Regional effects of craniotomy on cerebral circulation and metabolism: PET study on the un-ruptured aneurysmal surgery

Regional effects of craniotomy on cerebral circulation and metabolism, such as regional cerebral blood flow (rCBF), regional cerebral oxygen consumption (rCMRO2), regional oxygen extraction fraction (rOEF), and regional cerebral blood volume (rCBV) were examined by a PET (positron emission tomography) study concerning surgery that was performed on unruptured aneurysm patients. Eight patients with intracranial un-ruptured aneurysms were studied pre- and post-operatively by the 15O labelled-gas steady-state method, using HEADTOME-III. All patients underwent aneurysmal surgery performed by the transsylvian approach. There was a significant increase in the mean OEF values taken from the whole-brains of 8 patients, but there was not a significant change in CBF, CMRO2 or CBV. The increase in OEF was caused by decrease of O2 content, which was caused by post-operative decrease in the Hb value. So, this OEF increase was not the direct effect of craniotomy. In 2 patients, the rCBF and rCMRO2, in the fronto-temporal region (where craniotomy was performed) increased post-operatively. This regional effect suggests transient reactive hyperemia following compressive ischemia during the operative procedure, and metabolic demands for recovery of brain function. In 2 other patients, who had relatively low rCBFs during the pre-operative study, rCBF and rCMRO2 in the bi-frontal region had decreased more at the post-operative study. This change appears to have been caused by removal of cerebrospinal fluid and depression of the frontal lobe. From this study, it becomes evident that the regional effect of craniotomy on cerebral circulation and metabolism is not so great, when adequate microsurgical techniques are used.     

Preoperative staging of gastrointestinal tumors by endosonography

Summary Intracavitary application of ultrasound was first performed for diagnostic purposes in 1967; since that time, it has been more and more widely used. As far as the gastrointestinal tract is concerned, endoscopically controlled ultrasonic probes provide visualization of the various layers of the intestinal wall. It is therefore possible to describe lesions of the esophagus, stomach, and the rectum with regard to their nature and depth of infiltration. Furthermore, periesophageal and perigastric organs can be visualized. It has become evident that endosonography is particularly important for pretherapeutic staging of tumors of the esophagus, stomach, and rectum. Here prospective comparative studies confirm the superiority of this new diagnostic procedure when compared to the methods available to date.     

Interspecies comparisons in toxicology: the utility and futility of plasma concentrations of the test substance

A classical dilemma in toxicology is how the dose administered relates to the dose delivered to the target site. Plasma concentrations of the test substance may be misleading since the concentration of any given substance in the plasma may not be representative of its concentration in tissues. Furthermore, a given tissue concentration of a xenobiotic can evoke responses which are highly species-dependent. While evaluating toxicity data within one species, plasma concentrations reflect the effects of route of administration, bioavailability, dose level, multiple dosing, age, gender, etc. However, when toxicity data is compared across species, the relevance of plasma concentrations depends on the nature of the toxicity. Reversible, pharmacodynamic effects often correlate with plasma concentrations, although there may be marked interspecies differences in dose-response relationships. Irreversible effects, if pharmacodynamic in origin, often correlate better with the intensity/duration of the pharmacodynamic response, rather than with plasma concentration. On the other hand, irreversible effects, if chemically mediated, may not correlate at all with plasma concentration, the lesions being caused by reactive metabolites of fleeting existence, which rarely survive long enough to leave their site of synthesis. They cannot be measured in the plasma nor predicted from plasma concentrations of the parent xenobiotic. The limitations of plasma concentrations in interpreting the toxicology of substances which are tissue-sequestered, which are subject to pharmacogenetic factors, or which show plasma concentrations that are not proportional to dose are also discussed. Mention is made of possible alternatives to plasma concentrations in assessing exposure in toxicology studies.     

Uncertainty in Fitted Estimates of Apparent in Vivo Metabolic Constants for Chloroform

It has become common practice to rely on fitted estimates ofapparent in vivo metabolic constants (e.g., V_max and K_M) inparameterization of PBPK models. Yet, quantitative estimatesof precision in these fitted parameters are not routinely reported.Such information is needed to assess the reliability of modelpredictions. The purpose of this study was to assess the precisionin estimates of V_max and K_M for chloroform, accounting for boththe statistical uncertainties in parameter estimates from individualdata sets and any additional uncertainty due to differencesin the parameter estimates derived from various experiments.Joint confidence regions for V_max and K_M from each experiment,generated using maximum likelihood techniques, were used toevaluate these questions. Three previously published data setswere considered. Estimates of V_max and K_M obtained from thesedata sets differed more than could be explained as a consequenceof a limited number of observations, measurement error, or stochasticerror. Issues associated with the use of maximum likelihoodtechniques to estimate joint confidence regions, the estimationof metabolic constants from individual experiments within agas uptake study versus the full data set, the degree of overlapin the joint confidence regions for metabolic constants obtainedfrom separate data sets, and the implications for risk assessmentare discussed.     

猕猴桃汁抗环磷酰胺致突变作用的机理

目的用大鼠外周血双核淋巴细胞微核测试法（ＣＢＭＮＴ），在哺乳动物整体水平，研究猕猴桃汁抗环磷酰胺（ＣＰ）的致突变作用以及生物转化Ⅱ相酶的作用。方法测定大鼠外周血双核淋巴细胞微核细胞率及肝组织中总谷胱甘肽硫转移酶（ＧＳＴ）、尿苷二磷酸葡萄糖醛酸转移酶（ＵＤＰＧＴ）、谷氨酰胺转肽酶（γＧＴ）活性。结果猕猴桃汁对ＣＰ诱发的大鼠外周血双核淋巴细胞微核细胞率有显著抑制作用，能明显诱导大鼠肝脏总ＧＳＴ、ＵＤＧＴＰ活性，但对γＧＴ活性无显著影响。大鼠外周血双核淋巴细胞微核细胞率与总ＧＳＴ、ＵＤＧＴＰ活性呈明显负相关。结论猕猴桃汁抗ＣＰ致微核形成作用的机理可能是通过诱导机体外来化合物代谢解毒酶系，加速ＣＰ的代谢灭活     

Cytochrome P450 3A4 Activity in Premenopausal and Postmenopausal Women,Based on 6-β-Hydroxycortisol:Cortisol Ratios

Study Objective . To characterize cytochrome P450 (CYP) 3A4 activity in premenopausal and postmenopausal women by evaluating the urinary 6-β-hydroxycortisokcortisol ratio. Design . Prospective study. Subjects . Thirteen premenopausal and 13 postmenopausal women who were healthy and not receiving drugs known to affect CYP3A4 activity. Interventions . Beginning on day 2 of menses, premenopausal women collected first morning urine samples every other day for a complete menstrual cycle. Postmenopausal women collected first morning urine every other day for 28 days. Measurements and Main Results . Mean weekly 6-β-hydroxycortisol:cortisol ratios did not differ during the phase (week) of the menstrual cycle. Daily ratios did not differ in postmenopausal women. No difference between premenopausal and postmenopausal women was found on comparing overall median ratios. Conclusion . Cytochrome P450 3A4 activity as measured by 6-β-hydroxy cortisol:cortisol ratio did not differ by week of menstrual cycle, suggesting no menstrual cycle-related changes. Menopause does not appear to be associated with differences in CYP3A4 activity, compared with premenopause.