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PubMed2006

Sigmoidal release of indomethacin from pectin matrix tablets: effect of in situ crosslinking by calcium cations.

Sigmoidal release pattern is therapeutically beneficial for timed release and colonic drug delivery, and is always observed in coated systems. In this study, sigmoidal release from pectin matrix tablets with indomethacin as a model drug was investigated. The underlying mechanisms are calcium cation-induced in situ crosslinking that retard the initial drug release to a limited percentage. Power law equation n values were estimated for sigmoidal release profiles. Results indicated that calcium chloride incorporated in pectin matrix functioned as retarding mechanisms on drug release. Larger amount of calcium chloride led to slower drug release and matrix erosion. Even at extremely high levels, retarding on drug release and matrix erosion rate was obvious, which highlighted the effect of calcium-induced in situ crosslinking as calcium chloride was a freely water-soluble salt. The sigmoidal release profiles were characterized by power law equation with high correlation coefficients of about 0.99 or over. Power law n values increased up to as high as 1.20 when calcium chloride content kept increasing. Erosion correlated well with release in almost all pectin matrix tablets indicating erosion-controlled mechanisms. It is concluded that large amount of calcium induces in situ crosslinking of pectin matrix and leads to sigmoidal release of indomethacin, and power law n values, sometimes larger than 1.0, are suitable to be used to describe sigmoidal release profiles.

Algorithms↗
PubMed1990

Reversal of lethal citrate intoxication by intravenous infusion of calcium. An experimental study in pigs.

Intravenous infusions of 750 and 1000 ml 2.2% sodium citrate were given over a 60 min period to 17 pigs to study its effect on aortic pressure, electrocardiogram, ionised calcium, and citrate clearance. In group 1 (seven pigs) the animals did not receive calcium and the median survival time was 30 min (range 20-70 min). In groups 2 and 3 (five in each group) the pigs were treated with calcium chloride infusions (1 ml 10% calcium chloride to 10 ml citrate) and they all survived. In group 1 the ionised calcium concentrations in blood fell to values below 0.4 mmol/l, after which the blood pressure dropped abruptly. In the animals treated with calcium the mean ionised calcium concentration fell to 0.6 mmol/l, whereas total calcium increased to more than 7 mmol/l. The aortic pressure was consistently within normal values in the groups treated with calcium, but in the group that was not treated the blood pressure fell dramatically. There was no correlation between electrocardiographic changes and ionised calcium concentrations. In summary, calcium was an effective antidote to lethal citrate intoxication, and the only reliable method of determining the necessary dose of calcium was monitoring of ionised calcium concentrations.

Animals↗
PubMed2002

Chloride and calcium in Photosystem II: from effects to enigma(*).

This minireview focuses on the early evidence for roles of chloride and calcium ions in reactions of photosynthetic electron transport and on the reluctance with which an essential function of these inorganic ions in the process of water oxidation was accepted. For example, Daniel Arnon's group initially refuted the conclusion of Otto Warburg, the discoverer of a 'chloride effect,' that chloride was a 'coenzyme.' Their reasoning was that chloride had not been shown to be an essential mineral nutrient of plants. In the case of calcium, the problem was that the first 'calcium effects' had been seen with preparations from cyanobacteria rather than from green plants. While today the status of calcium and chloride as essential participants in the process of water oxidation is rarely disputed, the nature of their involvement still eludes all experimental inquiries. Substantial progress in this respect may come from recent refinements of the application of Fourier-transform infrared spectroscopy to the study of photosynthetic water oxidation.

Journal Article↗
PubMed1998

The murine calcium-sensitive chloride channel (mCaCC) is widely expressed in secretory epithelia and in other select tissues.

The tissue and cellular expression pattern of a recently cloned murine calcium-sensitive chloride channel (mCaCC) was determined. In situ hybridization was performed on formalin-fixed, paraffin-embedded murine tissues using digoxigenin-labeled, single-stranded RNA probes. The data were substantiated with northern blot and reverse transcriptase-polymerase chain reaction analyses. All three assays consistently indicated strong expression in tissues with secretory or ion regulatory functions, such as mammary gland, respiratory and intestinal epithelia, gall bladder, pancreas, kidney, uterus, and epididymis. Additional mCaCC expression was observed in germinal centers of lymphatic tissues, in spermatids, and in keratinocytes of the skin, esophagus, and cornea. The results are in accordance with previous electrophysiological reports on calcium-activated chloride conductances in various murine exocrine secretory epithelia and suggest a role of mCaCC in transepithelial ion transport. However, expression in other than secretory tissues indicates a more complex function.

