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1.
Eur J Endocrinol ; 183(2): G57-G65, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32396134

RESUMO

Endocrinologists have had to make rapid changes to services so that resources can be focused on the COVID-19 response to help prevent spread of the virus. Herein we provide pragmatic advice on the management of commonly encountered calcium metabolic problems and osteoporosis. Non-urgent elective appointments should be postponed, and remote consultations and digital health solutions promoted. Patients should be empowered to self-manage their conditions safely. Patients, their caregivers and healthcare providers should be directed to assured national or international online resources and specific patient groups. For patients in acute hospital settings, existing emergency guidance on the management of hyper- and hypo-calcaemia should be followed. An approach to osteoporosis management is outlined. IV zoledronic acid infusions can be delayed for 6-9 months during the pandemic. Patients established on denosumab, teriparatide and abaloparatide should continue planned therapy. In the event of supply issues with teriparatide or abaloparatide, pausing this treatment in the short term is likely to be relatively harmless, whereas delaying denosumab may cause an immediate increased risk of fracture. The challenge of this pandemic will act as a catalyst to innovate within our management of metabolic bone and mineral disorders to ensure best use of resources and resilience of healthcare systems in its aftermath.


Assuntos
Distúrbios do Metabolismo do Cálcio/terapia , Endocrinologia/métodos , Osteoporose/terapia , Guias de Prática Clínica como Assunto , Autogestão/métodos , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Endocrinologia/normas , Feminino , Humanos , Masculino , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão
2.
Dtsch Med Wochenschr ; 144(16): 1125-1132, 2019 08.
Artigo em Alemão | MEDLINE | ID: mdl-31416104

RESUMO

A finely balanced control system keeps the extracellular calcium concentration within narrow limits. Disorders of calcium metabolism are often based on altered parathormone levels. Symptoms are not always clear, sometimes they are even missing: the more it is important to know possible associated diseases. The author presents basics, current diagnostics and concrete therapy options. Central hormone for the regulation of the calcium balance is the parathyroid hormone. With decreasing calcium, PTH leads to an increase in extracellular free calcium concentration in three ways. The classic symptoms of pHPT (polyuria, polydipsia, "stone, leg, and stomach pain") are rare now, as the condition is diagnosed much earlier. Treatment of choice in all symptomatic patients with pHPT is surgery. FHH and pHPT are both characterized by hypercalcaemia and increased parathyroid hormone. The differential diagnosis of urinary calcium excretion, which is usually lower in FHH but normal or elevated in pHPT, is crucial. In primary hypoparathyroidism, parathyroid failure interferes with calcium homeostasis at a central location. Consequences are hypocalcaemia, hyperphosphatemia and lack of active vitamin D. Due to increased urinary calcium excretion, patients with ADH are at high risk for kidney stones, nephrocalcinosis and the development of renal insufficiency. Recently, rhPTH 1-84 has been available for the treatment of hypoparathyroidism. However, long-term data is still lacking to provide a safe indication, considering potential effects and side effects.


Assuntos
Distúrbios do Metabolismo do Cálcio , Cálcio na Dieta , Cálcio , Cálcio/metabolismo , Cálcio/fisiologia , Cálcio na Dieta/análise , Cálcio na Dieta/metabolismo , Humanos , Hipoparatireoidismo , Vitamina D
3.
Endocrinol Metab Clin North Am ; 48(3): 643-655, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31345528

RESUMO

Physiologic changes during pregnancy include calcium, phosphate, and calciotropic hormone status. Calcium metabolic disorders are rare in pregnancy and management with close calcium and vitamin D control and supplementation. Primary hyperparathyroidism is mostly asymptomatic and does not affect conception or pregnancy. It requires control of plasma calcium levels. Surgical intervention may be indicated. Data on severe cases are missing. Osteoporosis in or before pregnancy is rare but usually diagnosed from fractures. Medical treatment other than supplementation is contraindicated. Vitamin D deficiency is common and may affect conception and increase complications. Current evidence does not prove vitamin D supplements effective in improving outcomes.


