Abstract  Aim: The investigation of a genotoxic activity of the test item Gluconic acid technical 50/50 (batch SX4G6)provided by Members of the Gluconic Acid and its Derivatives REACH Consortium has been carried out in compliance with the OECD Guideline 473 (2014), using test for chromosome aberration by in vitro human lymphocyte metaphase analysis. Methods: In the experimental conditions with metabolic activation (5% of S9-mix) or without metabolic activation (4-hour treatment), no cytotoxicity was noted at the highest concentration tested of 10 mM, with 103.6 and 88.4% of mitotic index compared to the control, respectively. The concentration of 10 mM was retained as the maximum concentration to be tested in the assay with 5% of S9-mix and without metabolic activation following the 4-hour treatment. In return, when using a 20-hour treatment, a strong cytotoxicity was noted at the highest concentration tested of 10 mM, with 21% of mitotic index compared to the control. The immediately lower concentration of 5 mM induced a moderate cytotoxicity, with 63.8% of mitotic index compared to the control. Under these conditions, the concentration of 10 mM was retained as the maximum concentration to be tested in the assay without metabolic activation following the 20-hour treatment, but a narrowed range of concentrations was performed in order to reach a concentrations inducing 55±5% of cytotoxicity. Results: The test item Gluconic acid technical 50/50 did not induce any statistically significant increases in the frequency of aberrant cells excluding or including gaps or in the number of breaks per cell in the 4- hour treatment and in the 20-hour treatment without metabolic activation and in the 4-hour treatments with 5 % of S9-mix in human lymphocytes. Otherwise, no statistically significant increases in the number of cells with numerical aberrations were noted both with and without metabolic activation using a long or a short-term treatment.

Abstract  Since a pharmacological dose of prolactin has previously been reported to enhance calcium absorption and bone calcium turnover, the role of endogenous prolactin in the regulation of calcium metabolism was investigated in the balance studies of Wistar rats between days 17 and 20 of first (P1) and fourth (P4) pregnancy and between days 12 and 15 of lactation (L). Each group was divided into 3 subgroups: one subgroup was given 0.9% NaCl (control); one was given 0.3 mg bromocriptine/100 g body weight ip twice daily for 3 days (to suppress prolactin secretion); and one was given bromocriptine and 0.25 mg prolactin/100 g body weight sc daily for 3 days. All three groups received 1 mL/100 g body weight of 1.25 mM calcium gluconate containing 2 mCi (1 Ci = 37 GBq) Ca-45 daily for 3 days. Compared with the two pregnant controls, the L group had higher food consumption and higher fecal calcium excretion and lower urinary calcium excretion (% intake). Bromocriptine administration increased total calcium excretion from 59% intake to 84 and 66% intake in P1 and P4, respectively, suggesting that endogenous prolactin decreased total calcium excretion. On the other hand, exogenous prolactin had no effect on the calcium balance of P1 but increased the total calcium excretion in P4 from 57 to 66% intake. In contrast, the calcium balance of lactating rats was not altered by suppression of endogenous prolactin secretion or exogenous prolactin. Considering bone Ca-45 content as representing bone Ca turnover, a lower value of bone Ca-45 content indicated an accelerated bone Ca turnover. It was found that bromocriptine had no effect in P1 but decreased bone Ca turnover rate in the P4 and L groups, indicating an accelerating effect of endogenous prolactin on bone Ca turnover in the P4 and L groups. Exogenous prolactin, on the other hand, decreased bone Ca turnover rate in every group. Muscle Ca turnover was affected by bromocriptine and exogenous prolactin in the same manner as bone Ca-45 contents. Interestingly, the biphasic action of prolactin was demonstrated in both calcium absorption and bone calcium turnover. It could be concluded that during pregnancy and lactation, endogenous prolactin increases food consumption, fractional calcium absorption, and bone calcium turnover, apparently to increase calcium availability for fetal development and mill; calcium secretion.

Abstract  STUDY OBJECTIVE: Parenteral calcium is frequently administered to critically ill patients. However, animal studies demonstrate that calcium administration during critical illness heightens inflammation and leads to shock, organ dysfunction, and mortality. We sought to evaluate the association between calcium administration and adverse outcomes in critically ill patients receiving parenteral nutrition (PN).

DESIGN: Retrospective cohort examined before and during a calcium gluconate shortage. During the shortage, calcium was absent from PN, but calcium supplementation outside of PN was allowed. The shortage resulted in a natural experiment that included a group of patients who did not receive calcium.

SETTING: Intensive care units (ICUs) in three teaching hospitals.

