Abstract  1. Although calcium gluconate (CG) is recommended in the treatment of hydrofluoric acid (HF) eye burn its efficacy seems to be controversial, and controlled human or animal studies are limited. The study's objective is to compare the efficacy of 1% CG and normal saline irrigation for the treatment of HF eye injury in animals. 2. 0.05 ml 2% HF was instilled to anesthetized rabbit's eyes. One minute later, four treatment groups were studies: (1) irrigation with normal saline followed by topical antibiotics, corticosteroids and cycloplegics for 48 h (n = 10); (2) irrigation with 1% CG followed by the same topical treatment (n = 9); (3) as group 1 and 1% CG drops over 48 h (n = 10); (4) as group 3, and injection of 1% CG subconjunctivally after irrigation (n = 9). 3. Corneal erosion area, corneal haziness, conjunctival status, vascularization (pannus) and acidity were assessed before injury, immediately after initial treatment and 1, 2, 7 and 14 days thereafter by slit lamp aided by fluorescein staining. 4. Conjunctival pH dropped from 6.0-6.5 to 2.5-3 after injury and increased to 6-6.5 after irrigation. Corneal erosion: smaller in groups 2, 3, significantly so at 2 days, but not different at 14 days. Corneal haziness: more severe in group 4, at 14 days, insignificant. Conjunctival damage: significantly worse in group 4 at 2, 7 and 14 days. Pannus appeared in 2-4 eyes in each group. 5. It seems that for HF injury 1% CG did not have any significant advantage over saline irrigation and topical treatment only. It might have some initial and temporary effect on healing process especially that involving erosion. Given subconjunctivally, 1% CG may be toxic and worsens clinical outcome.

Abstract  The Na(+)/H(+) exchanger has been the only unequivocally demonstrated H(+)-transport mechanism in the synaptosomal preparation. We had previously suggested that a Cl(-)-H(+) symporter (in its acidifying mode) is involved in cytosolic pH regulation in the synaptosomal preparation. Supporting this suggestion, we now show that: (1) when synaptosomes are transferred from PSS to either gluconate or sulfate solutions, the Fura-2 ratio remains stable instead of increasing as it does in 50 mM K solution. This indicates that these anions do not promote a plasma membrane depolarization. (2) Based in the recovery rate from the cytosolic alkalinization, the anionic selectivity of the Cl(-)-H(+) symporter is NO(3)(-) > Br(-) > Cl(-) > I(-) = isethionate = sulfate = methanesulfonate = gluconate. (3) PCMB 10 muM inhibits the gluconate-dependent alkalinization by 30 +/- 6%. (4) Neither Niflumic acid, 9AC, Bumetanide nor CCCP inhibits the recovery from the cytosolic alkalinization.

Abstract  INTRODUCTION: Micronutrient deficiencies are one of the most important public health issues worldwide and iron (Fe) deficiency anemia is the most prevalent micronutrient deficiency. Iron deficiency often coexists with calcium deficiency and iron and calcium supplementation often overlap. This has led to investigations into the interaction between these two minerals, and whether calcium may inhibit iron absorption in the gut.

OBJECTIVE: To determine the effect of various calcium salts on non-heme iron bioavailability in fasted women of childbearing age.

METHODS: A randomized and single blinded trial was conducted on 27 women of childbearing age (35-45 years old) divided into 2 groups (n1 = 13 and n2 = 14, respectively). On four different days, after an overnight fast, they received 5 mg of Fe as FeSO4 (labeled with 55Fe or 59Fe) with 800 mg of elemental calcium in the form of either calcium chloride, calcium gluconate, calcium citrate, calcium carbonate, calcium lactate, calcium sulfate or calcium phosphate. Calcium chloride was used as the control salt in both groups. Iron was labeled with the radioisotopes 59Fe or 55Fe, and the absorption of iron was measured by erythrocyte incorporation of radioactive Fe RESULTS: 800 mg of elemental calcium as calcium citrate produced a significant decrease in non-heme iron bioavailability (repeated measures ANOVA, F = 3.79, p = 0.018).

CONCLUSION: Of the various calcium salts tested, calcium citrate was the only salt that decreased non-heme iron bioavailability relative to the calcium chloride control when taken on an empty stomach. These results suggest that inhibition of non-heme iron absorption in fasted individuals is dependent upon the calcium salt in question and not solely dependent on the presence of calcium.

