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  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  EPA is announcing its receipt of test data submitted pursuant to a test rule issued by EPA under the Toxic Substances Control Act (TSCA). As required by TSCA, this document identifies each chemical substance and/or mixture for which test data have been received; the uses or intended uses of such chemical substance and/or mixture; and describes the nature of the test data received. Each chemical substance and/or mixture related to this announcement is identified in Unit I. under SUPPLEMENTARY INFORMATION.

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 pituitary TSH cell structure of middle-aged (14-month-old) female Wistar rats chronically treated with estradiol dipropionate (EDP), calcium glucoheptonate (Ca) or with the combination of both was studied. TSH-producing cells were examined in the pituitary pars distalis using rabbit anti-rat beta-thyrotropin (TSH) serum and peroxidase-antiperoxidase immunohistochemistry. A stereological method for the determination of morphometric changes of the volume of TSH cells and nuclei as well as of their number and relative volume densities was used. All examined morphometric parameters in treated animals showed a significant decrease in comparison with immunoreactive TSH cells of the controls; the most significant decrease was observed in EDP-treated rats. These results together with structural features of immunoreactive TSH cells in the pituitary of middle-aged rats after chronic application of EDP or Ca indicate that both compounds inhibit these cells.

Abstract  The effect of calcitonin on pancreatic secretion was studied in unanesthetized dogs with a Thomas cannula implanted opposite the main pancreatic duct. Pancreatic juice was collected for a 60 minute control period, during which time secretion was stimulated by the intravenous infusion of secretin and pancreozymin. After the 60 minute control period, calcitonin was infused along with the secretin and pancreozymin. The infusion of calcitonin caused the volume, bicarbonate and enzyme output in the pancreatic juice to decrease to about one-half of that during the control period. During the one hour period, after calcitonin infusion was stopped, the volume, bicarbonate and enzyme content of the pancreatic juice increased but remained slightly lower than that of the control period. The infusion of calcium gluceptate, along with secretin and pancreozymin, overcame the inhibitory effect of calcitonin on pancreatic secretion.

Abstract  Several abstracts including antibiotic use in animals and the impact of the growth promoter ban in Europe, enzymatic degradation of prions and prevention of transmissible spongiform encephalopathies, and mycotoxin detoxification and microorganisms in feeds, among others, are presented.

Abstract  Introduction: The study was performed to assess the acute oral toxicity of the test item following a single oral administration in the Wistar strain rat. The method was designed to be compatible with the following: • OECD Guidelines for the Testing of Chemicals No. 425 "Acute Oral Toxicity - Up-and-Down-Procedure (UDP)" (adopted 03 October 2008) Method: A total of five female animals were dosed individually in sequence with sufficient time (at least 48 hours) between each animal, at dose levels of 354, 1112 or 4040 mg/kg bodyweight (equivalent to 175, 550 and 2000 mg active ingredient/kg bodyweight, respectively). The test item was administered orally undiluted at dose levels of 1112 and 4040 mg/kg bodyweight (equivalent to 550 and 2000 mg active ingredient/kg bodyweight, respectively) and as a solution in distilled water at a dose level of 354 mg/kg bodyweight (equivalent to 175 mg active ingredient/kg bodyweight). Clinical signs and bodyweight development were monitored during the study. AH animals were subjected to gross necropsy. Mortality. There were no deaths. Clinical Observations: Hunched posture was noted in the animal treated at a dose level of 1112 mg/kg (equivalent to 550 mg active ingredient/kg bodyweight). No other signs of systemic toxicity were noted. Bodyweight: Animals showed expected gains in bodyweight over the study period, except for one animal treated at a dose level of 4040 mg/kg (equivalent to 2000 mg active ingredient/kg bodyweight) which showed expected gain in bodyweight during the first week but no gain in bodyweight during the second week. Necropsy: No abnormalities were noted at necropsy. Conclusion: The acute oral median lethal dose (LD5o) of the test item in the female Wistar strain rat was found to be greater than 4040 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight).