Androgens correlate with increased erythropoiesis in women with congenital adrenal hyperplasia.

OBJECTIVE: Hyperandrogenism in congenital adrenal hyperplasia (CAH) provides an in vivo model for exploring the effect of androgens on erythropoiesis in women. We investigated the association of androgens with haemoglobin (Hb) and haematocrit (Hct) in women with CAH. DESIGN: Cross-validation study PATIENTS: Women with CAH from Sheffield Teaching Hospitals, UK (cohort 1, the training set: n=23) and National Institutes of Health, USA (cohort 2, the validation set: n=53). MEASUREMENTS: Androgens, full blood count and basic biochemistry, all measured on the same day. Demographic and anthropometric data. RESULTS: Significant age-adjusted correlations (P<0.001) were observed for Ln testosterone with Hb and Hct in cohorts 1 and 2 (Hb r=0.712 & 0.524 and Hct r=0.705 & 0.466), which remained significant after adjustments for CAH status, glucocorticoid treatment dose and serum creatinine. In the combined cohorts Hb correlated with androstenedione (P=0.002) and 17-hydroxyprogesterone (P=0.008). Hb and Hct were significantly higher in cohort 1 than those in cohort 2, while there were no group differences in androgen levels, glucocorticoid treatment dose or body mass index. In both cohorts, women with Hb and Hct in the highest tertile had significantly higher testosterone levels than women with Hb and Hct in the lowest tertile. CONCLUSIONS: In women with CAH, erythropoiesis may be driven by androgens and could be considered a biomarker for disease control

Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: identifying optimal monitoring times and novel disease biomarkers

Objectives: The treatment goal in congenital adrenal hyperplasia (CAH) is to replace glucocorticoids while avoiding androgen excess and iatrogenic Cushing's syndrome. However, there is no consensus on how to monitor disease control. Our main objectives were to evaluate hormonal circadian rhythms and use these profiles to identify optimal monitoring times and novel disease biomarkers in CAH adults on intermediate- and long-acting glucocorticoids. Design: This was an observational, cross-sectional study at the National Institutes of Health Clinical Center in 16 patients with classic CAH. Methods: Twenty-four-hour serum sampling for ACTH, 17-hydroxyprogesterone (17OHP), androstenedione (A4), androsterone, DHEA, testosterone, progesterone and 24-h urinary pdiol and 5β-pdiol was carried out. Bayesian spectral analysis and cosinor analysis were performed to detect circadian rhythmicity. The number of hours to minimal (TminAC) and maximal (TmaxAC) adrenocortical hormone levels after dose administration was calculated. Results: A significant rhythm was confirmed for ACTH (r2, 0.95; P<0.001), 17OHP (r2, 0.70; P=0.003), androstenedione (r2, 0.47; P=0.043), androsterone (r2, 0.80; P<0.001), testosterone (r2, 0.47; P=0.042) and progesterone (r2, 0.64; P=0.006). The mean (S.D.) TminAC and TmaxAC for 17OHP and A4 were: morning prednisone (4.3 (2.3) and 9.7 (3.5) h), evening prednisone (4.5 (2.0) and 10.3 (2.4) h), and daily dexamethasone (9.2 (3.5) and 16.4 (7.2) h). AUC0–24 h progesterone, androsterone and 24-h urine pdiol were significantly related to 17OHP. Conclusion: In CAH patients, adrenal androgens exhibit circadian rhythms influenced by glucocorticoid replacement. Measurement of adrenocortical hormones and interpretation of results should take into account the type of glucocorticoid and time of dose administration. Progesterone and backdoor metabolites may provide alternative disease biomarkers

