Short-Lived Active Prorenin:Precursor of So-Called Native Prorenin

The enzymatic activity of the aspartic protease, renin, is critical for its function in blood pressure regulation and sodium homeostasis. Incubation of so-called native prorenin at low pH leads to its activation. After binding to transition-state mimicking renin inhibitors at neutral pH, prorenin attains the active conformation, as indicated by immunosorbent assay using monoclonal antibodies specific for epitopes of the prosegment or the renin body. A comparison of immunosorbent assay with enzyme-kinetic assay revealed the intermediary steps of prorenin auto-activation/inactivation. The kinetically identified intermediary steps of activation/inactivation correspond with the published crystal structures of free renin, free prorenin, and renin in complex with inhibitors. Both renin and activated prorenin exist in 2 forms, α and β. The α form is active, and the α/β quantity ratio is 2.5. The kidney produces renin and prorenin, while the ovarium, placenta, and eye produce inactive prorenin. The production of renin by these organs has never been demonstrated. We propose that the so-called native prorenin in extracellular fluid, including the circulation, is derived, at least partly, from short-lived active prorenin. Its potential paracrine function is discussed.</p

Short-Lived Active Prorenin:Precursor of So-Called Native Prorenin

The enzymatic activity of the aspartic protease, renin, is critical for its function in blood pressure regulation and sodium homeostasis. Incubation of so-called native prorenin at low pH leads to its activation. After binding to transition-state mimicking renin inhibitors at neutral pH, prorenin attains the active conformation, as indicated by immunosorbent assay using monoclonal antibodies specific for epitopes of the prosegment or the renin body. A comparison of immunosorbent assay with enzyme-kinetic assay revealed the intermediary steps of prorenin auto-activation/inactivation. The kinetically identified intermediary steps of activation/inactivation correspond with the published crystal structures of free renin, free prorenin, and renin in complex with inhibitors. Both renin and activated prorenin exist in 2 forms, α and β. The α form is active, and the α/β quantity ratio is 2.5. The kidney produces renin and prorenin, while the ovarium, placenta, and eye produce inactive prorenin. The production of renin by these organs has never been demonstrated. We propose that the so-called native prorenin in extracellular fluid, including the circulation, is derived, at least partly, from short-lived active prorenin. Its potential paracrine function is discussed.</p

Good heart: telling stories of cardiovascular protective and risk factors for Aboriginal women

BACKGROUND:Aboriginal and Torres Strait Islander peoples' perspectives of health and cultural wellbeing encapsulate the spiritual, social and environmental health of individuals, their communities and country. Strategies designed to reduce the cardiovascular burden of Aboriginal and Torres Strait Islander people often fail to consider their unique knowledge and worldview. METHODS:This adapted, grounded theory study sought to explore Aboriginal women's views of cardiovascular protective and risk factors. RESULTS:Twenty-eight (28) women from five women's groups across Central and South Australia participated. Women distinguished the heart as core to their spiritual and physical wellbeing. Women identified six attributes that keep a woman's heart strong, four that can make the heart sick, and eight socio-ecological factors which affect a woman's capacity to care for their heart. Women described having a healthy heart when able to identify as Aboriginal women, being connected to family and community, having a healthy life and body, and being engaged in their health and health care. CONCLUSIONS:There are gaps in the provision of cardiovascular risk assessment and management, gaps in the cultural safety of primary health care services, and gaps in the communication of the sex-specific warning signs of a heart attack, all of which must be addressed.Katharine F.McBride, Christine Franks, Vicki Wade, Veronica King, Janice Rigney, Nyunmiti Burton ... et al

Hyperglycemia in pregnancy and developmental outcomes in children at 18-60 months of age: the PANDORA Wave 1 study

First published online: 4 April 2022This study aimed to explore the association between hyperglycemia in pregnancy (type 2 diabetes (T2D) and gestational diabetes mellitus (GDM)) and child developmental risk in Europid and Aboriginal women.PANDORA is a longitudinal birth cohort recruited from a hyperglycemia in pregnancy register, and from normoglycemic women in antenatal clinics. The Wave 1 substudy included 308 children who completed developmental and behavioral screening between age 18 and 60 months. Developmental risk was assessed using the Ages and Stages Questionnaire (ASQ) or equivalent modified ASQ for use with Aboriginal children. Emotional and behavioral risk was assessed using the Strengths and Difficulties Questionnaire. Multivariable logistic regression was used to assess the association between developmental scores and explanatory variables, including maternal T2D in pregnancy or GDM.After adjustment for ethnicity, maternal and child variables, and socioeconomic measures, maternal hyperglycemia was associated with increased developmental "concern" (defined as score ≥1 SD below mean) in the fine motor (T2D odds ratio (OR) 5.30, 95% CI 1.77-15.80; GDM OR 3.96, 95% CI 1.55-10.11) and problem-solving (T2D OR 2.71, 95% CI 1.05-6.98; GDM OR 2.54, 95% CI 1.17-5.54) domains, as well as increased "risk" (score ≥2 SD below mean) in at least one domain (T2D OR 5.33, 95% CI 1.85-15.39; GDM OR 4.86, 95% CI 1.95-12.10). Higher maternal education was associated with reduced concern in the problem-solving domain (OR 0.27, 95% CI 0.11-0.69) after adjustment for maternal hyperglycemia.Maternal hyperglycemia is associated with increased developmental concern and may be a potential target for intervention so as to optimize developmental trajectories.Angela Titmuss, Anita D, Aprano, Federica Barzi, Alex D.H. Brown, Anna Wood, Christine Connors, Jacqueline A. Boyle, Elizabeth Moore, Kerin O'Dea, Jeremy Oats, H. David McIntyre, Paul Zimmet, Jonathan E. Shaw, Maria E. Craig and Louise J. Maple-Brow

