Intestinal microsomal drug metabolism. A comparison of rat and guinea-pig enzymes, and of rat crypt and villous tip cell enzymes

A comparison was made of the properties of microsomes prepared from the small intestines of guinea pigs and rats. The NADPH2 cytochrome c reductase activity and cytochrome b5 and cytochrome P-450 content in rat microsomes was 42, 47 and 64% of that in the guinea pig, ethoxycoumarin deethylase activity was comparable, while arylesterase activity was twice as active in rats as guinea pigs. Investigation of the distribution of these and other parameters in rat intestinal epithelia revealed a preferential location of cytochrome P-450 in the villous tip while other parameters showed a more similar distribution between microsomes prepared from the villous tip and crypt.     

Mucinous epithelial ovarian cancer: a separate entity requiring specific treatment.

PURPOSE: Invasive mucinous carcinoma of the ovary (mucinous epithelial ovarian cancer [mEOC]) is a histologic subgroup of epithelial ovarian cancer (EOC). Chemotherapy for mEOC is chosen according to guidelines established for EOC. The purpose of this study is to determine whether this is appropriate. PATIENTS AND METHODS: Women with advanced mEOC (International Federation of Gynecology and Obstetrics stage III or IV) who underwent first-line platinum-based chemotherapy were compared with women with other histologic subtypes of EOC in a case-controlled study. RESULTS: Eighty-one patients (27 cases, 54 controls) treated with platinum-based regimens were analyzed. The response rates for cases and controls were 26.3% (95% CI, 9.2% to 51.2%) and 64.9% (95% CI, 47.5% to 79.8%), respectively (P=.01). The odds ratio for complete or partial response to chemotherapy for mEOC was 0.19 (95% CI, 0.06 to 0.66; P=.009) compared with other histologic subtypes of EOC. Median progression-free survival was 5.7 months (95% CI, 1.9 to 9.6 months) versus 14.1 months (95% CI, 12.0 to 16.2 months; P<.001) and overall survival was 12.0 months (95% CI, 8.0 to 15.6 months) versus 36.7 months (95% CI, 25.2 to 48.2 months; P<.001) for cases and controls, respectively. The hazard ratio for progression and death was 2.94 (95% CI, 1.71 to 5.07; P<.001) and 3.08 (95% CI, 1.69 to 5.6; P<.001), respectively, for mEOC patients as compared with controls. CONCLUSION: Patients with advanced mEOC have a poorer response to platinum-based first-line chemotherapy compared with patients with other histologic subtypes of EOC, and their survival is worse. Specific alternative therapeutic approaches should be sought for this group of patients, perhaps involving fluorouracil-based chemotherapy.     

Early stage nasopharyngeal carcinoma: radiotherapy dose and time factors in tumor control

OBJECTIVE: To evaluate radiotherapy dose and length of treatment in the control of early stage nasopharyngeal carcinoma (NPC) treated with a combination of external radiotherapy and brachytherapy, MATERIALS & METHODS: We reviewed the records of 133 patients with early stage nasopharyngeal carcinoma (stage I or II, AJC/UICC staging system) who received definitive radiotherapy in Chang Gung Memorial Hospital from 1979 to 1991. The median follow-up time was 7.1 years with a minimum of 2 years. All patients were treated with megavoltage external radiotherapy to the nasopharynx area (63-72 Gy) followed by high dose rate intracavitary brachytherapy (5-16.5 Gy in one to three fractions, spaced 1-2 weeks apart). The median total dose and time of irradiation was 75 Gy (69.8-81.4 Gy) and 11.6 weeks (7.8-20 weeks) respectively. Survival analysis was used to examine the effect of several variables on prognosis. RESULTS: The 5-year rates were 86.4% for local control, 84.7% for disease free survival, 88.5% for actuarial survival and 84.2% for overall survival. The treatment group (combination of time and dose of irradiation) was the most important prognostic factor according to Cox's proportional hazard model. Patients receiving radiation at a total dose of < or = 75 Gy completed in < 12 weeks showed the best prognosis. CONCLUSION: Treatment time and total treatment dose are both important factors in treating early stage NPC. Decreasing the total radiation time to < 12 weeks and not exceeding a radiation dose of 75 Gy gave the best results.      

A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

We examined the relationship between a functional polymorphism (667C-- >T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-- >carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.      

The gynaecological management of women on tamoxifen: a national questionnaire survey.

Tamoxifen is the standard adjuvant treatment for women with breast carcinoma, decreasing the incidence of contralateral disease. However, the risk of endometrial cancer is increased. To establish current gynaecological management of women receiving tamoxifen in the United Kingdom we conducted a postal questionnaire of consultant gynaecologists, enquiring about frequency of, and methods used to investigate women on tamoxifen. Ninety-five per cent investigate women on tamoxifen only if they are symptomatic. Pelvic ultrasound and endometrial sampling are used for first-line investigation by 68.7%. Interpreting ultrasound findings, endometrial thickness is the parameter regarded as most important. An endometrial thickness of greater than 5 mm is regarded abnormal by 47.8% of respondents and of 4 mm by 23.6%. As there is no consensus of opinion regarding normal values for endometrial thickness, further data are required to ensure consistency when interpreting ultrasound reports of women on tamoxifen.     

Myocardial laser revascularization: the controversy and the data

The clinical and experimental data relevant to the theoretical mechanisms and clinical results of laser myocardial revascularization are reviewed. Both transmyocardial and percutaneous approaches are considered. Both types result in a reduction in anginal symptoms in patients refractory to conventional therapy and are likely to act through common pathways. The proximate mechanisms for the transmyocardial revascularization effect most likely relate to myocardial inflammation, secondary stimulation of growth factors, and denervation of the myocardium.     

Opiate involvement in postpartum aggression in rats

Opiates and the endogenous opioids mediate maternal behavior and various forms of aggression. The present study sought to investigate the role of opiates in postpartum aggression (PPA), an intense form of agonistic behavior displayed by lactating females. Primiparous rats were screened for their PPA against adult males on day seven postpartum. They were then randomly assigned to one of four treatment groups [morphine, 5.0 mg/kg; naloxone alone, 0.5 mg/kg; morphine (5.0 mg/kg) plus naloxone (0.5 mg/kg); and saline] and tested for PPA on postpartum days eight and nine following the respective treatments. Morphine significantly lowered PPA, and naloxone antagonized the effect. Whereas the morphine plus naloxone, naloxone alone, and saline groups exhibited higher levels of PPA than that shown by the morphine group, there were no differences in PPA found among the morphine plus naloxone, naloxone alone, or saline groups. These results, in conjunction with evidence describing the state of the endogenous opioid system in the postpartum rat, suggest that some aspect of the endogenous opioid system may be involved in another form of maternal behavior, postpartum aggression.     

1-取代吡唑烷酮类抗惊构效关系的研究

1-正癸基吡唑烷-3-酮(Ⅱ结构式见表1)是欧洲专利报道的一种新型减肥剂。White等报道该化合物可通过血脑屏障,并对γ-氨基丁酸氨基转移酶(GABA-T)有强烈的抑制活性,但对谷氨酸脱羧酶的抑制作用较弱,因此可引起脑内γ-氨基丁酸(GABA)水平的升高,故我们相信应有抗惊活性。经我们合成后,发现Ⅱ确有良好的抗癲痫活性,抗小鼠最大电