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  Environmental Effect of Photoprocessing Chemicals Vol I and II (557).

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  From previous work, it was observed that during growth on mixtures of acetate and aldose sugars the growth yield of the bacterium Acinetobacter calcoaceticus was increased when aldonolactone hydrolysis occurred. In this paper, the underlying mechanism was investigated by studying the relationship between cellular yield and lactone hydrolysis in a quantitative way. The literature on the kinetics of acid formation from aldonolactones was reviewed. It appears that the reaction pattern is composed of lactone isomerization and hydrolysis steps which occur in series. In the acid pH range, lactone interconversion is the rate-limiting step for acid formation, whereas above pH 7 hydrolysis is slowest. Only for D-gluconolactone could the detailed mechanistic kinetics be evaluated. For a number of other aldonolactones, including D-xylono- and D-galactonolactone, an empirical kinetic equation was derived. The reaction rate constants of these lactones are much smaller than for gluconolactone. The kinetic model for the hydrolysis of xylonolactone was experimentally verified, by application of the electrical charge balance to measurement data from A.calcoaceticus cultures. Comparison of the published biomass yield data and the calculated rate of lactone hydrolysis revealed that they do not quantitatively agree. It can be concluded that the observed relation between biomass yield and lactone hydrolysis is only apparent. The results demonstrate the power of the electrical charge balance in the study of processes in which charged compounds are being converted.

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.

Abstract  The objective of this study was to evaluate the effect of adding antibiotics, probiotics, prebiotics, symbiotic and sodium gluconate for swine from 28 to 142 days of age, corresponding to the nursery, growing and finishing phases. One hundred and sixty-eight piglets were used weaned at 21 days in a randomized complete design in 42 pens with four male piglets in each experimental unit with six replications and seven treatments: control basal feed; basal feed + antibiotic; basal feed + probiotic; basal feed + prebiotic; basal feed + probiotic + prebiotic (symbiotic); basal feed + sodium gluconate; basal feed + sodium gluconate + probiotic. The animals performance differed among he treatments and was best in the animals that received feed with additive from 28 to 142 days of age. Among the feeds with additive, symbiotic was more efficient, presenting the best results in weight gain and feed conversion. Similarly, the addition of sodium + probiotic, prebiotic and probiotic in the feeds was more efficient than antibiotic addition. The use of the evaluated additives substituting the antibiotics did not harm the or the intestinal morphometry. The combination of probiotic and prebiotic (symbiotic) improves the swine performance in the nursery, growing and finishing phases.

Abstract  Acute toxicity of four relatively new chelating agents and their equimolar manganese and cadmium complexes was studied. The chelating agents studied were gluconic acid (GA), beta-alaninediacetic acid (ADA), diethylenetriaminepentakismethylenephosphonic acid (DTPMP), and nitrilotriacetic acid (NTA). Three common bioassays, namely Daphnia magna, Raphidocelis subcapitata, and Photobacterium phosphoreum (Microtox bioassay) were applied. R. subcapitata proved the most sensitive to these compounds. With D. magna bioassay the LC(50) values were 600-900 mg/L with all other studied chelates and their Mn complexes, except Mn-GA, which yielded LC(50) value of 240 mg/L. The Cd-chelate complexes proved highly more toxic compared to Mn-chelate complexes or uncomplexed chelates exhibiting LC(50) values of 130-200 microg/L. However, Cd-DTPMP was an exception exhibiting LC(50) value of 2170 microg/L. That is to say, DTPMP proved the strongest chelating agent to reduce the Cd toxicity in the present study. The results from these bioassays were well in agreement to each other as well as with the results published elsewhere.

