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41.
42.
Hydrophobic effects could play an important role in determining the selectivity of organic ions for ion-exchange resins in aqueous solutions. We used the octanol-water partition coefficient (P) and the chromatographic capacity factor (K') as indices of hydrophobicity of a series of primary and secondary amines, and examined their relationships with the amine selectivity coefficient (K) in binding to the Amberlite IRP-69 ion-exchange resin. Good correlations were found between log K versus log P and log K versus log K', but the relationship appears to be dependent on the degree of substitution at the amino nitrogen. These relationships may be useful for the estimation of selectivity coefficients of various amine drug candidates when they are considered for incorporation with ion-exchange resins in potential controlled-release systems. 相似文献
43.
S A Boyd A K Fung W R Baker R A Mantei Y L Armiger H H Stein J Cohen D A Egan J L Barlow V Klinghofer 《Journal of medicinal chemistry》1992,35(10):1735-1746
We describe the development of a series of soluble, potent, and bioavailable nonpeptide renin inhibitors. These inhibitors derived from a series of novel nonpeptide renin inhibitors which were recently identified in our laboratories, by alteration of the nature of the C-terminus (P2') of the molecules. Introduction of basic substituents into modified hydroxyethylene dipeptide isosteres gave inhibitors with improved solubility as well as improved potency against human plasma renin. In addition, these modifications produced inhibitors which displayed markedly improved intraduodenal bioavailability in both the ferret and cynomolgus monkey. We also present data which demonstrate excellent efficacy in the monkey for A-74273 (65), with an intraduodenal bioavailability of 16 +/- 4% in the monkey, compared to 1.7 +/- 0.5% for the dipeptide renin inhibitor enalkiren (A-64662, 75). A-74273 is an example of a nonpeptide inhibitor which possesses a good balance of the desirable properties of potency, solubility, and lipophilicity and which is well absorbed into the intestine. 相似文献
44.
H Furukawa O Imventarza R Venkataramanan M Suzuki Y Zhu V S Warty J Fung S Todo T E Starzl 《Transplantation》1992,53(4):722-725
Mongrel or beagle dogs were submitted to bile duct ligation, or to extraenteric biliary diversion by means of choledochoureterostomy. The kinetics of intravenously administered FK506 was not changed from control status two weeks after bile duct ligation, but the bioavailability of orally administered FK506 was nearly quadrupled. Following oral administration, the absorption of FK506 was highly variable. The results indicate that in dogs FK506 is absorbed from the intestine just as efficiently in the absence of enteric bile and in presence of exogenous bile salt supplement when compared with its absorption in presence of normal bile drainage. These findings with FK506 are different from those with cyclosporine after biliary obstruction or diversion and will have important practical as well as experimental ramifications. 相似文献
45.
BACKGROUND:Wilson disease (WD)damages liver,brain,kidney,cornea and nervous system severely.It is manifested in four ways:brain,liver,kidney and bone muscle.Whether or not magnetic resonance imagling (MRI)can clearly display the diseased region and range in brain of patient with WD,which provides imageological evidence for clinical practice,is unclear.OBJECTIVE:To observe the charactedstics of MRI of brain in patient with SD,and analyze the correlation of diseased region with clinical symptoms.DESIGN:Retrospective case-analysis.SETTING:Department of Radiology,Second Hospital Affiliated to the General Hospital of Chinese PLA.PARTICIPANTS:Thirty-one patients,including 18 males and 13 females,with WD admitted to the Department of Neurology,Second Hospital Affiliated to the General Hospital of Chinese PLA between January 1999and December 2005 were retrieved.The involved patients presented serum copper oxidase (sCP) activity decreasling and/or caruloplasmin Ievel decreasling and/or urinary copper content increasling;typical extrapyramidal symptoms and/or physical sign;abnormality showed by slit-lamp examination,Kayser-Fleischer rling positive.METHODS:①All the involved patients underwent MRI examination.A GE 1.5T imagling equipment was used.Spin-echo sequence was adopted to perform T2 and T1-weighed image at transverse axis level.Partial cases subjected to head scannling at coronal and/or sagittal level.Gd-DTPA With dosage of 0.1 mmol/kg was the strongest in 4 cases.