PATIENTS: A total of 259 adults who received PN in the ICU for 48 hours or longer.

MEASUREMENTS AND MAIN RESULTS: Patients were divided into quartiles based on amount of parenteral calcium received; the lowest quartile received no calcium. End points were in-hospital mortality, acute respiratory failure, new-onset shock, and a composite of any one of these end points. For patients not on mechanical ventilation or vasoactive support when PN started, logistic regression revealed that calcium administration was associated with mortality (odds ratio [OR] 2.48, 95% confidence interval [CI] 1.08-5.69), acute respiratory failure (OR 2.43, 95% CI 1.28-4.60), new-onset shock (OR 2.81, 95% CI 1.22-6.44), and the combined end point (OR 2.33, 95% CI 1.31-4.16). The odds of adverse outcomes increased as the calcium dose increased.

CONCLUSION: Calcium administration correlated with adverse outcomes in critically ill patients receiving PN. The data suggest that administration of parenteral calcium to critically ill patients may be harmful.

Abstract  This study was performed to determine how the calcium supplementation for a 4-week period affects the glucose and insulin levels at rest and at exhaustion in athletes. This is a 4-week study performed on 30 healthy subjects varying between 18 and 22 ages. Subjects were separated into three groups: first group (group supplemented with calcium, sedentary group), second group (calcium supplementations + exercise group), and third group (training group). Glucose and insulin parameters of the groups were measured four times, at rest and exhaustion in the beginning of the research and at rest and exhaustion after the end of 4 weeks application period. Exhaustion measurements both before and after the supplementations significantly decreased in compared to rest measurements in terms of insulin (p < 0.05). Significant difference was not determined in the glucose values of groups. In terms of glucose, values increased in all of the three groups occurred with exercise both before and after the supplementation by exercise and exhaustion (p < 0.05). The results of our study indicate that calcium gluconate supplementations for 4 weeks in sedentary subjects and athletes did not significantly affect plasma insulin levels at rest and exhaustion. However, glucose levels were affected by calcium supplementation and exhausting exercise in athletes.

Abstract  Gluconate was fermented selectively by the Bifidobacterium adolescentis group and some species of other genera, including Clostridium clostridiiforme, C. innocuum, Propionibacterium acnes, Megasphaera elsdenii, Enterococcus faecium and Klebsiella pneumoniae; however it was not utilised by most other bacteria including the Bacteroidaceae. No other organic acid salts were utilised by B. adolescentis. These salts weakly inhibited the growth of C. perfringens in vitro, as did gluconate. The absorption rate of gluconate from the ligated small intestinal loop in rats was 19.9 per cent under conditions when 100 per cent of glucose was absorbed. The effects of ingestion of gluconate on human faecal bacteria was studied in ten healthy adult males. They ingested 9 g/d or 3 g/d of glucono-delta-lactone (anhydride of gluconic acid). With the 9 g/d ingestion, the number of bifidobacteria significantly increased (P<0.001), whereas C. perfringens decreased and Enterobacteriaceae remained constant. The concentrations of bifidobacteria also increased (P<0.05) following 3 g/d ingestion.

Abstract  BACKGROUND: The clinical use of autologous platelet concentrates (also known as platelet-rich plasma) on the field of regenerative therapy, in the last decade has been the subject of several studies especially in equine medicine and surgery. The objectives of this study was: 1) to describe and compare the cellular population in whole blood, lower fraction (A) and upper fraction (B) of platelet concentrates, 2) to measure and compare the transforming growth factor beta 1 (TGF-β1) concentration in plasma and both platelet concentrates after be activated with calcium gluconate or batroxobin plus calcium gluconate and, 3) to determine correlations between cell counts in platelet concentrates and concentrations of TGF-β1. Blood samples were taken from 16 dogs for complete blood count, plasma collection and platelet concentrates preparation. The platelet concentrates (PC) were arbitrarily divided into two fractions, specifically, PC-A (lower fraction) and PC-B (upper fraction). The Platelet concentrates were analyzed by hemogram. After activated with calcium gluconate or batroxobin plus calcium gluconate, TGF-β1 concentration was determined in supernatants of platelet concentrates and plasma.

RESULTS: There were differences statistically significant (P < 0.05) for the platelet count and leukocyte count and TGF-β1 concentration between whole blood, plasma and both platelet concentrates. A significant correlation was found between the number of platelets in both platelet concentrates and TGF-β1 concentration. Platelet collection efficiency was 46.34% and 28.16% for PC-A and PC-B, respectively. TGF-β1 concentration efficiency for PC activated with calcium gluconate was 47.75% and 31.77%, for PC-A and PC-B, respectively. PC activated with batroxobin plus CG showed 46.87% and 32.24% for PC-A and PC-B, respectively.