Assuntos
Distúrbios do Metabolismo do Cálcio , Hiperparatireoidismo Primário , Osteoporose , Complicações na Gravidez , Deficiência de Vitamina D , Cálcio/sangue , Distúrbios do Metabolismo do Cálcio/complicações , Distúrbios do Metabolismo do Cálcio/diagnóstico , Distúrbios do Metabolismo do Cálcio/terapia , Cálcio na Dieta/uso terapêutico , Suplementos Nutricionais , Feminino , Humanos , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/etiologia , Hiperparatireoidismo Primário/terapia , Osteoporose/diagnóstico , Osteoporose/etiologia , Osteoporose/terapia , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/etiologia , Complicações na Gravidez/terapia , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/terapia
4.
J Alzheimers Dis ; 67(1): 137-147, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30636740

RESUMO

BACKGROUND: Disruption of intracellular Ca2+ homeostasis and associated autophagy dysfunction contribute to neuropathology in Alzheimer's disease (AD). OBJECTIVE: To study the effects of propofol on cell viability via its effects on intracellular Ca2+ homeostasis, and the impact of autophagy, in a neuronal model of presenilin-mutated familial AD (FAD). METHODS: We treated PC12 cells, stably transfected with either mutated presenilin-1 (L286V) or wild type (WT) controls, with propofol at different doses and durations, in the presence or absence of extracellular Ca2+, antagonists of inositol trisphosphate receptors (InsP3R, xestospongin C) and/or ryanodine receptors (RYR, dantrolene), or an inhibitor of autophagy flux (Bafilomycin). We determined cell viability, cytosolic Ca2+ concentrations ([Ca2+]c), vATPase protein expression, and lysosomal acidification. RESULTS: The propofol dose- and time-dependently decreased cell viability significantly more in L286V than WT cells, especially at the pharmacological dose (>50µM), and together with bafilomycin (40 nM). Clinically used concentrations of propofol (<20µM) tended to increase cell viability. Propofol significantly increased [Ca2+]c more in L286V than in WT cells, which was associated with decrease of vATPase expression and localization to the lysosome. Both toxicity and increased Ca2+ levels were ameliorated by inhibiting InsP3R/RYR. However, the combined inhibition of both receptors paradoxically increased [Ca2+]c, by inducing Ca2+ influx from the extracellular space, causing greater cytotoxicity. CONCLUSION: Impairment in autophagy function acts to deteriorate cell death induced by propofol in FAD neuronal cells. Cell death is ameliorated by either RYR or InsP3R antagonists on their own, but not when both are co-administered.


Assuntos
Doença de Alzheimer/genética , Anestésicos Intravenosos/toxicidade , Autofagia/genética , Distúrbios do Metabolismo do Cálcio/genética , Distúrbios do Metabolismo do Cálcio/patologia , Neurônios/efeitos dos fármacos , Síndromes Neurotóxicas/genética , Síndromes Neurotóxicas/patologia , Presenilina-1/genética , Propofol/toxicidade , Adenosina Trifosfatases/biossíntese , Animais , Distúrbios do Metabolismo do Cálcio/metabolismo , Humanos , Síndromes Neurotóxicas/metabolismo , Células PC12 , Ratos , Canal de Liberação de Cálcio do Receptor de Rianodina/efeitos dos fármacos
5.
Asian J Surg ; 42(1): 6-10, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29908897

RESUMO

BACKGROUND: Secondary hyperparathyroidism (SHPT) and calcium and phosphorus metabolism disorder are important complications in haemodialysis patients. Parathyroidectomy (PTX) may prevent or delay the progress of vascular calcification in haemodialysis patients. OBJECTIVE: To investigate the impacts of PTX on calcium and phosphorus metabolism, arterial calcification and arterial stiffness in haemodialysis patients with SHPT. METHODS: Twenty-one SHPT-haemodialysis patients were selected for PTX. The preoperative and postoperative 1-year scores of coronary artery calcification were measured via multislice spiral CT, along with the brachial-ankle pulse wave velocity (baPWV), and preoperative and postoperative 1-year indexes such as calcium, phosphorus, calcium-phosphorus product concentration and parathyroid hormone (PTH) level were compared. RESULTS: Compared with the preoperative score, the postoperative 1-year coronary artery calcification score was significantly reduced; the mean baPWVs of the bilateral limbs were reduced; and the levels of serum calcium, phosphorus, calcium-phosphorus product concentration and PTH were all reduced; all differences were statistically significant (P < 0.05). CONCLUSIONS: PTX can be used to correct calcium and phosphorus metabolism disorder, reduce arterial calcification, and improve arterial stiffness.