②MRI characteristics of patients with dliferent clinical symptoms were observed.MAIN OUTCOME MEASURES:MRI detection results of patients with WD and MRI characteristics of patients with different clinical symptoms.RESULTS:Thirty-one patients with WD participated in the result analysis.①Imageological examination results:WD lnvolved many regions in the brain:dorsal caudate putamen(n=28),thalamencephalon(n=25),mesencaphalon(n=25),globus pallidus(n=23),pons(n=21),posterlor limb of intemal capsule(n=16),dentate nucleus(n=16),caudata nucleus(n=15)and cerebral cortex(n=11).MRI presented hypo-intensity signal on T2-weighted image and T1-weighted image or isointensity signal on T1-weighted image in 24 patients,characteristic hypo-intensity signal of globus pallidus in 4 patients,mixed signal of hyper-and hypo-intensity in 2 patients,hypo-intensity signal of globus pallidus,pars anterior pedunculi carebd and pontine tegmentum on T1-weighted image in 1 patient.Pathological changes distdbuted in symmetry and focus of infection mostly presented mottling,lamellar or strip.Different degrses of cerebral cortex atrophy,especially subtentodal cerebellar atrophy,ware found in 20 patients.Four patients subjected to enhancement scannling,but no clear imaqling was found.③MRI characteristics of patients with different symptoms:Abnormal signal of dorsal caudate putamen was found in 28 patients with dystonia,21 patients with dysarthda and 16 patients with bradykinesia;Abnormal signal of mesencaphalon was found in 22 patients with trepidation,among which,18 presented abnormal signal of pons;Abnormal signal of caudate nucleus and lenticular nucleus was found in 15 patients with dysphagia;Abnormal signal of dentate nucleus was found in 16 patients with carebellar ataxia;Different degrees of changes in cerebral atrophy were found in 14 patients with detedoratling memory and dementia.CONCLUSION:MRI can clearly display the characteristics of diseased regions in brain of patient with WD.Diseased regions reflected by MRI have obvious differences in patients with different clinical neurosigns. 相似文献
46.
B. J. Nankivell M. D. Wavamunno R. J. Borrows M. Vitalone C. L-S Fung R. D. M. Allen J. R. Chapman P. J. O'Connell 《American journal of transplantation》2007,7(2):366-376
Mycophenolate mofetil (MMF) reduces acute rejection in controlled trials of kidney transplantation and is associated with better registry graft survival. Recent experimental studies have demonstrated additional antifibrotic properties of MMF, however, human histological data are lacking. We evaluated sequential prospective protocol kidney biopsies from two historical cohorts treated with cyclosporine (CSA)-based triple therapy including prednisolone and either MMF (n = 25) or azathioprine (AZA, n = 25). Biopsies (n = 360) were taken from euglycemic kidney-pancreas transplant recipients. Histology was independently assessed by the Banff schema and electron microscopic morphometry. MMF reduced acute rejection and OKT3 use (p < 0.05) compared with AZA. MMF therapy was associated with limited chronic interstitial fibrosis, striped fibrosis and periglomerular fibrosis (p < 0.05-0.001), mesangial matrix accumulation (p < 0.01), chronic glomerulopathy scores (p < 0.05) and glomerulosclerosis (p < 0.05). MMF was associated with delayed expression of CSA nephrotoxicity, reduced arteriolar hyalinosis, striped fibrosis and tubular microcalcification (p < 0.05-0.001). The beneficial effects of MMF remained in recipients without acute rejection. Retrospective analysis shows that MMF therapy was associated with substantially reduced fibrosis in the glomerular, microvascular and interstitial compartments, and a delayed expression of CSA nephrotoxicity. These outcomes may be due to a limitation of immune-mediated injury and suggest a direct effect of reduced fibrogenesis. 相似文献
47.
48.
Y K Fung 《The Journal of pharmacy and pharmacology》1990,42(8):595-596
Bilateral injections of either nicotine (200 micrograms) or cytisine (30 or 60 micrograms) into the nucleus accumbens elicited locomotor hyperactivity in rats. Pretreatment with mecamylamine (2 mg kg-1, s.c.) was effective in attenuating the stimulatory effect of either nicotine or cytisine. This study suggests that nicotinic agonists such as nicotine and cytisine produce their locomotor excitatory effects through stimulation of the mesolimbic dopaminergic pathway. 相似文献
49.
