Результаты поиска

Positive and negative allosteric modulators promote biased signaling at the calcium-sensing receptor.

The calcium-sensing receptor (CaSR) is a G protein-coupled receptor whose function can be allosterically modulated in a positive or negative manner by calcimimetics or calcilytics, respectively. Indeed, the second-generation calcimimetic, cinacalcet, has proven clinically useful in the treatment of chronic kidney disease patients with secondary hyperparathyroidism but is not widely used in earlier stages of renal disease due to the potential to predispose such patients to hypocalcaemia and hyperphosphatemia. The development of a biased CaSR ligand that is more selective for specific signaling …

Orbital augmentation with injectable calcium hydroxylapatite for correction of postenucleation/evisceration socket syndrome.

PURPOSE: To demonstrate the utility of injectable calcium hydroxylapatite (Radiesse) for orbital volume augmentation to correct postenucleation/evisceration socket syndrome (PESS). METHODS: A retrospective chart review of all consecutive patients in our practice who received injectable calcium hydroxylapatite placed in the extraconal space to augment orbital volume was conducted. Patients with at least 6 months follow-up were included in the study. RESULTS: Among 26 patients with PESS who received injectable calcium hydroxylapatite for orbital volume augmentation, 15 individuals were identif…

Essential role for calcium waves in migration of human vascular smooth muscle cells.

Vascular smooth muscle cell (SMC) migration is characterized by extension of the lamellipodia at the leading edge, lamellipodial attachment to substrate, and release of the rear (uropod) of the cell, all of which enable forward movement. However, little is known regarding the role of intracellular cytosolic Ca(2+) concentration ([Ca(2+)](i)) in coordinating these distinct activities of migrating SMCs. The objective of our study was to determine whether regional changes of Ca(2+) orchestrate the migratory cycle in human vascular SMCs. We carried out Ca(2+) imaging using digital fluorescence mic

Calcium-dependent inhibition of adrenal TREK-1 channels by angiotensin II and ionomycin.

Bovine adrenocortical cells express bTREK-1 K(+) (bovine KCNK2) channels that are inhibited by ANG II through a Gq-coupled receptor by separate Ca(2+) and ATP hydrolysis-dependent signaling pathways. Whole cell and single patch clamp recording from adrenal zona fasciculata (AZF) cells were used to characterize Ca(2+)-dependent inhibition of bTREK-1. In whole cell recordings with pipette solutions containing 0.5 mM EGTA and no ATP, the Ca(2+) ionophore ionomycin (1 μM) produced a transient inhibition of bTREK-1 that reversed spontaneously within minutes. At higher concentrations, ionomycin (5-1

Calcium dependence of damage to mouse motor nerve terminals following oxygen/glucose deprivation.

Motor nerve terminals are especially sensitive to an ischemia/reperfusion stress. We applied an in vitro model of this stress, oxygen/glucose deprivation (OGD), to mouse neuromuscular preparations to investigate how Ca(2+) contributes to stress-induced motor terminal damage. Measurements using an ionophoretically-injected fluorescent [Ca(2+)] indicator demonstrated an increase in intra-terminal [Ca(2+)] following OGD onset. When OGD was terminated within 20-30min of the increase in resting [Ca(2+)], these changes were sometimes reversible; in other cases [Ca(2+)] remained high and the terminal

Myofilament calcium sensitization delays decompensated hypertrophy differently between the sexes following myocardial infarction.

Contractile dysfunction is common to many forms of cardiovascular disease. Approaches directed at enhancing cardiac contractility at the level of the myofilaments during heart failure (HF) may provide a means to improve overall cardiovascular function. We are interested in gender-based differences in cardiac function and the effect of sarcomere activation agents that increase contractility. Thus, we studied the effect of gender and time on integrated arterial-ventricular function (A-V relationship) following myocardial infarction (MI). In addition, transgenic mice that overexpress the slow ske

Postoperative calcium requirements in 6,000 patients undergoing outpatient parathyroidectomy: easily avoiding symptomatic hypocalcemia.

BACKGROUND: To determine the amount and duration of supplemental oral calcium for patients with varying clinical presentations discharged immediately after surgery for primary hyperparathyroidism. STUDY DESIGN: A 4-year, prospective, single-institution study of 6,000 patients undergoing parathyroidectomy for primary hyperparathyroidism and discharged within 2.5 hours. Based on our previous studies, patients are started on a sliding scale of oral calcium determined by a number of preoperative measures (ie, serum calcium, body weight, osteoporosis) beginning 3 hours postoperation and decreasing…

Serum PTH and ionized calcium levels as predictors of symptomatic hypocalcemia after parathyroidectomy.