Animals↗
PubMed1988

A calcium-independent chloride current activated by hyperpolarization in Xenopus oocytes.

Hyperpolarization of oocytes of Xenopus laevis usually elicits mainly passive currents. However, when polarized to potentials more negative than about -100 mV, oocytes obtained from some donors show a relatively well maintained current that is carried mainly by chloride ions. This response does not depend upon external calcium, and is thus clearly different from the calcium-dependent transient chloride current previously described.

Animals↗
PubMed1993

Relaxant effects of mefloquine on vascular smooth muscle in vitro.

We have studied the effects of mefloquine on isolated rat aorta. Mefloquine (10(-8) to 1.6 x 10(-4) mol.l-1) relaxed aortic rings precontracted with both noradrenaline (10(-7) mol.l-1) and potassium chloride (60 mmol.l-1). The mefloquine-induced relaxation was somewhat attenuated by removal of the endothelium. Contractile responses to noradrenaline, potassium chloride, and calcium chloride were reduced by incubating the aortic rings in physiological salt solution containing mefloquine, suggesting that mefloquine reduces calcium influx, which is required for excitation-contraction coupling. The results show that mefloquine relaxes vascular smooth muscle via mechanisms which are partly endothelium-dependent and which is also associated with inhibition of Ca2+ influx from the extracellular medium.

Animals↗
PubMed2004

Fat and sodium chloride reduction in sausages using kappa-carrageenan and other salts.

Fat and sodium chloride were reduced in a sausage formulation including kappa-carrageenan and other salts, as potassium and calcium chloride, in different concentrations, in order to compensate the ionic strength during myofibrillar protein extraction and solubilisation, and to promote the carrageenan stable conformation and gelation. Four different treatments were employed reducing fat from 15 to 10% and sodium chloride from 2.5 to 1.5% and 1%. Potassium chloride was added at 0.5% to all the treatments, and calcium chloride to 0.5% and 0.01% in the last two. The cooking yield was higher for all the treatments but expressible moisture was not significantly different, meaning that the water is not chemically entrapped by carrageenan at the ionic strength conditions employed. However, since no detrimental cooking losses or fat release were detected, myofibrillar proteins maintain a good functionality at these conditions together with kappa-carrageenan. Low-fat sodium-reduced treatment results were slightly darker but redder than the control, probably due to less fat in the formulation. Textural profile analysis demonstrated that, at the fat level employed and the different sodium, potassium and calcium chloride concentrations, similar textures could be created. Sensory analysis indicated that from the formulations employed, 1.5% NaCl with 0.5% KCl and 0.01% CaCl(2) was similar in controlling flavour (juiciness) and texture (hardness). These results established the possibility to reduce significantly the fat and sodium chloride content employing kappa-carrageenan with potassium and calcium chloride, without detrimental effects on texture and sensory characteristics.

Carrageenan↗
PubMed1999

Modulation of a calcium-activated chloride current by Maitotoxin.

The effect of Maitotoxin (MTX) on the calcium-activated chloride current (ICl-Ca) from Xenopus oocytes was studied, applying the two-electrode voltage clamp technique. MTX increased the current amplitude at all the voltages explored and reduced the time to reach the maximum current level (time to peak). At low toxin concentrations (15 pM), both effects were fully reversible. Activation of ICl-Ca by MTX was secondary to the increment in the intracellular Ca2+ concentration induced by this toxin, since incubation of the oocytes with the cell-permeant Ca2+ chelator BAPTA-AM, greatly reduced the effect of MTX on ICl-Ca. Furthermore, external chloride ions removal also diminished the MTX effect on the current, strongly suggesting that the main current activated by MTX is ICl-Ca. Subsequent applications of a fixed toxin concentration after toxin washout resulted in enhanced ICl-Ca, suggesting that the toxin effect potentiates.

Animals↗
PubMed1989

Characterization and partial purification of a chloride- and calcium-dependent glutamate-binding protein from rat brain.