Assuntos
Distúrbios do Metabolismo do Cálcio/etiologia , Distúrbios do Metabolismo do Cálcio/prevenção & controle , Hiperparatireoidismo/etiologia , Paratireoidectomia , Distúrbios do Metabolismo do Fósforo/etiologia , Distúrbios do Metabolismo do Fósforo/prevenção & controle , Diálise Renal/efeitos adversos , Calcificação Vascular/etiologia , Calcificação Vascular/prevenção & controle , Rigidez Vascular , Adulto , Índice Tornozelo-Braço , Distúrbios do Metabolismo do Cálcio/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distúrbios do Metabolismo do Fósforo/terapia , Análise de Onda de Pulso
6.
Nephrology (Carlton) ; 24(10): 1001-1008, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30537427

RESUMO

BACKGROUND: Klotho G-395-A gene polymorphism is associated with several diseases; however, its association with calcium-phosphate metabolism disorders in end-stage renal disease (ESRD) is unknown. METHODS: A total of 137 patients with ESRD and 80 healthy adults (control) were enrolled in the study. Patients with ESRD were divided into three subgroups: haemodialysis (A1, n = 52), peritoneal dialysis (A2, n = 30), and non-dialysis (A3, n = 55). The klotho G-395-A genotype was detected by TaqMan PCR assay, and ELISA was used to detect the soluble klotho protein (sKL) and fibroblast growth factor (FGF23). Intact parathyroid hormone (iPTH) and other related clinical biochemical parameters were also analyzed for all subjects. RESULTS: (i) Three genotypes (GG, GA and AA) of KL G-395A were detected, and a significant difference between the ESRD and control groups was observed, (ii) sKL was inversely associated with FGF23 in each subgroup and phosphate and positively associated with calcium in A1 and A3. FGF23 was positively associated with phosphate and inversely associated with calcium in each subgroup, (iii) a statistical difference in levels of sKL and FGF23 was observed between GG and AA, as well as between GA and AA. The expression of sKL was lowest and the level of FGF23 was highest in AA and (iv). GA + AA genotypes and FGF23 were risk factors and sKL might be protective factor of calcium-phosphate metabolism disorders. CONCLUSION: Soluble klotho protein and FGF23 were associated with the regulation of calcium and phosphate metabolism, and the A allele of the G-395A klotho gene polymorphism could be a risk factor on calcium-phosphate metabolism disorders in patients with ESRD.


Assuntos
Distúrbios do Metabolismo do Cálcio , Cálcio/metabolismo , Fatores de Crescimento de Fibroblastos/sangue , Glucuronidase/genética , Falência Renal Crônica , Fosfatos/metabolismo , Distúrbios do Metabolismo do Fósforo , Adulto , Distúrbios do Metabolismo do Cálcio/diagnóstico , Distúrbios do Metabolismo do Cálcio/genética , Feminino , Glucuronidase/sangue , Humanos , Falência Renal Crônica/genética , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Masculino , Distúrbios do Metabolismo do Fósforo/diagnóstico , Distúrbios do Metabolismo do Fósforo/genética , Polimorfismo Genético , Terapia de Substituição Renal/métodos
7.
J Appl Oral Sci ; 26: e20170495, 2018 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-30043933

RESUMO

OBJECTIVES: To analyze the association between periodontal conditions and inflammation, nutritional status and calcium-phosphate metabolism disorders in hemodialysis (HD) patients. MATERIAL AND METHODS: We analyzed 128 HD patients divided into two groups: dentate (n = 103) and edentulous (n=25). The following items were assessed: baseline characteristics, age at the start and duration of HD, biochemical data: C-reactive protein (CRP), serum albumin, calcium, phosphorus, alkaline phosphatase, parathormone. A single dentist performed a complete dental/periodontal examination, including parameters of oral hygiene and gingival bleeding. RESULTS: One person had healthy periodontium, 62.14% of the patients had gingivitis, and 36.9% had moderate or severe periodontitis. The age at HD onset had a positive impact on periodontal status and negatively correlated with the number of teeth. A positive correlation between age and CRP level and negative correlations between age and serum albumin and phosphorus were found. Pocket depth (PD) was negatively correlated with serum albumin. The number of teeth was negatively correlated with serum CRP. CONCLUSIONS: High prevalence and severity of periodontal disease are observed in hemodialysis patients. There is a high probability that periodontal disease may be present at the early stages of chronic kidney disease (CKD) before the hemodialysis onset.


