Abstract  Low total blood calcium concentration after calving has been demonstrated to be a risk factor for reduced neutrophil function. The objective of this study was to evaluate whether administration of an injectable calcium supplement product soon after calving increased neutrophil oxidative burst or phagocytosis capacity. Cows (n = 27) from 4 farms were blocked by parity and randomly assigned to receive either calcium gluconate (35% wt/vol) in combination with calcium glucoheptonate (10% wt/vol; Theracalcium, Vétoquinol Canada Inc., Lavaltrie, Quebec, Canada) or a placebo within 12 h after calving and again 24 h later. Each dose of 120 mL was injected subcutaneously over 2 sites. Total serum calcium concentration, neutrophil oxidative burst, and neutrophil phagocytosis capacity were measured from coccygeal blood samples before (time 0) and 72 h after first treatment. There was no difference between treatment groups in lactation number, total calcium concentration, oxidative burst, or phagocytosis at time of enrollment. There was no effect of treatment on oxidative burst or phagocytosis by neutrophils. This preliminary study does not support an effect of supplemental calcium to improve neutrophil oxidative burst or phagocytosis capacity of low-parity parturient cows.

Abstract  To evaluate the effect of various anesthetic agents on hyperosmolar blood-brain barrier disruption (BBBD), Sprague-Dawley rats were given pentobarbital (PB), ketamine-xylazine (KX), isoflurane (IF), methoxyflurane (MF), or fentanyl-droperidol (FD) before intracarotid infusion of mannitol or saline. Physiological monitoring showed that the effects of mannitol infusion differed significantly from those of saline infusion and were associated with transient bradycardia, hypotension, metabolic acidosis, and electroencephalographic depression. With PB, KX, or IF anesthesia, we obtained excellent BBBD as evidence by 3+ Evans blue staining of the mannitol-infused cerebral hemisphere. FD anesthesia was associated with tachycardia and MF anesthesia resulted in hypotension; both showed poor Evans blue staining. Radioisotope delivery to the disrupted hemisphere averaged 0.80% of the administered 125I-albumin compared to 0.03% in the contralateral and 0.06% in control (saline-infused) hemispheres. 99mTc-glucoheptonate delivery measured 0.49% of the administered dose after BBBD, 0.03% contralaterally, and 0.05% in control hemispheres. Pharmacological manipulation to normalize the cardiac index in the FD and MF groups resulted in 3+ Evans blue staining and significantly increased delivery of albumin and glucoheptonate. This study suggests that the cardiovascular changes of these specific anesthetic agents are important in obtaining optimal hyperosmolar BBBD.

Abstract  This study attempted to evaluate the role of glucoheptonate (GHA) in captopril renography in an in vivo laboratory investigation in which postcaptopril glucoheptonate uptake was analysed in awake 2KlC hypertensive rats. Clamped kidney uptake in a previous study was greater in the poststenotic kidney than in the normal kidney (P = 0.01) in rats with mild renal artery stenosis. A glucoheptonate renogram protocol was developed for use in rats anaesthetized with sodium pentobarbital. An 123I-hippuran scan was performed to determine the relative renal function, followed by a control 99Tcm-GHA scan. Five minutes after administering captopril, another 99Tcm-GHA scan was performed. Relative renal uptake was determined between 30 and 90 s postinjection. 99Tcm-GHA uptake in the clamped kidney was more than 50% of total uptake in 3/9 of the abnormal rats' control scans. No abnormal rats clamped kidney 99Tcm-GHA uptake was greater than 50% in the postcaptopril scans. Captopril reduced GHA uptake in all nine of the animals with baseline scans. These findings suggest that the laboratory observation of captopril induced paradoxically increased 99Tcm-GHA uptake in renal artery stenosis may not be observed scintirenographically. Moreover, the data support a potential value of glucoheptonate in captopril renography.

Abstract  Trials were carried out to compare the efficacy of copper heptonate with other available therapeutic products. On nine farms with a copper deficiency problem, over 2000 ewes were treated in mid-pregnancy. All the treatments increased whole blood copper levels and plasma caeruloplasmin (ferroxidase) activity in ewes, and protected their lambs from swayback. The lambs from ewes treated with copper heptonate and copper oxide needles had significantly higher blood copper levels than lambs from untreated control ewes. Treatment with copper heptonate was shown to have a therapeutic index of at least 5 in Swaledale ewes of normal copper status. In two groups of Welsh mountain sheep from different backgrounds, both with normal blood copper levels before treatment, the therapeutic indices were 3 to 5.

