Abstract  To assess directly the effect of ionic dissociation on the bioavailability of calcium, we used the double isotope inverse convolution method to compare the absorption of calcium gluconate and calcium pyrrolidone carboxylate, an organic, highly dissociated salt. Two tests were performed at a 2 day interval, using in random sequence either salt as a carrier. Forty-eight subjects of various age and clinical condition were studied. The use of the more dissociated salt consistently and significantly increased fractional absorption in a rather constant ratio. Moreover, it slowed absorption in normal subjects whatever their age, and accelerated it in patients with chronic renal failure or osteoporosis, leading to inferences on the alteration of calcium absorption in these conditions.

Abstract  Calcium (Ca) preparations are widely used in the treatment of osteoporosis, usually as soluble salts. Tolerance might be improved by prescription of slowly dissolved Ca preparations, since Ca is also absorbed distally, even in the colon. In this regard the use of natural forms of Ca might be advantageous, but natural products cannot be labeled reliably for easy evaluation of their absorption. To study the intestinal absorption of an osseino-mineral complex (Ossopan) in comparison with Ca-gluconate, healthy males were investigated by means of conventional blood and urinary measurements before and after ingestion of either substance containing 1.58 g Ca. All subjects were placed on a standard diet 2 days before and during test day. Ca-gluconate (n = 7) evoked a marked and transient rise in plasma ionized calcium; total plasma calcium and urinary calcium followed a parallel course, while plasma and urinary phosphate decreased. After administration of osseino-mineral complex (n = 6), a slow but sustained elevation of plasma ionized calcium was observed while total calcium remained unchanged when corrected by the plasma proteins. Plasma phosphate and proteins increased, as did urinary phosphate. Comparing the 24-hour urine of the test day with that of the previous day, the rise in calcium excretion was slightly greater in the subjects treated by osseino-mineral complex than in those who were given Ca-gluconate, while phosphate excretion increased in the first group and decreased in the second. It is concluded that the bioavailability of Ca in osseino-mineral complex is as good as, if not better than, that of Ca-gluconate.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract  Under hypercalcemia induced by calcium gluconate the degranulation of renomedullary interstitial cells accompanied with the increase in volume of the rough and smooth surfaced endoplasmic reticulum and enlargement of the Golgi apparatus were observed. The ultrastructural changes can be regarded as an expression of the increase of a synthetic and secretory activity of these cells. Because the changes of renomedullary cells observed in hypercalcemia induced by calcium gluconate are not really different from that observed in hypercalcemia induced by vitamin D3 (Roszkiewicz et al. 1979) it can suppose that these changes may be connected solely with a calcium serum elevation and that the renomedullary interstitial cells rather do not play any important role in vitamin D3 metabolism.

Abstract  A stable isotope labeling (13C and D) was administered to 8 subjects in order to observe the short-term effect of phytosterols (Cytellin 9 g/day) or calcium (calcium gluconate 3 g/day) on the processes involved in cholesterol elimination in the feces. Under control conditions, the mean fraction of fecal cholesterol having a plasmatic origin was 69% and that of cholesterol secreted by the digestive tract 11%. The remaining fraction represented unabsorbed dietary cholesterol. While both treatments reduced the absorption of cholesterol, Cytellin enhanced the fecal excretion of plasma cholesterol and calcium lowered it. The change observed in the rate of intestinal external secretion did not follow the change in the fecal excretion of cholesterol.

Abstract  We have performed a first series of experiments using our stop flow technique to localize renal transport of calcium in dogs. Calcium is found to be actively reabsorbed in a far distal area but does not appear to be actively lowered in concentration in proximally derived samples. In a second series of dogs, elevation of plasma calcium by infusion of the salt CaCl2 caused a 43% reduction in the additional volume of water reabsorbed by the proximal tubule during stop flow. Calcium does not interfere with the active reabsorption of sodium in the distal area and does not cause significant increases in sodium excretion. In contrast calcium causes a considerable increase in potassium secretion at a far distal site. When calcium gluconate was employed, severe impairment of distal sodium and calcium reabsorption occurred in addition to the increased potassium secretion. We suggest that the gluconate anion restricts the movement of sodium, calcium and potassium electrostatically thus obligating cations to remain in the tubular urine depending upon their reabsorption potential.

Abstract  In the present study, experiments were designed to investigate if supplementation with calcium during 4 weeks had an effect on blood parameters in sedentary male athletes at rest and exhaustion. Thirty healthy subjects of ages ranging from 18 to 22 years were included in the study. The subjects were separated into three groups, as follows: Group 1 consisted sedentary athletes receiving 35 mg/kg/day calcium gluconate. Group 2 included subjects equally supplemented with calcium training 90 min/day for 5 days/week. Group 3 were subject to the same exercise regime but did not receive calcium supplements. Blood parameters were determined in the experimental subjects at rest and after exhaustion. The leukocyte count (WBC) of athletes in groups 2 and 3 were significantly higher at exhaustion (p < 0.05). There were no significant differences in the WBC of the two supplemented groups. The erythrocyte count (RBC) was increased in the supplemented athletes after training (p < 0.05), but hemoglobin, hematocrit, and thrombocyte levels remained unchanged. The mean corpuscular volume increased in the calcium-supplemented group at rest (p < 0.05). These results suggest that calcium supplementation only causes increases in white and red blood cell counts in athletes after exhaustion while other hematological parameters remain unchanged.