Single-center experience with primary orthotopic liver transplantation with FK 506 immunosuppression. 总被引:1,自引:0,他引:1 下载免费PDF全文
S Todo J J Fung T E Starzl A Tzakis H Doyle K Abu-Elmagd A Jain R Selby O Bronsther W Marsh et al. 《Annals of surgery》1994,220(3):297-309
OBJECTIVE: The efficacy for primary orthotopic liver transplantation of a new immunosuppressive agent, FK 506 (tacrolimus, Prograf, Fujisawa USA, Deerfield, IL), was determined. SUMMARY BACKGROUND DATA: After 3 years of preclinical research, a clinical trial of FK 506 for orthotopic liver transplantation was begun in February 1989, first as a rescue therapy for patients with intractable rejection with conventional immunosuppression, then as a primary drug. METHODS: Between August 1989 and December 1993, 1391 recipients (1188 adult and 203 pediatric) of primary liver allografts were treated with FK 506 from the outset. Results from these patients were analyzed and compared with those of 1212 historical control patients (971 adult and 241 pediatric) given cyclosporine-based immunosuppression. RESULTS: Actuarial survival at 4 years was 86.2% with FK 506 versus 65.5% with cyclosporine in the pediatric patients (p < 0.0000) and 71.4% versus 65.5% in the adults (p < 0.0005). The need for retransplantation was reduced significantly for FK 506 patients. Four-year graft survival was 77.0% with FK 506 versus 48.4% with cyclosporine in the pediatric patients (p < 0.0000), and 61.9% with FK 506 versus 51.4% with cyclosporine in the adult recipients (p < 0.0000). Regression analysis revealed that reduction in mortality or graft loss from uncontrollable rejection, sepsis, technical failure, and recurrent original liver disease were responsible for the improved results with FK 506 therapy. CONCLUSIONS: FK 506 is a potent and superior immunosuppressive agent for orthotopic liver transplantation. 相似文献
50.
Liver transplantation for chronic hepatitis B with lamivudine-resistant YMDD mutant using add-on adefovir dipivoxil plus lamivudine. 总被引:5,自引:0,他引:5
Chung Mau Lo Chi Leung Liu George K Lau See Ching Chan Irene O Ng Sheung Tat Fan 《Liver transplantation》2005,11(7):807-813
Lamivudine treatment in patients with chronic hepatitis B virus (HBV) infection may improve clinical state and suppress viral replication before liver transplantation. Emergence of lamivudine-resistant YMDD mutant is common. We report the results of liver transplantation in 16 patients with pretransplantation YMDD mutants after receiving lamivudine treatment for a median of 738 days (range, 400-1799 days). Adefovir dipivoxil (10 mg daily) was added on to lamivudine for a median of 20 days (range, 8-271 days) before (n = 11) or at (n = 5) liver transplantation, and the combination was continued indefinitely thereafter. Eight patients received additional intravenous hepatitis B immune globulin (HBIG) for a median of 24 months. Fifteen patients with known pre-adefovir HBV DNA levels had a median titer of 14,200 x 10(3) copies/mL (2 x 10(3) to 4,690,000 x 10(3) copies/mL), and 14 had HBV DNA >10(5) copies/mL. All but 1 patient remained positive for HBV DNA (by quantitative polymerase chain reaction [qPCR]) at the time of liver transplantation, and the titer was greater than10(5) copies/mL in 8 patients. The median follow-up after liver transplantation was 21.1 (range, 4.4-68.9) months. One patient (6%) died of an unrelated cause 12.2 months after transplantation, and 15 patients (94%) were alive with the original graft. All patients cleared HBV DNA and had no detectable HBV DNA by qPCR at the latest follow-up. Fourteen patients had cleared hepatitis B surface antigen (HBsAg), but 2 patients who received only adefovir dipivoxil and lamivudine without HBIG remained HBsAg positive after 7.7 and 9.5 months. Serum HBV DNA, however, was negative, and there was no biochemical or histological evidence of recurrence. Adefovir dipivoxil was well tolerated with no significant renal toxicity. In conclusion, a combination of add-on adefovir dipivoxil plus lamivudine therapy provides effective prophylaxis in patients with pretransplantation YMDD mutant that may be actively replicating. The cost effectiveness of additional passive immunoprophylaxis remains to be defined. 相似文献