Perkembangan Pandemic Dan Capaian Kontrasepsi Di Provinsi Jawa Timur

The impact of the Covid-19 pandemic is being felt all over the world, especially in Indonesia. Covid-19 has had an impact on the health, economic and social sectors. The large number of deaths due to disease causes changes in the composition of the population. To prevent the spread from becoming more widespread, the government implemented large-scale social restrictions. Travel restrictions and long stays at home have the government fearing a post-pandemic boom in births. Therefore the government focuses on birth control. This study aims to determine the development of a pandemic and its impact on the number of new users of family planning methods in East Java Province.The research used secondary data that came from the website of the East Java Provincial Health Office and the Population and Family Planning Agency from March 2020 to November 2021. The results of the regression test showed that there was no effect between the number of positive confirmed cases of Covid-19 and the number of new users of contraceptive methods. This shows that the policies developed have been successful and it is hoped that there will be a strategy for family planning services for other emergencies. Socialization and establishing cooperation between health workers in the field also need to be improved, especially for health workers in the private sector

Age-performance and intensity of grooming behavior toward Varroa destructor in resistant and susceptible Apis mellifera colonies

Grooming behavior confers resistance to honey bees against Varroa destructor, being of interest to social immunity studies and breeding programs. The objective of this study was to characterize at the individual level the grooming behavior of mite-resistant (R) and susceptible (S) A. mellifera stocks from Argentina. Assays were performed in experimental arenas by applying two treatments to nurse bees: (1) placing a V. destructor mite on the bee’s thorax and (2) touching the bee with a paintbrush. Grooming reactions were recorded on bees from both stocks at the ages of 6, 10, and 14 days after emergence. R bees exhibited lower time of first response against the mite, performed more cleaning attempts, and used all their legs with a higher probability compared to S bees. The same pattern was evident when younger and older bees from the R stock were compared. The results demonstrate that bee age and genetic origin are critical factors of grooming behavior in honey bees.Fil: Russo, Romina Maria. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; ArgentinaFil: Landi, Lucas. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Recursos Naturales. Instituto de Recursos Biológicos; ArgentinaFil: Muntaabski, Irina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; ArgentinaFil: Liendo, María Clara. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; ArgentinaFil: Pietronave, Hernán Pablo. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Reconquista; ArgentinaFil: Merke, Julieta. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Rodríguez, Graciela A.. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Hilario Ascasubi; ArgentinaFil: Palacio, María A.. Universidad Nacional de Mar del Plata; Argentina. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Basilio, Alicia Mabel. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal. Cátedra de Avicultura, Cunicultura y Apicultura; ArgentinaFil: Lanzavecchia, Silvia Beatriz. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; ArgentinaFil: Scannapieco, Alejandra Carla. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo | Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular. Grupo Vinculado Instituto de Genética "Ewald A. Favret" al Iabimo; Argentin

Recruitment, augmentation and apoptosis of rat osteoclasts in 1,25-(OH)2D3 response to short-term treatment with 1,25-dihydroxyvitamin D3in vivo

Background Although much is known about the regulation of osteoclast (OC) formation and activity, little is known about OC senescence. In particular, the fate of of OC seen after 1,25-(OH)2D3 administration in vivo is unclear. There is evidence that the normal fate of OC is to undergo apoptosis (programmed cell death). We have investigated the effect of short-term application of high dose 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on OC apoptosis in an experimental rat model. Methods OC recruitment, augmentation and apoptosis was visualised and quantitated by staining histochemically for tartrate resistant acid phosphatase (TRAP), double staining for TRAP/ED1 or TRAP/DAPI, in situ DNA fragmentation end labelling and histomorphometric analysis. Results Short-term treatment with high-dose 1,25-(OH)2D3 increased the recruitment of OC precursors in the bone marrow resulting in a short-lived increase in OC numbers. This was rapidly followed by an increase in the number of apoptotic OC and their subsequent removal. The response of OC to 1,25-(OH)2D3 treatment was dose and site dependent; higher doses producing stronger, more rapid responses and the response in the tibiae being consistently stronger and more rapid than in the vertebrae. Conclusions This study demonstrates that (1) after recruitment, OC are removed from the resorption site by apoptosis (2) the combined use of TRAP and ED1 can be used to identify OC and their precursors in vivo (3) double staining for TRAP and DAPI or in situ DNA fragmentation end labelling can be used to identify apoptotic OC in vivo