Assuntos
Distúrbios do Metabolismo do Cálcio/etiologia , Gengivite/etiologia , Estado Nutricional/fisiologia , Periodontite/etiologia , Distúrbios do Metabolismo do Fósforo/etiologia , Diálise Renal/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Fosfatase Alcalina/sangue , Proteína C-Reativa/análise , Cálcio/sangue , Distúrbios do Metabolismo do Cálcio/sangue , Índice de Placa Dentária , Feminino , Gengivite/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Higiene Bucal , Hormônio Paratireóideo/sangue , Índice Periodontal , Periodontite/sangue , Fósforo/sangue , Distúrbios do Metabolismo do Fósforo/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Fatores de Risco , Albumina Sérica/análise , Índice de Gravidade de Doença
9.
J Bras Nefrol ; 39(2): 217-219, 2017.
Artigo em Inglês, Português | MEDLINE | ID: mdl-29069247

RESUMO

Tumoral calcinosis is an uncommon type of extraosseous calcification characterized by large rubbery or cystic masses containing calcium-phosphate deposits. The condition prevails in the periarticular tissue with preservation of osteoarticular structures. Elevated calcium-phosphorus products and severe secondary hyperparathyroidism are present in most patients with uremic tumoral calcionosis (UTC). Case report of an obese secondary to chronic glomerulonephritis, undergoing continuous ambulatory peritoneal dialysis (CAPD) reported the appearance of painless tumors in the medial surface of fifth finger and left arm. Tumoral calcinosis was confirmed by left biceps biopsy. Poor adherence to CAPD. The patient was transferred to the "tidal" modality of peritoneal dialysis and after was treated by hemodialysis, despite the persistence of severe hyperparathyroidism progressive reduction of UTC until near to its complete disappearance. Nowadays, one year after patient received deceased-donor kidney transplantation, he presents with an improvement in secondary hyperparathyroidism. UTC should be included in the elucidation of periarticular calcification of every patient on dialysis. Relevant laboratory findings such as secondary hyperparathyroidism and elevated calcium- phosphorus products in the presence of periarticular calcification should draw attention to the diagnosis of UTC.


Assuntos
Doenças Ósseas Metabólicas/complicações , Calcinose/complicações , Distúrbios do Metabolismo do Cálcio/complicações , Distúrbios do Metabolismo do Fósforo/complicações , Uremia/complicações , Doenças Ósseas Metabólicas/terapia , Distúrbios do Metabolismo do Cálcio/terapia , Humanos , Masculino , Distúrbios do Metabolismo do Fósforo/terapia , Adulto Jovem
10.
Curr Med Chem ; 24(38): 4229-4244, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28901272

RESUMO

Prostate cancer significantly affects the overall morbidity and mortality of malignant tumours in highly developed countries. Important risk factors include family predisposition and regional, racial and dietary determinants. The scientific literature contains a great deal of data on the role of calcium and dairy products in general in the process of neoplastic transformation of the prostate. This is most likely linked to the fact that changes in the concentration of calcium ions control such varied life processes as secretion of hormones and neurotransmitters, the level of cyclic nucleotides, and cell growth, division and differentiation. Research is conducted to demonstrate that disorders of cell cycle control due to differences in calcium ion concentrations may be crucial for the development and prevention of cancer. Disturbances of calcium homeostasis in the body can be caused by various mechanisms, such as excessive calcium intake in the diet, vitamin D deficiency, structural and functional changes in vitamin D receptor (VDR), Calcium-Sensing Receptor (CaSR), and parathyroid hormone receptor (PTH-1-R), changes in calcium ion channels, phosphate metabolism disorders (phosphatonin and the Klotho protein), changes in the level of parathyroid hormone-related protein (PTHrP), and others. The article presents data on the mechanisms maintaining calcium homeostasis at the molecular level and genetic aspects playing a role in the pathogenesis of prostate cancer. The data cited on the occurrence of abnormal mechanisms of calcium metabolism in prostate cancer suggest the need for individualized intake of this element in the diet, especially in the case of patients with a family history of PCa.


Assuntos
Distúrbios do Metabolismo do Cálcio/metabolismo , Cálcio/metabolismo , Homeostase , Neoplasias da Próstata/metabolismo , Animais , Distúrbios do Metabolismo do Cálcio/genética , Humanos , Masculino , Neoplasias da Próstata/genética , Fatores de Risco
11.
Clin Calcium ; 27(4): 521-527, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-28336828

RESUMO

Sensing of extracellular calcium(Ca2+)levels involves the Ca-sensing receptor(CaSR), its downstream signaling molecule Gα11, and the adaptor-related protein complex 2(AP2)that plays a role in clathrin-dependent endocytosis of CaSR. Inactivating mutations in CaSR cause familial hypocalciuric hypercalcemia type 1(FHH1)and neonatal severe hyperparathyroidism(NSHPT), while activating mutations lead to autosomal dominant hypocalcemia type 1(ADH1)and Bartter syndrome type Ⅴ. Recent studies have identified that inactivating mutations in Gα11 and σ-subunit of AP2(AP2σ)also cause FHH, and these conditions have been classified as FHH2 and FHH3, respectively. In addition, it has been revealed that activating mutations in Gα11 are responsible for ADH(ADH2). Calcimimetics and calcilytics may be beneficial in the treatment of these disorders.