Abstract  An in vitro model was used to simulate the intestinal permeation of calcium ions depending on the type of salt (carbonate, fumarate, citrate, or gluconate), its concentration (1.0, 2.5, 5.0, or 10 mM/l), and pH (1.3, 4.2, 6.2, or 7.5). To simulate the conditions for calcium permeation in a patient in a fasting state, the solutions were placed in contact with segments of small intestine of pig: stomach, duodenum, jejunum, and ileum. The percent permeation, its rate, and half-time were measured in each case. In all cases, the maximum permeation was seen at 1 mM concentration, depending on pH: 100% for carbonate at pH 1.3; 82% for fumarate, pH 6.2; 79.5% for citrate at pH 4.2, and 81% for gluconate at pH 7.4. The maximum rate of permeation (% h(-1)) was also observed at 1 mM: 2.16 for carbonate at pH 1.3, 0.29 for fumarate at pH 6.2, 0.26 for citrate at pH 4.2, and 0.28 for gluconate at pH 7.4. The shortest half-time permeation (t (1/2), h) for 1 mM solutions depended also on pH (in parentheses): carbonate 0.3 (1.3), fumarate 2.4 (6.2), citrate 2.6 (4.2), and gluconate 2.5 (7.4). The results suggest that calcium carbonate and citrate can be recommended to patients with normal gastric acidity and hyperacidity while fumarate and gluconate to patients with hypoacidity.

Abstract  Calcium supplementation is widely used in deficiency status and as an adjuvant in the treatment of osteoporosis. The objective of this study was to compare the oral bioavailability of calcium from tablets containing calcium fumarate to that of calcium gluconate. Twelve healthy volunteers participated in the study. Single-dose, two-treatment, two-sequence-crossover, randomized design test methodology was applied. The tablets were prepared by direct compression and were subjected to tests: drug content, hardness, friability, disintegration time and in vitro dissolution studies. The preparations were compared using pharmacokinetic parameters such as the area under the plasma concentration - time curve AUC((0-11)), peak plasma concentration C(max), time to reach maximum plasma concentration T(max). No statistically significant difference was observed for any of the parameters, and the 90% confidence intervals calculated for the ratio of the logarithmically transformed AUC((0-11)) values of both formulations were within the bioequivalence limit of 0.80-1.25. It can be concluded that the two tablet preparations of calcium are likely to be bioequivalent.

Abstract  Investigations of the effects of plasma calcium concentration on the relationship between biliary secretion of bile acid and calcium were performed in normocalcemic, calcium gluconate-induced hypercalcemic, thyroparathyroidectomy-induced hypocalcemic (TPTX) rats, and TPTX rats that received calcium gluconate to maintain normocalcemia. Studies were done at normal bile flow and at sodium taurocholate-stimulated bile flow. The results showed that biliary calcium secretion, which could occur in the absence of parathyroid hormone and calcitonin, was dependent mainly on plasma calcium concentration and was only partly influenced by bile acid secretion. Concerning the route of biliary calcium secretion, 80% was by the transcellular pathway and 20% was by the paracellular pathway. During theophylline-stimulated bile-acid-independent bile flow, the increase in bile-acid-independent calcium was found to be secreted by both pathways.

Abstract  Whether ingested calcium is absorbed more efficiently from freely water-soluble calcium salts than from poorly soluble salts is unclear. It is also unknown whether calcium is absorbed better from dairy products than from calcium salts. Using a method by which the net absorption of calcium can be accurately measured after a single dose, we studied eight healthy fasting subjects after they took a 500-mg dose of calcium from each of five calcium salts with various degrees of water solubility and from milk. The order of administration of the agents given was randomly determined. The mean (+/- SEM) net calcium absorption, in decreasing order of the solubility of the salts, was 32 +/- 4 percent from calcium acetate, 32 +/- 4 percent from calcium lactate, 27 +/- 3 percent from calcium gluconate, 30 +/- 3 percent from calcium citrate, and 39 +/- 3 percent from calcium carbonate. The differences in absorption were not statistically significant according to analysis of variance. On the basis of in vitro solubility experiments in acid mediums, we hypothesize that acid dissolution in the gastrointestinal tract may be responsible for the similar absorption of calcium from salts with widely different water solubilities. Calcium absorption from whole milk (31 +/- 3 percent) was similar to absorption from calcium salts. We conclude that calcium absorption from carbonate, acetate, lactate, gluconate, and citrate salts of calcium, and from whole milk, is similar in fasting healthy young subjects. Further study will be required to determine whether the results would be different in older subjects, with a higher dose of calcium, or if the calcium was ingested with food.