Abstract  Heinen et al reported the use of [U-13C6]gluconolactone to trace the PPP in microorganisms (Appl. Environ. Microbiology 07/2006, P 4743). We adapted this technique for use in perfused hearts and livers from rats. The tissue was extracted in acetonitrile:water (50:50) and the supernatant applied to an ion exchange solid phase extraction cartridge. The sugar phosphates were eluted with 50 mM ammonium formate in 50% methanol-water (recovery was 90%). We used a hybrid triple quadrupole/linear ion trap mass spectrometer (Applied Biosystems) coupled with HPLC to monitor the sugar phosphates using the enhanced resolution mode. We used hydrophilic interaction liquid chromatography to avoid ion pairing reagents and to increase the detection sensitivity. The flux through the PPP is calculated as (uptake of [U-13C6]gluconolactone)/(M6 enrichment of 6-P-gluconate). The latter can be used in tracer amounts because of low background of analytes at M6 and M5. The production of NADPH in the PPP is equal to twice its flux. The contribution of the oxidative branch of the PPP is the enrichment ratio (M5 ribose-5-P)/(M6 6-P-gluconate). Supported by NIH Roadmap grant 5 R33 DK070291.

Abstract  Maintenance of physiological levels of intracellular and extracellular calcium is essential for life. Increased intracellular calcium levels are involved in cell death (apoptosis and necrosis) and are associated with positive responses in the Comet assay in vitro. In addition, high calcium and vitamin D intakes were reported to induce apoptosis in adipose tissue in obese mice and to increase DNA-migration in the Comet assay. To investigate increased serum concentration of calcium as a potential confounding factor in the regulatory Comet assay in vivo, we induced mild hypercalcemia in male Wistar rats by 3-day continuous intravenous infusion of calcium gluconate and performed the Comet assay in the liver in line with regulatory guidelines. The results of the study showed that mild increases in serum calcium concentration (up to 1.4 times above the concurrent control) and increased urinary calcium concentration (up to 27.8 times above the concurrent control) results in clinical signs like mild tremor, faster respiration rate and decreased activity in a few animals. However, under the conditions of the study, no increase in the %Tail DNA in the Comet assay and no indication of liver damage as determined by histopathological means were observed. Thus, mild increases in plasma calcium did not lead to positive results in a genotoxicity assessment by the Comet assay in the rat liver. This result is important as it confirms the reliability of this assay for regulatory evaluation of safety.

Abstract  Two independent isolates of a Gram-stain-positive, facultatively anaerobic, motile, rod-shaped bacterium were recovered from cheonggukjang, a Korean fermented soybean paste food product. Preliminary sequencing analysis of the 16S rRNA gene indicated that these strains were related most closely to Bacillus sonorensis KCTC-13918T and Bacillus licheniformis DSM 13T. In phenotypic characterization, the novel strains were found to grow between 15 and 55 °C and to tolerate up to 8 % (w/v) NaCl. Furthermore, the strains grew in media of pH 5-10 (optimal growth at pH 7.0). The predominant cellular fatty acids were anteiso-C15 : 0 and iso-C15 : 0.The isoprenoid quinone was menaquinone 7 (MK-7). The cell-wall peptidoglycan contained meso-diaminopimelic acid. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unknown glycolipid. Draft genomes of the two strains were determined and in silico DNA-DNA hybridizations with their nearest neighbour (B. sonorensis KCTC-13918T) revealed 29.9 % relatedness for both strains. Phylogenomic analysis of the genomes was conducted with the core genome (799 genes) of all strains in the Bacillus subtilis group and the two strains formed a distinct monophyletic cluster. In addition, the strains differed from the two most closely related species in that they did not metabolize maltose, d-galactose, d-sorbitol or d-gluconic acid. The DNA G+C content was 45.9 mol%. Based upon the consensus of phylogenetic and phenotypic analyses, these strains represent a novel species of the genus Bacillus, for which the name Bacillus glycinifermentans sp. nov. is proposed. The type strain is GO-13T ( = KACC 18425T = NRRL B-65291T).