Modified-release hydrocortisone in congenital adrenal hyperplasia

Context Standard glucocorticoid therapy in congenital adrenal hyperplasia (CAH) regularly fails to control androgen excess, causing glucocorticoid overexposure and poor health outcomes. Objective We investigated whether modified-release hydrocortisone (MR-HC), which mimics physiologic cortisol secretion, could improve disease control. Methods A 6-month, randomized, phase 3 study was conducted of MR-HC vs standard glucocorticoid, followed by a single-arm MR-HC extension study. Primary outcomes were change in 24-hour SD score (SDS) of androgen precursor 17-hydroxyprogesterone (17OHP) for phase 3, and efficacy, safety and tolerability of MR-HC for the extension study. Results The phase 3 study recruited 122 adult CAH patients. Although the study failed its primary outcome at 6 months, there was evidence of better biochemical control on MR-HC, with lower 17OHP SDS at 4 (P = .007) and 12 (P = .019) weeks, and between 07:00h to 15:00h (P = .044) at 6 months. The percentage of patients with controlled 09:00h serum 17OHP (< 1200 ng/dL) was 52% at baseline, at 6 months 91% for MR-HC and 71% for standard therapy (P = .002), and 80% for MR-HC at 18 months’ extension. The median daily hydrocortisone dose was 25 mg at baseline, at 6 months 31 mg for standard therapy, and 30 mg for MR-HC, and after 18 months 20 mg MR-HC. Three adrenal crises occurred in phase 3, none on MR-HC and 4 in the extension study. MR-HC resulted in patient-reported benefit including menses restoration in 8 patients (1 on standard therapy), and 3 patient and 4 partner pregnancies (none on standard therapy). Conclusion MR-HC improved biochemical disease control in adults with reduction in steroid dose over time and patient-reported benefit

Modified-Release and Conventional Glucocorticoids and Diurnal Androgen Excretion in Congenital Adrenal Hyperplasia

Context: The classic androgen synthesis pathway proceeds via dehydroepiandrosterone, androstenedione, and testosterone to 5α-dihydrotestosterone. However, 5α-dihydrotestosterone synthesis can also be achieved by an alternative pathway originating from 17α-hydroxyprogesterone (17OHP), which accumulates in congenital adrenal hyperplasia (CAH). Similarly, recent work has highlighted androstenedione-derived 11-oxygenated 19-carbon steroids as active androgens, and in CAH, androstenedione is generated directly from 17OHP. The exact contribution of alternative pathway activity to androgen excess in CAH and its response to glucocorticoid (GC) therapy is unknown. Objective: We sought to quantify classic and alternative pathway-mediated androgen synthesis in CAH, their diurnal variation, and their response to conventional GC therapy and modified-release hydrocortisone. Methods: We used urinary steroid metabolome profiling by gas chromatography–mass spectrometry for 24-hour steroid excretion analysis, studying the impact of conventional GCs (hydrocortisone, prednisolone, and dexamethasone) in 55 adults with CAH and 60 controls. We studied diurnal variation in steroid excretion by comparing 8-hourly collections (23:00–7:00, 7:00–15:00, and 15:00–23:00) in 16 patients with CAH taking conventional GCs and during 6 months of treatment with modified-release hydrocortisone, Chronocort. Results: Patients with CAH taking conventional GCs showed low excretion of classic pathway androgen metabolites but excess excretion of the alternative pathway signature metabolites 3α,5α-17-hydroxypregnanolone and 11β-hydroxyandrosterone. Chronocort reduced 17OHP and alternative pathway metabolite excretion to near-normal levels more consistently than other GC preparations. Conclusions: Alternative pathway-mediated androgen synthesis significantly contributes to androgen excess in CAH. Chronocort therapy appears superior to conventional GC therapy in controlling androgen synthesis via alternative pathways through attenuation of their major substrate, 17OHP