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Properties of a new calcium ion antagonist on cellular uptake and mitochondrial efflux of calcium ions.

Compound YS 035 [NN-bis-(3,4-dimethoxyphenethyl)-N-methylamine] is a new synthetic compound capable of inhibiting Ca2+ uptake by different cells. The inhibition of Ca2+ uptake by muscle cells isolated from chicken embryo is dose-dependent in the compound YS 035 concentration range 10-30 microM. The new compound also inhibits Ca2+ entry into rat brain synaptosomes and less effectively into baby-hamster kidney cells. Compound YS 035 partially inhibits the slow Ca2+ release induced by Ruthenium Red and the rapid Na+-dependent efflux from heart mitochondria. The inhibition of the Na+/Ca2+ exchange appears to be of a non-competitive type with an apparent Ki of 28 microM. The new Ca2+ antagonist totally inhibits the Ca2+ efflux from liver mitochondria induced by Ruthenium Red, but it does not affect the release induced by uncoupler, respiratory inhibitor or chelator, nor the mitochondrial ATP synthesis and membrane potential. The properties shown by the new compound indicate it to be a Ca2+ antagonist and a useful tool for studies on the mitochondrial Ca2+ transport.

Animals↗

Is there life after Buckley's Formocresol? Part I -- a narrative review of alternative interventions and materials.

OBJECTIVES: (1) To present a narrative review of the currently available alternative interventions and materials to formocresol pulpotomy for the management of extensive caries in the primary molar, and (2) to produce a clinical protocol for pulp therapy techniques in the extensively carious primary molar. INTRODUCTION: The International Agency for Research on Cancer has recently classified formaldehyde as carcinogenic to human beings. Since Buckley's Formocresol contains 19% formaldehyde in its full strength and, therefore, 1% in a 20% dilution, a safer alternative should be identified. METHODS: A narrative review of the published literature for primary molar pulp therapy techniques was undertaken following an extensive and appropriate literature search. A specialist group of paediatric dentists was formed to arrive at a consensus and establish an evidence-based protocol for the management of extensively carious primary molar teeth. Part I of this paper explores the currently available alternative interventions and materials to formocresol in the form of a narrative review. The second part of the paper will present the formation of a specialist group to arrive at a consensus and establish an evidence-based protocol for the management of the extensively carious primary molar. CONCLUSIONS: After consideration of a review of extensively searched literature, a protocol and key points document have been developed to assist clinicians in their treatment planning. Further long-term studies with the highest level of evidence (i.e. randomized controlled trials) are required to enable us to identify acceptable alternatives which can replace formocresol.

Aluminum Compounds↗

Effects of low concentrations of organochlorine compounds in women on calcium transfer in human placental syncytiotrophoblast.

For most Canadians, food represents one of the major sources of environmental contaminants. Among them, organochlorine compounds (OCs) are known to affect calcium (Ca2+) homeostasis. They are neurotoxic by perturbation of Ca2+ channels and pumps, and they interfere with protein kinase C (PKC) and Ca2+ binding protein (CaBP). Ca2+ is an essential element to adequate fetal growth and development. The aim of the present study is to determine the relation between low environmental maternal exposure to OCs, such as polychlorinated biphenyls (PCB 153), Aroclor 1260, p,p'-dichlorodiphenyltrichloroethane (DDT) and p,p'-dichlorodiphenyl-dichloroethane (DDE), Ca2+ levels in serum and placenta, placental Ca2+ transfer, and newborn development. Total Ca2+ and OCs were measured in women's serum samples, as well as in umbilical cord's serum and placenta at term. Placentas were taken for trophoblast cells isolation and Ca2+ incorporation kinetic experiments. Our results were obtained from 30 pregnant women from the southwestern area of Quebec. Concentrations of Aroclor 1260, PCB 153, DDE, and DDT were respectively 6.1, 6.0, 3.1, and 2.9 times lower in the umbilical cord serum than in the mother's serum at term. In the placenta, DDE was accumulated at higher levels than other contaminants. A tendency towards an inverse relation was observed for in OCs found in three compartments and Ca2+ levels in maternal serum and in placental tissues. Maternal Ca2+ concentrations do not influence Ca2+ uptake by syncytiotrophoblast. Only DDE (>/=0.70 mug/l) in maternal serum significantly was associated with a small increase in Ca2+ uptake by syncytiotrophoblast. This study will help us determine if low OC contamination significantly modifies Ca2+ transfer in syncytiotrophoblast.

