Effect of estradiol and progesterone on muscle weight and acetylcholine receptors in “myasthenic” rats

Summary Clinical evidence suggests that endocrinal factors are involved in fluctuations of the symptoms of women with myasthenia gravis. We studied the effect of estradiol and progesterone in an animal model for myasthenia gravis in rats. Although it was found that the mass of muscles was dependent on sex, and in female rats affected by estradiol, the number of acetylcholine receptors in these muscles was independent of sex and hormone administration. Sex hormones failed to influence the severity of muscle weakness in myasthenic rats.     

Cerebral blood flow, cerebral metabolic rate of oxygen and relative CO2 reactivity during neurolept anaesthesia in patients subjected to craniotomy for supratentorial cerebral tumours

In 10 patients subjected to craniotomy for supratentorial cerebral tumours in neurolept anaesthesia, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice peroperatively by a modification of the Kety & Schmidt technique, using 133Xe. The relative CO2 reactivity was assessed indirectly as the % change of the arteriovenous oxygen difference (AVDO2) per mm change in PaCO2. The patients were premedicated with diazepam 10-15 mg perorally. For induction, thiopentone 4-6 mg/kg, droperidol 0.2 mg/kg and fentanyl 5 micrograms/kg were used, and for maintenance N2O 67% and fentanyl 4 micrograms/kg/h. During the first flow measurement the median and range of CBF was 30 ml/100 g/min (range 17-45), of AVDO2 8.0 vol % (range 4.1-9.5), and of CMRO2 2.28 ml O2/100 g/min (range 1.57-2.84). During the second CBF study, AVDO2 increased to 9.3 vol % (range 3.4-11) (P less than 0.05), and CMRO2 increased to 2.51 ml O2/100 g/min (range 1.88-3.00) P less than 0.05, while CBF was unchanged. The CO2 reactivity was present in all studies, median 1.8%/mmHg (range 0.5-15.1). The correlation coefficients between jugular venous oxygen tension/saturation, respectively, and CBF were high at tensions/saturations exceeding 4.0 kPa and 55%, indicating that hyperperfusion is easily unveiled by venous samples from the jugular vein during this anaesthesia.     

青海玉树健康人甲状腺激素测定

本文对玉树(海拔3700米)正常人58例的甲状腺激素用放射免疫法进行了测定,与西宁地区和平原地区对比,结果说明玉树地区T3、T4值明显或显著低于西宁和平原地区。TSH值又明显或显著高于西宁和平原地区、西宁地区P3、T4和TSH值均明显或显著低于平原。玉树地区藏、汉之间;男、女之间也有一定差异。这可能是高原低气压,缺氧对肝脏代谢的影响,调节甲状腺激素,以求机体对高原坏境的适应。     

A method for calculating the mean absorption time of drugs undergoing reversible and first-pass metabolism

A method has been derived for calculating the mean absorption time of an oral drug and its interconversion metabolite which is generated from the drug systemically and presystemically. The method evolves from the convolution integral and requires plasma AUC and AUMC values after separate intravenous administration of the drug and its interconversion metabolite and oral administration of the drug. It can also be used to calculate the mean input time of a drug undergoing reversible metabolism and administered by any other extravascular route. Results of a simulation study using both errorless and errant data indicate that, when the absorption rate constant of a drug or its interconversion metabolite is not much larger than the apparent elimination rate constant, the proposed method performs satisfactorily. However, when the absorption rate constant of a drug or its interconversion metabolite is much larger than the apparent elimination rate constant, the proposed method appears to be inaccurate.     

Heterocyclic amines: evaluation of their role in diet associated human cancer

1 Heterocyclic amines are formed in parts per billion levels when meat is cooked.
2 The heterocyclic amines MeIQx and PhIP are efficiently absorbed into the systemic circulation after ingestion of cooked food.
3 We have shown that MeIQx and PhIP, both in vitro and in vivo , are substrates for human hepatic CYP1A2, which exclusively and efficiently catalyses their conversion to genotoxic hydroxylamines.
4 MeIQx and PhIP are promutagens. MeIQx is a very powerful bacterial mutagen whereas PhIP is a more potent mammalian cell mutagen. Using a mammalian cell target gene, hprt , we have shown that PhIP induces a characteristic mutational 'fingerprint'.
5 MeIQx and PhIP are carcinogenic in bioassays. The PhIP mutational 'fingerprint' has been detected in the Apc gene of 5/8 colonic tumours induced by PhIP in rats.     

Population toxicokinetics of tetrachloroethylene

 In assessing the distribution and metabolism of toxic compounds in the body, measurements are not always feasible for ethical or technical reasons. Computer modeling offers a reasonable alternative, but the variability and complexity of biological systems pose unique challenges in model building and adjustment. Recent tools from population pharmacokinetics, Bayesian statistical inference, and physiological modeling can be brought together to solve these problems. As an example, we modeled the distribution and metabolism of tetrachloroethylene (PERC) in humans. We derive statistical distributions for the parameters of a physiological model of PERC, on the basis of data from Monster et al. (1979). The model adequately fits both prior physiological information and experimental data. An estimate of the relationship between PERC exposure and fraction metabolized is obtained. Our median population estimate for the fraction of inhaled tetrachloroethylene that is metabolized, at exposure levels exceeding current occupational standards, is 1.5% [95% confidence interval (0.52%, 4.1%)]. At levels approaching ambient inhalation exposure (0.001 ppm), the median estimate of the fraction metabolized is much higher, at 36% [95% confidence interval (15%, 58%)]. This disproportionality should be taken into account when deriving safe exposure limits for tetrachloroethylene and deserves to be verified by further experiments. Received: 20 April 1995/Accepted: 24 August 1995     

Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?

Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases. Received 14 April and in revised form 5 July 1997     

早期肠道营养对烧伤后肠源性高代谢的影响

从８０年代末起，通过对６００只大（豚）鼠、６０只兔和６０头小香猪所建立的４种烧伤后早期营养的动物模型，以及２１例严重烧伤病人对比分析，发现烧伤后早期肠道喂养可改善胃肠道血流供应，减轻肠道缺血再灌流损伤；可维护肠粘膜结构以及吸收、分泌、运动功能，降低门脉、中心静脉血内毒素水平，减少肠道内毒素易位；可降低伤后枯否细胞获得数、吞噬墨汁枯否细胞数和面积，以及其培养上清中肿瘤坏死因子（ＴＮＦ）量，对伤后枯否细胞的活化有刺激作用；可降低血胰高糖素、皮质醇、儿茶酚胺、ＴＮＦ、ＩＬ－８前列腺素Ｅ２（ＰＧＥ２）等递质的水平，降低高代谢，使烧伤４５％成人静息能量消耗（ＲＥＥ）在烧伤后４、８、１４ｄ的均值降低２８．６％。通过相关分析发现ＲＥＥ与血丙二醛（ＭＤＡ）、内毒素、分解激素、ＴＮＦ均呈显著正相关（ｒ＝０．７３８６～０．９９２２，Ｐ＜０．０５～０．０１）。