CONCLUSIONS: The methodology used in this study allows the concentration of a number of platelets and TGF-β1 that might be acceptable for a biological effect for clinical or experimental use as a regenerative therapy in dogs.

Abstract  IPA COPYRIGHT: ASHP The case of an infant who developed idiopathic infantile hypercalcemia in the postnatal period while receiving breast milk and calcium gluconate supplements is reported. The mother was taking ergocalciferol (vitamin D2) supplements (400 U/day) since early in pregnancy. Breast feeding was continued but all vitamin D supplements were stopped and the infant was given prednisone (0.5 mg/kg; I) 2 times/day. The serum calcium concentration decreased from 17.6 to 13.6 mg/dl. In an attempt to promote growth I therapy was reduced and 5 units of thyrocalcitonin (Calcimar; calcitonin; II) was injected SC each morning and 0.5 g cellulose sodium phosphate (Calcibind; III) was given orally 5 times a day before feeding. It was concluded that daily II injection to reduce ongoing flux of calcium from the bone to blood and III to reduce absorption of dietary calcium may be successful in maintaining normocalcemia while permitting discontinuation of I.

Abstract  The combination use of dexamethasone and calcium gluconate can be applied to hypersensitivity. Severe hypokalemia is a usual complication of dexamethasone and calcium gluconate therapy, which occurs frequently with therapeutic use. Fatal cases, accidental and intentional, occur frequently in forensic practice. The current case report presented a 43-year-old man with diabetes mellitus with infection, to whom dexamethasone and calcium gluconate were administered in the private clinic. With the development of such clinical symptoms of severe hypokalemia as quadriplegia, he was confirmed to have severe hypokalemia through a biochemical test before dying of arrhythmia. And also it presented pathophysiologic mechanism underlying severe hypokalemia as well as suggestions for clinical practice regarding combination use of dexamethasone and calcium gluconate.

Abstract  OBJECTIVE: A calcium load to suppress parathyroid hormone (PTH) secretion can help to perform the diagnosis in some case of primary hyperparathyroidism (PHPT) with atypical presentation. A similar test with calcimimetic, which avoids hypercalcaemia, would be of interest. Our proof of concept study was conducted to compare firstly the results of a single-dose cinacalcet testing with those of the standardized short-time calcium load in healthy control (HC) and secondly the results of the single-dose cinacalcet testing in HC and in PHPT.

METHODS: Twelve HCs received in a random order, at a 2-week interval, either 0·33 mmol/kg calcium gluconate intravenously for 3 h, or a single oral dose of 30 mg or 60 mg cinacalcet. Twelve PHPTs received 30 mg cinacalcet and twelve other PHPTs 60 mg cinacalcet orally. Calcaemia and serum PTH levels were measured basally and then hourly for 6 h.

RESULTS: In HC, plasma calcium did not significantly change after cinacalcet intake, whereas calcaemia rose up to 3·47 ± 0·05 mmol/l (mean ± SEM) at the end of the calcium load. PTH dropped from basal level to a similar extend (≥80%) with 60 mg cinacalcet and calcium load, whereas the decrease was significantly lesser (P < 0·01) with 30 mg cinacalcet. In PHPT, serum PTH levels dropped by 44·8 ± 6·9% and 58·2 ± 5·3% 1 h after the respective intake of 30 and 60 mg cinacalcet. One hour after the oral intake of 60 mg cinacalcet, serum PTH levels were <8 ng/l in HC and ≥8 ng/l in PHPT.

CONCLUSION: Sixty milligrams of cinacalcet provides similar results as the standardized calcium load test; PHPT patients have a lower response to 60 mg cinacalcet than HC.

Abstract  Calcium binding kinetic by tissue structures was analysed in 19 health volunteers (13 men and 6 women) of the age group of 33 +/- 6.5 under conditions of acute hypercalcaemia followed by a drip i.v. infusion of calcium gluconate over 2.5 hours. At the end of each 30-minute period the calcium amount retained by tissue structures was recorded and the kinetic parameters of calcium binding were determined according to Langmuir and Scatchard. In all volunteers there was a segment of binding isotherm with positive cooperativity (direct regression in Scatchard) with analogous buffer capacity (beta) for calcium in Langmuir (0.58 +/- 0.24 L kg). One half of volunteers demonstrated cooperativity at [Ca++] 1.3-1.5, while another--at [Ca++] 1.0-1.3 mmol/L which corresponded to the differences in the association constant (Ka) and the number of interactive sites (n) with [Ca++] 1 mmol/L. Additionally, two segments of binding isotherm were detected with the successive binding of calcium to one set of noninteractive sites with similar kinetic parameters of calcium binding (beta, K(a), n). Four different curves of calcium binding in healthy volunteers were established. This study may serve as the basis for a functional diagnostic test of disorders of the tissue calcium-binding properties in different pathological conditions.

