单纯性肥胖儿童头发钙、血钙与红细胞钙的关系

目的:探讨儿童单纯性肥胖与钙的关系。方法:对65名12~14岁单纯性肥胖儿童的头发钙、血钙与红细胞钙用原子分光光度法进行检测,应用SPSS软件进行统计学分析。结果:与正常儿童比较,单纯性肥胖儿童发钙水平降低(P<0.05),红细胞钙升高(P<0.05),血浆钙差异无显著性(P>0.05)。结论:钙缺乏是单纯性肥胖的原因之一,提示应对单纯性肥胖儿童增加日照和机体补钙。     

Treatment with alendronate plus calcium,alendronate alone,or calcium alone for postmenopausal low bone mineral density

ABSTRACT

Objective: Bisphosphonates such as alendronate are widely used for postmenopausal osteoporosis. Supplemental calcium is also generally recommended. This trial directly compares alendronate to supplemental calcium and examines the effect of calcium supplementa­tion on alendronate treatment.

Methods: This 2-year, randomized, double-blind, multicenter trial enrolled healthy, postmenopausal women with low bone mineral density (BMD). Patients with a dietary calcium intake ≥?800?mg/day received daily vitamin D 400?IU and alendronate 10?mg/calcium-placebo, alendronate 10?mg/elemental calcium 1000?mg, or alendronate-placebo/calcium 1000?mg (2:2:1). Endpoints included BMD, bone turnover markers (BTMs), and adverse events.

Results: Randomized patients (N = 701) were an average of 20.4 years postmenopausal. After 24 months, increases in lumbar spine BMD differed significantly between patients receiving calcium alone (0.8%) and either alendronate alone (5.6%) or alendronate + calcium (6.0%) (?p < 0.001). Significant differences were also seen at the trochanter and femoral neck (?p < 0.001). BTMs were significantly lower with alendronate-containing treatments than calcium alone (?p < 0.001). Addition of calcium supplementation to alendronate did not signif­icantly increase BMD compared to alendronate alone (?p = 0.29 to 0.97), but did result in a statistically significant, though small, additional reduction in urinary NTx. Adverse events were similar among treatment groups. Limitations include no assessment of vitamin D levels and a discontinuation rate of approximately 30%, although discontinuation rates were similar among treatment groups.

Conclusions: In postmenopausal women with a daily intake of ≥?800?mg calcium and 400?IU vitamin D, 24-month treatment with alendronate 10?mg daily with or without calcium 1000?mg resulted in significantly greater increases in BMD and reduction of bone turnover than supplemental calcium alone. Addition of supplemental calcium to alendronate treatment had no effect on BMD and resulted in a small, though statistically significant, additional reduction in NTx.     

Fractional excretion of calcium,a sensitive marker for calcium wasting in cadmium-exposed women

In Cadmium (Cd)-exposed populations there is urinary calcium (Ca) loss which reflects Ca loss from the bone, decreased bone mass, and osteoporosis later in life, to which women are particularly vulnerable. A sensitive screening method to detect critical Ca wasting is required to provide warning of an increased osteoporosis risk. We used Fractional Excretion of Calcium (FECa) to study Ca wasting in Cd-exposed population. FECa sensitivity to Ca loss was compared to that of serum Ca, urinary Ca and intact parathyroid hormone. Mean FECa in the exposed group was 1.5 times higher than in the control group, and a dose-effect relationship to Cd exposure level was observed. FECa showed a relationship to Cd exposure level even following adjustment for a renal dysfunction marker. We conclude that FECa has a better sensitivity than urinary Ca and serum Ca. The use of FECa as an indicator of Ca wasting in Cd exposed women is recommended.     

