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171.
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173.
Kyoung-Ah Kim Min-Jung Kim Ji-Young Park Ji-Hong Shon Young-Ran Yoon Sang-Seop Lee Kwang-Hyeon Liu Jin-Ho Chun Myung-Ho Hyun Jae-Gook Shin 《Drug metabolism and disposition》2003,31(10):1227-1234
The stereoselective metabolism of lansoprazole enantiomers was evaluated by incubation of human liver microsomes and cDNA-expressed cytochrome p450 (p450) enzymes to understand and predict their stereoselective disposition in humans in vivo. The intrinsic clearances (Clint) of the formation of both hydroxy and sulfone metabolites from S-lansoprazole were 4.9- and 2.4-fold higher than those from the R-form, respectively. The sums of formation Clint of both metabolites were 13.5 and 57.3 microl/min/mg protein for R- and S-lansoprazole, respectively, suggesting that S-lansoprazole would be cleared more rapidly than the R-form. The p450 isoform selective inhibition study in liver microsomes, and the incubation study of cDNA-expressed enzymes, demonstrated that the stereoselective sulfoxidation is mediated by CYP3A4 and that the hydroxylation is mediated by CYP2C9 and CYP3A4 as well as by CYP2C19. Total Clint values of hydroxy and sulfone metabolite formation catalyzed by all these p450 enzymes were consistently higher for S-lansoprazole than for the R-form. The CYP3A4 produced the greatest difference of Clint between S- and R-enantiomers, mainly due to a difference of sulfoxidation metabolism (Clint 76.5 versus 10.8 microl/min/nmol of p450, respectively), whereas CYP2C19-catalyzed hydroxylation resulted in a minor difference of Clint between S- and R-enantiomers (179.6 versus 143.3 microl/min/nmol of p450, respectively). However, the affinity of CYP2C19 on hydroxylation was 5.7-fold higher for S-enantiomer than for the R-form (Km 2.3 versus 13.1 microM), suggesting that the role of CYP2C19 on stereoselective hydroxylation would be more prominent at concentrations around the usual therapeutic level. These findings suggest that both CYP2C19 and CYP3A4 are major enzymes contributing to the stereoselective disposition of lansoprazole, but stereoselective hydroxylation of lansoprazole enantiomers is mainly influenced by CYP2C19, especially at the usual therapeutic doses. 相似文献
174.
Poly(arylene-1,2,4-oxadiazole)s (PAOs) bearing flexible, linear side chains, 3a - c , were prepared by solution cyclodehydration of their precursors, poly(arylene acyloylamide oxime)s (PAAs), 2a - c , which were synthesized by solution polycondensation of 2,5-bis(n-alkoxymethyl)-terephthaldiamide oximes (DIS-TADO), 1a - c , with terephthaloyl dichloride (TPC). The length of the n-alkoxy group was varied from methoxy via butoxy to octyloxy. The reduction of the phase transition temperatures and the enhancement of the solubilities of 3a - c were greatly affected by the length of the side chains. PAOs with longer side chains, 3b and 3c , are nematic type liquid-crystalline polymers. 相似文献
175.
Kaufmann SJ; Sharif K; Sharma V; McVerry BA 《Human reproduction (Oxford, England)》1998,13(2):498-499
The patient was diagnosed in childhood as having severe congenital
neutropenia and had recurrent admissions with severe infections. In 1987,
prior to getting married, she was sterilized. She continued to require i.v.
antibiotics when she contracted a severe infection. On one occasion, she
was treated with growth colony stimulating factor (G- CSF). Her increased
neutrophil count was sustained following this treatment. In June 1993, she
wished to start a family and underwent in- vitro fertilization (IVF)
treatment. G-CSF was given prior to oocyte retrieval. She conceived on her
first cycle and an ultrasound scan revealed a singleton pregnancy.