Biological Transport↗

Further studies on the therapy of organophosphorous anti-cholinesterase intoxication with veratrinic compounds; the role of calcium.

Experiments were carried out to investigate the role of calcium in the therapy of soman intoxication with 9-anthroic acid (ANCA), a compound with veratrine-like pharmacological properties. The effects of ANCA on the respiratory paralysis and on the calcium content of the blood and that of the hindleg muscles were determined in anaesthetized, atropinized rats injected with 4 times LD50 soman. The respiratory paralysis which in control animals occurs within a few min after the injection of soman can be delayed about 2.5 hr by treatment with ANCA. It was found that ANCA causes a small decrease of the blood calcium content, an effect which is potentiated by soman. A comparison was made between the calcium accumulation in the indirectly stimulated gastrocnemius-soleus muscles in these animals with that in the non-stimulated muscles on the other side. Whereas the injection of soman or ANCA alone caused no change, the combination of the two drugs induced a two-fold increase in the accumulation of calcium in the stimulated muscles. The non-stimulated muscles remained unaffected. The accumulation of calcium in the stimulated muscles induced by soman and ANCA could be partly antagonized by lowering the free calcium concentration of the blood by EDTA. Moreover, treatment with EDTA improved the therapeutic effects of ANCA. It is concluded that the therapy of soman poisoning with ANCA falls short in completely preventing respiratory failure since ANCA causes an accumulation of calcium in the stimulated muscles of soman-poisoned animals.

Animals↗

In vivo characterization of combination antitumor chemotherapy with calcium channel blockers and cis-diamminedichloroplatinum(II).

We have examined nifedipine, a dihydropyridine class calcium channel blocker, for ability to overcome cis-diamminedichloroplatinum(II) (cisplatin) resistance in a murine tumor line variant, B16a-Pt, which we developed for resistance to cisplatin. Nifedipine significantly enhanced the antitumor actions of cisplatin against primary subcutaneous B16a-Pt tumors and their spontaneous pulmonary metastases. We have characterized, in vivo, the pharmacokinetics and dose-response interactions between nifedipine and cisplatin. We now report our studies designed to compare, in vivo, the efficacy of nifedipine and other calcium active compounds including: (a) structurally similar calcium channel blockers (nimodipine, nicardipine) from the dihydropyridine class, (b) structurally different calcium channel blockers from the benzothiazepine (diltiazem) and the phenylalkylamine (verapamil) classes, and (c) calmodulin antagonists (trifluoperazine and calmidazolium) for ability to enhance the antitumor action of cisplatin. Nifedipine was included as the standard or reference compound. In these studies verapamil and diltiazem failed to enhance the antitumor actions of cisplatin as did both calmodulin antagonists. Our findings suggest that nifedipine has a greater degree of specificity for B16a-Pt cells than structurally different calcium channel blockers from other chemical classes (i.e., diltiazem and verapamil), or the two calmodulin antagonists (i.e., trifluoperazine and calmidazolium). We concluded that nifedipine interacts with specific target site(s) which are not accessible by verapamil, by diltiazem, or by the calmodulin antagonists. Surprisingly, the two dihydropyridine class calcium channel blockers, nimodipine and nicardipine, also failed to enhance cisplatin's antitumor actions despite the fact that their specificity and kinetics for binding to the dihydropyridine receptor component of the calcium channel favors them (nimodipine and nicardipine) over nifedipine. Therefore, we postulate that the synergism between cisplatin and nifedipine is independent of the latter's effect on the voltage sensitive, slow inward calcium channel. We suggest that cisplatin cytotoxicity is enhanced by nifedipine's interaction with an as yet unidentified specific "target site," as opposed to nonspecific interactions with the tumor cell plasma membrane or specific interactions with calmodulin or the P-glycoprotein (which is responsible for pleiotropic resistance).

Animals↗

Cytotoxicity of endodontic materials.

