Initial Calcium Concentration Research Articles

Evidence of competitive inhibition of methotrexate absorption by leucovorin calcium in rat small intestine

The effect of leucovorin calcium on the intestinal absorption of methotrexate in rat small intestine was investigated using an in situ rat gut technique. First, the kinetic absorption in situ parameters for methotrexate in solution were obtained: V m=21.54 (±2.22) μM/h; K m=10.51 (±1.08) μM; k a=0.26 (±0.03) h −1 and AIC=−188.63. The inhibitory effect of leucovorin calcium in methotrexate intestinal absorption has been investigated by perfusing of 10 μM methotrexate isotonic solutions containing increasing concentrations of leucovorin calcium (10–500 μM), and the remaining concentrations of both compounds were measured. A competitive inhibition of methotrexate absorption was detected: the apparent absorption rate constant of the drug decreased as the initial leucovorin calcium concentration increased. Higher leucovorin calcium concentrations, however, did not completely abolish the absorption of the drug (at 500 μM of leucovorin calcium, only 84% inhibition was observed). Apparent parameters characterizing the absorption of leucovorin calcium in the presence of methotrexate 10 μM were: V mi=14.70 (±1.74) μM; K mi=9.43 (±1.59) μM; k ai=0.28 (±0.02) h −1; AIC=−191.53). We can concluded that methotrexate and leucovorin calcium compete for the same intestinal carrier system. This means that since leucovorin calcium, because of its ready conversion to other tetrahydrofolic derivatives (McEvoy, 1996. AHFS Drug Information, Bethesda, MD, pp. 751–758), is administered together with methotrexate in order to prevent the hematopoietic and reticuloendothelial toxic effects of folic acid antagonists, using high leucovorin calcium concentrations, when the urine excretion is decreased, could prevent intestinal drug reabsorption and the drug could then be excreted in the feces, thereby decreasing the risk of poisoning.

Growth of Salt Sensitive Bedding Plants in Media Amended with Composted Urban Waste

Growth of Impatiens wallerana Hook.f (impatiens) and Antirrhinum majus L. (snapdragon) was evaluated in media containing 0, 30, 60, or 100 percent compost made from biosolids and yard trimmings. Shoot dry mass, size, and height of both impatiens and snapdragon linearly increased as the percentage of compost in the medium increased. Initial media soluble salt, nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), and magnesium (Mg) concentrations also linearly increased as the percentage of compost in the medium increased. However, final shoot N, P, K, Ca, and Mg concentrations in both impatiens and snapdragon plants were not different among the media examined. Results suggest that impatiens and snapdragons can be successfully grown in 100 percent compost made from biosolids and yard trimmings.

Improvement of heavy metal biosorption by mycelial dead biomasses (Rhizopus arrhizus, Mucor mieheiandPenicillium chrysogenum): pH control and cationic activation

Fungal mycelial by-products from fermentation industries present a considerable affinity for soluble metal ions (e.g. Zn, Cd, Ni, Pb, Cr, Ag) and could be used in biosorption processes for purification of contaminated effluents. In this work the influence of pH on sorption parameters is characterized by measuring the isotherms of five heavy metals (Ni, Zn, Cd, Ag and Pb) with Rhizopus arrhizus biomass under pH-controlled conditions. The maximum sorption capacity for lead was observed at pH 7.0 (200 mg g-1), while silver uptake was weakly affected. The stability of metal-biosorbent complexes is regularly enhanced by pH neutralization, except for lead. A transition in sorption mechanism was observed above pH 6.0. In addition, comparison of various industrial fungal biomasses (R. arrhizus, Mucor miehei and Penicillium chrysogenum) indicated important variations in zinc-binding and buffering properties (0.24, 0.08 and 0.05 mmol g-1, respectively). Without control, the equilibrium pH (5.8, 3.9 and 4.0) is shown to be related to the initial calcium content of the biosorbent. pH neutralization during metal adsorption increases zinc sorption in all fungi (0.57, 0.52 and 0.33 mmol g-1) but an improvement was also obtained (0.34, 0.33 and 0.10 mmol g-1) by calcium saturation of the biomass before heavy metal accumulation. Breakthrough curves of fixed bed biosorbent columns demonstrated the capacity of the biosorbent process to purify zinc and lead solutions in continuous-flow systems, and confirmed the necessity for cationic activation of the biosorbent before contact with the heavy-metal solution.

Inhibition of bovine dentin demineralization by a glutardialdehyde pretreatment: an in vitro caries study.

Intact bovine dentin specimens were demineralized in 25 mmol acetic acid buffers (pH 5), with and without a 5-min pretreatment with an acidic 2% glutardialdehyde (GDA) solution. The results demonstrate that GDA inhibits dentin demineralization and that the inhibition depends strongly on the initial calcium and phosphate concentration in the demineralization solution. The observed inhibition increases from about 5% without calcium and phosphate to 38% with a calcium and phosphate concentration initially of 6.4 mmol and 4.1 mmol, respectively. The inhibition can be explained either by a reduction of calcium and phosphate diffusion out of the lesion or by the retention of mineral inhibitors in the dentin.

Effects of calcium on the dynamic process of transmitter release which generates either skew- or bell-MEPPs

Miniature endplate potential (MEPP) amplitudes, MEPP frequencies and ratios of skew: bell-MEPPs were determined as well as synaptic vesicle diameters and densities at the mouse diaphragm neuromuscular endplate during exposure to elevated calcium concentrations. Additions of external Ca 2+ had variable effects on MEPP frequencies and percentages of skew-MEPPs, regardless of concentrations used (1–25 mM). Nevertheless, changes in MEPP amplitudes were most sensitive (4-fold decrease) to low value increases of Ca 2+. Changes in MEPP frequencies produced by an increase in Ca 2+ were very sensitive to initial frequencies as well as the initial calcium concentration. An increase in Ca 2+ usually increased MEPP frequency (providing skew-MEPPs were measured). Changes in the percentage of skew-MEPPs were extremely variable (4–90%) and these changes depended on initial frequencies, initial skew- to bell-MEPP ratios and age of the mouse. With a change in Ca 2+ concentration, synaptic vesicle diameters and densities remained constant during changes in MEPP frequencies and large changes in the skew:bell-MEPP ratios; and vesicle numbers were sometimes slightly increased. Because of the wide range in MEPP frequencies and amplitudes, this study demonstrates that the effect of various treatments should be evaluated on identified endplates and that analyses of randomly selected endplates must consider the large variability between endplates. These results show that the skew-MEPP class must not be ignored in studies of spontaneous MEPP release, and that initial frequencies and age of the mouse are also important in evaluating changes in skew-MEPP to bell-MEPP ratios. The rapid changes in skew- to bell-MEPP classes indicate that MEPP class and size are determined at the moment of release by the state of the release process as proposed by Kriebel et al. (1990). Because changes in calcium concentration can immediately alter the ratio of skew- to bell-MEPPs we conclude that the release process has two states to generate the two classes of MEPPs, and that the release process is very sensitive to conditions so that states are easily changed. We propose that the release process meters transmitter in subunit amounts to form both classes of MEPPs and that the calcium ions modulate the process.

Effect of Calcium Channel Blockers on Platelet GPIIb-IIIa as a Calcium Channel in Liposomes: Comparison with Effects on the Intact Platelet

The platelet membrane glycoprotein IIb-IIIa complex is essential for platelet aggregation and functions as a fibrinogen receptor on the activated platelet. When incorporated into phospholipid vesicles, this glycoprotein complex can function as an apparent calcium channel which facilitates the transit of calcium across a phospholipid barrier. In order to further evaluate this calcium channel, the effect of calcium channel blockers of the dihydropyridine (nifedipine and nicardipine), arylalkylamine (verapamil) and benzothiazepine (diltiazem) classes were evaluated on GPIIb-IIIa liposomes with encapsulated fura-2 (a fluorescent calcium indicator). Nicardipine, verapamil, and nifedipine significantly inhibited calcium influx into GPIIb-IIIa liposomes; however, this required 190 microM, 400 microM, and 140 microM drug, respectively. These concentrations are 10-1,000 fold greater than those clinically obtainable. In contrast, diltiazem at concentrations greater than 220 microM and amiloride at concentrations greater than 800 microM showed no inhibitory effects. When aspirinized platelets were activated with 30 micrograms/ml bovine fibrillar collagen, both nicardipine and diltiazem produced a decrease in both the initial rise and maximum cytoplasmic calcium concentration. Parallel experiments were performed to assess the effects of verapamil, nicardipine, and diltiazem on platelet aggregation in platelet rich plasma. Nicardipine, 190-380 microM, induced a prolongation of the lag phase, but no effect on the final degree of platelet aggregation to collagen. Similar inhibition of platelet aggregation was seen with diltiazem and verapamil although the effect of diltiazem was less pronounced particularly at higher concentrations of collagen. No effect was seen on aggregation with 32 microM ADP which is release independent, or on the primary wave of low dose ADP induced platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of anionic polyelectrolytes on the crystallization of calcium oxalate hydrates

Calcium oxalate was precipitated from supersaturated calcium oxalate solutions in the presence of different water soluble polymers: poly(acrylic acid), poly(methacrylic acid), poly(styrene sulfonate-alt-maleic anhydride), poly(maleic anhydride), and poly(vinyl sulfonate). The supersaturated solutions were made with initial calcium and oxalate concentrations of 4×10 -3M and 1.5×10 -3M respectively. In the presence of anionic polyelectrolytes there was a change in the hydrate from of calcium oxalate which precipitated. With low concentrations of polyelectrolyte (up to 1 ppm) only the monohydrate was formed, at intermediate concentration (1–50 ppm) trihydrate was the predominant product, and at high concentrations (above 50 ppm) the dihydrate form was the dominant product. Nonpolyelectrolytes had no effect on the crystallization and thus only calcium oxalate monohydrate was formed. This effect was found to occur with all polyelectrolytes used regardless of molecular weight or charge. The change from one hydrate from to another occured at a lower polymer concentration with the low molecular weight polymers.

Neutralizing strategies for acid waters: sodium and calcium products generate different acid neutralizing capacities

A computer model was developed to calculate the final alkalinity of waters at equilibrium with air and solid phase calcite, after neutralization by a sodium or calcium-based product. Results are presented for waters of various initial composition, with the initial concentration of calcium varying from 0.01 to 10 mmol dm −3 and the initial pH from 2 to 6. Waters which were initially very acid, and deficient in calcium, could sustain a much higher final alkalinity, a measure of the water's resistance to further supply of acid, if they were neutralized by either sodium hydroxide or sodium carbonate rather than calcium hydroxide or calcium carbonate. Soft waters acidified by acid rain, and acid mine waters low in calcium, would benefit most from using sodium-based neutralizing agents. The higher cost of sodium products is offset by their greater solubility and ease of application.

Precipitation of calcium oxalate hydrate by titration of acidified calcium nitrate solutions with potassium oxalate

The precipitation of calcium oxalate during the titration of acidified solutions of calcium nitrate with potassium oxalate was studied in the temperature range 13–69°C by monitoring changes in pH with time. A critical supersaturation ratio of 30 for incipient precipitation of the solid phase at 25°C was measured that proved to be independent of the titration speed or initial calcium concentration. With increasing temperature this critical supersaturation is observed to decrease. An analysis of the observed change in supersaturation with titration time at relatively high supersaturation, but under conditions where three-dimensional nucleation is not possible, indicates that the rate of growth of the precipitated phase, calcium oxalate monohydrate, varies with the relative supersaturation raised to the power 3.4. This empirical result is different from the observed parabolic rate law in seeded growth experiments and can be explained by a layer-by-layer growth mechanism based on a polynuclear, surface nucleation model.

Theophylline-induced hypercalcemia.

Sixty patients with theophylline toxicity were hospitalized during a 2-year period. Eleven patients had hypercalcemia; their calcium levels returned to normal as theophylline levels fell to therapeutic or subtherapeutic levels. Serum calcium levels also fell significantly in three additional patients with theophylline toxicity, although the initial serum calcium concentration was not outside normal limits. A significant increase in serum calcium levels associated with therapeutic levels of theophylline in normal volunteers was reversed by propranolol. It appears that theophylline causes elevation of serum calcium by a system subject to beta-adrenergic regulation.

