RESUMO
Hypertension causes complications such as coronary atherosclerosis and thrombosis wherein inflammatory factors play significant role. In the present study inflammatory molecules such as cell adhesion molecules (CAMs); endothelial (E)-selectin, platelet (P)-selectin, intercellular CAM-1 (ICAM-1), vascular CAM-1 (VCAM-1) and platelet endothelial CAM-1 (PECAM-1) were analysed in subjects newly diagnosed with hypertension with no secondary cause against normotensive healthy individuals. In each group 57 subjects were recruited and soluble (s) levels of CAMs were analysed by ELISA. As compared to controls median of sE-selectin (49.2%, P=0.001), sP-selectin (54.3%, P=0.001), and sICAM-1 (18.9%, P=0.012) were significantly elevated in hypertensive subjects. Significant negative correlation was observed of sP-selectin (spearman rank correlation coefficient (rs) =-0.345, p=0.027) and sPECAM-1 (rs =-0.446, p=0.003) with age in hypertension group. Hypertension may increase expression of certain CAMs while younger hypertensives in addition are also at increased risk of atherothrombosis.
RESUMO
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
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
OBJECTIVE: 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. METHODS: 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. RESULTS: 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 (p<0.001) mean 1.1 vs 4.7 y. Mean height SDS was -7 vs. -4.5 in Groups I/II (p<0.01), age at presentation 5.1 vs 8.6 y. Overhanging forehead, prominent eyes, hypoplastic facies characterized Group I with FBS <50 mg/dl in 50% and very low peak GH <0.04 vs 2.04 ng/ml (p<0.001) 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). CONCLUSIONS: 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 GH<1 ng/ml and hypoglycemia characterised IGHD Type IA.
Assuntos
Sequência de Bases , Nanismo Hipofisário/genética , Hormônio do Crescimento Humano/genética , Deleção de Sequência , Adolescente , Criança , Pré-Escolar , Nanismo Hipofisário/diagnóstico , Eletroforese em Gel de Ágar , Feminino , Humanos , Índia , Lactente , Masculino , Fenótipo , Reação em Cadeia da Polimerase , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Platelet-endothelial cell adhesion molecule-1 (PECAM-1) has role in atherosclerotic plaque development as well as in thrombosis leading to myocardial infarction (MI). Present study was aimed to analyse the association of PECAM-1 Leu125Val gene polymorphism with MI in Indian population. Subjects included healthy individuals as control (N = 116) and MI patients (N = 100) divided into two groups; MI patients at presentation of the acute event (MI-Group-1, N = 46) and patients with recent event of MI stabilized with treatment 4.5 days from their symptoms (MI-Group-2, N = 54). The difference in the distribution of Leu125Val genotype frequencies of controls and patients did not reach statistical significance. However Leu allele frequency (0.57) was more associated with MI patients as compared to control (0.504). sPECAM-1 levels were significantly elevated in patients at acute event of MI (MI-Group-1) by 44.1% (P = 0.009) as compared to controls and by 95.2% (P = 0.001) as compared to stabilized MI patients (MI-Group-2).