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561.
YS Suzuki Y Momose N Higashi A Shigematsu KB Park YM Kim JR Kim JM Ryu 《Canadian Metallurgical Quarterly》1998,39(12):2161-2166
The fate of 166Ho-chitosan complex, a radiopharmaceutical drug for cancer therapy, was determined by studying its absorption, distribution and excretion in rats and mice. METHODS: Holmium-166-chitosan complex [0.75 mg of Ho(NO3)3 x 5H2O and 1 mg chitosan/ head] was administered intrahepatically to male rats. Radioactive concentrations in blood, urinary and fecal excretion and radioactive distribution in tissues were examined. To determine the effects of chitosan in 166Ho-chitosan complex, 166Ho alone [0.75 mg of Ho(NO3)3 x 5H2O/head] was intrahepatically administered to male rats, and radioactive concentrations in blood, urinary and fecal excretion and radioactive distribution were examined. In B16 melanoma-transplanted nude mice, radioactive distribution after intratumoral administration of 166Ho-chitosan complex [0.075 mg of Ho(NO3)3 x 5H2O and 0.10 mg chitosan/head] was investigated also. RESULTS: After administration of 166Ho-chitosan complex, the radioactive concentrations in blood were low, and cumulative urinary and fecal excretions over a period of 0-72 hr were 0.53% and 0.54%, respectively. The radioactive concentrations in tissues and the whole-body autoradiography images showed that most of the administered radioactivity was localized at the administration site, and only slight radioactivity was detected from the liver, spleen, lungs and bones. On the other hand, results of intrahepatic administration of 166Ho alone showed high radioactive concentrations in the blood, and the whole-body autoradiographs showed that the administered radioactivity was distributed in many organs and tissues. These results strongly suggest that 166Ho is retained at the administration site only when it forms a chelate complex with chitosan. Autoradiographs after intratumoral administration of 166Ho-chitosan complex showed that radioactivity was localized at the site of administration without distribution to the other organs and tissues. CONCLUSION: Administered 166Ho-chitosan complex is retained at the administration site after either intrahepatic or intratumoral administration to rats or tumor-transplanted nude mice. 相似文献
562.
563.
KB Rasmussen 《Canadian Metallurgical Quarterly》1993,155(21):1639-1642
A retrospective study of 145 inpatients who during a five-year period underwent 147 percutaneous liver biopsies is presented. 8.2% of the biopsies were undertaken with ultrasound detection, 91.8% a.m. Menghini. Forty-four percent of the patients were suspected of alcohol induced liver disease, 20% had suspected malignancies. 7.5% had minor complications and 2.7% major complications after biopsy. The presence of risk factors was more pronounced among the patients who had complications than among those who did not. Seven patients underwent treatment for their liver disease after biopsy; none of these had alcohol induced liver disease, 1.6% of the bed days in the department were occupied by liver biopsy patients. It is concluded that percutaneous liver biopsy is a common, simple and cheap diagnostic procedure, but is not without risks. Risk patients can often be identified before biopsy. 相似文献
564.
565.
CA Briggs DJ Anderson JD Brioni JJ Buccafusco MJ Buckley JE Campbell MW Decker D Donnelly-Roberts RL Elliott M Gopalakrishnan MW Holladay YH Hui WJ Jackson DJ Kim KC Marsh A O'Neill MA Prendergast KB Ryther JP Sullivan SP Arneric 《Canadian Metallurgical Quarterly》1997,57(1-2):231-241
(2.4)-Dimethoxybenzylidene anabaseine dihydrochloride (GTS-21), a compound that interacts with rat neuronal nicotinic acetylcholine receptors (nAChRs), was evaluated using human recombinant nAChRs in vitro and various pharmacokinetic and behavioral models in rodents, dogs and monkeys. GTS-21 bound to human alpha 4 beta 2 nAChR (K1-20 nM) 100-fold more potently than to human alpha 7 nAChR, and was 18- and 2-fold less potent than (-)-nicotine at human alpha 4 beta 2 and alpha 7 nAChR, respectively. Functionally. GTS-21 stimulated [5H]dopamine release from rat striatal slices with an EC50 of 10 +/- 2 microM (250-fold less potent and 70% as efficacious as (-)-nicotine), an effect blocked by the nAChR antagonist dihydro-beta-erythroidine. However, GTS-21 did not stimulate human alpha 4 beta 2 nor human ganglionic nAChRs significantly. In vivo, GTS-21 had no adverse effect on dog blood pressure (< or = 2.5 micromol/kg i.v. bolus infusion), in marked contrast with (-)-nicotine, GTS-21 (-62 micromol/kg.s.e.) also did not cross-discriminate significantly with (-)-nicotine in rats and did not reduce temperature or locomotion in mice. Neither was it active in the elevated plus maze anxiety model (0.19-6.2 micromol/kg.IP) in normal mice. However, GTS-21 did improve learning performance of monkeys in the delayed matching-to-sample task (32-130 nmol/kg.i.m.). 相似文献
566.