Long term follow up of untreated primary hyperparathyroidism.

Fourteen patients with primary hyperparathyroidism and whose initial serum calcium concentrations were 2.75 mmol/l (11.0 mg/100 ml) or more were followed up for five to 23 years without operative treatment. One had osteitis fibrosa when seen and died with a fibrosarcoma 22 years later. The remaining 13 patients, who were followed up for a mean of 10 years, came to little obvious harm from not being operated on. Their serum calcium concentrations did not rise and there was no evidence of progressive renal impairment. In four patients who presented originally with renal calculi there were three further episodes of renal colic in 54 patient years of follow up. Conservative management of primary hyperparathyroidism is not an unreasonable option, and patients who do not have symptoms need not necessarily be pressed to accept surgery.

Calcium control of passive permeability to calcium in sarcoplasmic reticulum vesicles.

Calcium efflux from sarcoplasmic reticulum vesicles that have been equilibrated with 1-100 mM CaCl2 in the absence of ATP has two apparently first order components. The initial calcium content of each component increases with the total Ca content of the sarcoplasmic reticulum, which reaches 5, 24, and 80 nmol/mg of protein after equilibration with 1, 10, and 100 mM CaCl2, respectively. Initial rates of Ca efflux into a medium containing 10 mM EGTA increase in proportion to Ca in the loading medium up to 20 mM. Above 20 mM, efflux from the slow component clearly saturates, whereas efflux from the fast component continues to increase. The rate constant for the smaller, faster component to efflux (k congruent to 0.5 min-1) is not affected by changing the concentration of Ca either inside or outside the vesicles. The rate constant of the larger, slower component (k congruent to 0.05 min-1) is also unaffected by changes in internal Ca concentration. However, external [Ca2+] diminishes the rate constant of the slow component 6-10-fold. Inhibition by external [Ca2+] is characterized by cooperative interaction between two sites with an apparent Kd of 5.3 X 10(-6) M. The two components may represent two populations of sarcoplasmic reticulum vesicles that differ 10-fold in passive permeability to Ca when external [Ca2+] is less than 10(-6) M, and 60-100-fold when external [Ca2+] is greater than 10(-5) M. The passive permeability in one of these populations seems to be regulated by external, high affinity Ca binding sites.

The effect of calcitonin on calcium uptake in mouse molars in vitro.

Mouse maxillary second molars were removed at either 24 or 96 h of age and maintained in vitro. Half of the teeth, of each age group, were treated with 50 m-units of synthetic salmon calcitonin. By comparing the initial and final calcium concentrations in the medium, the net uptake or release of calcium was inferred. The treated molars took up significantly more calcium than the untreated groups.

Miscible displacement of reactive solutes in saline-sodic soils under varying flow conditions

SummaryThe paper reports a laboratory study on miscible displacement of reactive solutes during leaching a highly saline-sodic soil rich in soluble sodium carbonate with solutions of calcium chloride. The effect of varying flow velocities, initial soil moisture content and concentration of calcium in the leaching water on the extent of carbonate precipitation and replacement of sodium by calcium from the exchange positions was studied in soil columns. The results showed that precipitation of soluble carbonates in the soil increased with increasing flow velocity, initial soil moisture content and concentration of calcium in the leaching solution. The results further showed that the calcium exchange capacity of the soil was reduced significantly and nearly proportionally with decrease in the degree of water saturation as a consequence of decreased water application rate and initial soil moisture content. In view of the results obtained, a simple model to describe calcium-sodium exchange under unsaturated flow conditions in saline-sodic soils under consideration has been proposed. Possible implications of the results in actual field situations is discussed.