Throughout the course of the pregnancy, her white cell count was monitored
closely and remained at <1.0x10(9)/l. The pregnancy progressed
uneventfully and at 37 weeks gestation she was admitted for G-CSF
injections. At 38 weeks she was delivered of a boy weighing 3350 g, by
elective Caesarean section. His white cell count was normal. This is the
first case of G-CSF being used before conception and during pregnancy in a
patient with congenital neutropenia. It shows that advances in cytokine
therapy and close interdisciplinary liaison can lead to a successful
outcome and help patients, who would otherwise remain childless, to achieve
a family.
相似文献
176.
Silber SJ; Nagy Z; Devroey P; Tournaye H; Van Steirteghem AC 《Human reproduction (Oxford, England)》1997,12(11):2422-2428
The aim of the study was to determine whether a prior diagnostic testicle
biopsy can predict success or failure of testicular sperm extraction (TESE)
with intracytoplasmic sperm injection (ICSI) in patients with
non-obstructive azoospermia caused by testicular failure, and what is the
minimum threshold of sperm production in the testis which must be surpassed
for spermatozoa to reach the ejaculate. Forty- five patients with
non-obstructive azoospermia caused by testicular failure underwent
diagnostic testicle biopsy prior to a planned future TESE-ICSI procedure.
The diagnostic testicle biopsy was analysed quantitatively, and correlated
with the quantitative findings of spermatogenesis in patients with normal
spermatogenesis, as well as with the results of subsequent attempts at
TESE-ICSI. Men with non- obstructive azoospermia caused by germinal failure
had a mean of 0-6 mature spermatids/seminiferous tubule seen on a
diagnostic testicle biopsy, compared to 17-35 mature spermatids/tubule in
men with normal spermatogenesis and obstructive azoospermia. These findings
were the same for all types of testicular failure whether Sertoli cell
only, maturation arrest, cryptorchidism, or post-chemotherapy azoospermia.
Twenty-two of 26 men with mature spermatids found in the prior testis
biopsy had successful retrieval of spermatozoa for ICSI, 12 of their
partners became pregnant, and are either ongoing or delivered. The study
suggests that 4-6 mature spermatids/tubule must be present in the testis
biopsy for any spermatozoa to reach the ejaculate. More than half of
azoospermic patients with germinal failure have minute foci of
spermatogenesis which are insufficient to produce spermatozoa in the
ejaculate. Prior diagnostic testicle biopsy analysed quantitatively (for
the presence of mature spermatids) can predict subsequent success or
failure with TESE-ICSI. Incomplete testicular failure may involve a sparse
multi-focal distribution of spermatogenesis throughout the entire testicle,
rather than a regional distribution. Therefore, it is possible that massive
testicular sampling from many different regions of the testes may not be
necessary for successful TESE-ICSI.
相似文献
177.
Toluene diisocyanate (TDI), a low molecular weight reactive chemical, is known to be a main cause of occupational asthma (OA) in Korea. Although it is thought that inhaled TDI may act as a hapten, the precise mechanisms of TDI-induced OA are unknown. In this study, TDI-human serum albumin (HSA) conjugates (5, 10, 20 and 30 min) were prepared in the range of 1.5 to 5.0 TDI mole/HSA mole. Specific binding of serum IgE to TDI-HSA (30 min) was observed using IgE ELISA as well as ELISA inhibition assay. Around 40% of TDI-induced OA patients were positive for serum specific IgE by ELISA. Degrees of serum IgE binding were different depending on which TDI-HSA conjugate was used as an antigen. Moreover, binding patterns were different depending on the individuals. Interestingly, higher binding of IgE to TDI-HSA (5 min) than to TDI-HSA (30 min) which was more highly substituted was observed in some patients. Probably new antigenic epitopes on carrier proteins were targets of the specific IgE. The results of this study indicated that IgE responses to TDI-HSA conjugates were heterogeneous in TDI-induced OA patients and self-proteins modified by reactive chemicals can become a major target antigen of IgE in certain cases. 相似文献
178.