Assuntos
Distúrbios do Metabolismo do Cálcio/metabolismo , Mutação , Receptores de Detecção de Cálcio/metabolismo , Cálcio/metabolismo , Distúrbios do Metabolismo do Cálcio/genética , Sinalização do Cálcio , Humanos , Transporte Proteico , Receptores de Detecção de Cálcio/genética
12.
Rev Med Chil ; 144(8): 990-997, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27905644

RESUMO

BACKGROUND: Knowledge about the variability in the request of calcium-phosphate metabolism laboratory tests in primary care is important to design strategies to improve health system efficiency. AIM: To compare the inter-practice variability in calcium-phosphate metabolism laboratory tests requested by general practitioners from diverse regions across Spain. MATERIAL AND METHODS: One hundred and forty one clinical laboratories were invited to participate in an observational cross-sectional study. They informed the number of serum calcium, phosphate, parathyroid hormone and 25-hydroxyvitamin D requested by general practitioners. Appropriateness indicators were calculated as number of test requests per 1,000 inhabitants and ratio of related tests requests. The differences according to hospital setting, region and type of management were analyzed. RESULTS: We recruited 76 laboratories (17,679,195 inhabitants). General practitioners requested 3,260,894 calcium-phosphate metabolism tests. The rate of request ranged from 2.97 per 1,000 inhabitants for 25-hydroxyvitamin D to 98.89 per 1,000 inhabitants for calcium. The rates of request for calcium, phosphate, parathyroid hormone in some areas were 30, 100 and 340 times higher than in other areas. Parathyroid hormone and 25-hydroxyvitamin D were highly requested in private management areas. There were also differences in phosphate, parathyroid hormone and 25-hydroxyvitamin D requesting between regions across Spain. CONCLUSIONS: The high variability observed is difficult to explain by differences in patient case mix between regions. Depending on the area, calcium could be under requested to detect primary hyperparathyroidism.


Assuntos
Distúrbios do Metabolismo do Cálcio/diagnóstico , Técnicas de Laboratório Clínico/estatística & dados numéricos , Clínicos Gerais , Programas de Rastreamento/métodos , Padrões de Prática Médica , Atenção Primária à Saúde/estatística & dados numéricos , Fosfatos de Cálcio/sangue , Fosfatos de Cálcio/metabolismo , Estudos Transversais , Feminino , Humanos , Hipercalcemia/diagnóstico , Hiperparatireoidismo/diagnóstico , Masculino , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Espanha , Vitamina D/análogos & derivados , Vitamina D/sangue
13.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 45(4): 432-438, 2016 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-27868419

RESUMO

With the population aging and declining incidence of rheumatic heart disease, calcific aortic valve disease (CAVD) has become the most frequent valve disease and the common cause of aortic valve replacement. Patients with CAVD need to cope with a deteriorating quality of life and valve replacement is the only effective clinical option for the patients. Therefore, early pharmacotherapy is of great significance in prevention or slow-down of the progression of CAVD. For years CAVD was considered to be a passive wear and tear process of valves, but now it is recognized as an active and multi-factorial process. Histopathologic studies have revealed that inflammation, disorder of calcium and phosphorus metabolism and dyslipidemia are involved in the process of CAVD. Clinical trials of CAVD pharmacotherapy have been carried out based on those histopathologic studies. Statin, renin-angiotensin inhibitors and anti-osteoporosis drug are well studied in recent years. This article reviews the recent research progress of the pharmacotherapy for CAVD.