Association between hyperglycaemia in pregnancy and growth of offspring in early childhood: The PANDORA study

First published: 29 May 2022Background: Few studies have assessed whether children exposed to in utero hyperglycaemia experience different growth trajectories compared to unexposed children.Objectives:To assess association of type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) with early childhood weight, length/height and body mass index(BMI) trajectories, and with timing and magnitude of peak BMI in infancy.Methods:PANDORA is a birth cohort recruited from an Australian hyperglycaemia in pregnancy register, and women with normoglycaemia recruited from the community.Offspring growth measures were obtained from health records over a median follow-up of 3.0 years (interquartile range 1.9–4.0). This analysis included children born to Aboriginal mothers with in utero normoglycaemia (n=95), GDM (n=228) or T2D(n=131). Growth trajectories (weight, length/height and BMI) were estimated usinglinear mixed models with cubic spline functions of child age. Results:After adjustment for maternal factors (age, BMI, parity, smoking, and socio-economic measures) and child factors (age, gestational age at birth, and sex), children born to mothers with T2D or GDM had lower weight, length/height and BMI trajectories in infancy than children born to mothers with normoglycaemia, but similar weight and BMI by completion of follow-up. Children exposed to T2D had lower mean peak BMI 17.6 kg/m2(95% confidence interval [CI] 17.3–18.0) than childrenexposed to normoglycaemia (18.6 kg/m2[18.1–18.9]) (p=0.001). Conclusions: Maternal hyperglycaemia was associated with differences in early child-hood growth trajectories after adjustment for maternal BMI. Exploration of associations between in utero hyperglycaemia exposure and growth trajectories into later childhood is required.Angela Titmuss, Danielle K. Longmore, Federica Barzi, Elizabeth L. M. Barr, Vanya Webster, Anna Wood, Alison Simmonds, Alex D. H. Brown, Christine Connors, Jacqueline A. Boyle, Jeremy Oats, H. David McIntyre, Jonathan E. Shaw, Maria E. Craig, Louise J. Maple-Brown, the PANDORA Study Research Tea

Postpartum uptake of diabetes screening tests in women with gestational diabetes: The PANDORA study

OnlinePublAims To determine rates and predictors of postpartum diabetes screening among Aboriginal and/or Torres Strait Islander and non-Indigenous women with gestational diabetes mellitus (GDM). Methods PANDORA is a prospective longitudinal cohort of women recruited in pregnancy. Postpartum diabetes screening rates at 12 weeks (75-g oral glucose tolerance test (OGTT)) and 6, 12 and 18 months (OGTT, glycated haemoglobin [HbA₁Cₓ ] or fasting plasma glucose) were assessed for women with GDM (n = 712). Associations between antenatal factors and screening with any test (OGTT, HbA₁Cₓ, fasting plasma glucose) by 6 months postpartum were examined using Cox proportional hazards regression. Results Postpartum screening rates with an OGTT by 12 weeks and 6 months postpartum were lower among Aboriginal and/or Torres Strait Islander women than non-Indigenous women (18% vs. 30% at 12 weeks, and 23% vs. 37% at 6 months, p < 0.001). Aboriginal and/or Torres Strait Islander women were more likely to have completed a 6-month HbA₁Cₓ compared to non-Indigenous women (16% vs. 2%, p < 0.001). Screening by 6 months postpartum with any test was 41% for Aboriginal and/or Torres Strait Islander women and 45% for non-Indigenous women (p = 0.304). Characteristics associated with higher screening rates with any test by 6 months postpartum included, insulin use in pregnancy, first pregnancy, not smoking and lower BMI. Conclusions Given very high rates of type 2 diabetes among Aboriginal and Torres Strait Islander women, early postpartum screening with the most feasible test should be prioritised to detect prediabetes and diabetes for intervention.Anna J. Wood, I-Lynn Lee, Elizabeth L. M. Barr, Federica Barzi, Jacqueline A. Boyle, Christine Connors, Elizabeth Moore, Jeremy J. N. Oats, Harold D. McIntyre, Angela Titmuss, Alison Simmonds, Paul Z. Zimmet, Alex D. H. Brown, Sumaria Corpus, Jonathan E. Shaw, Louise J. Maple-Brown, on behalf of PANDORA Study tea