Biochemical, Anatomical, and Pharmacological Characterization of Calcitonin-Type Neuropeptides in Starfish: Discovery of an Ancient Role as Muscle Relaxants

Calcitonin (CT) is a peptide hormone released by the thyroid gland that regulates blood Ca2+ levels in mammals. The CT gene is alternatively spliced, with one transcript encoding CT and another transcript encoding the CT-like neuropeptide calcitonin-gene related peptide (α-CGRP), which is a powerful vasodilator. Other CT-related peptides in vertebrates include adrenomedullin, amylin, and intermedin, which also act as smooth muscle relaxants. The evolutionary origin of CT-type peptides has been traced to the bilaterian common ancestor of protostomes and deuterostomes and a CT-like peptide (DH31) has been identified as a diuretic hormone in some insect species. However, little is known about the physiological roles of CT-type peptides in other invertebrates. Here we characterized a CT-type neuropeptide in a deuterostomian invertebrate—the starfish Asterias rubens (Phylum Echinodermata). A CT-type precursor cDNA (ArCTP) was sequenced and the predicted structure of the peptide (ArCT) derived from ArCTP was confirmed using mass spectrometry. The distribution of ArCTP mRNA and the ArCT peptide was investigated using in situ hybridization and immunohistochemistry, respectively, revealing stained cells/processes in the nervous system, digestive system, and muscular organs, including the apical muscle and tube feet. Investigation of the effects of synthetic ArCT on in vitro preparations of the apical muscle and tube feet revealed that it acts as a relaxant, causing dose-dependent reversal of acetylcholine-induced contraction. Furthermore, a muscle relaxant present in whole-animal extracts of another starfish species, Patiria pectinifera, was identified as an ortholog of ArCT and named PpCT. Consistent with the expression pattern of ArCTP in A. rubens, RT-qPCR revealed that in P. pectinifera the PpCT precursor transcript is more abundant in the radial nerve cords than in other tissues/organs analyzed. In conclusion, our findings indicate that the physiological action of CT-related peptides as muscle relaxants in vertebrates may reflect an evolutionarily ancient role of CT-type neuropeptides that can be traced back to the common ancestor of deuterostomes

Health service utilization and direct healthcare costs associated with obesity in older adult population in Ghana

Obesity is a major risk factor for many chronic diseases and disabilities, with severe implications on morbidity and mortality among older adults. With an increasing prevalence of obesity among older adults in Ghana, it has become necessary to develop cost-effective strategies for its management and prevention. However, developing such strategies is challenging as body mass index (BMI)-specific utilization and costs required for cost-effectiveness analysis are not available in this population. Therefore, this study examines the associations between health services utilization as well as direct healthcare costs and overweight (BMI ≥25.00 and 2) and obesity (BMI ≥30.00 kg/m2) among older adults in Ghana. Data were used from a nationally representative, multistage sample of 3350 people aged 50+ years from the World Health Organization's Study on global AGEing and adult health (WHO-SAGE; 2014/15). Health service utilization was measured by the number of health facility visits over a 12-month period. Direct costs (2017 US dollars) included out-of-pocket payments and the National Health Insurance Scheme (NHIS) claims. Associations between utilization and BMI were examined using multivariable zero-inflated negative binomial regressions; and between costs and BMI using multivariable two-part regressions. Twenty-three percent were overweight and 13% were obese. Compared with normal-weight participants, overweight and obesity were associated with 75% and 159% more inpatient admissions, respectively. Obesity was also associated with 53% additional outpatient visits. One in five of the overweight and obese population had at least one chronic disease, and having chronic disease was associated with increased outpatient utilization. The average per person total costs for overweight was $78 and obesity was$132 compared with $35 for normal weight. The NHIS bore approximately 60$121 million compared with $64 million for normal weight in the entire older adult Ghanaian population. Compared with normal weight, the total costs per person associated with overweight increased by 73% and more than doubled for obesity. Even though the total prevalence of overweight and obesity was about half of that of normal weight, the sum of their cost burden was almost doubled. Implementing weight reduction measures could reduce health service utilization and costs in this population

Rapidly increasing prevalence of overweight and obesity in older Ghanaian adults from 2007-2015: evidence from WHO-SAGE Waves 1 & 2