Assuntos
Estenose da Valva Aórtica/tratamento farmacológico , Valva Aórtica/patologia , Calcinose/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/etiologia , Calcinose/complicações , Calcinose/etiologia , Distúrbios do Metabolismo do Cálcio/complicações , Progressão da Doença , Dislipidemias/complicações , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inflamação/complicações , Distúrbios do Metabolismo do Fósforo/complicações , Qualidade de Vida
14.
Physiol Res ; 65 Suppl 1: S139-48, 2016 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-27643936

RESUMO

We aimed to determine the impact of Ca(2+)-related disorders induced in intact animal hearts on ultrastructure of the cardiomyocytes prior to occurrence of severe arrhythmias. Three types of acute experiments were performed that are known to be accompanied by disturbances in Ca(2+) handling. Langedorff-perfused rat or guinea pig hearts subjected to K(+)-deficient perfusion to induce ventricular fibrillation (VF), burst atrial pacing to induce atrial fibrillation (AF) and open chest pig heart exposed to intramyocardial noradrenaline infusion to induce ventricular tachycardia (VT). Tissue samples for electron microscopic examination were taken during basal condition, prior and during occurrence of malignant arrhythmias. Cardiomyocyte alterations preceding occurrence of arrhythmias consisted of non-uniform sarcomere shortening, disruption of myofilaments and injury of mitochondria that most likely reflected cytosolic Ca(2+) disturbances and Ca(2+) overload. These disorders were linked with non-uniform pattern of neighboring cardiomyocytes and dissociation of adhesive junctions suggesting defects in cardiac cell-to-cell coupling. Our findings identified heterogeneously distributed high [Ca(2+)](i)-induced subcellular injury of the cardiomyocytes and their junctions as a common feature prior occurrence of VT, VF or AF. In conclusion, there is a link between Ca(2+)-related disorders in contractility and coupling of the cardiomyocytes pointing out a novel paradigm implicated in development of severe arrhythmias.


Assuntos
Arritmias Cardíacas/etiologia , Distúrbios do Metabolismo do Cálcio/complicações , Miócitos Cardíacos/ultraestrutura , Animais , Arritmias Cardíacas/metabolismo , Distúrbios do Metabolismo do Cálcio/patologia , Cobaias , Homeostase , Miócitos Cardíacos/metabolismo , Norepinefrina , Potássio , Ratos , Suínos
15.
Kidney Blood Press Res ; 41(5): 507-518, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27487342

RESUMO

BACKGROUND/AIMS: Parathyroid hormone (PTH) derivatives exert pronounced renal and osteoanabolic properties when given intermittently. The current study was performed to assess the pharmacokinetic and pharmacodynamic properties as well as safety of subcutaneously applied PTH-1-37 after repeated dosing in healthy subjects. METHODS: This randomized, double-blind, dose-escalating, placebo and active comparator controlled study was conducted in 33 healthy postmenopausal women. Subjects were allocated to one of five treatment options: 10, 20, or 40 µg PTH-1-37, 20 µg PTH-1-34 or placebo, administered as once daily subcutaneous doses for three days. Plasma drug concentrations and serum levels of endogenous PTH-1-84, and calcium as markers of biological activity were monitored during the treatment. RESULTS: PTH was absorbed rapidly from the subcutaneous tissue with a median tmax of 30 minutes for 20 and 40 µg of PTH-1-37. tmax was 45 minutes for 20 µg PTH-1-34. Elimination half-lives were estimated as 76 ± 34 min and 70 ± 13 min for 20 µg and 40 µg PTH-1-37 (mean ± SD), and 78 ± 34 for 20 µg PTH-1-34. Both PTH fragments (PTH-1-37 and PTH-1-34) increased serum calcium. For PTH-1-37 the effect on serum calcium was dose-dependent. Suppression of endogenous PTH-1-84 was seen after the application of both PTH-1-37 and PTH-1-34. During the study period, the subjects experienced no unexpected or serious adverse events. CONCLUSIONS: PTH-1-37 is rapidly absorbed after s.c. injection, has a short plasma elimination half-life, and does not accumulate during multiple dosing. Biological activity was demonstrated by rising serum calcium and decreasing endogenous PTH-1-84 in blood plasma. The study drugs were well tolerated and safe. Our investigation presents data that PTH-1-37 is an excellent drug candidate for intervening with syndromes of dysregulation of calcium metabolism.