DM Feng SJ Gardell SD Lewis MG Bock Z Chen RM Freidinger AM Naylor-Olsen HG Ramjit R Woltmann EP Baskin JJ Lynch R Lucas JA Shafer KB Dancheck IW Chen SS Mao JA Krueger TR Hare AM Mulichak JP Vacca 《Canadian Metallurgical Quarterly》1997,40(23):3726-3733
A novel class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position has been discovered. Four of these thrombin inhibitors (13b,c,e and 14d) showed nanomolar potency (Ki 0.8-12 nM), 300-1500-fold selectivity for thrombin compared with trypsin, and good oral bioavailability (F = 40-76%) in rats or dogs. The neutral P1 was expected to increase metabolic stability and oral absorption. Identification of this novel aminopyridyl group at P1 was a key step in our search for a clinical candidate. 相似文献
567.
CC Chao S Hu KB Shark WS Sheng G Gekker PK Peterson 《Canadian Metallurgical Quarterly》1997,281(2):998-1004
Opiates modulate many macrophage functions. Microglia, the resident macrophages of the brain, migrate to sites of inflammation within the CNS. Using primer sets designed to span the entire open reading frame of the human brain mu opioid receptor (MOR), we found that microglial cells constitutively expressed MOR mRNA. The cDNA sequences of the MOR open reading frame in microglia were identical to those of human brain tissue. Using enriched human fetal microglial cell cultures, we found that morphine potently inhibited the directed migration (chemotaxis) of microglial cells toward C5a in a dose-dependent manner with an IC50 value of 1 fM morphine. We also found that DAMGO, a selective MOR ligand, dose-dependently suppressed microglial cell chemotaxis with an IC50 value of 1 nM, which was significantly attenuated by 10 nM beta-funaltrexamine. Taken together, these findings suggest that activation of constitutively expressed MOR inhibits microglial cell chemotaxis and support the notion of an anti-inflammatory role of MOR within the brain. 相似文献
568.
569.
T Shipkowitz VG Rodgers LJ Frazin KB Chandran 《Canadian Metallurgical Quarterly》1998,31(11):995-1007
The three-dimensional flow through a rigid model of the human abdominal aorta complete with iliac and renal arteries was predicted numerically using the steady-state Navier Stokes equations for an incompressible. Newtonian fluid. The model adapted for our purposes was determined from data obtained from cine-CT images taken of a glass chamber that was constructed based on anatomical averages. The iliac arteries had a bifurcation angle of approximately 35 and a branch-to-trunk area ratio of 1.27. whereas the renal arteries had left and right branch angles of 40 and an area ratio of 0.73. The numerical tool FLOW3D (AEA Industrial Technology, Oxfordshire, UK) utilized body-fitted coordinates and a finite volume discretization procedure. Purely axial velocity profiles were introduced at the entrance of the model for a range of cardiac outputs. The four-branch numerical model developed for this investigation produced flow and shear conditions comparable to those found in other reported works. The total wall shear stress distribution in the iliac and renal arteries followed standard trends. with maximum shear stresses occurring in the apex region and lower shear stresses occurring along the lateral walls. Shear stresses and flow rate ratios in the downstream arteries were more effected by inlet Re than the upstream arteries. These results will be used to compare further simulations which take into effect the rotational component of flow which is present in the aortic arch. 相似文献
570.
BACKGROUND: Cigarette smokers with a history of major depression are at risk for developing depressive mood when they attempt cessation. Whether cessation can also provoke more severe depressions, however, has not been well documented. METHOD: Six case reports of severe depressive episodes after smoking cessation are described. RESULTS: Four cases occurred among smokers with a history of major depression but who were not depressed at the time of cessation. Two cases involved smokers with no previous history of major depression. Variability in both the timing and the outcome of the postcessation depressions was observed. CONCLUSION: The risk that depressive states may emerge or be exacerbated after smoking cessation, particularly in patients with a history of major depression, must be kept in mind in the treatment of nicotine dependence. 相似文献