DOCSLIB.ORG

Interrelationships of Vitamin D and Parathyroid Hormone in Calcium Homeostasis Michael T

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Interrelationships of Vitamin D and Parathyroid Hormone in Calcium Homeostasis Michael T POSTGRAD. MED. J. (1964), 40, 497 Postgrad Med J: first published as 10.1136/pgmj.40.466.497 on 1 August 1964. Downloaded from INTERRELATIONSHIPS OF VITAMIN D AND PARATHYROID HORMONE IN CALCIUM HOMEOSTASIS MICHAEL T. HARRISON, M.D., M.R.C.P. Lecturer in Medicine, University of Glasgow. From ihe Gardiner Institute of Medicine, Western Infirmary, Glasgow. IN man and most mammals the concentration and showed that reciprocal changes in con- of calcium in the blood and body fluids remains centration of calcium in the systemic circula- almost constant under normal conditions, with tion resulted. The mechanism by which the only slight fluctuations. For the various cellular parathyroid glands regulate their secretion in functions which are dependent on calcium, for response to changing levels of serum calcium example neuromuscular transmission, it is the is quite unknown. ionized fraction of calcium (approximately The parathyroid hormone has been puri- 50 per cent of the total serum calcium level) fied from bovine glands, and its properties which is important, and it is this fraction which have been studied (Rasmussen and Craig is so carefully maintained at a constant level 1961, 1962). It is a protein of molecular weight in the body fluids. In order to stabilize this approximately 9,000, composed of a single level, an elaborate regulating mechanism is chain containing 76 to 83 amino-acid residues. necessary, since there are many routes of entry It is antigenically pure, and antibodies have Protected by copyright. into and exit from the blood available to been prepared to it which provide the basis calcium. Thus, calcium is added to the blood for a sensitive immunoassay (Berson, Yalow, by absorption from the intestine and by resorp- Aurbach and Potts, 1963; Tashjian, Levine tion from bone, and leaves via formation of new and Munson, 1963). The most striking action bone, and by excretion into urine, fweces, sweat of the hormone is that on the skeleton, which and milk. Changes in other components of the results in release of calcium into the blood. body fluids, protein, citrate and phosphate, There is abundant evidence for this direct action affect the concentration of ionized calcium. of parathyroid hormone on bone, which has The magnitude of all these factors will vary been reviewed by Munson (1960), and strength- in response to growth, dietary intake, changes ened by the striking experiments of Gaillard in activity, or pregnancy, and yet the net effect (1961), who demonstrated resorption of bone on concentration of ionized calcium is almost in tissue culture in response to the hormone. undetectable. Two factors of major importance The mechanism by which parathyroid hormone http://pmj.bmj.com/ in the regulation of serum levels of calcium increases resorption of bone is not known. The are the parathyroid glands and vitamin D, and solubility of bone depends on pH of the sur- both of these are necessary to maintain normal rounding fluid; as pH falls solubility increases, levels. so that bone is resorbed. A possible mechanism for the action of parathyroid hormone on bone Parathyroid Glands would therefore be through a lowering of pH of If the parathyroid glands are removed, calcium the fluid immediately in contact with the bone. in the serum falls rapidly to a level at which This is the basis of the "acid theory" of action on September 24, 2021 by guest. increased neuromuscular irritability occurs, with of parathyroid hormone (Neuman, Firschein, the syndrome of tetany. The parathyroid Chen, Mulryan and DiStefano, 1956; Firschein, hormone raises the level of serum calcium, and Neuman, Martin and Mulryan 1959). These a fall in this level is the principal stimulus to the workers showed that the concentration of secretion of hormone by the parathyroid glands. citrate in blood obtained from the spongy bone When the level of serum calcium exceeds of the dog's femur increased strikingly after normal, secretion of parathyroid hormone is injection of parathyroid hormone. They postu- suppressed until the level has returned to normal lated that as a result of accumulation of citrate, (McLean, 1957). These effects have been clearly pH of the fluids surrounding the bone falls, and demonstrated by Copp and Davidson (1961), increased resorption of bone then occurs. The who perfused a dog's parathyroid glands with citrate may also chelate some of the calcium blood of low or high calcium concentration, released by bone resorption, and thus raise the 498 POSTGRADUATE MEDICAL JOURNAL August, 1964Postgrad Med J: first published as 10.1136/pgmj.40.466.497 on 1 August 1964. Downloaded from gradient of ionic calcium between bone and has been shown (Komarkova, Vostal and the