triagem Neonatal/métodos , Hiperplasia Suprarrenal Congênita/diagnóstico , Feminino , Humanos , Índia , Recém-Nascido , Masculino , Gravidez , Estudos Prospectivos , Centros de Atenção TerciáriaRESUMO
Primary sporadic congenital hypothyroidism (CH) is the most common cause of hypothyroidism infancy early childhood in iodine sufficient region. Screening for neonatal CH began in 1970s. The rationale and reason for neonatal screening for CH (NSCH) are well established. It is mandatory in most developed countries along with the screen for metabolic disorder. The possibility of measuring TSH and thyroid hormones in cord blood paved the way for newborn screening (NS) for CH. Worldwide it is estimated that 25% of the live born population of 130 million babies undergo NSCH. Klein et al., by 1972 had shown improved CNS prognosis in CH treated by age 3 months. NSCH has largely eradicated the severe irreversible neurodevelopmental damage and reversed the chances of growth failure in infancy and early childhood.