Abstract  The pharmacokinetics of fluoride and calcium were studied after administration of a combined fluoride and calcium preparation (Tridin) (1, 2 and 3 tablets) in 9 healthy male volunteers, using a cross-over study design. The total estimation of the pharmacokinetic data was performed by a simultaneous curve fitting to all single values, using a direct search procedure based on an open two-compartment model and three-compartment model, respectively. Maximum plasma concentrations and areas under the curve are proportional to the dose administered. Inter-subject variations are comparatively small, computerized multiple dose simulation for 3 days does not show any cumulation. The data fit the two-compartment model and the three-compartment model as well. The behaviour of the calcium concentrations reflects the immediate response of calcium homeostasis: plasma calcium concentrations are not affected.

Abstract  Mutagenic test results are reported in microbial and mammalian cell systems.

Abstract  IPA COPYRIGHT: ASHP Potassium chloride, as a sugar coated tablet embedded in a wax matrix (Slow-K) and potassium gluconate solution (Kaon), were compared in 20 outpatients suffering from hypertension and receiving potassium wasting diuretics, capable of producing hypokalemia. The patients were randomly divided into 2 groups of 10 each. One group received the solution for 4 weeks (40 meq potassium/day) and was then switched to the tablet (48 meq/day) for another 4 weeks. The second group began treatment with the tablet, crossing over to the solution after 4 weeks. The patients completed a self rating questionnaire on preference and GI side effects after each 4 week period. Both medications appeared equally effective in maintaining serum levels of potassium and chloride. GI side effects were not severe with either preparation. No gross or occult blood was detected in the stools for any patient. Patient preferences favored the tablet. Ninety-five per cent of the subjects found the tablets more acceptable than the liquid, and 90% found them more convenient. Based upon these findings, the tablet appears to possess decided clinical advantage over a solution with respect to patient compliance and acceptance.

Abstract  The authors of this study reported that compound-related effects were observed in the stomach of rats and consisted of thickening of the stratified squamous epithelieum at the anterior stomach, which is perceived to pertain to the rat forestomach. The area particularly affected was the transitional area continuous with the pyloric stomach, which is consistent with a description of the limiting ridge. The effect was observed in all dose groups and was reported with dose dependency in frequency and severity, and therefore, a NOAEL for glucono delta lactone could not be determined based on the results of this study. However, given that the forestomach and limiting ridge are structures unique to the rodent, the effects observed in the stomach of rats in this study are not relevant to humans. It should be noted that the results reported herein were taken from a partial English translation of a study report written in Japanese.

Abstract  Background: Aliphatic (poly)hydroxy carboxylic acids [(P)HCA] occur in natural, e.g. soils, and in technical (waste disposal sites, nuclear waste repositories) compartments . Their distribution, mobility and chemical reactivity, e.g. complex formation with metal ions and radionuclides, depend, among others, on their adsorption onto mineral surfaces. Aluminium hydroxides, e.g. gibbsite [α-Al(OH)3], are common constituents of related solid materials and mimic the molecular surface properties of clay minerals. Thus, the study was pursued to characterize the adsorption of glycolic, threonic, tartaric, gluconic, and glucaric acids onto gibbsite over a wide pH and (P)HCA concentration range. To consider specific conditions occurring in radioactive wastes, adsorption applying an artificial cement pore water (pH 13.3) as solution phase was investigated additionally.

Results: The sorption of gluconic acid at pH 4, 7, 9, and 12 was best described by the "two-site" Langmuir isotherm, combining "high affinity" sorption sites (adsorption affinity constants [Formula: see text] > 1 L mmol-1, adsorption capacities < 6.5 mmol kg-1) with "low affinity" sites ([Formula: see text] < 0.1 L mmol-1, adsorption capacities ≥ 19 mmol kg-1). The total adsorption capacities at pH 9 and 12 were roughly tenfold of that at pH 4 and 7. The S-shaped pH sorption edge of gluconic acid was modelled applying a constant capacitance model, considering electrostatic interactions, hydrogen bonding, surface complex formation, and formation of solved polynuclear complexes between Al3+ ions and gluconic acid. A Pearson and Spearman rank correlation between (P)HCA molecular properties and adsorption parameters revealed the high importance of the size and the charge of the adsorbates.