Background: Studies on changes in the prevalence and determinants of obesity in older adults living in sub-Saharan Africa are scarce. We examined recent changes in obesity prevalence and associated factors for older adults in Ghana between 2007/08 and 2014/15.Methods: Data on adults aged 50 years and older in Ghana were drawn from the WHO SAGE 2007/08 (Wave 1; n = 4158) and 2014/15 (Wave 2; n = 1663). The weighted prevalence of obesity, overweight, normal weight and underweight, and of high central adiposity were compared in 2007/08 and 2014/15. Multinomial and binomial logistic regressions were used to examine whether the determinants of weight status based on objectively measured body mass index and waist circumference changed between the two time periods.Results: The prevalence of overweight (2007/08 = 19.6%, 95% CI: 18.0-21.4%; 2014/15 = 24.5%, 95% CI: 21.7-27.5%) and obesity (2007/08 = 10.2%, 95% CI: 8.9-11.7%; 2014/15 = 15.0%, 95% CI: 12.6-17.7%) was higher in 2014/15 than 2007/08 and more than half of the population had high central adiposity (2007/08 = 57.7%, 95% CI: 55.4-60.1%; 2014/15 = 66.9%, 95% CI: 63.7-70.0%) in both study periods. While the prevalence of overweight increased in both sexes, obesity prevalence was 16% lower in males and 55% higher in females comparing 2007/08 to 2014/15. Female sex, urban residence, and high household wealth were associated with higher odds of overweight/obesity and high central adiposity. Those aged 70+ years had lower odds of obesity in both study waves. In 2014/15, females who did not meet the recommended physical activity were more likely to be obese.Conclusion: Over the 7-year period between the surveys, the prevalence of underweight decreased and overweight increased in both sexes, while obesity decreased in males but increased in females. The difference in obesity prevalence may point to differential impacts of past initiatives to reduce overweight and obesity, potential high-risk groups in Ghana, and the need to increase surveillance

Impact of overweight and obesity on life expectancy, quality-adjusted life years and lifetime costs in the adult population of Ghana

Introduction: Prior studies have revealed the increasing prevalence of obesity and its associated health effects among ageing adults in resource poor countries. However, no study has examined the long-term and economic impact of overweight and obesity in sub-Saharan Africa. Therefore, we quantified the long-term impact of overweight and obesity on life expectancy (LE), quality-adjusted life years (QALYs) and total direct healthcare costs. Methods: A Markov simulation model projected health and economic outcomes associated with three categories of body mass index (BMI): healthy weight (18.5≤BMI 2) in simulated adult cohorts over a 50-year time horizon from age fifty. Costs were estimated from government and patient perspectives, discounted 3% annually and reported in 2017 US$. Mortality rates from Ghanaian lifetables were adjusted by BMI-specific all-cause mortality HRs. Published input data were used from the 2014/2015 Ghana WHO Study on global AGEing and adult health data. Internal and external validity were assessed. Results: From age 50 years, average (95$619 (95% CI: 616 to 622), US$1298 (95$2057 (95% CI: 2043 to 2071) for healthy weight, overweight and obesity, respectively. QALYs and costs were lower in males. Conclusion: Overweight and obesity have substantial health and economic impacts, hence the urgent need for cost-effective preventive strategies in the Ghanaian population

The role of intergenerational educational mobility and household wealth in adult obesity: evidence from wave 2 of the World Health Organization's study on global ageing and adult health

Background: Obesity has emerged as a major risk factor for non-communicable diseases in low and middle-income countries but may not follow typical socioeconomic status (SES)-related gradients seen in higher income countries. This study examines the associations between current and lifetime markers of SES and BMI categories (underweight, normal weight, overweight, obese) and central adiposity in Ghanaian adults.Methods: Data from 4,464 adults (2,610 women) who participated in the World Health Organization's Study on global AGEing and adult health (SAGE) Wave 2 were examined. Multilevel multinomial and binomial logistic regression models were used to examine associations. SES markers included parental education, individual education, intergenerational educational mobility and household wealth. Intergenerational educational mobility was classified: stable-low (low parental and low individual education), stable-high (high parental and high individual education), upwardly (low parental and high individual education), or downwardly mobile (high parental and low individual education).Results: The prevalence of obesity (12.9%) exceeded the prevalence of underweight (7.2%) in the population. High parental and individual education were significantly associated with higher odds of obesity and central adiposity in women. Compared to the stable low pattern, stable high (obesity: OR = 3.15; 95% CI: 1.96, 5.05; central adiposity: OR = 1.75; 95% CI: 1.03, 2.98) and upwardly (obesity: OR = 1.71; 95% CI: 11.13, 2.60; central adiposity: OR = 1.60; 95% CI: 1.08, 2.37) mobile education patterns were associated with higher odds of obesity and central adiposity in women, while stable high pattern was associated with higher odds of overweight (OR = 1.88; 95% CI: 1.11, 3.19) in men. Additionally, high compared to the lowest household wealth was associated with high odds of obesity and central adiposity in both sexes.Conclusion: Stable high and upwardly mobile education patterns are associated with higher odds of obesity and central adiposity in women while the stable high pattern was associated with higher odds of overweight in men

Haemodynamic consequences of changing potassium concentrations in haemodialysis fluids