Influence of endothelium on the response to calcium agonists, calcium, potassium and noradrenaline in rat aorta

We have studied the influence of endothelium on BAY K 8644, CGP 28392, potassium, noradrenaline and calcium induced responses in isolated thoracic aorta from rats. In aortic preparations with intact endothelium BAY K 8466 and CGP 28392 (10(-9)-10(-5) M) had a concentration dependent contractile effect, but BAY K 8644 was more effective in contracting the vessels than CGP 28932. Removal of endothelium increased the contractile response to both substances without affecting the difference in contractile effect between the two calcium agonists. In high concentrations (10(-4) M) BAY K 8644 and CGP 28392 had an equal relaxing effect on potassium precontracted preparations, which was unaffected by removal of endothelium. Removal of endothelium caused a shift to the left of the potassium and noradrenaline concentration response curves without any change in maximal contractile response. The contractile response to calcium in BAY K 8644 and potassium activated vessels was unaffected by removal of endothelium. We conclude that endothelium derived factor(s) depress the contractile response to calcium agonists, potassium, and noradrenaline but has no influence on the relaxant effect of BAY K 8644 and CGP 28392 in rat aorta. The influence of endothelium on the contractile effect on BAY K 8644 and potassium seems not to be due to a direct effect on calcium influx but rather to an influence on the membrane potential of the smooth muscle cells.     

钙增敏剂MCI-154对内毒素血症大鼠心肌收缩系统钙敏感性的影响(英文)

目的:研究MCI-154对内毒素血症大鼠心肌收缩系统钙敏感性的影响.方法:利用皂素500 mg/L制备内毒素血症大鼠蜕膜右心室乳头状肌标本,用不同钙浓度的含或不含强心药物的激活液进行顺序激活,记录Ca~(2 )激活张力.结果:同正常对照组相比,内毒素血症大鼠蜕膜乳头状肌钙最大激活张力(T_(max))降低,pCa_(50)值下降.甲腈吡酮50μmol/L对上述异常无明显的改善作用.内毒素血症大鼠蜕膜乳头状肌经含MCI-154 10 μmol/L的激活液处理后,T_(max)和pCa_(50)值明显增加,与假休克组类似,明显高于内毒素血症组和内毒素血症 甲腈吡酮组值.MCI-154的上述作用还具有剂量依赖性.结论:大鼠内毒素血症后,心肌收缩系统对Ca~(2 )敏感性降低,MCI-154可明显增加内毒素血症大鼠心肌收缩蛋白对钙的敏感性,增加心肌钙最大激活张力.     

Presynaptic calcium channels: structure, regulators, and blockers

The central and peripheral nervous systems express multiple types of ligand and voltage-gated calcium channels (VGCCs), each with specific physiological roles and pharmacological and electrophysiological properties. The members of the Ca(v)2 calcium channel family are located predominantly at presynaptic nerve terminals, where they are responsible for controlling evoked neurotransmitter release. The activity of these channels is subject to modulation by a number of different means, including alternate splicing, ancillary subunit associations, peptide and small organic blockers, G-protein-coupled receptors (GPCRs), protein kinases, synaptic proteins, and calcium-binding proteins. These multiple and complex modes of calcium channel regulation allow neurons to maintain the specific, physiological window of cytoplasmic calcium concentrations which is required for optimal neurotransmission and proper synaptic function. Moreover, these varying means of channel regulation provide insight into potential therapeutic targets for the treatment of pathological conditions that arise from disturbances in calcium channel signaling. Indeed, considerable efforts are presently underway to identify and develop specific presynaptic calcium channel blockers that can be used as analgesics.     

Mitochondria, the calcium uniporter, and reperfusion-induced ventricular fibrillation

The role of the mitochondria, and in particular the calcium (Ca) uniporter, in mediating reperfusion-induced arrhythmias is a novel investigative area. This commentary assesses the importance of a new article on this topic, published in this issue of the journal. Ventricular arrhythmogenesis remains an important area of research in the search of novel targets. The article by García-Rivas et al in this issue represents a possible novel focus for investigation.     

Effect of MCI-176, a new calcium antagonist, on the calcium induced contraction of isolated porcine coronary arteries

Calcium antagonistic activity of MCI-176, a new calcium antagonist, was compared with those of diltiazem and nifedipine in isolated depolarized porcine coronary arteries. MCI-176, diltiazem and nifedipine competitively inhibited calcium contraction of the large coronary arteries, and their pA2 values were 7.49, 6.89 and 9.55, respectively. Similar competitive inhibition by MCI-176, diltiazem and nifedipine of calcium contraction was also observed in the small coronary arteries, and their pA2 values were 7.38, 6.83 and 9.91, respectively. Although calcium antagonistic activity of nifedipine was several hundreds times more potent than MCI-176 and diltiazem, the action of nifedipine, unlike MCI-176 and diltiazem, favored the small coronary arteries rather than the large coronary arteries.     