Conclusions: The adsorption behaviour of (P)HCAs is best described by a combination of adsorption properties of carboxylic acids at acidic pH and of polyols at alkaline pH. Depending on the molecular properties of the adsorbates and on pH, electrostatic interactions, hydrogen bonding, and ternary surface complexation contribute in varying degrees to the adsorption process. Linear distribution coefficients Kd between 8.7 and 60.5 L kg-1 (1 mmol L-1 initial PHCA concentration) indicate a considerable mineral surface affinity at very high pH, thus lowering the PHCA fraction available for the complexation of metal ions including radionuclides in solution and their subsequent mobilization.

Abstract  The analysis of retainment and release kinetics of deposited in tissue structures calcium was made in the hypercalcemic conditions in 28 healthy volunteers (22 males and 6 females) of the age of 33 ± 6.5 years via drip infusion (Groups 1, 2) and in 9 individuals (3 males and 6 females) in 12 trials via stream infusion (Group 3). By the end of each hour after the termination of calcium infusion the amount of calcium retained in tissues was calculated (Mtis./kg); the parameters of its binding (specific buffer volume--β3 sp, association constant--Ka, number of binding centers--n) were established using the Langmuir and Scetchard coordinates. The Group 1 volunteers (n = = 12) showed a section of positive cooperativity (a direct regression on Sketchard coordinates, Hill coefficient 3.36 ± 1.63) and 2 sections of the consecutive calcium separation from one set of noninteracting centers. 5 volunteers of Group 2 and 8 volunteers of Group 3 demonstrated a slight calcium delivery to tissues after 1 hour of observation which then followed for 2 volunteers of Group 2 and for 2 volunteers of Group 3. Other volunteers of Groups 2 and 3 showed a release of tissue-deposited calcium via the mechanism of the consecutive separation from one set of noninteracting centers with βsp 3 times less and Ka 7 times higher than with the calcium infusion. The excretion of calcium in urine was the highest in Group 1 and the lowest in Group 3. The [Ca2+] and Mtis./kg values were normalized in Groups 1 and 2 the next morning and in Group 3 after 2-3 hours of observation. An assumption was made about the relationship between the tissue and kidney [Ca2+] normalizing mechanisms with hypercalcemia.

Abstract  Cardiomyocytes (CMs) undergo a rapid transition from hyperplastic to hypertrophic growth soon after birth, which is a major challenge to the development of engineered cardiac tissue for pediatric patients. Resting membrane potential (Vmem) has been shown to play an important role in cell differentiation and proliferation during development. We hypothesized that depolarization of neonatal CMs would stimulate or maintain CM proliferation in vitro. To test our hypothesis, we isolated postnatal day 3 neonatal rat CMs and subjected them to sustained depolarization via the addition of potassium gluconate or Ouabain to the culture medium. Cell density and CM percentage measurements demonstrated an increase in mitotic CMs along with a ~2 fold increase in CM numbers with depolarization. In addition, depolarization led to an increase in cells in G2 and S phase, indicating increased proliferation, as measured by flow cytometry. Surprisingly depolarization of Vmem with either treatment led to inhibition of proliferation in cardiac fibroblasts. This effect is abrogated when the study was carried out on postnatal day 7 neonatal CMs, which are less proliferative, indicating that the likely mechanism of depolarization is the maintenance of the proliferating CM population. In summary, our findings suggest that depolarization maintains postnatal CM proliferation and may be a novel approach to encourage growth of engineered tissue and cardiac regeneration in pediatric patients.

Abstract  A 6-month-old, female border collie was referred for evaluation of hypocalcemia, hyperphosphatemia, fever, and painful ventral abdominal skin. She had recently been treated intravenously and subcutaneously (SC) with a diluted 10% calcium gluconate solution. The medical evaluation supported the diagnosis of primary hypoparathyroidism, but the subsequent hospital course was complicated by severe calcinosis cutis, which caused extensive skin necrosis and marked debilitation. This patient illustrates that administration of a calcium gluconate solution SC can be associated with extensive morbidity when administered to hyperphosphatemic patients.