surrounding fluid. This theory has led to Pacovsky 1960) that parathyroid hormone a large amount of research into the effect of produces a rise in tissue level of citrate in the parathyroid hormone on the production of kidney. There is some evidence that the level organic acids by Ibone in vitro, and unfortun- of renal citrate controls the tubular reabsorp- ately there has been little agreement between tion of calcium (Karam, Harrison, Hartog and different workers. Massive doses of parathyroid Fraser, 1961), so that an increase in citrate hormone have usually been necessary in order level provides a possible explanation for the to produce an increase in levels of bone citrate, effects of parathyroid hormone on urinary perhaps because of the relatively large amount excretion of calcium. of citrate present in bone in the basal state. Parathyroid hormone probably increases the Moreover, lactate is produced by bone in absorption of calcium from the intestine, but amounts approximately a hundred times less is known about the effect of the hormone greater than those of citrate in response to the on calcium absorption than about that of hormone (Vaes and Nichols, 1961), and it is vitamin D. Rasmussen (1959) showed that therefore possible that lactate is of greater active transport of calcium by segments of rat importance than citrate in producing resorp- duodenum in vitro was increased by parathyroid tion of ,bone. The conflicting results of in vitro hormone. Balance studies in rats (Cramer, studies have been reviewed by Firschein Suiker and Copp, 1961) indicated a marked (1963). Many workers still believe, however, increase in the net absorption of calcium in that parathyroid hormone stimulates the release response to parathyroid hormone, provided of citrate from bone, either by increasing its that intake of calcium was adequate. In Thiry- rate of formation (Ranney, 1960; Lekan, Laskin Vella fistulas in dogs, Cramer (1963) showed and Engel, 1960), or by inhibiting its oxidation that administration of the hormone increasedProtected by copyright. (Neuman and Dowse, 1961; Hekkelman, 1961). absorption of calcium while parathyroidectomy Although the skeleton is probably the most resulted in a decrease. In man, Jaworski, Brown, important site of action for parathyroid hor- Fedoruk and Seitz (1963), using a tracer test mone it is not the only one. There is evidence of calcium absorption with calcium-45, de- that the hormone affects the transport of monstrated increased intestinal absorption of calcium in the kidney, gut and mammary gland. calcium in a patient with hyperparathyroidism. In the kidney, Talbot, Sobel, McArthur and In lactating rats, administration of para- Crawford (1954) first suggested that parathy- thyroid hormone results in a decrease of calcium roid hormone increases the reabsorption of concentration in the milk, while parathyroid- filtered calcium by the renal tubules, so that ectomy leads to increased secretion of calcium, the urinary clearance of calcium is reduced. suggesting that the parathyroid glands inhibit Thus in hypoparathyroidism there may be the secretion of calcium by the mammary gland normal or even high levels of urinary calcium (Toverud, 1963). in spite of hypocalcxmia, while in hyperpara- It can be seen that all the effects of para-http://pmj.bmj.com/ thyroidism, in spite of hypercalcemia, an ab- thyroid hormone described on calcium trans- normally raised urinary excretion of calcium is port lead to an increase in the amount of not always present. Kleeman, Bernstein, Rock- calcium in the blood and body fluids, so that ney, Dowling and Maxwell (1961) showed that through several different mechanisms the para- parathyroid extract produced a significant re- thyroid glands effectively counter falling levels duction in urinary calcium clearance at all levels of serum calcium. From a teleological point of of diffusible calcium, both in the majority of view, it seems most appropriate that calcium, on September 24, 2021 by guest. normal and in hypoparathyroid individuals. made available through resorption of bone, Low clearances of calcium were noted in is not all lost to the body through urinary or patients with primary hyperparathyroidism, and fwecal excretion but is retained in the blood. these rose after removal of the tumour. In The parathyroid has been justly called "glande carefully controlled studies on dogs, in which de protection du capital calcique" (Lichtwitz, filtered loads of other ions were maintained 1961). constant, Widrow and Levinsky (1962) showed Indirect Effects of Parathyroid Hormone on that urinary excretion of calcium fell after Calcium administration of parathyroid extract, although Parathyroid hormone also affects the meta- filtered calcium remained constant or increased. bolism of inorganic phosphorus and probably Similar findings have been reported
Load more

Recommended publications
  • What Can I Do to Protect Myself and My Family During COVID-19?