OBJECTIVE: To evaluate whether perioperative PTH levels or ionized calcium levels are associated with symptomatic hypocalcaemia, in patients undergoing parathyroidectomy for primary hyperparathyroidism. STUDY DESIGN: Prospective noncontrolled study of a cohort of 100 patients, undergoing parathyroidectomy at a single tertiary care medical centre. METHODS: Prospectively collected data from January 2002 to April 2008 on 100 unique patients undergoing parathyroidectomy for primary hyperparathyroidism were evaluated for age, sex, preoperative and intraoperative PTH levels, and preoperative and p…

FAD mutations in amyloid precursor protein do not directly perturb intracellular calcium homeostasis.

Disturbances in intracellular calcium homeostasis are likely prominent and causative factors leading to neuronal cell death in Alzheimer's disease (AD). Familial AD (FAD) is early-onset and exhibits autosomal dominant inheritance. FAD-linked mutations have been found in the genes encoding the presenilins and amyloid precursor protein (APP). Several studies have shown that mutated presenilin proteins can directly affect calcium release from intracellular stores independently of Abeta production. Although less well established, there is also evidence that APP may directly modulate intracellular …

Calcium, vitamin D, VDR genotypes, and epigenetic and genetic changes in rectal tumors.

Calcium, vitamin D, exposure to sunshine, and vitamin D receptor (VDR) genotypes have been associated rectal cancer. We used data from 750 rectal tumors and 1,205 population-based controls examine associations with TP53, KRAS2, and CpG Island methylator phenotype (CIMP) markers. Rectal tumors were associated with high levels of calcium overall and with TP53 tumor mutations specifically (OR = 0.6, 95% CI = 0.42-0.84). High levels of sunshine exposure had a borderline protective effect for TP53 tumor mutations (OR = 0.78, 95% CI = 0.59-1.03). A mutation at codon 248 was significantly associated …

Calcium signals and caspase-12 participated in paraoxon-induced apoptosis in EL4 cells.

In order to investigate whether calcium signals participate in paraoxon (POX)-induced apoptosis in EL4 cells, real-time laser scanning confocal microscopy (LSCM) was used to detect Ca(2+) changes during the POX application. Apoptotic rates of EL4 cells and caspase-12 expression were also evaluated. POX (1-10nM) increased intracellular calcium concentration ([Ca(2+)]i) in EL4 cells in a dose-dependent manner at early stage (0-2h) of POX application, and apoptotic rates of EL4 cells after treatment with POX for 16h were also increased in a dose-dependent manner. Pre-treatment with EGTA, heparin …

Biomimetic calcium phosphate coatings as bone morphogenetic protein delivery systems in spinal fusion.

BACKGROUND CONTEXT: Use of recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to enhance spinal fusion rates. Case reports of soft-tissue swelling, ectopic bone formation, and osteolysis have recently surfaced. It is hypothesized that incorporation of rhBMP-2 within a calcium phosphate (CaP) coating may help to localize delivery and mitigate these complications. PURPOSE: To compare the characteristics of posterolateral fusion between rabbits receiving rhBMP-2 delivered via physical adsorption to a collagen sponge or rhBMP-2 incorporated within the physical structure of a …

Prion protein misfolding affects calcium homeostasis and sensitizes cells to endoplasmic reticulum stress.

Prion-related disorders (PrDs) are fatal neurodegenerative disorders characterized by progressive neuronal impairment as well as the accumulation of an abnormally folded and protease resistant form of the cellular prion protein, termed PrP(RES). Altered endoplasmic reticulum (ER) homeostasis is associated with the occurrence of neurodegeneration in sporadic, infectious and familial forms of PrDs. The ER operates as a major intracellular calcium store, playing a crucial role in pathological events related to neuronal dysfunction and death. Here we investigated the possible impact of PrP misfold…

Поток кальция между эндоплазмическим ретикулумом и митохондрионом способствует апоптозу, вызванному полиомиелитвирусом.

Мы показываем, что полиомиелитвирусная инфекция (PV) вызывает увеличение концентрации цитосолического кальция (Ca(2+)) в нейробластомных клетках IMR5, по крайней мере частично через Ca(2+) высвобождение из эндоплазмического ретикулума люмена через каналы иноситола 1,4,5-трифосфатного рецептора (IP(3)R) и рианодина рецептора (RyR). Это приводит к аккумулированию Ca(2+) в митохондрии через митохондриальный канал Ca(2+) и анионный канал, зависящий от напряжения (VDAC). Это увеличение концентрации митохондриала Ca(2+) в PV-зараженных клетках ведет к митохондриальной дисфункции и апоптозу.