Abstract  The object of this study was to obtain acute oral toxicity information of Polycalcium, a mixed composition of Polycan and Calcium lactate-gluconate 1:9 (g/g), in Sprague-Dawely (SD) rats. In order to investigate the toxicity and identify target organs, Polycalcium were once orally administered to female and male SD rats at dose levels of 2000, 1000, 500 and 0 (control) mg/kg body weights. The mortality, changes on body weight and clinical signs were monitored during 14 days after treatment with gross observation, changes on the organ weights and histopathology of principle organs and treatment sites based on the recommendation of KFDA Guidelines [2009-116, 2009]. As the results of single oral treatment of Polycalcium, no treatment related mortalities were observed within 14 days after end of treatment up to 2000 mg/kg, the limited dosage of rodents in the both genders. In addition, no Polycalcium treatment related changes on the body and organ weights, clinical signs, necropsy and histopathological findings were detected. The results obtained in this study suggest that the Polycalcium is non-toxic in rats. The LD50 and approximate LD in rats after single oral dose of Polycalcium were considered over 2000 mg/kg in both female and male, respectively.

Abstract  Alpha hydroxy acids (AHA's) or "fruit acids" are a special group of organic acids found in many natural foods. They have been described in the literature for the treatment of a number of conditions in which abnormal keratinization consistently contributes to pathogenesis. These include the icthyoses, warts, psoriasis, eczema and acne. We have performed a double-blind clinical trial on 150 patients to evaluate the efficacy and skin tolerance of the alpha hydroxy acid gluconolactone 14% in solution (Nuvoderm lotion) in the treatment of mild to moderate acne when compared with its vehicle (placebo) and 5% benzoyl peroxide lotion. The results of this study showed that both gluconolactone and benzoyl peroxide had a significant effect in improving patients' acne by reducing the number of lesions (inflamed and non-inflamed). Furthermore, fewer side-effects were experienced by patients treated with gluconolactone when compared with benzoyl peroxide.

Abstract  Cell composition of the parathyroid gland was studied under normal conditions, after the hypo- or hyperloading with calcium gluconate and at hyperfunction. Three types of parathyrocytes were established that probably reflect different stages of their life cycle: the first--poorly differentiated cell, the second--mature differentiated cell and the third--degenerated cell. The majority of cells were represented by the parathyrocytes of the 2nd type the varieties of which reflect a non-active (A-subtype) and active (B-subtype) phases of secretion. The number of A-cells is increased under the condition of the hyposecretion and the relative number of B-cells under the condition of experimental hypersecretion.

Abstract  Effect of potassium gluconate (K-GL) on K+ uptake of rat erythrocytes was investigated. K-GL produced a significant increase in active K+ transport of Na+-rich erythrocytes, while Na+,K+-ATPase activity of hemoglobin-free ghosts without a glycolytic system was unaffected. When the experiment was carried out in intact erythrocytes, K-GL increased the lactate production and ATP content, and it promoted the methemoglobin reduction rate. In Na+-rich erythrocytes, the glycolysis inhibitors which produced a marked reduction in lactate content abolished the K-GL-induced increase in K+ and ATP content without affecting the KCl-induced increase. These results suggest that K-GL enhances K+ transport of erythrocytes through acceleration of glycolytic process.

Abstract  Parenteral calcium may augment the degree of calcification within brains of human neonates (p less than 0.01). This observation is supported by histochemistry, atomic absorption of ashed brain, selected area diffraction, and energy dispersive microanalysis. Survival analysis indicates that a standard replacement dose may have an adverse effect of severely stressed neonates (p less than 0.01). Nuclei within the optic-tract, circumferential pons and temporal lobe showed calcium salt deposits before other cytologic evidence of necrosis was discernible. Most calcification occurred in regions of ongoing necrosis primarily in the neuropil. But Purkinje cell and supraoptic neurons and apparent neurons from the fascia dentata, Ammon's Horn, were densely calcified in several brains. In those infants surviving longer periods both the neuropil and nuclei of glial scar stained for calcium salts.