A glutamate-binding protein was solubilized from rat brain synaptic plasma membranes using sodium cholate. Its properties were characterized after addition of exogenous phospholipids and formation of proteoliposomes. Glutamate binding was dependent on calcium and chloride ions with maximal binding at concentrations of 10(-5) M calcium and 10 mM chloride ions. The effects of the two ions were synergistic rather than additive. In addition, glutamate binding was not affected by inhibitors specific for N-methyl-D-aspartate and kainate receptor subtypes, but was inhibited by quisqualate (Ki = 50 microM) and DL-2-amino-4-phosphonobutyrate (Ki = 1.3 mM). Furthermore, binding was abolished by 100 microM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid and 1 mM dithiothreitol. These properties resemble those of the chloride- and calcium-dependent binding site. Starting from the detergent extract, the glutamate-binding protein was purified 123-fold using fractionated ammonium sulfate precipitation, chromatography on hydroxyapatite and on DEAE-Sephacel as sequential purification steps. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified protein fraction showed two major bands migrating with Mr values of 51,000 and 105,000. The properties of the partially purified binding protein were similar to those of the detergent extract. Glutamate binding to the partially purified protein is not due to a sequestration process or product binding to N-acetylated alpha-linked dipeptidase. Thus, the functional role of the binding protein remains to be established.

Animals↗
PubMed1991

Risk factors for pancreatic cellular injury after cardiopulmonary bypass.

BACKGROUND: Pancreatitis is a known complication of cardiac surgery with cardiopulmonary bypass. Although ischemia is believed to be a factor, the cause of pancreatitis after cardiopulmonary bypass remains unknown. METHODS: We prospectively studied 300 consecutive patients undergoing cardiac surgery with cardiopulmonary bypass. Serum amylase, pancreatic isoamylase, and serum lipase were measured on postoperative days 1,2,3,7, and 10. Pancreatic cellular injury was defined as the presence of hyperamylasemia (greater than 123 U per liter) with an increase in either the serum level of lipase (greater than 24 U per liter) or the peak level of pancreatic isoamylase. Trypsinogen-activation peptides, which indicate intrapancreatic enzyme activation, were measured in the urine of the last 101 patients studied. RESULTS: Evidence of pancreatic cellular injury was detected in 80 patients (27 percent), of whom 23 had associated abdominal signs or symptoms and 3 had severe pancreatitis (2 with pancreatic abscess and 1 with necrotizing hemorrhagic pancreatitis). Two of 19 postoperative deaths were secondary to pancreatitis. In multivariate analyses, the development of pancreatic cellular injury was significantly associated with preoperative renal insufficiency, valve surgery, postoperative hypotension, and perioperative administration of calcium chloride. The administration of more than 800 mg of calcium chloride per square meter of body-surface area was an independent predictor of pancreatic cellular injury, and the increase in risk was dose-related. No differences were found in the level of trypsinogen-activation peptides between patients who had pancreatic cellular injury and those who did not. CONCLUSIONS: Pancreatic cellular injury, as indicated by hyperamylasemia of pancreatic origin, is common after cardiac surgery. The administration of large doses of calcium chloride is an independent predictor of pancreatic cellular injury and may be a cause of it.

Aged↗
PubMedDate not supplied

Thrombin clotting time and fibrin polymerization in liver cirrhosis.

The thrombin clotting time and the fibrin polymerization test were performed in 64 patients with liver cirrhosis. Each test was made with thrombin diluted with 150 mmol/l sodium chloride and 25 mmol/l calcium chloride. The thrombin-in-NaCl clotting time was found to be prolonged in 39% of cirrhotic patients, whereas fibrin polymerization was defective in 65% of them. Dilution of thrombin with calcium chloride diminished the number of abnormal results of both tests in patients with liver cirrhosis. Among the performed tests most sensitive test proved to be the polymerization of fibrin induced by thrombin diluted with sodium chloride.

Adult↗
PubMedDate not supplied

Decreased in vitro fluoroquinolone concentrations after admixture with an enteral feeding formulation.

BACKGROUND: The purpose of this study was to determine if mixing of fluoroquinolones with a common enteral feeding formulation, Ensure (Ross Products Division, Abbott Laboratories, Columbus, OH), would alter the measured in vitro quinolone concentrations over a 24-hour period. METHODS: Tablets of ciprofloxacin (500 mg), levofloxacin (500 mg), and ofloxacin (300 mg) were crushed and mixed with 240 mL of Ensure, water and calcium chloride (500 mg/L), water and magnesium chloride (200 mg/L), water and calcium chloride and magnesium chloride, and water alone. Fluoroquinolone concentrations of the mixtures were measured, via high-performance liquid chromatography, at baseline and serially over 24 hours. Experiments were performed in duplicate, at three temperatures (5 degrees C, 25 degrees C, and 37 degrees C). RESULTS: Average decreases of 82.5% +/- 1.5% for ciprofloxacin, 61.3% +/- 5.2% for levofloxacin, and 45.7% +/- 10.1% for ofloxacin (mean +/- 95% CI) were observed in vitro for Ensure over the two experimental sets at baseline. Serial analysis revealed no further significant change in any of the quinolone concentrations over the remaining 24-hour period. No significant decrease was noted with the quinolones when mixed in water and calcium, water and magnesium, water and calcium and magnesium, or water alone. This phenomenon appears to be unaffected by time and temperature. CONCLUSIONS: These data suggest there is an immediate and significant loss of fluoroquinolone when mixed with Ensure. An explanation for the loss of fluoroquinolone remains unclear.