Abstract  Conventional renal diagnostic agents, [131I]hippuran, [99mTc]glucoheptonate (GHA), and [99mTc] dimercaptosuccinate (DMS) were compared with [99mTc] or [111In] diethylenetriaminepentaacetic (DTPA) for the detection of glomerular damage in rats compared with controls. The glomerular lesions were induced by the i.v. injection of puromycin aminonucleoside (PA) 9 days before the radionuclide studies, a model of spontaneous "minimal change" glomerulonephritis in humans. Computer-generated early renal uptake of [99mTc]DTPA or GHA correlated with the glomerular filtration rate (GFR) quantitated by biexponential plasma clearance of DTPA administered by single i.v. injection. The early renal uptake of hippuran and DMS correlated poorly with GFR as assessed by DTPA clearance. However, the 2-hr renal retention of DMS correlated well with the DTPA clearance. None of the parameters measured with [131I]hippuran correlated well with DTPA clearance, probably because of decreased protein plasma binding of hippuran secondary to hypoproteinemia in this experimental model. It was concluded that none of these agents was superior to labeled DTPA for the detection of glomerular damage in this experimental model.

Abstract  Calcium gluconate glucoheptonate (GGCa) is known to interact with glass containers, leading to the leaching of aluminum from the glass into the solution at toxic level. Therefore, plastic containers seem to be a preferable packaging alternative. Nevertheless, plastics contain potentially toxic additives which could be released into the solution. In order to study content container interaction between GGCa and two plastic containers (polypropylene PP and polyethylene PE containers), an HPLC-PDA method was developed to separate, detect and quantify eleven additives commonly found in plastic materials, with good limit of detection and quantification. This method was then applied to evaluate the compatibility between GGCa and the two plastic containers. After 3 months of storage at 25 °C, none of the eleven additives were detected in GGCa solutions. The safety concern threshold (SCT) and of the analytical evaluation threshold (AET) were evaluated to discriminate the need to identify and qualify unknown peaks.

Abstract  Recently, [Tc-99m]TRODAT-1, the first Tc-99m-labeled tracer for imaging CNS dopamine transporters in humans, was reported. This tracer displayed excellent specific binding to dopamine transporters in the basal ganglia region of the brain, thus it is potentially useful for the diagnosis of deficit of dopamine transporters in neurodegenerative diseases, such as Parkinson's disease. Preparation of [Tc-99m]TRODAT-1 was previously achieved by a multistep kit formulation. It is highly desirable to further improve the preparation by developing a simplified one-vial formulation with a reduced amount of TRODAT-1 ligand for routine clinical use. To achieve this goal, a series of studies to optimize labeling efficiency by varying a combination of factors (amount of free ligand, reaction reagents, and reaction pH) was carried out. [Tc-99m]TRODAT-1 prepared by this new kit formulation was evaluated by assessing the brain uptake and target (striatum) versus nontarget (cerebellum) ratios in rats. Appropriate amounts of various ingredients for a one-vial kit formulation providing > or =90% radiolabeling yields were identified. The most consistent and reliable formulation contained 10 microg of TRODAT-1 (a reduction of free ligand from 200 microg to 10 microg), 32 microg of SnCl2, 10 mg of sodium glucoheptonate, and 840 microg of disodium EDTA in one vial as a lyophilized kit. It is feasible to reconstitute the vial with [Tc-99m]pertechnetate (0.5-2 mL, < or =1110 MBq, 30 mCi), resulting in a final solution with a pH value of 4.5-5.0. [Tc-99m]TRODAT-1, prepared by this new kit, was stable at room temperature for 6 h. Biodistribution studies of this agent in rats with the new formulation showed similar regional brain distribution as compared with those obtained with the previous preparation (high striatum-to-cerebellum ratio). In conclusion, using this lyophilized one-vial kit formulation, [Tc-99m]TRODAT-1 can be prepared with greater than 90% radiochemical purity. This simplified kit will significantly improve the reliability of preparation of this agent for routine clinical use.