    What Can I Do to Protect Role for Myself, My Complementary Family and My and Integrative Patients During Health? COVID-19? Karen H. Seal, MD, MPH Chief, Integrative Health Service San Francisco VA Medical Center Professor of Medicine and Psychiatry, UCSF Disclaimer 1. Material presented here is supplemental; does not replace public health guidelines emphasizing hand-washing, masking, social distancing and testing if symptoms present. 2. No CIH measures have been validated in human trials as effective against COVID-19; evidence is from pre-clinical trials or trials related to boosting immunity in general. 3. Opinions expressed here do not reflect those of the Department of Veterans Affairs or the University of California, San Francisco. Poll Question #1 In addition to public health measures (masking, distancing, handwashing etc.), have you implemented anything new in an attempt to protect you or family members against COVID-19? YES NO Poll Question # 2 If you have implemented new health measures, in which of the following areas have you made changes? (Indicate all that apply.) A. Sleep habits B. Diet or dietary supplements (vitamins, minerals, other natural products) C. Exercise D. Stress Reduction (other than exercise) E. None of the above Overview – Virology and pathogenicity of SARS-CoV-2 (Coronavirus disease 2019; COVID-19) – Strategies to help prevent infection and promote recovery – Nutrition – Dietary Supplements – Sleep – Exercise and Stress Reduction – Summary Virology and Pathogenicity of COVID-19 SARS-CoV-2 RNA virus enters human cells through angiotensin-converting–enzyme 2 (ACE2) receptors SARS-CoV-2 virus penetrates host cell Main Goal of Virus injects its blueprint Viruses: Hijacks cell’s “factory” to make new virus proteins Reproduction Assembles new SARS-CoV-2 virions Mature RNA virus released into bloodstream infects other cells Virology of COVID-19 – Virulence and pathogenicity develops from COVID-19 virus activating cytoplasmic NLRP3 inflammasome within immune cells.