An in vitro cell culture model of human gingival fibroblasts and L-929 cells was used to measure the cytotoxicity of currently used root canal sealers Endomet, CRCS, and AH26 and root-end filling materials Amalgam, Gallium GF2, Ketac Silver, mineral trioxide aggregate (MTA), and Super-EBA. Cytotoxic effects were assessed using the MTT assay for mitochondrial enzyme activity and the CV assay for cell numbers. Using inserts culture and L-929 fibroblasts. All-Bond-2 was also evaluated. The statistical analysis of results showed that CRCS was the least cytotoxic sealer followed by Endomet and AH26. Among root-end filling materials, MTA was not cytotoxic; Gallium GF2 displayed little cytotoxicity; and Ketac Silver, Super-EBA, and Amalgam showed higher levels of cytotoxicity. All Bond-2 also displayed a high degree of cytotoxicity. CRCS was the best root canal sealer and MTA the best root-end filling material. The outcome was favorable also for Gallium GF2 as a retrofilling material.

Alloys↗

Surface characterization of radio-frequency glow discharged and autoclaved titanium surfaces.

To characterize titanium surfaces treated with radio-frequency glow discharge (RFGD) after media exposure, surface chemical analyses were performed using x-ray photoelectron spectroscopy. Auger electron spectroscopy, and Fourier transform infrared-reflection absorption spectroscopy (FTIR-RAS). The RFGD treatments resulted in a cleaner surface as compared to as-sputtered or as-autoclaved titanium specimens. The oxide thickness of RFGD-treated titanium specimens was not statistically different from the as-autoclaved and as-sputter cleaned titanium specimens. Exposure to a phosphate-buffered saline solution revealed a greater deposition of calcium and phosphorous on the RFGD-treated surfaces. Auger electron spectroscopy depth profiles showed that calcium and phosphorous ions diffused into the titanium oxide layer. The calcium and phosphorous deposits were identified as amorphous calcium phosphate compounds using FTIR-RAS. These results suggest that RFGD treatments of titanium enhance calcium and/or phosphate affinity because of an increase in elemental interactions at the surface, thereby resulting in the formation of amorphous calcium phosphate compounds.

Buffers↗

Calcimimetics: therapeutic potential in hyperparathyroidism.

Calcium homeostasis is essential for the normal function of many organ systems. The recently cloned extracellular calcium-sensing receptor plays a central role in this process and thus represents an important target for therapeutic agents aimed at treating disorders of calcium metabolism. Compounds, such as the phenylalkylamines NPS 568 and AMG 073, act as agonists of calcium at this receptor. These calcimimetic agents hold promise as potential treatments for diseases of parathyroid hyperfunction, such as primary and secondary hyperparathyroidism.

Aniline Compounds↗

[Factors influencing fluorine absorption and excretion in people and animals].

Factors that make fluorine absorption and excretion easy or difficult from organisms of people and animals have been analysed. Fluorine is easily absorbed in presence of alimentary fat from soluble dust, from water environment, especially from an acid one. Compounds of calcium, magnesium, aluminium, microelements and various high protein diet make fluorine absorption difficult. Compounds that easily absorb fluorine, namely compounds of calcium, magnesium, aluminium, boron, phosphorus and vitamin C as well as climatic conditions (increasing perspiration) make fluorine excretion from organisms easy. Fluorine excretion is made difficult in the period of intensified mineralization and lactation processes. The age of the person is also important.

Absorption↗

Calcimimetic compound upregulates decreased calcium-sensing receptor expression level in parathyroid glands of rats with chronic renal insufficiency.