Anti-Infective Agents↗
PubMed2001

Nitric oxide/cGMP-induced inhibition of calcium and chloride currents in retinal pericytes.

In the CNS, contractile pericytes positioned on endothelium-lined lumens appear to play a role in regulating capillary blood flow. This function may be particularly important in the retina where pericytes are more numerous than in other tissues. Despite the importance of pericytes, knowledge of the effects of vasoactive molecules, such as nitric oxide (NO), on the physiology of these cells is limited. Since it is likely that ion channels play a role in the response of pericytes to signaling molecules from other cells, we used the perforated-patch configuration of the patch-clamp technique to record the whole-cell currents of pericytes located on microvessels freshly isolated from the rat retina. We found that voltage-gated calcium currents and calcium-activated chloride currents were inhibited during exposure to the NO donor, sodium nitroprusside (SNP). 8-Bromo-cyclic guanosine monophosphate (cGMP) mimicked these effects. In contrast, neither SNP nor the cGMP analog significantly affected the potassium or nonspecific cation conductances, which establish the resting membrane potential of retinal pericytes. Consistent with endogenous NO suppressing pericyte channel activity, exposure of isolated microvessels to an inhibitor of NO synthase increased the calcium and chloride currents. Since our experiments indicate that chloride channel activity is dependent, in part, upon the function of voltage-gated calcium channels, we postulate that a NO/cGMP-mediated inhibition of calcium channels reduces calcium influx and, thereby, lessens the opening of the calcium-activated chloride channels. This may be one mechanism by which NO decreases the contractile tone of pericytes.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

[Effects of saponins from stems and leaves of Panax quinquefolium L. on the contraction of rabbit aortic strips].

It has been found out that the saponins from stems and leaves of Panax quinquefolium (PQS) can non-competitively antagonize the dose-response curves of norepinephrine (NE), potassium chloride and calcium chloride on the isolated aortic strips of rabbits, and obviously inhibit intracellular and extracellular Ca2(+)-dependent contraction of the aortic strips induced by NE. These effects of PQS are similar to verapamil.

Animals↗
PubMed2001

Induction of laccase activity in Rhizoctonia solani by antagonistic Pseudomonas fluorescens strains and a range of chemical treatments.

Fungi often produce the phenoloxidase enzyme laccase during interactions with other organisms, an observation relevant to the development of biocontrols. By incorporating the laccase substrate 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) into agar, we analyzed laccase induction in the plant-pathogenic fungus Rhizoctonia solani when paired against isolates of the soil bacterium Pseudomonas fluorescens. Substantial induction of R. solani laccase was seen only in pairings with strains of P. fluorescens known to produce antifungal metabolites. To study laccase induction further, a range of chemical treatments was applied to R. solani liquid cultures. p-Anisidine, copper(II), manganese(II), calcium ionophore A23187, lithium chloride, calcium chloride, cyclic AMP (cAMP), caffeine, amphotericin B, paraquat, ethanol, and isopropanol were all found to induce laccase; however, the P. fluorescens metabolite viscosinamide did not do so at the concentrations tested. The stress caused by these treatments was assessed by measuring changes in lipid peroxidation levels and dry weight. The results indicated that the laccase induction seen in pairing plate experiments was most likely due to calcium or heat shock signaling in response to the effects of bacterial metabolites, but that heavy metal and cAMP-driven laccase induction was involved in sclerotization.

Antibiosis↗
PubMed1993

The influence of high glucose levels and/or hyperosmolarity on rat isolated aorta.

We investigated the influence of high-glucose levels (30.5 mmol/L) and/or hyperosmolarity on pharmacological responses in aortic ring preparations taken from nondiabetic rats. Moderate changes were observed for the concentration-response curves of noradrenaline and phenylephrine, but not for methoxamine and cirazoline. Maximal active forces of the concentration-response curves of potassium chloride and calcium chloride were significantly reduced by the elevated glucose levels per se, but neither the slopes of the curves nor the -logEC50 values were affected. Concentration-response curves of serotonin and U 46619 were not affected. For angiotensin II, the -logEC50 values and maximal active forces of the concentration-response curves were significantly lower under both hyperglycemic and hyperosmolar conditions. The present study suggests that potential changes in contractile behavior in isolated vessels from diabetic animals cannot be attributed to high glucose levels and/or hyperosmolarity as such, but indeed reflect vascular changes associated with the diabetic state. An exception has to be made for the depolarization of aortic ring preparations of nondiabetic rat; the elevated glucose level leads to an impaired calcium influx via the (slow) L-type calcium channels.