    [Show full text]
  • Association of Hypogonadism with Vitamin D Status
    European Journal of Endocrinology (2012) 166 77–85 ISSN 0804-4643 CLINICAL STUDY Association of hypogonadism with vitamin D status: the European Male Ageing Study David M Lee, Abdelouahid Tajar, Stephen R Pye, Steven Boonen1, Dirk Vanderschueren2, Roger Bouillon3, Terence W O’Neill, Gyorgy Bartfai4, Felipe F Casanueva5,6, Joseph D Finn7, Gianni Forti8, Aleksander Giwercman9, Thang S Han10, Ilpo T Huhtaniemi11, Krzysztof Kula12, Michael E J Lean13, Neil Pendleton14, Margus Punab15 and Frederick C W Wu7, the EMAS study group† Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, The University of Manchester, Manchester M13 9PT, UK, 1Division of Gerontology and Geriatrics and Centre for Musculoskeletal Research, Department of Experimental Medicine, 2Department of Andrology and Endocrinology and 3Department of Experimental Medicine, Katholieke Universiteit Leuven, Leuven B-3000, Belgium, 4Department of Obstetrics, Gynaecology and Andrology, Albert Szent-Gyorgy Medical University, Szeged H-6725, Hungary, 5Department of Medicine, Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago (CHUS), 15076 Santiago de Compostela, Spain, 6CIBER de Fisiopatologı´a Obesidad y Nutricion (CB06/03), Instituto Salud Carlos III, 15076 Santiago de Compostela, Spain, 7Developmental and Regenerative Biomedicine Research Group, Andrology Research Unit, Manchester Academic Health Science Centre, Manchester Royal Infirmary, The University of Manchester, Grafton Street, Manchester M13 9WL, UK, 8Andrology Unit,
    [Show full text]
  • A Novel Androgen–Vitamin D Link
    RESEARCH HIGHLIGHTS Nature Reviews Endocrinology | Published online 09 Feb 2018; doi:10.1038/nrendo.2018.14 BONE A novel androgen–vitamin D link Androgen deficiency in men, which observations were corroborated in mice, suggesting that androgen can result from normal ageing or human cell lines. stimulation decreases 24-hydroxy- prostate cancer therapy, is associated Next, the effect of PR loss on lase-dependent vitamin D3 with reduced levels of vitamin D3 and vitamin D-related gene expression inactivation. Indeed, DHT increased an increased risk of osteoporosis. Now, was investigated. In mouse proximal serum levels of vitamin D3 in these new research has uncovered a novel convoluted tubule (PCT) cells, mice, confirming the link between link between vitamin D3 metabolism Pgr-targeted small interfering RNA androgens and vitamin D homeostasis. and sex hormone levels, a finding that (siRNA) reduced levels of Cyp24a1 “Using modulators of PR, we want could be exploited therapeutically to (encoding 24-hydroxylase), a vitamin to further investigate the role of PR in treat vitamin D deficiency. D3-inactivating enzyme, whereas the metabolism of vitamin D,” explains Eui-Ju Hong and colleagues first human PGR overexpression increased Hong. “We also wish to investigate the assessed whether endogenous Cyp24a1 expression. Subsequent biosynthesis and metabolism of androgens altered androgen- ChIP-sequencing showed that vitamin D in renal tissue during responsive gene expression in the progesterone treatment increased PR pregnancy, during which the kidney, a known androgen target recruitment to the Cyp24a1 expression of sex steroid hormones organ. Dihydrotestosterone (DHT) promoter, inferring a transcriptional and their receptors is increased.” treatment markedly decreased renal mechanism for DHT-dependent Conor A.
    [Show full text]
  • Activin and Estrogen Crosstalk Regulates Transcription in Human Breast Cancer Cells
    Endocrine-Related Cancer (2007) 14 679–689 Activin and estrogen crosstalk regulates transcription in human breast cancer cells Joanna E Burdette1,2 and Teresa K Woodruff1,2,3 1Feinberg College of Medicine, Institute for Women’s Health Research, Northwestern University, Chicago, Illinois 60611, USA 2Center for Reproductive Science, Northwestern University, Evanston, Illinois 60208, USA 3Robert H Lurie Comprehensive Cancer Center of Northwestern University, O T Hogan 4-150, Chicago, Illinois 60611, USA (Correspondence should be addressed to T K Woodruff; Email: [email protected]) Abstract Activin is a member of the transforming growth factor b superfamily that regulates mammary cell function during development, lactation, and in cancer. Activin slows the growth of breast cancer cells by inducing G0/G1 cell cycle arrest. Estrogen is a steroid hormone that stimulates the proliferation of mammary epithelial cells in development and oncogenesis. The crosstalk between estrogen and activin that regulates activin ligand expression, activin and estrogen signal transduction, and cell cycle arrest was investigated in this study. Estrogen antagonized activin- dependent production of plasminogen activator inhibitor 1 (PAI-1) mRNA, while activin repressed estrogen-dependent transcription of trefoil factor 1. The repression of estrogen signaling by activin was recapitulated using a simple estrogen response element-luciferase construct and was enhanced in the presence of overexpressed estrogen receptor a (ERa). In contrast, estrogen- mediated repression of activin signaling could not be recapitulated on a simple CAGA Smad- binding element but did inhibit the short PAI-1 promoter, p3TP-luciferase, especially when ERa was overexpressed. Repression of both estrogen- and activin-regulated transcription was found to be ligand induced and Smad3 dependent.
