Isolation of a somatomedin binding protein from human preterm amniotic fluid : development of a radioimmunoassay

This thesis study was undertaken in order to investigate the nature and biological behavior of a somatornedin binding protein, identified in preterrn amniotic fluid (AF). Somatomedin (SM) is the generic designation applied to a family of serum peptide growth factors which are growth hormone dependent, stimulate incorporation of sulphate into cartilage, have insulin-like actions on nonskeletal tissues and increase mitosis in a wide variety of cultured cells. Thusfar two peptides have been fully characterized: insulin-like growth factor I (IGF-I), shown to be identical to sornatomedin-C, and insulin-like growth factor II (IGF-II). IGF-I and IGF-II have a 62% aminoacid sequence identity and are 38-48% homologous with the A and B domains of human pro-insulin

Etiology and Clinical Presentation of Disorders of Sex Development in Kenyan Children and Adolescents

Objective. )e purpose of this study was to describe baseline data on etiological, clinical, laboratory, and management strategies in Kenyan children and adolescents with Disorders of Sex Development (DSD). Methods. )is retrospective study included patients diagnosed with DSD who presented at ages 0–19 years from January 2008 to December 2015 at the Kenyatta National (KNH) and Gertrude’s Children’s (GCH) Hospitals. After conducting a search in the data registry, a structured data collection sheet was used for collection of demographic and clinical data. Data analysis involved description of the frequency of occurrence of various variables, such as etiologic diagnoses and patient characteristics. Results. Data from the records of 71 children and adolescents were reviewed at KNH (n � 57, 80.3%) and GCH (n � 14, 19.7%). )e mean age at the time of diagnosis was 2.7 years with a median of 3 months. )irty-nine (54.9%) children had karyotype testing done. )e median age (IQR) of children with reported karyotypes and those without was 3.3 years (1.3–8.9) and 8.3 years (3.6–12.1), respectively (p � 0.021). Based on karyotype analysis, 19 (48.7%) of karyotyped children had 46,XY DSD and 18 (46.2%) had 46,XX DSD. )ere were two (5.1%) children with sex chromosome DSD. Among the 71 patients, the most common presumed causes of DSD were ovotesticular DSD (14.1%) and CAH (11.3%). Majority (95.7%) of the patients presented with symptoms of DSD at birth. )e most common presenting symptom was ambiguous genitalia, which

The ESPE e-learning webportal: A global tool for instruction and formative assessment of pediatric endocrinology

The ESPE e-learning portal (http://www.espe-elearning.org) aims at supporting the learning of cognitive objectives, competencies and skills at two levels: core (medical students) and advanced (fellow/postdoc). It provides a rich source of up-to-date information on various Pediatric Endocrinology topics. The ESPE elearning webportal offers a set of functionalities consisting of a general learning content (chapters, problem solving cases, self-tests, glossary, community) and the option to construct specific courses for an event (ESPE school) or organization: a client, university or institution. Moreover, a set of question types has been developed allowing scoring and assessment of competencies. The content is being expanded and includes chapters and/or cases on the topics of growth, puberty, DSD, calcium and bone, diabetes, hyperinsulinism, thyroidal disorders, adrenal disorders, dis-electrolytemia. Since the portal has been moved to its definite address the global use of the portal has increased: during the period September - December 2013 there were 1264 visits; during the period January-April 2014 there were 2393 visits. The availability of the portal for members and non-members of ESPE needs to be emphasized and needs to be made public widely. Moreover, relevant feedback from users should be translated by the editorial board to make practical improvements. As demonstrated during two courses held in Varna, Bulgaria the portal facilitates the combination of online learning and face-to-face instruction: blended learning. Finally, the next step in extending the impact of the e-learning portal is the further development of learning and competency assessment tools. Furthermore, in demonstrating its applicability at a global level, regional and cultural aspects should be fully recognized

Bone mineral density and body composition before and during treatment with gonadotropin-releasing hormone agonist in children with central precocious and early puberty

Major changes in bone mineral density (BMD) and body composition occur during puberty. In the present longitudinal study, we evaluated BMD and calculated volumetric BMD [bone mineral apparent density (BMAD)], bone metabolism, and body composition of children (32 girls and 2 boys) with central precocious and early puberty before and during treatment with GnRH agonist (GnRH). Patients were studied at baseline and during treatment for 6 months (n = 34), 1 yr (n = 33), and 2 yr (n = 16). Lumbar spine and total body BMD and body composition were measured with dual-energy x-ray absorptiometry. The variables were compared with age- and sex-matched reference values of the same population and expressed as SD score (SDS). Bone age was assessed. Serum calcium, phosphate, alkaline phosphatase, osteocalcin, the carboxyterminal propeptide of type I collagen (PICP), cross-linked telopeptide of collagen I (ICTP), 1,25 dihydroxyvitamin D and urinary hydroxyproline/creatinine, and calcium/ creatinine ratios were measured. Mean lumbar spine BMD SDS was significantly higher than zero at baseline (P < 0.02) and did not differ from normal, after 2 yr of treatment. Mean spinal BMAD SDS and total body BMD SDS were not significantly different from zero at baseline and had not changed significantly after 2 yr of treatment. During therapy, fat mass and percentage body fat SDS increased, whereas lean tissue mass SDS decreased. Mean lumbar spine BMD and BMAD and total body BMD SDS, calculated for bone age, were all lower than zero at baseline (BMD P < 0.001 and BMAD P < 0.05) and also after 2 yr treatment (respectively, P < 0.001, P < 0.05, and P < 0.01). Biochemical bone parameters were significantly higher than prepubertal values at baseline, and they decreased during treatment. In conclusion, patients with central precocious and early puberty had normal BMD for chronological age but low BMD for bone age, after 2 yr of treatment with GnRH. Bone turnover decreased during treatment. Changes in body composition resembled those seen in patients with GH deficiency