Animals↗
PubMed1994

Generation of alginate-poly-l-lysine-alginate (APA) biomicrocapsules: the relationship between the membrane strength and the reaction conditions.

Alginate-poly-l-lysine-alginate (APA) microcapsules have proven effective in protecting enclosed live cells from immune rejection following transplantation into experimental animals, thereby eliminating the need for immunosuppressive therapy. However, in order for the capsules to remain intact for extended periods in vivo, the thickness of the membrane material must be optimized. In this study, the membrane thickness was examined as an indicator of membrane strength and measured under different reaction conditions. The thickness was found to increase 1) from 4.6 microns to 6.6 microns with an increase in the concentration of sodium alginate from 1.25 (w/v) to 2.0% (w.v); 2) from 4.2 microns to 6.2 microns with an increase in the concentration of the calcium solution from 20 mM to 100mM; 3) from 3.9 microns to 10.3 microns with an increase in the concentration of poly-l-lysine (PLL) from 0.02% (w/v) to 0.08% (w/v); and 4) from 2.3 microns to 7.4 microns with an increase in the reaction time with the PLL from two to seven minutes. On the other hand, membrane thickness decreased 1) from 9.8 microns to 8.6 microns with an increase of the pH in the PLL solution from 5.8 to 9.2; 2) from 13.2m to 5.8 microns with an increase in the molecular weight of PLL from 14,000 to 57,000; 3) from 8.4 microns to 6.0 microns with an increase in the treatment time with 0.9 (w/v) NaCl solution from zero to fifteen minutes and; 4) from 7.5 microns to 6.1 microns with an increase in the treatment time of the second sodium alginate coating from zero to ten minutes. Membrane thickness was inversely proportional to capsule volume expansion during membrane synthesis. By replacing calcium chloride by calcium lactate and eliminating the use of CHES in the construction of capsule membranes, we improved the strength and biocompatibility of our capsules, as evidenced by marked improvements in the survival rates of diabetic mice treated with islet transplants enclosed in the new capsules. These results indicate that it is possible to obtain optimal membrane thickness for a given purpose by creating specific reaction conditions under which membranes are synthesized.

Alginates↗
PubMed2002

Advanced wound care materials: developing an alginate fibre containing branan ferulate.

OBJECTIVE: This laboratory-based study set out to establish whether branan ferulate--a polysaccharide compound available in gels such as as Sterigel (SSL International, UK)--could be successfully added to the fibre of an alginate dressing to provide a superior wound-care dressing. METHOD: A wet extruder (Howden Engineering Services, UK) was used to produce the fibres. Researchers examined the effect of spinning-bath calcium chloride concentration (used as the coagulant in the fibre-spinning process) on the tensile and absorption properties of alginate fibres containing 25% w/w branan ferulate. Sodium alginate and branan ferulate were separately dissolved in de-ionised water and then stirred together to make up a 5% dope solution. The dope was then forced through a spinneret and into the calcium chloride bath, where fibres were precipitated and then carried over the first set of rollers. The fibres were washed in the next bath and drawn at different rates to enhance their tensile properties. At the 'winding-up' stage the filaments were either passed over a contact heater and into a furnace (dry pick-up) or transferred into acetone baths of increasing concentrations of 50, 80 and 100% aqueous acetate to remove the water (wet pick-up). The moisture content of standard alginate fibres and those with branan ferulate were measured and compared. Breaking load, tenacity and breaking extension, and the quantity of branan ferulate in the fibres were also measured. The process was repeated four times, using different strengths of calcium chloride. Using various draw ratios, the effects of liquid uptake were measured using water, saline and a solution called A (to mimic human blood and exudate-type fluids). RESULTS: Out of the four calcium chloride concentrations used, 1% concentration appeared to give the highest and most conclusive results for fibre-breaking load, tenacity and breaking extension. CONCLUSION: A 1% w/v concentration of calcium chloride provides the optimum conditions for achieving suitably strong fibres with adequate absorption capacity, while allowing the least branan ferulate loss during wash and post-production treatments. In a laboratory setting the product showed promise. Research is now needed in a clinical setting and for comparison with existing wound-care products.

Alginates↗