    [Show full text]
  • Vitamin D and Growth Hormone in Children
    Esposito et al. J Transl Med (2019) 17:87 https://doi.org/10.1186/s12967-019-1840-4 Journal of Translational Medicine REVIEW Open Access Vitamin D and growth hormone in children: a review of the current scientifc knowledge Susanna Esposito* , Alberto Leonardi, Lucia Lanciotti, Marta Cofni, Giulia Muzi and Laura Penta Abstract Background: Human growth is a complex mechanism that depends on genetic, environmental, nutritional and hormonal factors. The main hormone involved in growth at each stage of development is growth hormone (GH) and its mediator, insulin-like growth factor 1 (IGF-1). In contrast, vitamin D is involved in the processes of bone growth and mineralization through the regulation of calcium and phosphorus metabolism. Nevertheless, no scientifc study has yet elucidated how they interact with one another, especially as a dysfunction in which one infuences the other, even if numerous biochemical and clinical studies confrm the presence of a close relationship. Main body: We reviewed and analyzed the clinical studies that have considered the relationship between vitamin D and the GH/IGF-1 axis in pediatric populations. We found two main areas of interest: the vitamin D defciency status in patients afected by GH defcit (GHD) and the relationship between serum vitamin D metabolites and IGF-1. Although limited by some bias, from the analysis of the studies presented in the scientifc literature, it is possible to hypothesize a greater frequency of hypovitaminosis D in the subjects afected by GHD, a reduced possibility of its correction with only substitution treatment with recombinant growth hormone (rGH) and an improvement of IGF-1 levels after sup- plementation treatment with vitamin D.
    [Show full text]
  • Vitamin D, Skeletal Muscle Function and Athletic Performance in Athletes—A Narrative Review
    nutrients Communication Vitamin D, Skeletal Muscle Function and Athletic Performance in Athletes—A Narrative Review Anna Ksi ˛a˙zek* , Aleksandra Zagrodna and Małgorzata Słowi ´nska-Lisowska Department of the Biological and Motor Basis of Sport, University School of Physical Education, Wrocław 51612, Poland * Correspondence: [email protected]; Tel.: +48-71-347-35-63 Received: 24 June 2019; Accepted: 2 August 2019; Published: 4 August 2019 Abstract: The active form of vitamin D (calcitriol) exerts its biological effects by binding to nuclear vitamin D receptors (VDRs), which are found in most human extraskeletal cells, including skeletal muscles. Vitamin D deficiency may cause deficits in strength, and lead to fatty degeneration of type II muscle fibers, which has been found to negatively correlate with physical performance. Vitamin D supplementation has been shown to improve vitamin D status and can positively affect skeletal muscles. The purpose of this study is to summarize the current evidence of the relationship between vitamin D, skeletal muscle function and physical performance in athletes. Additionally, we will discuss the effect of vitamin D supplementation on athletic performance in players. Further studies are necessary to fully characterize the underlying mechanisms of calcitriol action in the human skeletal muscle tissue, and to understand how these actions impact the athletic performance in athletes. Keywords: 25(OH)D; calcidiol; calcitriol; muscle performance; muscle strength; physical activity; athlete 1. Introduction Recent years have seen an increased interest in the research studies investigating vitamin D status in athletes. The growing number of scientific reports suggests a pleiotropic nature of vitamin D, suggested by the demonstration of vitamin D receptors (VDRs) nearly in every nucleated cell of our bodies.