Assuntos
Hormônio Paratireóideo/farmacocinética , Fragmentos de Peptídeos/farmacocinética , Cálcio/sangue , Cálcio/metabolismo , Distúrbios do Metabolismo do Cálcio/tratamento farmacológico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Meia-Vida , Voluntários Saudáveis , Humanos , Injeções Subcutâneas , Pessoa de Meia-Idade , Hormônio Paratireóideo/administração & dosagem , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/administração & dosagem
16.
J Orthop Res ; 34(11): 1914-1921, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26945509

RESUMO

Efficient calcium absorption is essential for skeletal health. Patients with impaired gastric acidification display low bone mass and increased fracture risk because calcium absorption is dependent on gastric pH. We investigated fracture healing and post-traumatic bone turnover in mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells. Cckbr-/- mice display hypochlorhydria, calcium malabsorption, and osteopenia. Cckbr-/- and wildtype (WT) mice received a femur osteotomy and were fed either a standard or calcium-enriched diet. Healed and intact bones were assessed by biomechanical testing, histomorphometry, micro-computed tomography, and quantitative backscattering. Parathyroid hormone (PTH) serum levels were determined by enzyme-linked immunosorbent assay. Fracture healing was unaffected in Cckbr-/- mice. However, Cckbr-/- mice displayed increased calcium mobilization from the intact skeleton during bone healing, confirmed by significantly elevated PTH levels and osteoclast numbers compared to WT mice. Calcium supplementation significantly reduced secondary hyperparathyroidism and bone resorption in the intact skeleton in both genotypes, but more efficiently in WT mice. Furthermore, calcium administration improved bone healing in WT mice, indicated by significantly increased mechanical properties and bone mineral density of the fracture callus, whereas it had no significant effect in Cckbr-/- mice. Therefore, under conditions of hypochlorhydria-induced calcium malabsorption, calcium, which is essential for callus mineralization, appears to be increasingly mobilized from the intact skeleton in favor of fracture healing. Calcium supplementation during fracture healing prevented systemic calcium mobilization, thereby maintaining bone mass and improving fracture healing in healthy individuals whereas the effect was limited by gastric hypochlorhydria. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1914-1921, 2016.


Assuntos
Acloridria/complicações , Reabsorção Óssea/etiologia , Distúrbios do Metabolismo do Cálcio/fisiopatologia , Fraturas do Fêmur/complicações , Consolidação da Fratura , Animais , Cálcio/metabolismo , Cálcio/uso terapêutico , Distúrbios do Metabolismo do Cálcio/complicações , Suplementos Nutricionais , Feminino , Fraturas do Fêmur/metabolismo , Camundongos , Distribuição Aleatória , Receptor de Colecistocinina B/genética
17.
Clin Calcium ; 25(7): 1029-36, 2015 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-26119316

RESUMO

Following the discovery of the calcium-sensing receptor (CaSR) in 1993, its pivotal role in disorders of calcium homeostasis was demonstrated. Compelling evidence suggests that the CaSR plays multiple roles extending well beyond not only regulating the level of extracellular Ca(2+), but also controlling diverse and crucial roles in human physiology and pathophysiology. This review covers current knowledge of the role of the CaSR in disorders of calcium homeostasis (familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, autosomal dominant hypocalcemia, primary and secondary hyperparathyroidism, hypercalcemia of malignancy) as well as unrelated diseases such as breast and colorectal cancer, Alzheimer's disease and pancreatitis. In addition, it examines the use or potential use of CaSR agonists or antagonists in the management of disorders as diverse as hyperparathyroidism and Alzheimer's disease.


Assuntos
Distúrbios do Metabolismo do Cálcio/etiologia , Cálcio/metabolismo , Receptores de Detecção de Cálcio/fisiologia , Doença de Alzheimer/etiologia , Animais , Neoplasias da Mama/etiologia , Neoplasias Colorretais/etiologia , Feminino , Homeostase , Humanos , Masculino , Camundongos , Terapia de Alvo Molecular , Mutação , Pancreatite , Receptores de Detecção de Cálcio/agonistas , Receptores de Detecção de Cálcio/antagonistas & inibidores , Receptores de Detecção de Cálcio/genética
18.
Clin Calcium ; 25(2): 189-94, 2015 Feb.
Artigo em Japonês | MEDLINE | ID: mdl-25634043

RESUMO

Bone and calcium metabolism disorders are closely linked with dementia. Screening for dementia is important since chronic hypercalcemia and hypocalcemia resulting from parathyroid function abnormalities can become a cause of dementia onset. In recent years, it has become clear that vitamin D deficiencies inducing cardiovascular disease and other factors are involved in the pathogenesis of various diseases that in turn become risk factors in dementia, especially Alzheimer's disease. Moreover, osteoporosis and dementia both commonly occur among the elderly. Treating dementia patients for osteoporosis is important since fragility fractures, especially femoral neck fractures, resulting from osteoporosis greatly affect the prognosis of patients with dementia.


