Abstract  Renal calcification was produced in mice by the administration of parathyroid extract or 10% calcium gluconate. The pattern of renal calcification produced by parathyroid extract differed from that produced by calcium gluconate in four respects: (1) Calcified and (2) necrotic renal tubular epithelial cells formed the background for most of the calcification. This was seen especially at the corticomedullary junction. In addition, there was (3) depletion of alkaline phosphatase activity and (4) thickening of the renal tubular basement membranes in the affected areas. The last two alterations are considered to be nonspecific and secondary to the necrosis of renal tubular epithelial cells. It is suggested that parathyroid extract has a direct effect on renal tubular epithelium and that the calcification is not related either to the hypercalcemia produced by parathyroid extract or the action of parathyroid extract on renal tubular basement membrane. In addition, we found no evidence to support the hypothesis that polysaccharide delivered to the kidney as the result of the action of the parathyroid extract elsewhere in the body, was altered so that it becomes calcifiable.

Abstract  The metabolism of gluconate is well characterized in prokaryotes where it is known to be degraded following phosphorylation by gluconokinase. Less is known of gluconate metabolism in humans. Human gluconokinase activity was recently identified proposing questions about the metabolic role of gluconate in humans. Here we report the recombinant expression, purification and biochemical characterization of isoform I of human gluconokinase alongside substrate specificity and kinetic assays of the enzyme catalyzed reaction. The enzyme, shown to be a dimer, had ATP dependent phosphorylation activity and strict specificity towards gluconate out of 122 substrates tested. In order to evaluate the metabolic impact of gluconate in humans we modeled gluconate metabolism using steady state metabolic network analysis. The results indicate that significant metabolic flux changes in anabolic pathways linked to the hexose monophosphate shunt (HMS) are induced through a small increase in gluconate concentration. We argue that the enzyme takes part in a context specific carbon flux route into the HMS that, in humans, remains incompletely explored. Apart from the biochemical description of human gluconokinase, the results highlight that little is known of the mechanism of gluconate metabolism in humans despite its widespread use in medicine and consumer products.

Abstract  A long-term toxicity experiment was carried out in rats fed a diet containing 40% canned meat treated with either 0-5 or 0.02 % sodium nitrite with or without glucono-8-1actone. This experiment, in which special attention was paid to the detection of a possible carcinogenic effect, was designed to study the possible formation of nitrosamines from nitrite and the secondary amines present in meat, under the conditions of an acid pH and pasteurization. The parameters studied included haematology, clinical biochemistry, histopathology, a-foetoprotein in the serum and the DNA content of the liver cell nuclei. There was no evidence of any preneoplastic change or tumour formation that could be attributed to the feeding of this canned meat.

Abstract  Potassium is a shortfall nutrient according to the 2010 Dietary Guidelines for Americans. Only 3% of Americans meet the recommended Adequate Intake of 4700 mg/d for potassium. Bioavailability of potassium has not been considered in setting requirements as no food has been tested. Among adult potato consumers potatoes provide 19-20% of potassium in the diet. The aim of this study was to compare bioavailability and dose response of potassium from non-fried white potatoes with skin with potassium gluconate. Thirty five healthy, normotensive men and women with a mean age of 29.7 (+/- 11.2) years and BMI of 24.3 (+/- 4.4) kg/m2 (mean +/- (SD)) were enrolled in this single-blind, cross-over, randomized controlled trial. Participants were randomized to 1 of 8 interventions of potassium: 0 (control repeated twice), 720 (~18.5), 1440 (~37), 2160 (~55.5) mg/day (mEq/day) consumed as a potassium gluconate supplement or white potato with skin added to the basal diet containing ~2300 mg/day (~60 mEq/day) potassium. Bioavailability of potassium was determined from AUC of serial blood draws and cumulative urinary excretion. Serum potassium AUC increased with dose (p<0.0001) and did not differ due to source (p=0.52). Cumulative 24 h urinary potassium also increased with dose (p<0.0001) and was greater with potato than supplement (p<0.0001). There were no significant sex differences. Bioavailability of potassium is as high from potatoes as from supplements. Future studies that include fecal potassium measurements will be necessary to determine whether retention varies due to source. This research was funded by the Alliance for Potato Research and Education.