Changes in the Plasma Content of Calcium, Phosphorus, and Yolk Lipophosphoprotein Precursor during the Production Season in Turkeys

The plasma concentration of a lipophosphoprotein complex (LPP) averaged higher in nonbroody hens from a line selected for increased egg production (E) than in nonbroody hens from three growth strains of turkeys. The total plasma pool of LPP averaged higher in the growth lines. The concentration and total amount of LPP significantly declined during the 180-day production period in all lines. Plasma total calcium and total phosphorus concentrations increased greatly with the onset of egg production. Further significant increases in calcium (P<.05) and phosphorus (P<.01) concentrations were observed in medium-bodied hens after approximately three months of production. Plasma total calcium concentration declined (P<.01) in all lines during the last three months of the laying period.Number of broody periods from 0 to 84 days in production and effective length of the laying period were negatively correlated (P<.05) with initial (prior to stimulatory lighting) total phosphorus concentration in medium-bodied hens. Initial total calcium concentration was positively correlated (P<.05) with total days lost from broodiness for the total production period (0–180 days) and negatively correlated (P<.05) with effective length of the laying period in large-bodied hens. All correlation coefficients were small, however (less than .30).

Differences in the calcium concentration of serum and plasma initially and after storage.

Calcium concentrations of plasma and serum in glass and plastic containers initially and after storage for up to 8 months at--20 degrees C were compared. The mean initial calcium concentration of the plasma samples was 2.491 nnol/l and this was significantly higher than the mean serum concentration of 2.440 nnol/l. There were no significant differences in the mean calcium concentrations attributable to differences in glass or plastic as materials for storage containers for either serum or plasma. The mean calcium concentration of serum remained stable over the entire storage period, but that of the plasma samples fell significantly between one month and six months, with no further fall between six months and eight months.

FUNCTIONAL HYPOPARATHYROIDISM AND PARATHYROID HORMONE END‐ORGAN RESISTANCE IN HUMAN MAGNESIUM DEFICIENCY

Hypocalcaemia is a well-recognized manifestation of magnesium deficiency. We have studied seventeen patients with this syndrome in an attempt to determine the pathogenesis of the hypocalcaemia. Mean initial serum calcium concentration was 5-6 mg/dl and mean initial serum magnesium concentration was 0-75 mg/dl. Serum immunoreactive parathyroid hormone (IPTH) was measured in sixteen patients in the untreated state. Despite severe hypocalcaemia, serum IPTH was either undetectable (less than 150 pg/ml) or normal (less than 550 pg/ml) in all but two patients. Serial measurements made during the initial 4 days of magnesium therapy in four patients showed an increase in serum IPTH within 24h, but a delayed increase in serum calcium, which required approximately 4 days to reach normal values. The effect of the rapid normalization of serum magnesium on serum IPTH and serum calcium concentration was studied in three patients. Within 1 min after 144-300 mg of elemental magnesium was administered i.v., serum IPTH had risen from undetectable to 3600 pg/ml and 1725 pg/ml in two patients and from 425 pg/ml to 937 pg/ml in the third. Serum calcium concentrations were unchanged after 30-60 min. These data provide evidence for impaired parathyroid gland function in most of the magnesium deficient patients. The rapidity with which serum IPTH rose in response to magnesium therapy indicates that this may reflect a defect in parathyroid hormone (PTH) secretion rather than its biosynthesis. The failure of serum calcium concentration to increase during the initial days of magnesium repletion, at a time when serum IPTH concentrations were normal or elevated, suggests end-organ resistance to PTH in these patients. The renal response to PTH was examined in two magnesium deficient patients by measurement of urinary cyclic AMP excretion following administration of parathyroid extract. In both patients there was a minimal increase in urinary cyclic AMP concentrations. In contrast, when the hepatic response to glucagon was tested on the same patients by measurement of plasma cyclic AMP concentrations following administration of glucagon, normal increases were observed. These results suggest that adenylate cyclase systems of various organs may be affected differentially by a state of magnesium deficiency. It is suggested that magnesium deficiency may result in defective cyclic AMP generation in the parathyroid glands and in the PTH target organs. This could be the principal mechanism operative in both impaired PTH secretion and end-organ resistance to PTH which together contribute to the development of hypocalcaemia.

Net uptake and release of calcium and phosphate by bone in vitro: effects of medium calcium and phosphate concentrations.