Abstract  Rapid and efficient delivery of radioactive metal complexes to the cell interior would enable novel applications in medical imaging and radiotherapy. Membrane permeant peptide conjugates incorporating HIV-1 Tat transactivation protein sequences (GRKKRRQRRR) and an appropriate peptide-based motif (epsilon-KGC) that provides an N(3)S donor core for chelating technetium and rhenium were synthesized. Oxotechnetium(V) and oxorhenium(V) Tat-peptide complexes were prepared by facile transchelation reactions with permetalates, tin(II) chloride and sodium glucoheptonate. RP-HPLC showed two major [(99m)Tc]Tat-peptide species (4) that differed in retention time by approximately 2 min corresponding to two [Re]Tat-peptide species (7) shown to have identical mass, consistent with formation of two isomers, likely the oxo-metal diastereomers. [(99m)Tc]Tat-peptides were stable to transchelation in vitro. In human Jurkat cells, [(99m)Tc]Tat-peptide 4 showed concentrative cell accumulation (30-fold greater than extracellular concentration) and rapid uptake kinetics (t(1/2) < 2 min) in a diastereomeric-comparable manner. Paradoxically, uptake was enhanced in 4 degrees C buffer compared to 37 degrees C, while depolarization of membrane potential as well as inhibition of microtubule function and vesicular trafficking showed no inhibitory effect. Cells preloaded with 4 showed rapid washout kinetics into peptide-free solution. Modification of [(99m)Tc]Tat-peptide by deletion of the N-terminus Gly with or without biotinylation minimally impacted net cell uptake. In addition, the C-terminus thiol of the prototypic Tat-peptide was labeled with fluorescein-5-maleimide to yield conjugate 8. Fluorescence microscopy directly localized conjugate 8 to the cytosol and nuclei (possibly nucleolus) of human Jurkat, KB 3-1 and KB 8-5 tumor cells. Preliminary imaging studies in mice following intravenous administration of prototypic [(99m)Tc]Tat-peptide 4 showed an initial whole body distribution and rapid clearance by both renal and hepatobiliary excretion. Analysis of murine blood in vivo and human serum ex vivo revealed >95% intact complex, while murine urine in vivo showed 65% parent complex. Thus, these novel Tat-peptide chelate conjugates, capable of forming stable [Tc/Re(V)]complexes, rapidly translocate across cell membranes into intracellular compartments and can be readily derivatized for further targeted applications in molecular imaging and radiotherapy.

Abstract  Hypocalcemia is a serious condition which has a major impact on the transmission of nerve impulses, contraction and relaxation of muscles (including myocardial) and pathological secretion of some hormones. The basic causal treatment is the parenteral administration of calcium, namely calcium gluconate, calcium chloride or calcium gluceptate. Parenteral formulations of these compounds must meet pharmacopoeial requirements, including the aluminum content limit. Each of these molecules has its specific properties that predict their clinical use. In addition to hypocalcemia, they are used to influence a variety of other conditions, such as fluoride or oxalic acid poisoning, decreased myocardial contractility caused by overdose of calcium intake blockers or beta blockers. They are also used as part of parenteral nutrition AIO or as an ancillary treatment for acute allergic conditions, itchy dermatitis, weeping and generalized eczema, continuous renal replacement therapy, seizure convulsion, laryngospasm, bronchospasm and altered mental status. The role of calcium replacement in septic patients remains unclear and requires further study. Although it may appear that calcium chloride infusion solutions provide greater and more highly ionized amounts of calcium, gluconate salts are preferred due to considerably less irritation of the vessel wall and better compatibility with other nutrients in parenteral nutrition.Key words: hypocalcemia calcium gluconate calcium chloride aluminum parenteral nutrition.

Abstract  To test whether mobilisation of immunoreactive calcitonin in response to calcium challenge is reduced in postmenopausal osteoporosis, seventeen postmenopausal osteoporotic women with compression fractures and ten normal age-matched women were given intravenous infusions of 3 mg/kg elemental calcium over a 10 min period. Blood samples were obtained 5 min before and at 0, 10, 20, and 60 min after start of infusion for the measurement of serum calcium and plasma immunoreactive calcitonin. Serum calcium increased significantly from baseline in both normal and osteoporotic groups; immunoreactive calcitonin increased significantly in the controls 10 min and 20 min after the start of infusion, but in the women with osteoporosis calcitonin levels did not change significantly at any time. 20 min after the start of infusion the change in immunoreactive calcitonin from baseline was significantly less in osteoporotic women than in the controls. These data are consistent with a decreased immunoreactive calcitonin response to calcium infusion in postmenopausal osteoporotic women, and suggest that calcitonin deficiency may be involved in the development of postmenopausal osteoporosis.

Abstract  One novel styrylpyridine derivatives(AV-45) coupled with Tc-99m complex was synthesized. Tc-99m-BAT-AV-45 was prepared by a ligand exchange reaction employing sodium glucoheptonate, and effects of the amount of ligand, stannous chloride, sodium glucoheptonate and pH value of reaction mixture on the radiolabeling yield were studied in details. Quality control was performed by thin layer chromatography and high performance liquid chromatography. Besides the stability, partition coefficient and electrophoresis of Tc-99m-BAT-AV-45 were also investigated. The results showed that the average radiolabeling yield was (95 +/- 1%) and Tc-99m-BAT-AV-45 with suitable lipophilicity was stable and uncharged at physiological pH.