Совпадение в аннотации оригинала
We show that poliovirus (PV) infection induces an increase in cytosolic calcium (Ca(2+)) concentration in neuroblastoma IMR5 cells, at least partly through Ca(2+) release from the endoplasmic reticulum lumen via the inositol 1,4,5-triphosphate receptor (IP(3)R) and ryanodine receptor (RyR) channels. This leads to Ca(2+) accumulation in mitochondria through t…

Cross-sectional study of vitamin D and calcium supplementation effects on chronic periodontitis.

BACKGROUND: A low dietary intake of vitamin D and calcium hastens bone loss and osteoporosis. Because vitamin D metabolites may also alter the inflammatory response and have antimicrobial effects, we studied whether the use of vitamin D and calcium supplements affects periodontal disease status. METHODS: A cohort of 51 subjects receiving periodontal maintenance therapy was recruited from two dental clinics; 23 were taking vitamin D (>or=400 IU/day) and calcium (>or=1,000 mg/day) supplementation, and 28 were not taking such supplementation. All subjects had at least two interproximal sites wit…

The calcium-sensing receptor regulates parathyroid hormone gene expression in transfected HEK293 cells.

BACKGROUND: The parathyroid calcium receptor determines parathyroid hormone secretion and the response of parathyroid hormone gene expression to serum Ca2+ in the parathyroid gland. Serum Ca2+ regulates parathyroid hormone gene expression in vivo post-transcriptionally affecting parathyroid hormone mRNA stability through the interaction of trans-acting proteins to a defined cis element in the parathyroid hormone mRNA 3'-untranslated region. These parathyroid hormone mRNA binding proteins include AUF1 which stabilizes and KSRP which destabilizes the parathyroid hormone mRNA. There is no parathy…

Modified autonomic regulation in mice with a P/Q-type calcium channel mutation.

Recent genetic analyses revealed an important association between P/Q-type channels and hereditary neurological disorders. The alpha1 subunit of P/Q-type channels is coded by a single CaV2.1 gene. Since calcium entry via neuronal calcium channels is essential for neurotransmission, P/Q-type channels may play an important role in cardiac autonomic neurotransmission. To elucidate the physiological importance of P/Q-type channels in autonomic nerve control, we used rolling Nagoya (tg(rol)) mice, which have a mutation in the CaV2.1 gene and decreased P/Q-type channel currents with reduced voltage …

Serum potassium, calcium and magnesium in patients receiving ESHAP chemotherapy for relapsed lymphomas.

UNLABELLED: Etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) is one of the mostly widely used chemotherapy regimens for patients with relapsed lymphomas. Cisplatin administration is commonly associated with electrolyte imbalance. Careful monitoring of renal function and serum electrolytes is therefore essential in this setting. AIMS: To review the practice of electrolyte monitoring - potassium (K), calcium (Ca) and magnesium (Mg) - in patients receiving ESHAP and the frequency and severity of abnormalities and their management. METHODS: Twenty-one consecutive patients received…

Ectopic bone formation in adipose-derived stromal cell-seeded osteoinductive calcium phosphate scaffolds.

The phenomenon of osteoinduction by biomaterials has been proven and used in animals. However, whether the ability of a biomaterial to initiate bone formation in ectopic implantation sites improves the performance of such osteoinductive biomaterial as a scaffold for tissue-engineered (TE) bone remains unclear. In this study, we compared ectopic bone formation by combining autologous adipose-derived stromal cells (ADSCs) with an osteoinductive and a nonosteoinductive biphasic calcium phosphate (BCP) ceramic to create a tissue engineering construct in the muscle of dogs. Two groups of BCP scaffo…

Fluorescent recognition of potassium and calcium ions using functionalised CdSe / ZnS quantum dots.

Schiff base receptor 1a has been synthesised and attached to the surface of preformed CdSe/ZnS Quantum Dots (QDs) to form QD-conjugate 2a. While 1a was determined to be selective for Mg2+, 2a demonstrated selectivity for both K+ and Ca2+ when tested against a range of physiologically and environmentally relevant cations by changes in the fluorescence spectra. Thus, the nanoparticle surface functions as a scaffold for the organisation of receptors enabling semi-selective binding. The fluorescence response was shown to be linear between 15-50 microM for K+ and 2-35 microM for Ca2+. It was also d