Abstract  BACKGROUND: Stanniocalcin (STC) is a polypeptide hormone first discovered in fish and more recently in mammals. In mammals, STC is produced in many tissues and does not normally circulate in the blood. In kidney and gut, STC regulates phosphate fluxes across the transporting epithelia, whereas in brain it protects neurons against cerebral ischemia and promotes neuronal cell differentiation. The gene is highly expressed in ovary and dramatically up-regulated during pregnancy and nursing. Gene expression also is high during mammalian embryogenesis, particularly in kidney where the hormone signals between epithelial and mesenchymal cells during nephrogenesis.

METHODS: This study examined the patterns of STC gene expression and protein distribution in the mouse kidney over the course of post-natal development. Further, because STC is a regulator of renal phosphate transport, we also examined the effects of changing levels of dietary calcium and phosphate on renal levels of STC gene expression in adult rats.

RESULTS: STC mRNA levels in the neonate kidney were found to be tenfold higher than adults. Isotopic in situ hybridization of neonate kidneys revealed that most, if not all, STC mRNA was confined to collecting duct (CD) cells, as is the case in adults. STC protein on the other hand was found in proximal tubule, thick ascending limb and distal tubules in addition to CD cells. This suggests that, as in adults, the more proximal nephron segments in neonates are targeted by CD-derived STC and sequester large amounts of hormone. The addition of 1% calcium gluconate to the drinking water significantly reduced STC mRNA levels in inner medullary CD cells of both males and females, but not those in the cortex and outer medulla. Placing animals on low phosphate diets also reduced STC mRNA levels, but uniquely in outer medullary and cortical CD cells, whereas a high phosphate diet increased transcript levels in the same regions.

CONCLUSIONS: These findings suggest that STC may be of unique importance to neonates. They also suggest that changes in dietary calcium and phosphate can alter renal levels of STC gene expression, but that these effects vary between the early and late segments of the collecting duct.

Abstract  The effects of serum and brain calcium concentration on rat behavior were tested by maintaining animals on either distilled water (N = 60) or water containing 1% calcium gluconate (N = 60) for 3 days. Animals that were maintained on high calcium drinking water presented increased serum calcium levels (control = 10.12 +/- 0.46 vs calcium treated = 11.62 +/- 0.51 mug/dl). Increase of brain calcium levels was not statistically significant. In the behavioral experiments each rat was used for only one test. Rats that were maintained on high calcium drinking water showed increased open-field behavior of ambulation (20.68%) and rearing (64.57%). On the hole-board, calcium-supplemented animals showed increased head-dip (67%) and head-dipping (126%), suggesting increased ambulatory and exploratory behavior. The time of social interaction was normal in animals maintained on drinking water containing added calcium. Rats supplemented with calcium and submitted to elevated plus-maze tests showed a normal status of anxiety and elevated locomotor activity. We conclude that elevated levels of calcium enhance motor and exploratory behavior of rats without inducing other behavioral alterations. These data suggest the need for a more detailed analysis of several current proposals for the use of calcium therapy in humans, for example in altered blood pressure states, bone mineral metabolism disorders in the elderly, hypocalcemic states, and athletic activities.

Abstract  Changes in the extracellular calcium concentration have important effects on hormone secretion. In vitro, kidney juxtaglomerular cells have been shown to secrete renin in an inverse relationship to the extracellular calcium concentration. The effect of physiologic changes in calcium on renin secretion in humans is less clear. We therefore investigated the effects of physiologic changes in extracellular calcium levels on renin and aldosterone secretion in 7 healthy men. Serum ionized calcium, ACTH, plasma renin activity (PRA), and aldosterone levels were serially measured during 90-min infusions of dextrose, disodium edetate (EDTA) and calcium gluconate, and the latter two infusions were repeated with dexamethasone pre-treatment. ACTH levels decreased during the 5% dextrose in water and the EDTA infusions but increased during the calcium infusion. Similarly, PRA and aldosterone levels fell during the D5W and EDTA infusions but this decrease was absent with increments in calcium levels. Dexamethasone administration suppressed ACTH and the aldosterone response to calcium but did not affect the PRA response to the calcium infusion. Our data indicate that increases in calcium within the physiological range blunt the diurnal decline in both PRA and aldosterone. This appears to be a direct effect of calcium on PRA but mediated through ACTH in the case of aldosterone.