CDNA cloning and mRNA expression of the six mouse insulin-like growth factor binding proteins

The insulin-like growth factor binding proteins (IGFBPs) comprise a family of six distinct proteins which modulate insulin-like growth factor action. We have isolated cDNAs encoding the six mouse IGFBPs (mIGFBPs). In addition, we studied the mRNA expression of the six mIGFBPs during development and in various adult tissues. Our results show that each of the six mIGFBPs is highly homologous to their human and rat counterparts, whereas only the N and C terminal ends are conserved between the six mIGFBPs. Northern blotting revealed that mIGFBP-2, -3, -4 and -5 genes are already expressed at gestational day 11.5, suggesting a role for these mIGFBPs in embryonal development. In liver, a peak of mIGFBP-1 mRNA expression was found around birth, suggesting a function for mIGFBP-1 in the newborn mouse. Finally, tissue-specific expression of the six mouse IGFBP genes was observed in adult tissues suggesting different roles or modes of actions in adult life

Insulin-like growth factor binding protein-2, 28 kDa an 24 kDa insulin-like growth factor binding protein levels are decreased in fluid of dominant follicles, obtained from normal and polycystic ovaries

In order to investigate potential changes in insulin-like growth factor binding proteins (IGFBPs) during human follicle maturation, we examined the IGFBP profiles in follicular fluid from follicles in different stages of maturation. Samples were obtained from ovaries of women with regular menstrual cycles and of subjects with cycle abnormalities and polycystic ovaries (diagnosed as polycystic ovary syndrome (PCOS)) and analyzed by Western ligand blotting. IGFBPs of 43 kDa, 37 kDa, 31 kDa, a doublet around 28 kDa and a minor band of 24 kDa were detected in follicle fluid of normal non-dominant (size 4) follicles of both regularly menstruating women and PCOS patients. The 43 and 37 kDa IGFBPs could be identified as IGFBP-3 and the 31 kDa IGFBP as IGFBP-2, whereas the 28 kDa IGFBP could not be identified as IGFBP-1, all by immunoblotting techniques. A dramatic decrease in IGFBP-2, the 28 kDa and 24 kDa IGFBPs was observed in follicular fluid of dominant follicles (size > 10 mm) of both regular menstruating individuals and one PCOS patient as compared with follicular fluid of normal non-dominant or atretic follicles. These observations indicate that the PCOS follicle may not be different from normal with respect to IGFBP profiles. Furthermore, these results suggest that at least one of these IGFBPs might be involved in human folliculogenesis

Gender Development in Indonesian Children, Adolescents, and Adults with Disorders of Sex Development

Abstract In most Western countries, clinical management of disorders of sex development (DSD), including ambiguous gen-italia, begins at diagnosis soon after birth. For many Indonesian patients born with ambiguous genitalia, limited medical treat-ment is available. Consequently, affected individuals are raised with ambiguous genitalia and atypical secondary sex character-istics. We investigated gender identity and gender role behavior in 118 Indonesian subjects (77 males, 41 females) with different types of DSD in comparison with 118 healthy controls matched forgender,age,andresidentialsetting(rural,suburban,orurban).In Study 1, we report on methodological aspects of the investigation, including scale adaptation, pilot testing, and determining reliability and validity of measures. In Study 2, we report on gender devel-opment in 60 children (42 boys, 18 girls), 24 adolescents (15 boys, 9 girls), and 34 adults (19 men, 15 women) with DSD. The majority of participants with DSD never received any medical or surgical treatmentpriortothisstudy.Weobservedagenderchangeinallage groups, with the greatest incidence in adults. Among patients who changed, most changed from female to male, possessed a 46,XY karyotype, and had experienced significant masculinization during life. Gender identity confusion and cross-gender behavior was more frequently observed in children with DSD raised as girls compared to boys. Puberty and associated masculinization were related to gender problems in individuals with 46,XY DSD raised female. An integrated clinical and psychological follow-up on gender outcome is necessary prior to puberty and adulthood