    [Show full text]
  • The Interfaces Between Vitamin D, Sleep and Pain
    234 1 D L DE OLIVEIRA and others Sleep and pain: the role of 234:1 R23–R36 Review vitamin D The interfaces between vitamin D, sleep and pain Correspondence Daniela Leite de Oliveira, Camila Hirotsu, Sergio Tufik and Monica Levy Andersen should be addressed to C Hirotsu Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil Email [email protected] Abstract The role of vitamin D in osteomineral metabolism is well known. Several studies have Key Words suggested its action on different biological mechanisms, such as nociceptive sensitivity f sleep and sleep–wake cycle modulation. Sleep is an important biological process regulated f vitamin D by different regions of the central nervous system, mainly the hypothalamus, in f pain combination with several neurotransmitters. Pain, which can be classified as nociceptive, f hyperalgesia neuropathic and psychological, is regulated by both the central and peripheral nervous systems. In the peripheral nervous system, the immune system participates in the inflammatory process that contributes to hyperalgesia. Sleep deprivation is an important condition related to hyperalgesia, and recently it has also been associated with vitamin D. Poor sleep efficiency and sleep disorders have been shown to have an important role Endocrinology in hyperalgesia, and be associated with different vitamin D values. Vitamin D has been of inversely correlated with painful manifestations, such as fibromyalgia and rheumatic diseases. Studies have demonstrated a possible action of vitamin D in the regulatory Journal mechanisms of both sleep and pain. The supplementation of vitamin D associated with good sleep hygiene may have a therapeutic role, not only in sleep disorders but also in Journal of Endocrinology the prevention and treatment of chronic pain conditions.
    [Show full text]
  • Effect of Progesterone-Only Contraception on Vitamin D In
    Iran J Ped Original Article Mar 2008; Vol 18 ( No 1), Pp:25-30 Effect of Progesterone­only Contraception on Vitamin D in Human Milk Shahnaz Khaghani*1, PhD of Biochemistry; Narjes Ardestani2, MSc of midwifery; Parvin Pasalar 1, PhD of Biochemistry; Sedigeh Shams1, PhD of Biochemistry; Azin Nowrouzi 1, PhD of Biochemistry; Samira Heidary1, Medical Student 1. Department of Biochemistry, Tehran University of Medical Sciences, Tehran, IR Iran 2. Department of midwifery, Islamic Azad University, Varamin, IR Iran Received: 18/10/06; Revised: 11/07/07; Accepted: 06/10/07 Abstract Objective: Nowadays progesterone contraceptives are being used by lactating women. In the last century elements effective in bone growth in infants, such as calcium, phosphorus and vitamin D have been evaluated. Vitamin D has been mentioned mainly in relation to rickets prevention in infants. This study was initiated in order to investigate the effect of Progestin‐ only contraceptives on breast milk vitamin D. Material & Methods: In this cohort study 138 lactating women were assigned to either the hormonal (52 participants) or non‐hormonal (86 participants) groups according to their chosen method of contraception. The characteristics and goals of the study were explained in detail and informed consent was obtained from all subjects before inclusion in the study. Research units started their method of contraception 45 (7) days postpartum and continued at least for 6 months afterward. 10 ml milk samples were obtained before the baby nursed at 6 mos postpartum, and kept at ‐20 °C until analysis. Vitamin D levels were measured with RIA method. Findings: Vitamin D levels were found to be 11.2 (7.2) nmol/L in the hormonal and 10.67±6.6 nmol/L in the non‐hormonal groups, which was lower than other cultures.