Abstract  An indirect method to measure the reaction of glucono delta lactone with protein was developed. Glucono delta lactone reacts with lysine, tyrosine, threonine, arginine, and serine residues of protein, protecting them from attack by nitrous acid.

Abstract  Part 28 includes a supplement purported to combat fatigue and enhance growth hormone (ornithine); a well-known ingredient (phenylalanine) of a well-known sweetener (aspartame); a possible energy enhancer via 2,3 diphosphoglycerate (phosphate); and a rather dubious supplement purported in the early 1940s to have a wide range of medicinal effects (pangamic acid). Of these, only phosphate appears to have some credible evidence to support the claims of an ergogenic effect.

Abstract  The effect of diet on metabolites found in rat urine samples has been investigated using nuclear magnetic resonance (NMR) and a new ambient ionization mass spectrometry experiment, extractive electrospray ionization mass spectrometry (EESI-MS). Urine samples from rats with three different dietary regimens were readily distinguished using multivariate statistical analysis on metabolites detected by NMR and MS. To observe the effect of diet on metabolic pathways, metabolites related to specific pathways were also investigated using multivariate statistical analysis. Discrimination is increased by making observations on restricted compound sets. Changes in diet at 24-h intervals led to predictable changes in the spectral data. Principal component analysis was used to separate the rats into groups according to their different dietary regimens using the full NMR, EESI-MS data or restricted sets of peaks in the mass spectra corresponding only to metabolites found in the urea cycle and metabolism of amino groups pathway. By contrast, multivariate analysis of variance from the score plots showed that metabolites of purine metabolism obscure the classification relative to the full metabolite set. These results suggest that it may be possible to reduce the number of statistical variables used by monitoring the biochemical variability of particular pathways. It should also be possible by this procedure to reduce the effect of diet in the biofluid samples for such purposes as disease detection.

Abstract  Nonenzymatic glycation of proteins and oxidative stress are considered independent factors important in the development of the complications of diabetes but may be interrelated by the process of autoxidative glycation. This pathway involves monosaccharide autoxidation to a reactive ketoaldehyde analogue and subsequent reaction with protein to form a ketoimine adduct. This study demonstrates that delta-gluconolactone (delta-GL), an oxidised analogue of glucose, is a potent glycating agent in vitro of haemoglobin present in blood samples from insulin-dependent diabetic and non-diabetic human subjects and from spontaneously diabetic, insulin-dependent BB/Edinburgh (BB/E) rats. The percentage glycated haemoglobin after incubation (37 degrees C, 5 h) with delta-GL (25 mmol/l) was significantly (P < 0.002) higher than that observed using an equimolar concentration of glucose. Intravenous administration of delta-GL (1 g/kg) to non-diabetic BB/E rats also significantly increased glycation of haemoglobin (6.0 +/- 0.1% vs 4.9 +/- 0.1%, P < 0.01) whereas intravenous injection of an identical dose of glucose had no significant effect (5.1 +/- 0.1% vs 5.0 +/- 0.2%). These results support the hypothesis that nonenzymatic glycation of proteins involves attachment by both native and oxidised monosaccharides. Further investigation of the interactions between diabetes-associated increases in oxidative stress and glycation on the development and progression of the vascular complications of diabetes is necessary.

Abstract  1.5-Gluconolactone was shown to inhibit in a competitive manner the activity of both I- and D-forms of rabbit skeletal muscle glycogen synthase. Unlike other known inhibitors (UDP and adenyl nucleotides) the affinity of the enzyme D-form for 1.5-gluconolactone is lower than that of the I-form. The joint inhibition of glycogen synthase by UDP and 1.5-gluconolactone is characterized by positive cooperativity. It was supposed that the binding of the nucleotide part of the substrate molecule is preceded by the UDPglucose glucosyl residue interaction with the enzyme and induces a closer resemblance to the transient state. The effect of the allosteric inhibitor, ADP, on the enzyme activity is conditioned by its effect on the conformational state of UDP-glucose glucosyl residue binding site. Phosphorylation of glycogen synthase results in conformational changes in the same active site region, although the pyrimidine base binding site also seems to be involved in this process.

Abstract  Diisopropylamine dichloroacetate, the active component of many formulations of pangamic acid (trade-named "vitamin B15"), and diisopropylamine, a component of diisopropylamine dichloroacetate, both demonstrate mutagenicity in the Ames Salmonella/mammalian microsome mutagenicity test. Ninety percent of such agents prove carcinogenic, and this long-term possibility must be considered in any proposed use of pangamic acid containing diisopropylamine or diisopropylamine dichloroacetate.