Abstract  Aberration yields were determined from Tradescantia micro-spores subjected to 400 r of X-radiation and pre- or post-treated in chemical compounds. In material irradiated at 30[degree] C, the control yielded 0.24 aberrations per cell while material treated in ATP gave 0.14, in potassium gluconate 0.13, and in 6-phosphogluconate 0.12. Material simultaneously treated in ATP and gluconate gave 0.10. Material irradiated at 40[degree] C gave 0.66 for the controls, 0.19 for ATP, 0.21 for gluconate, 0.23 for 6-phosphogluconate, and 0.17 for the simultaneous treatment with ATP and gluconate. Material irradiated at 0.2[degree] C gave 0.14 for the control 0.10 for ATP, 0.11 for gluconate, 0.09 for 6-phosphogluconate, and 0.10 for the simultaneous use of ATP and gluconate. The postirradiative treatment with ATP or gluconate indicated that these compounds act on the recovery mechanism of radiation damage. Both the glycolytic and the hexose monophosphate pathways appear capable of releasing energy for repair from radiation damage. || ABSTRACT AUTHORS: Auth. summ

Abstract  Introduction: The pathophysiology of potassium imbalances has been a dynamic area of medical research over the years. Controversy exists about the effectiveness and safety of various treatment strategies for hyperkalemia. Areas covered: The following discussion reviews potassium homeostasis, highlights common etiologies responsible for hyperkalemia and describes the associated clinical manifestations. An in-depth discussion about treatment strategies focuses on: i) stabilizing myocardial cell membranes, ii) enhancing cellular uptake of potassium and iii) the removal of excess potassium. The data for safety and efficacy of various therapies are reviewed. Expert opinion: Certain aspects of treating hyperkalemia remain controversial. Serum potassium is tightly regulated within a narrow range and precisely assessing the degree of risk associated with a given degree of hyperkalemia can be difficult. For this reason, it's important to individualize treatment strategies. Concerns regarding the risks of calcium administration in patients with digitalis toxicity continue to impact practice patterns for hyperkalemia. A review of the literature in this area allows us to apply reasonable caution in these situations. Finally, reviewing the incidence of adverse events associated with low potassium dialysate solutions provides insight into the safety of this practice.

Abstract  We have previously shown that local infusion of calcium, but not potassium induces acute necrotizing pancreatitis in the cat. In the present experiments the same experimental set up was used in the rat to test the effect of different divalent cations. MATERIALS AND METHODS: In anesthetized rats weighing 250-350g, the inferior splenic artery was intubated at the tail of the pancreas. Retrograde infusion (flow 0.5-l.Omlih) of Mg++ (MgCI), Ca++ (CaGluconate), Ba++ (BaCI), Mn++ (MnCI) (at 0.6mmolkgh. each), Zn++ (ZnCI, at 0.1,0.06.0.01, and0.002, mmolkgh), and NaCl 0.9% was performed. Groups of four animals were treated for three hours. RESULTS: The pancreas of animals treated with Ca-Gluconate and MnCl showed acute necrotizing pancreatitis with necrosis of acinar lobuli, hemorrhage and leucocytic infiltrates only in the perfused region at three hours. Animals treated with BaCl spontaneously died 49215 minutes after starting the experiment. They also showed pancreatitis in the perfused region, but not in the residual pancreas. ZnCl at doses of 0.1 - 0.01 mmolkgh lead to immediate blood-clotting, obstruction of capillaries, and subsequent ischemic necrosis of the pancreas. Lower ZnCl concentrations (0.002 mmolkgh) induced pancreatitis as seen after calcium. MgCl and NaCl infusion did not induce any changes in pancreas histology Serum calcium levels in Ca-treated rats were 4.0k1.6 mol/L (controls: 2.4?0.2), and serum magnesium levels in Mg-treated rats were 2.8?1.2 mom (controls: 1.320.2). CONCLUSIONS: Local infusion of the divalent cations Ca++, Mn++, Ba++. aild Zn++ leads to acute necrotizing pancreatitis in the rat within three hours, whereas Mg++ has no effect on histological appearance.

Abstract  CONTEXT: Calcitonin (CT) measurement is crucial to the early diagnosis and the follow-up of medullary thyroid cancer (MTC). If the evaluation of stimulated CT levels is required, a provocative test can be performed, being the high-dose Ca test recently reintroduced in clinical practice.

OBJECTIVE: Our objective was to identify gender-specific thresholds for MTC diagnosis in a large series of patients who underwent the Ca test.

PATIENTS AND METHODS: A total of 91 patients (49 females and 42 males) underwent the Ca test (calcium gluconate, 25 mg/kg) before thyroidectomy and both basal CT (bCT) and stimulated CT (sCT) were compared with histological results by receiver operating characteristic plot analyses. To evaluate possible side effects of Ca administration, cardiac function has been extensively studied.

RESULTS: bCT levels were found to harbor the same accuracy as sCT in the preoperative diagnosis of MTC. The best Ca thresholds for the identification of MTC were >26 and >68 for bCT and >79 and >544 pg/mL for sCT in females and males, respectively. The high tolerability and safety of the Ca test was demonstrated and advice offered to be followed before and during the test.

CONCLUSIONS: Gender-specific bCT and sCT cutoffs for the identification of C-cell hyperplasia and/or MTC have been defined. The bCT and sCT were found to have a similar accuracy, indicating that serum CT assays with improved functional sensitivity may likely decrease the relevance of the stimulation test in several conditions. Finally, systematic cardiac monitoring confirms the safety of the Ca test.