<p>Abstract</p> <p>Background</p> <p>A rapid decrease of serum potassium concentrations during haemodialysis produces a significant increase in blood pressure parameters at the end of the session, even if effects on intra-dialysis pressure are not seen. Paradoxically, in animal models potassium is a vasodilator and decreases myocardial contractility. The purpose of this trial is to study the precise haemodynamic consequences induced by acute changes in potassium concentration during haemodialysis.</p> <p>Methods</p> <p>In 24 patients, 288 dialysis sessions, using a randomised single blind crossover design, we compared six dialysate sequences with different potassium profiles. The dialysis sessions were divided into 3 tertiles, casually modulating potassium concentration in the dialysate between the value normally used K and the two cut-off points K+1 and K-1 mmol/l. Haemodynamics were evaluated in a non-invasive manner using a finger beat-to-beat monitor.</p> <p>Results</p> <p>Comparing K-1 and K+1, differences were found within the tertiles regarding systolic (+5.3, +6.6, +2.3 mmHg, p < 0.05, < 0.05, ns) and mean blood pressure (+4.3, +6.4, -0.5 mmHg, p < 0.01, < 0.01, ns), as well as peripheral resistance (+212, +253, -4 dyne.sec.cm^-5, p < 0.05, < 0.05, ns). The stroke volume showed a non-statistically-significant inverse trend (-3.1, -5.2, -0.2 ml). 18 hypotension episodes were recorded during the course of the study. 72% with K-1, 11% with K and 17% with K+1 (p < 0.01 for comparison K-1 vs. K and K-1 vs. K+1).</p> <p>Conclusions</p> <p>A rapid decrease in the concentration of serum potassium during the initial stage of the dialysis-obtained by reducing the concentration of potassium in the dialysate-translated into a decrease of systolic and mean blood pressure mediated by a decrease in peripheral resistance. The risk of intra-dialysis hypotension inversely correlates to the potassium concentration in the dialysate.</p> <p>Trial Registration Number</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01224314">NCT01224314</a></p

Interactive effects of obesity and physical fitness on risk of ischemic heart disease

Background/Objectives:Obesity and low physical fitness are known risk factors for ischemic heart disease (IHD), but their interactive effects are unclear. Elucidation of interactions between these common, modifiable risk factors may help inform more effective preventive strategies. We examined interactive effects of obesity, aerobic fitness and muscular strength in late adolescence on risk of IHD in adulthood in a large national cohort.Subjects/Methods:We conducted a national cohort study of all 1 547 407 military conscripts in Sweden during 1969-1997 (97-98% of all 18-year-old males each year). Aerobic fitness, muscular strength and body mass index (BMI) measurements were examined in relation to IHD identified from outpatient and inpatient diagnoses through 2012 (maximum age 62 years).Results:There were 38 142 men diagnosed with IHD in 39.7 million person years of follow-up. High BMI or low aerobic fitness (but not muscular strength) was associated with higher risk of IHD, adjusting for family history and socioeconomic factors. The combination of high BMI (overweight/obese vs normal) and low aerobic fitness (lowest vs highest tertile) was associated with highest IHD risk (incidence rate ratio, 3.11; 95% confidence interval (CI), 2.91-3.31; P<0.001). These exposures had no additive and a negative multiplicative interaction (that is, their combined effect was less than the product of their separate effects). Low aerobic fitness was a strong risk factor even among those with normal BMI.Conclusions:In this large cohort study, low aerobic fitness or high BMI at age 18 was associated with higher risk of IHD in adulthood, with a negative multiplicative interaction. Low aerobic fitness appeared to account for a similar number of IHD cases among those with normal vs high BMI (that is, no additive interaction). These findings suggest that interventions to prevent IHD should begin early in life and include not only weight control but aerobic fitness, even among persons of normal weight

The Importance of LDL and Cholesterol Metabolism for Prostate Epithelial Cell Growth

Cholesterol-lowering treatment has been suggested to delay progression of prostate cancer by decreasing serum LDL. We studied in vitro the effect of extracellular LDL-cholesterol on the number of prostate epithelial cells and on the expression of key regulators of cholesterol metabolism. Two normal prostatic epithelial cell lines (P96E, P97E), two in vitro immortalized epithelial cell lines (PWR-1E, RWPE-1) and two cancer cell lines (LNCaP and VCaP) were grown in cholesterol-deficient conditions. Cells were treated with 1–50 µg/ml LDL-cholesterol and/or 100 nM simvastatin for seven days. Cell number relative to control was measured with crystal violet staining. Changes in mRNA and protein expression of key effectors in cholesterol metabolism (HMGCR, LDLR, SREBP2 and ABCA1) were measured with RT-PCR and immunoblotting, respectively. LDL increased the relative cell number of prostate cancer cell lines, but reduced the number of normal epithelial cells at high concentrations. Treatment with cholesterol-lowering simvastatin induced up to 90% reduction in relative cell number of normal cell lines but a 15–20% reduction in relative number of cancer cells, an effect accompanied by sharp upregulation of HMGCR and LDLR. These effects were prevented by LDL. Compared to the normal cells, prostate cancer cells showed high expression of cholesterol-producing HMGCR but failed to express the major cholesterol exporter ABCA1. LDL increased relative cell number of cancer cell lines, and these cells were less vulnerable than normal cells to cholesterol-lowering simvastatin treatment. Our study supports the importance of LDL for prostate cancer cells, and suggests that cholesterol metabolism in prostate cancer has been reprogrammed to increased production in order to support rapid cell growth