β-Lactoglobulin was isolated from infant formulae that were ultra high temperature (UHT) -treated, sterilized or spray-dried. The effect of the isolated β-lactoglobulin on SfaII-fimbriae-mediated adhesion of Escherichia coli to human ileostomy glycoproteins was studied in vitro. β-Lactoglobulin isolated from sterilized formulae was found to perform significantly less well than preparations from spray-dried formulae (p = 0:05). Great heterogeneity was observed in the adhesion inhibitory capacity of β-lactoglobulin isolated from UHT-treated formulae. Therefore, no significant difference was observed between UHT-treated and sterilized formulae or spray-dried formulae (p < 0:10). It can be hypothesized that β-lactoglobulin from spray-dried and some UHT-treated infant formulae may affect the colonization of mucous membranes by E. coli strains causing neonatal septicaemia and meningitis. 相似文献
179.
Mortality among ferrous foundry workers 总被引:8,自引:0,他引:8
M Silverstein N Maizlish R Park B Silverstein L Brodsky F Mirer 《American journal of industrial medicine》1986,10(1):27-43
Mortality analyses were carried out for 278 male hourly workers who were employed for at least 10 years at a gray iron foundry and who died between January 1, 1970 and December 31, 1981. Statistically significant excess proportional mortality due to non-malignant respiratory disease (SPMR = 177), lung cancer (SPMR = 148), and leukemia (SPMR = 284) was found among the 221 white males. Among nonwhite males there was a significant excess in proportional mortality due to circulatory diseases (SPMR = 143). White males in the Finishing classification experienced a significant excess of proportional mortality due to nonmalignant respiratory disease (SPMR = 279) and lung cancer (SPMR = 179). White males in the Core Room classification experienced an excess of proportional mortality due to nonmalignant respiratory disease (SPMR = 321). Case-control studies demonstrated a significant association between nonmalignant respiratory disease and the Finishing classification after controlling for the effects of age, prior occupations in coal mining or foundries, and smoking. A positive but nonsignificant association between lung cancer and Finishing was also found after controlling for age, prior work history, and smoking in case control studies. 相似文献
180.
Gi-Young Park Jong-Min Kim Sung-Il Sohn Im-Hee Shin Michael Y Lee 《Journal of rehabilitation medicine》2007,39(7):526-530
OBJECTIVE: To evaluate the ultrasonographic measurement of shoulder subluxation in patients with post-stroke hemiplegia. DESIGN: Prospective, single blind study. PATIENTS: A total of 41 patients with post-stroke hemiplegia were included (24 men and 17 women, mean age 56 years (standard deviation 11), age range 34-78 years). METHODS: Clinical evaluation of the affected shoulder was assessed using the Motricity Index scores and the Modified Ashworth Scale. Two ultrasonographic measurements were taken to check intra-rater reliability. The shoulder subluxation ratio was determined as the ratio of the radiographic vertical and horizontal distance, and the ultrasonographic lateral and anterior distances in the affected shoulder divided by that in the unaffected shoulder. RESULTS: Intraclass correlation coefficients of the repeated ultrasonographic lateral/anterior distance measurements in the unaffected and affected shoulders were 0.979/0.969 and 0.950/0.947, respectively. Ultrasonographic lateral/anterior distance ratios were negatively correlated with Motricity Index scores of the affected shoulder abduction (r = -0.490, p < 0.001/ r = -0.671, p < 0.001). Ultrasonographic anterior distance ratio was negatively correlated with Modified Ashworth Scale score of the affected shoulder (r = -0.374, p < 0.05). However, there was no correlation between radiographic distance ratios and clinical evaluation scores. CONCLUSION: We strongly recommend ultrasonography as a diagnostic tool to measure the degree of shoulder subluxation in patients with post-stroke hemiplegia. 相似文献