Abstract  This book was written to be used by the clinician who deals with pregnant patients. Everyday in an obstetrical, pediatric or other medical practice, one encounters frequent questions about the use of drugs in pregnancy and lactation. These questions may involve the use of a drug for therapy of an associated condition, an inquiry about some drug a patient has already taken and then decides to ask about or the determination if an untoward pregnancy outcome or an adverse effect observed in the infant was caused by the consumption of some therapeutic agent by the patient. Other health professionals, such as nurses and pharmacists, also are often confronted with questions concerning drug usage in the pregnant or breast feeding woman. Of course, this book is of necessity lacking in giving absolute answers on most drugs in question because experience in humans is not easy to gather. One seldom knows, even when the drug history is thought to be realistic, whether there is an actual cause-effect relationship between a specific drug and an adverse pregnancy outcome. Because the answers are generally inconclusive, physicians caring for pregnant patients should counsel their patients accordingly either when answering a question about some drug already ingested or when explaining the cost/benefit ratio to a patient who is being considered for some specific drug therapy. For the breast feeding patient, the risks from a particular drug are usually much clearer although there are frequent examples where the risk must be inferred from related drugs. Unfortunately, many drugs have not been studied during nursing so the effects on the infant, if any, are completely unknown. A good rule to follow is if the drug can safely be given directly to the infant, it is generally safe to give to the mother during lactation. This book allows the clinician to have at his or her fingertips an up-to-date summary of available data bearing on specific drugs. It is easy to read and organized in a logical manner to save the busy clinician time.

Abstract  Eight psychrotolerant, xylan-degrading strains of bacteria that were catalase-positive, oxidase-negative and able to reduce nitrate to nitrite were isolated from soil beneath moist non-acidic and acidic tundra in northern Alaska. The DNA G+C contents for the strains ranged from 46.4-50.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that each strain belonged to the genus Paenibacillus. The highest level of 16S rRNA gene similarity was found between the eight strains and Paenibacillus amylolyticus NRRL NRS-290(T) (98.9-99.1 %). However, despite relatively high 16S rRNA gene similarity, DNA-DNA hybridization, repetitive elements genotyping and phenotypic analysis revealed that at least two of the strains differed from P. amylolyticus NRRL NRS-290(T). DNA-DNA hybridization values between strain A10b(T) and P. amylolyticus NRRL NRS-290(T) (4.3 %), between strain B22a(T) and P. amylolyticus NRRL NRS-290(T) (48.8 %) and between strain A10b(T) and strain B22a(T) (11.0 %) were below those recommended by the ad hoc committee for those belonging to the same species. Significant phenotypic features that differentiate these novel strains from P. amylolyticus included their inability to utilize l-arabinose and ability to utilize glycogen as sole carbon sources. Unlike strains 1B4a and B22a(T), strains A6a and A10b(T) produced ethanol as an end product of glucose fermentation, utilized acetic acid and 2,3-butanediol and did not utilize d-gluconic acid. MK-7 was the major isoprenoid quinone and anteiso-C(15 : 0) was the most abundant fatty acid for strains A10b(T) and B22a(T). On the basis of these results, strains A10b(T) and B22a(T) are each considered to represent a novel species of the genus Paenibacillus, for which the names Paenibacillus tundrae sp. nov. and Paenibacillus xylanexedens sp. nov. are proposed, respectively. The type strain of Paenibacillus tundrae sp. nov. is A10b(T) (=NRRL B-51094(T)=DSM 21291(T)). The type strain of Paenibacillus xylanexedens sp. nov. is B22a(T) (=NRRL B-51090(T)=DSM 21292(T)).

Abstract  The calcium-sensing receptor (CaSR) has been detected in human antral gastrin-secreting cells, where, upon calcium and/or amino acid allosteric activation, it stimulates gastrin secretion. Patients with absorptive hypercalciuria (AH) display an enhanced gastric acid output; therefore, we evaluated the secretion of gastrin in subjects with AH (30 subjects vs. 30 healthy female controls, all postmenopausal) after oral calcium administration (1 g calcium gluconate) and, on a separate occasion, after peptone loading test (protein hydrolyzed, 10 g). Gastrin and monomeric calcitonin responses were higher in AH after both oral calcium administration (P < 0.01) and peptone loading (P < 0.01). Because the activation of CaSR by oral calcium and peptones directly induces gastrin release, the higher gastrin responses to these stimuli suggest an increased sensitivity of gastrin-secreting cells CaSR in patients with AH. A similar alteration in thyroid C cells might explain the enhanced calcitonin responses to both calcium and peptones. If the same alterations should in addition be present in the distal tubule (where CaSR is expressed as well), then a possible explanation for amino acid-induced hypercalciuria in AH would have been identified.