    [Show full text]
  • Vitamin D in Children with Growth Hormone Deficiency Due to Pituitary Stalk Interruption Syndrome Cécile Delecroix1, Raja Brauner1* and Jean-Claude Souberbielle2
    Delecroix et al. BMC Pediatrics (2018) 18:11 DOI 10.1186/s12887-018-0992-3 RESEARCH ARTICLE Open Access Vitamin D in children with growth hormone deficiency due to pituitary stalk interruption syndrome Cécile Delecroix1, Raja Brauner1* and Jean-Claude Souberbielle2 Abstract Background: Recent studies have shown a relationship between vitamin D status and growth hormone (GH) and insulin-like growth factor 1 (IGF1). The objective of this study was to assess vitamin D status in children with GH deficiency due to pituitary stalk interruption syndrome (PSIS) and to investigate the relationship between 25- hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25 (OH) 2D) serum levels and patient characteristics. Methods: A retrospective single-center study of 25OHD and 1,25(OH)2D serum concentrations in 50 children with PSIS at the initial evaluation before treatment. Results: Mean concentrations of 33.2 ± 18.0 ng/mL for 25OHD and 74.5 ± 40.7 ng/L for 1,25(OH)2D were measured. Additionally, 25OHD concentrations were significantly higher in boys than in girls (p = 0.04) and lower in the cold season than in the sunny season (p = 0.03). Significant positive correlations were observed between the GH peak and serum 1,25 (OH) 2D concentrations (Rho = 0.35; p = 0.015) and the 1,25(OH)2D/25OHD ratio (Rho = 0.29; p <0.05).No correlation was found for other characteristics, including IGF1. Conclusions: Vitamin D status in children with hypothalamic-pituitary deficiency due toPSISwassimilartothatreported in national and European studies in healthy children. The positive significant correlations between the GH peak and the 1,25 (OH)2D concentration as well as with the 1,25 (OH)2D/25OHD ratio suggest that even in these patients who had severely impaired GH secretion and low IGF1 levels, an interplay between the GH/IGF1 axis and the vitamin D system still exists.
    [Show full text]
  • Araştırma/Research Does the Deficiency of 25-Hydroxy Vitamin D Effect the Placental Peptides (Free Β-Human Chorionic Gonadotr
    Adıyaman Üni. Sağlık Bilimleri Derg, 2017;3 (3):589-597. Araştırma/Research Does the deficiency of 25-hydroxy vitamin D effect the placental peptides (free β-human chorionic gonadotropin and pregnancy-associated plasma protein A) levels? Tuğba Gürbüz 1, Nur Dokuzeylül Güngör1, Gökmen İyigün1, Seyhan Özcan1 1 Medical Park Göztepe Hospital Gynecology and obstetric clinic Abstract Objective In this study, we analysed that low maternal 25 hydroxy vitamin D (25(OH)D) levels cause an increase in the level of 1,25 dihydroxy vitamin D in the syncytiotrophoblasts by placental hydroxilation and also we analysed the effects of low syncystiotrofoblastic stimulation on placental peptides (free β-human chorionic gonadotropin and pregnancy-associated plasma protein A) secretion.. Material and Methods This retrospective study was included 225 pregnant women at 11-14 weeks of gestation attending the outpatient clinic of our hospital for first trimester screening test from January 2017 to December 2017. Vitamin D levels were deficient in 145 pregnant women and adequate in 80 pregnant women. Serum 25(OH)D concentrations were measured at 11–14 weeks gestation in 225 singleton pregnancies using liquid chromatography-tandem mass spectrometry in the same labaratory. We assessed the relationship between vitamin D, free β-human chorionic gonadotropin ( free β-hCG) and pregnancy associated plasma protein A (PAPP-A) levels during pregnancy. Results: There was a negative correlation between PAPP-A levels and maternal age at sampling (p=0.219). There was a positive correlation between free β-hCG levels and maternal age at sampling (p=0.034). There was a negative correlation between Low 25(OH)D levels and free β-hCG levels (p=0.071).