Abstract  Salmonella/microsome tests (Ames tests) and chromosomal aberration tests in vitro using a Chinese hamster fibroblast cell line were carried out on 190 synthetic food additives and 52 food additives derived from natural sources, all of which are currently used in Japan. Fourteen out of 200 tested in the Ames assay showed positive effects and 54 out of 242 were positive in the chromosome test. Three additives (erythorbic acid, chlorine dioxide and beet red) were positive only in the Ames test, although their mutagenic potentials were relatively weak, while 43 additives were positive only in the chromosome test. Eleven additives (calcium hypochlorite, cinnamic aldehyde, l-cysteine monohydrochloride, Food Green No. 3 (Fast Green FCF), hydrogen peroxide, potassium bromate, sodium chlorite, sodium hypochlorite, sodium nitrite, cacao pigment and caramel) were positive in both the Ames test and the chromosome test. The usefulness of such primary screening tests combining two different genetic end-points, gene mutation and chromosomal aberration, and some correlation between mutagenicity and carcinogenicity of food additives are discussed.

Abstract  The in vitro permeation and absorption of calcium ions across the small intestine were measured at different concentrations of calcium gluconate solutions (1.0, 10.0 and 20.0 mM) with or without prolactin. The calcium ions permeated through the small intestine from a donor environment to an acceptor environment that mimicked the conditions in the stomach to ileum segment of the digestive tract. The permeation and absorption of calcium were directly dependent on the calcium concentration of the solutions. At 10 and 20 mM permeation was significantly higher than that at 1.0 mM (p<0.05). In the presence of prolactin both permeation and absorption increase considerably. At the lowest concentration (1.0 mM) simulating calcium deficiency, there was compensation by the small intestine, suggesting that such deficiency stimulates its mobilization from intestinal tissue. Prolactin enhances the calcium mobilization process even at sufficient calcium intakes. It is suggested that prolactin takes part in regulation of calcium homeostasis in the organism.

Abstract  Slow-healing wounds contain insufficient amounts of intrinsic collagenases to provide sufficient wound debridement, so that the use of products containing synergistic collagenases and proteases may be helpful. We report the successful use of collagenase clostridipeptidase A in two newborns, a premature infant with 3rd degree burns, and a term neonate with an extravasation necrosis caused by calcium gluconate. Surgical excision of necrotic tissue is a serious intervention and prolongs the duration of hospitalization. Enzymatic eschar removal may have an advantage over surgery especially in newborns with a high risk for surgery, with its possible complications, need for anesthesia, and perhaps for blood transfusion.

Abstract  Collagen hydrolysates from porcine bone were prepared using Papain and Flavourzyme, and the degree of hydrolysis was 17.34%. Subsequently, collagen hydrolysates combined with calcium to develop collagen-hydrolysate calcium, and calcium accounted for 4.65%. Wistar rats were given tretinoin for inducing the osteoporosis to investigate prevention of collagen-hydrolysate calcium. Then rats were randomly divided into five groups involved in control group without treatment, model group, low-dose, high-dose and group treated with Calcium Gluconate. Results shown that collagen-hydrolysate calcium can significantly improved bone mass, calcium content and BMD (P<0.05) of thighbone. In the meantime, feeding collagen-hydrolysate calcium with high dose increased significantly phosphorus content and ALP activity (P < 0.05). Histopathologic analysis with paraffin sections in shinbones of low dose and high dose groups, showing symmetrical shinbone trabeculae.

Abstract  UNLABELLED: Bisphosphonates reduce skeletal loss and fracture risk, but their use has been limited in patients with chronic kidney disease. This study shows skeletal benefits of zoledronic acid in an animal model of chronic kidney disease.

INTRODUCTION: Bisphosphonates are routinely used to reduce fractures but limited data exists concerning their efficacy in non-dialysis chronic kidney disease. The goal of this study was to test the hypothesis that zoledronic acid produces similar skeletal effects in normal animals and those with kidney disease.

METHODS: At 25 weeks of age, normal rats were treated with a single dose of saline vehicle or 100 μg/kg of zoledronic acid while animals with kidney disease (approximately 30% of normal kidney function) were treated with vehicle, low dose (20 μg/kg), or high dose (100 μg/kg) zoledronic acid, or calcium gluconate (3% in the drinking water). Skeletal properties were assessed 5 weeks later using micro-computed tomography, dynamic histomorphometry, and mechanical testing.

RESULTS: Animals with kidney disease had significantly higher trabecular bone remodeling compared to normal animals. Zoledronic acid significantly suppressed remodeling in both normal and diseased animals yet the remodeling response to zoledronic acid was no different in normal and animals with kidney disease. Animals with kidney disease had significantly lower cortical bone biomechanical properties; these were partially normalized by treatment.

CONCLUSIONS: Based on these results, we conclude that zoledronic acid produces similar amounts of remodeling suppression in animals with high turnover kidney disease as it does in normal animals, and has positive effects on select biomechanical properties that are similar in normal animals and those with chronic kidney disease.