Abstract  The subject of these studies was the thyroid gland tissue of middle-aged (14-month-old) female rats chronically treated with calcium glucoheptonate. The peripheral and central zone of the thyroids were stereologically analysed and the following morphometric parameters determined: the height and volumetric density of follicular epithelium, colloid, interstitium and follicles and index of activation rate. The height of follicular epithelium, its volume density and index of activation rate were significantly reduced (by 8%, p < 0.05, 18%, p < 0.025 and 34%, p < 0.01, respectively) as compared to the controls. However, the volumetric density of colloid and interstitium were increased (by 10% and 14% respectively). These morphometric results indicate that Ca treatment expressed an inhibitory effect on thyroid follicular cells structure in middle-aged female rats.

Abstract  The synthesis and labeling of (99m)Tc-N(3)-{N'-[2-sulfanyl-ethylamino)acetyl]-2-aminoethyl-sulfanyl-1-hexanamide]thymidine ((99m)Tc-NHT) were studied. In the presence of sodium glucoheptonate (GH) and ethylene diamine tetraacetic acid (EDTA), (99m)Tc-NHT was obtained by using bisaminoethanethiol (N(2)S(2)) as a bifunctional coupling agent. The radiochemical purity of the (99m)Tc-NHT was over 95%. Biodistribution of (99m)Tc-NHT was performed in hepatoma HepA tumor-bearing mice. At 2 h p.i., the ratios of tumor-to-muscle, tumor-to-bone and tumor-to-blood were 4.41 +/- 0.32, 2.45 +/- 0.24 and 1.51 +/- 0.18, respectively. (C) 2011 Chun Xiong Lu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Abstract  Foliar calcium applications are used in many fruiting crops to minimize disease and physiological disorders. In blueberry (Vaccinium spp), it is used to improve fruit firmness with varying success. Two applications of foliar calcium applied to rabbiteye blueberry (V. virgatum Aiton) cvs. Alapaha and Powderblue as calcium nitrate [Ca(NO3)(2)], neutralized calcium carbonate (CaCO3), and chelated calcium (calcium glucoheptonate, C-14 H-26 CaO16) were made at the label rate of 2.3 L. ha(-1) applied in a volume of 935.3 L. ha(-1) (697 ppm, 108 ppm, and 604 ppm Ca per application, respectively). The applications were made at 30 and 15 days preharvest in 2013 and 2014. Fruit were hand harvested at 40% ripe and evaluated for berry weight, color, firmness, soluble solids, and acidity. In 2013, fruit were stored at 1 degrees C with 85% relative humidity and evaluated again at 7 and 15 days. In 2014, fruit and tissue samples were evaluated for Ca concentration. In 2013, 'Powderblue' had a 5% increase in firmness from the CaCO3 treatment when compared to control fruit. The chelated calcium treatment significantly increased fruit weight by 12% compared to the control for 'Alapaha'. Fruit firmness increased 5% and fruit weight decreased 10% for the Ca(NO3)(2) treatment compared to control for 'Alapaha' fruit sampled after 2 weeks of storage. In 2014, none of the treatments significantly increased fruit firmness or berry calcium concentration. For 'Powderblue' in 2014, all treatments significantly decreased firmness. Leaf Ca concentration was increased by 18% for 'Alapaha' and decreased by 26% for 'Powderblue' when comparing the chelated calcium treatment to non-treated leaves.

Abstract  Stannous chloride (SnCl2) has been used in many sectors of human activities such as food manufacturing and in nuclear medicine to produce radiopharmaceuticals labeled with technetium-99m (99mTc). Due to its importance and genotoxic potentiality, we decided to evaluate the biological effect induced by a nuclear medicine kit, which includes SnCl2, in association with glucoheptonic acid (GHA) which is employed for brain and renal scintigraphies. These studies were carried out with the Escherichia coli AB1157 strain and the deoxyribonucleic acid (DNA) plasmid pUC 9.1. The experiments, with different concentrations of SnCl2 and GHA, show an inverse relationship between both agents. When the GHA concentration was increased, the cellular inactivation induced by SnCl2 was reduced, as measured by the number of viable cells. Moreover, GHA protects the DNA molecule against the damage induced by SnCl2.