The effects of varying the initial calcium and phosphate concentrations of the culture media on bone calcium and phosphate release were examined, using whole calvaria from 3-day-old mice in 48-hour cultures. The initial calcium and phosphate concentrations of the culture media were varied in the range 3-10 mg/100 ml; either calcium or phosphate alone was changed while the other ion was held constant, or the concentrations of both were varied while the Ca:P ratio was held constant. For all combinations, 3 treatment groups were used: i) control (no added hormone); ii) 0.5 U/ml PTH; iii) 50 mU/ml CT. The release of calcium and phosphate from the bones was greatest at low initial calcium or phosphate concentrations in the media, and least at high initial concentrations. High concentrations of both ions together abolished hormonal responses and resulted in extensive uptake of calcium and phosphate by the bones. The response to PTH was lost at a high concentration of either ion alone, while a response to CT was observed under all experimental conditions except simultaneously high calcium and phosphate concentrations.

Effect of heterovalent impurities codiffusing with monovalent tracers in ionic crystals

Tracer-diffusion measurements have been made for $^{45}\mathrm{Ca}$ and $^{22}\mathrm{Na}$ codiffusing into pure NaCl as a function of temperature, initial calcium concentration, and diffusion anneal time. The measured penetration profiles deviate markedly from the Gaussian dependence expected for diffusion from a thin source. The curvature is caused by each divalent Ca ion introducing an extra "extrinsic" vacancy into the diffusion zone in order to maintain charge neutrality. In such cases, the limiting slope has been shown not to be a valid measure of the tracer diffusivity. Computer fits have been generated by a model which corrects for the effect and is found to give excellent agreement with the data except for the most extreme cases. The model can find the initial concentration of the impurity and the diffusivity of the impurity within a factor of 2 from the penetration profile for the monovalent tracer. The effect enters to first order into the measurement of the isotope effect in ionic crystals and can result in major errors in the measured isotope effect for even small deviations from a Gaussian profile. The diffusion coefficients for $^{22}\mathrm{Na}$ diffusing in NaCl over the temperature range of (575-775)\ifmmode^\circ\else\textdegree\fi{}C are given by ${D}_{\mathrm{Na}}=73\mathrm{exp}(\ensuremath{-}2.04\ifmmode\pm\else\textpm\fi{}0.02 \frac{\mathrm{eV}}{\mathrm{kT}})$ ${\mathrm{cm}}^{2}$/sec, and for $^{45}\mathrm{Ca}$, ${D}_{\mathrm{Ca}}=0.23\mathrm{exp}(\ensuremath{-}1.61\ifmmode\pm\else\textpm\fi{}0.03 \frac{\mathrm{eV}}{\mathrm{kT}})$ ${\mathrm{cm}}^{2}$/sec.

The mechanics of esophageal muscle contraction. Evidence of an inotropic effect of gastrin.

To compare the mechanical properties of lower esophageal sphincter (LES) and esophageal circular smooth muscle, force-velocity determinations were made under various physiological conditions. Isotonic and isometric recordings of opossum circular muscle were used to obtain the velocity of shortening and force, respectively, during alterations in: (a) initial muscle length (preload), (b) afterload, (c) calcium concentration, and (d) gastrin I. Muscle contraction was elicited to the neurogenic response at the termination of electrical stimulation. A change in preload (muscle length) altered the peak force (Po) developed during an afterloaded contraction, but had only a minor effect on the maximum velocity of shortening (V max). At the length of optimal tension development, Lo, (preload, 1.5 g), the LES muscle had a V max of 6.1+/-0.2 mm/s and a Po of 17.7+/-0.7 g. The esophageal muscle at its Lo (preload, 2.0 g) had a V max of 6.3+/-0.5 mm/s and a Po of 18.1+/-1.2 g. A decrease in calcium from 2.5 mM to 1.0 mM significantly reduced the V max and Po of all muscle, but an increase in calcium to 5.0 mM increased these parameters only minimally. At a calcium of 1.0 mM, gastrin I increased both V max and Po of all muscle. This inotropic effect of gastrin I occurred at lower concentrations in LES muscle than in muscle from the upper esophagus. The power (force x velocity) and work (force x muscle shortening) of esophageal and LES muscle were calculated from these data. Both the work and power generated during esophageal and LES muscle contraction were determined by: (a) the initial muscle length as produced by the preload, (b) the afterload against which the muscle was contracting, and (c) the contractility of inotropism of the muscle, that is, the force-velocity curve on which the muscle was operating.