    [Show full text]
  • Potential Effects of Melatonin and Micronutrients on Mitochondrial Dysfunction During a Cytokine Storm Typical of Oxidative/Inflammatory Diseases
    diseases Review Potential Effects of Melatonin and Micronutrients on Mitochondrial Dysfunction during a Cytokine Storm Typical of Oxidative/Inflammatory Diseases Virna Margarita Martín Giménez 1, Natalia de las Heras 2 , León Ferder 3, Vicente Lahera 2, Russel J. Reiter 4 and Walter Manucha 5,6,* 1 Instituto de Investigaciones en Ciencias Químicas, Facultad de Ciencias Químicas y Tecnológicas, Universidad Católica de Cuyo, San Juan, Argentina; [email protected] 2 Departamento de Fisiología, Facultad de Medicina, Universidad Complutense, 28040 Madrid, Spain; [email protected] (N.d.l.H.); [email protected] (V.L.) 3 Departamento de Fisiología, Facultad de Ciencias Médicas, Universidad Maimónides, Buenos Aires, Argentina; [email protected] 4 Department of Cell Systems and Anatomy, UT Health San Antonio Long School of Medicine, San Antonio, TX 78229, USA; [email protected] 5 Área de Farmacología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina 6 Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Mendoza, Argentina * Correspondence: [email protected] or [email protected] Citation: Martín Giménez, V.M.; Abstract: Exaggerated oxidative stress and hyper-inflammation are essential features of oxida- de las Heras, N.; Ferder, L.; Lahera, V.; tive/inflammatory diseases. Simultaneously, both processes may be the cause or consequence of Reiter, R.J.; Manucha, W. Potential mitochondrial dysfunction, thus establishing a vicious cycle among these three factors. However, Effects of Melatonin and several natural substances, including melatonin and micronutrients, may prevent or attenuate mito- Micronutrients on Mitochondrial chondrial damage and may preserve an optimal state of health by managing the general oxidative Dysfunction during a Cytokine Storm and inflammatory status.
    [Show full text]
  • Multipledose, Safety, Pharmacokinetic
    Pharmackinetics and Pharmacodynamic The Journal of Clinical Pharmacology Multiple‐Dose, Safety, Pharmacokinetic, and 53(11) 1121–1130 ©2013, The American College of Pharmacodynamic Study of Sotatercept Clinical Pharmacology DOI: 10.1002/jcph.160 (ActRIIA‐IgG1), a Novel Erythropoietic Agent, in Healthy Postmenopausal Women Matthew L. Sherman, MD1, Niels G. Borgstein, MD1, Louisa Mook, MD1, Dawn Wilson, BS1, Yijun Yang, ScD1, Nianhang Chen, PhD2, Ravindra Kumar, PhD1, Kenneth Kim, MD3, and Abderrahmane Laadem, MD2 Abstract Ligands of the transforming growth factor‐beta superfamily and activin‐receptor signaling play an important role in erythropoiesis. Sotatercept, an activin receptor type IIA (ActRIIA) ligand trap, is a novel, recombinant, fusion protein comprising the extracellular domain of human ActRIIA linked to the Fc portion of human immunoglobulin G1. Sotatercept, originally developed to increase bone mineral density, was noted to have robust effects on erythropoiesis. Here, we evaluated the safety, pharmacokinetic properties, and pharmacodynamic effects of sotatercept in 31 healthy postmenopausal women. Sotatercept was administered at dose level 0.1, 0.3, or 1 mg/kg every 28 days subcutaneously for up to four doses. Sotatercept was generally safe and well tolerated, and elicited clinically significant, dose‐dependent increases in hemoglobin, hematocrit, and red blood cell counts that persisted for up to 4 months. The effect of sotatercept on hemoglobin was dose‐limiting. Sotatercept also increased bone mineral density and biomarkers of bone formation. The sotatercept serum exposure–dose relationship was linear, with a mean terminal half‐life of approximately 23 days. ActRIIA ligands are important regulators of erythrocyte production in healthy individuals. Clinical studies are ongoing to explore the potential of sotatercept to treat anemia and diseases of ineffective erythropoiesis as well as an agent to increase bone mineral density.
    [Show full text]