The reduced expression level of the calcium-sensing receptor (CaR) is attributed to the hyposensitivity of parathyroid cells to extracellular calcium concentration [Ca2+]o, which plays a crucial role in the pathogenesis of secondary hyperparathyroidism (SHPT) in patients and rats with chronic renal insufficiency (CRI). Calcimimetic compounds have been demonstrated to improve the decreased sensitivity of CaR to extracellular calcium concentration and to suppress both parathyroid hormone (PTH) oversecretion and parathyroid cell proliferation. However, the effect of calcimimetics on the reduced CaR expression level in parathyroid cells in CRI remains unclarified. The aim of this investigation was to examine the effect of the calcimimetic compound NSP R-568 (R-568) on the CaR expression in the parathyroid cells of rats with experimental CRI. Subtotally nephrectomized rats were fed a high-phosphorus diet for 8 (n = 12; Nx-8 group) or 9 wk (n = 11; Nx-9 group) to induce severe SHPT. Another group of uremic rats were fed a high-phosphorus diet for 8 wk and then orally administered R-568 (100 micromol/kg body wt) once a day for 7 d (n = 11; Nx+R-568 group). Sham-operated rats that were fed a standard diet for 9 wk were used as controls (n = 8). R-568 treatment induced a significant reduction in plasma PTH level with significant decrease in serum calcium and without change in serum phosphorus concentration. Serum 1,25(OH)2D3 level was not affected by R-568 administration. CaR mRNA and protein levels in the Nx-8 and Nx-9 groups significantly decreased compared with those in the controls; however, no significant difference in these parameters was observed between the Nx-8 and Nx-9 groups. In the Nx+R-568 group, CaR mRNA and protein levels significantly increased compared with those in either the Nx-8 or Nx-9 group. R-568 was effective in reducing the number of proliferating cell nuclear antigen-positive cells along with parathyroid gland growth suppression in the Nx+R-568 group compared with that in the Nx-9 group. The results suggest that the calcimimetic compound R-568 upregulates decreased CaR expression, and the upregulation possibly has an enhancement effect on PTH secretion and parathyroid cell hyperplasia through the improved sensitivity of CaR to [Ca2+]o.

Analysis of Variance↗

Space maintenance--a review of treatment options to repair the iatrogenic perforation.

Management of intra-canal and furcation perforations can pose a significant clinical challenge. In such cases a biological matrix can provide the framework for healing of injured periodontal tissues and will facilitate placement of the perforation repair material. As a consequence the long-term prognosis for treatment of the iatrogenic perforation can be significantly improved and the need for surgical intervention can often be eliminated.

Aluminum Compounds↗

Influences of calcium oxide content in marine fuel oil on emission characteristics of marine furnaces under varying humidity and temperature of the inlet air.

A marine furnace made of stainless steel. combined with an automatic small-size oil-fired burner, was used to experimentally investigate the influences of calcium oxide content in fuel oil on the combustion and emission characteristics under varying temperatures and humidity of the inlet air. Marine fuel oil generally contains various extents of metallic oxides such as CaO, Fe2O3, V2O5, etc which might affect its burning properties. In this study, an air-conditioner was used to adjust the humidity and temperatures of the inlet air to preset values prior to entering the burner. The adjusted inlet air atomized the marine diesel oil A containing a calcium oxide compound, to form a heterogeneous reactant mixture. The reactant mixture was thereafter ignited by a high-voltage electrode in the burner and burned within the marine furnace. The probes of a gas analyzer, H2S analyzer and a K-type thermocouple were inserted into the radial positions of the furnace through the eight rectangular slots which were cut in the upper side of the furnace. The experimental results showed that an increase of either humidity or temperature of the inlet air caused the promotion of the reaction rate of the fuel. The existence of calcium oxide compound in the diesel fuel also facilitated the oxidation reaction in the combustion chamber. The addition of CaO in the diesel fuel under the conditions of higher temperature or higher relative humidity of the inlet air produced the following: higher concentrations of CO2, SO2, and H2S emissions, an increased burning efficiency, a lowered O2 level, production of excess air and NOx emissions as well as a lower thermal loss and a lower burning gas temperature, as compared with the conditions of a lower temperature or a lower humidity of the inlet air. In addition, the burning of diesel fuel with added CaO compound caused a large variation in the burning efficiency, thermal loss, plus CO2, O2, and excess air emissions between the conditions of higher temperature/higher humidity and lower temperature/lower humidity inlet air compared with no CaO addition in the fuel. Moreover, the burning efficiency and the concentrations of excess air and O2 emissions increased, while the thermal loss, burning gas temperature and H2S, SO2, NOx, and CO2 emissions decreased with the increase of the axial distance from the measured location to the burner nozzle.

Air Movements↗

The importance of drug ionization for the action of calcium-antagonists and related compounds.

pK-Values of Ca-antagonists and related cardiodepressive drugs have been measured by means of potentiometric microtitration. The presumable active species for all compounds investigated is the protonated molecule except nifedipine. This drug must exert its action via the uncharged form. From these results it could be concluded that protonization of ionizable nitrogen is one molecular prerequisite for voltage- or frequency dependence of action. Drug ionization does not correlate with the negative inotropic potency of the compounds investigated.

Calcium Channel Blockers↗