Assuntos
Osso e Ossos/metabolismo , Distúrbios do Metabolismo do Cálcio/metabolismo , Cálcio/metabolismo , Demência/metabolismo , Osteoporose/metabolismo , Animais , Distúrbios do Metabolismo do Cálcio/complicações , Distúrbios do Metabolismo do Cálcio/terapia , Cognição/fisiologia , Demência/complicações , Demência/terapia , Humanos , Osteoporose/complicações , Osteoporose/terapia
19.
Internist (Berl) ; 55(11): 1313-26, 2014 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-25326053

RESUMO

The majority of clinical complaints derive from disorders of calcium metabolism and are associated with a wide variety of clinical symptoms caused by numerous diseases with entirely different types of pathophysiology. The prognosis varies from favorable to fatal depending on the pathophysiology of the underlying disorder of calcium metabolism; therefore, the diagnostic work-up aims to quickly identify the underlying disease causing the disturbance in calcium homeostasis. Every clinical situation with a diminished state of calcium absorption is treated with calcium and vitamin D in varying doses whereas every disorder with an increased calcium absorptive or resorptive state is treated with improved diuresis in addition to antiresorptive drugs, such as bisphosphonates. In many situations the management of a disturbed calcium balance requires an interdisciplinary approach in order to treat the underlying disease in parallel with correction of the calcium homeostasis.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Doenças Ósseas/prevenção & controle , Distúrbios do Metabolismo do Cálcio/diagnóstico , Distúrbios do Metabolismo do Cálcio/tratamento farmacológico , Cálcio/administração & dosagem , Difosfonatos/administração & dosagem , Vitamina D/administração & dosagem , Doenças Ósseas/diagnóstico , Doenças Ósseas/etiologia , Distúrbios do Metabolismo do Cálcio/complicações , Diagnóstico Diferencial , Humanos
20.
Ter Arkh ; 86(6): 52-6, 2014.
Artigo em Russo | MEDLINE | ID: mdl-25095656

RESUMO

AIM: To evaluate the efficacy and safety of alfacalcidol and paracalcitol used to correct impaired phosphorus-calcium metabolism (PCM) in patients with predialysis chronic kidney disease (CKD). SUBJECTS AND METHODS: Examinations were made in 128 patients with Stages III-V CKD, including 89 (69.5%) patients with chronic glomerulonephritis, 30 (23.4%) with chronic tubulointerstitial nephritis, and 9 (7.1%) with hypertensive nephrosclerosis. Impaired PCM was detected in 90 (70.3%) of the examined patients. According to the pattern of the previous therapy, all the 90 CKD patients with PCM disorders were divided into 3 groups: 1) 32 patients with Stages IIIB-V CKD who had taken oral alfacalcidol 0.25 microg/day; 2) 28 patients with Stages IIIB-V CKD who had used oral paricalcitol 1 microg/day; 3) 30 patients with Stages IIIB-V CKD who had not received, as self- motivated, active vitamin D metabolites at the predialysis stage. RESULTS: Alfacalcidol and paricalcitol were quite satisfactorily tolerated by the patients. After 3 months of initiation of the use of these agents, Groups 1 and 2 patients with predialysis CKD and baseline elevated blood intact parathyroid hormone (iPTH) levels could not only achieve, but also maintain target blood iPTH levels. In the patients taking paricalcitol, the urinary protein level decreased more promptly; moreover, by the end of month 6 the reduction in blood pressure (BP) was more significant than in those using alfacalcidol (p < 0.05). Comparison of the effects of angiotensin-converting enzyme inhibitors in combination with alfacalcidol or paricalcitol on BP changes and left ventricular mass index indicated that the most pronounced positive changes occurred when angiotensin-converting enzyme inhibitors were used in combination with paricalcitol. CONCLUSION: The use of paricalcitol in predialysis CKD with PTH hyperproduction results in not only normalization of the levels of both PTH and osseous isoenzyme of alkaline phosphatase, but also in significantly reduced daily proteinuria and regression of left ventricular hypertrophy and chronic heart failure.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Distúrbios do Metabolismo do Cálcio/tratamento farmacológico , Ergocalciferóis/farmacologia , Hidroxicolecalciferóis/farmacologia , Distúrbios do Metabolismo do Fósforo/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Adolescente , Adulto , Idoso , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Distúrbios do Metabolismo do Cálcio/epidemiologia , Comorbidade , Ergocalciferóis/administração & dosagem , Ergocalciferóis/efeitos adversos , Feminino , Humanos , Hidroxicolecalciferóis/administração & dosagem , Hidroxicolecalciferóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Distúrbios do Metabolismo do Fósforo/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/metabolismo , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
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