Carboxyethylester-polyrotaxanes as a new calcium chelating polymer: synthesis,calcium binding and mechanism of trypsin inhibition

A carboxyethylester-polyrotaxane was synthesized as a novel calcium chelating polymer in the field of oral drug delivery and characterized in terms of mechanism of trypsin inhibition. Here, carboxyethylester (CEE) groups are introduced to all the primary hydroxyl groups in alpha-cyclodextrins (alpha-CDs), which are threaded onto a poly(ethylene glycol) chain capped with bulky end-groups (polyrotaxane). The solubility of the CEE-polyrotaxane in physiological conditions increased with pH, indicating ionization-related solubility similar to conventional polyacrylates. The ability of calcium (Ca2+) chelation was found to increase in the order of poly(acrylic acid) (PAA)>CEE-polyrotaxanez.Gt;CEE-alpha-CD, suggesting that the increased density of carboxyl groups enhances the Ca2+ chelating ability. The activity of trypsin was inhibited by these compounds in the same order of the calcium chelation. However, the inhibitory effect of CEE-polyrotaxane was reduced by adding excess Ca2+ without precipitation that was observed in the presence of PAA. Such the reduced inhibition and precipitation by CEE-alpha-CD was not observed. Therefore, the inhibitory effect of CEE-polyrotaxane is due to Ca2+ chelation from trypsin without non-specific interaction.     

The action of forskolin on muscle cells is modified by hormones, calcium ions and calcium antagonists

Forskolin, a drug isolated from the Indian plant Coleus forskohlii, exerts its actions on cells by directly activating the catalytic subunit of adenylatecyclases. The primary effect on heart muscles is the positive inotropic one, at higher forskolin concentrations, an acceleration of the pacemaker activity can be observed. External Ca2+ is required for this augmentation of contraction, verapamil, prenylamine and tetrodotoxin depress these effects. The action of forskolin and digitalis glycosides are to a certain degree additive. Incubation of rat heart slices with forskolin depresses the membrane bound Na+K+-ATPase activity. In smooth muscle cells, forskolin lowers the contractions, evoked by K+, norepinephrine and by angiotensin II. The results are discussed in respect to a forskolin induced enlargement of the Ca2+-uptake of heart muscle cells and a lowering of the Ca2+-sensitivity of the contractile system of smooth muscle cells.     

Slow calcium channel blockers and calmodulin. Effect of felodipine, nifedipine, prenylamine and bepridil on cardiac sarcolemmal calcium pumping ATPase

The effect of four slow Ca2+ channel blockers (felodipine, nifedipine, prenylamine and bepridil) that possess the ability to bind to calmodulin (CaM) section and to inhibit myosin light chain kinase (MLCK) on CaM-regulated Ca2+ pumping ATPase of cardiac sarcolemma (SL) and brain cyclic AMP phosphodiesterase (PDE) was studied. The ability of these drugs to inhibit Ca2+ pumping ATPase correlated with their inhibitory effect on CaM-activated Ca2+-dependent PDE. Nifedipine was unable to inhibit markedly both enzymes. Prenylamine also was a weak inhibitor, which was unexpected because of its CaM binding potency. Felodipine (10-50 microM) and bepridil (50 microM) markedly reduced activities of SL Ca2+ pumping ATPase and PDE. Striking differences were, however, demonstrated when Ca2+ and CaM concentrations, respectively, were increased. Previously it was reported that inhibition of the SL Ca2+ pumping ATPase by the CaM antagonist calmidazolium could be overcome by increasing Ca2+ concentrations (J. M. J. Lamers and J. T. Stinis, Cell Calcium 4, 281-294, 1983). Felodipine (10-50 microM) in the present study, appeared to be equipotent with calmidazolium in reducing Ca2+ pumping ATPase, but increasing Ca2+ up to 12.2 microM could not counteract this effect. Felodipine (2-10 microM) also inhibited brain PDE noncompetitively with respect to CaM contrary to the competitive effectors calmidazolium and bepridil. On the other hand, bepridil (10-20 microM) decreased or increased Ca2+ pumping ATPase activity depending on the Ca2+ concentration (0.29 and 12.2 microM, respectively) used. These findings suggest at least two types of CaM antagonists, which can be discriminated on basis of their inhibition patterns of PDE and heart SL Ca2+ pumping ATPase.