Xenobiotic metabolism in rat, dog, and human precision-cut liver slices, freshly isolated hepatocytes, and vitrified precision-cut liver slices

Human, rat, and dog phase I and phase II xenobiotic metabolism in precision-cut liver slices and freshly isolated hepatocytes was compared using a range of substrates. Carbamazepine (50 microM) and styrene (2 mM) were used as probes to study the maintenance of cytochrome P450 and epoxide hydrolase-mediated metabolism in male Sprague-Dawley rat, precision-cut liver slices and hepatocytes. Carbamazepine metabolism in both models resulted in the formation of the bioactive 10,11-epoxide (KM = 766 microM and Vmax = 2.5 pmol/min/mg protein in precision-cut slices). Epoxide formation was higher (2.4-fold) in hepatocytes than slices. Styrene was deactivated to styrene diol at a higher rate in hepatocytes (9.7-fold) than slices. The lower rate of metabolism in slices compared with hepatocytes confirms our previous observations using testosterone, 7-ethoxycoumarin, 1-chloro-2,4-dinitrobenzene and 2-(5'-chloro-2'-phosphoryloxyphenyl)-6-chloro-4-(3H)-quinazolinone in the rat. Testosterone 6 beta-hydroxylation in human liver slices was similar to cultured hepatocytes, but lower than in freshly isolated hepatocytes. 7-Ethoxycoumarin O-deethylation was higher in freshly isolated human hepatocytes, as was the ratio of glucuronide to 7-hydroxycoumarin. Testosterone hydroxylations, 7-ethoxycoumarin O-deethylation, and 1-chloro-2,4-dinitrobenzene conjugation were also lower in male beagle dog slices, compared with freshly isolated hepatocytes. Attempts at long-term preservation of dog liver slices using vitrification and storage for up to 9 days at -196 degrees C resulted in the retention of phase I and phase II metabolism, although conjugation was lower than in freshly prepared slices. Xenobiotic metabolism in short-term incubations is consistently lower in dog and rat precision-cut slices than in freshly isolated hepatocytes; whereas, in humans, this quantitative difference is partly hidden by the large interindividual variation.     

Urinary excretion of vanilmandelic acid in the glossalgia syndrome

Under observation there were 78 patients aged 41 to 70 years suffering from the glossalgia syndrome, as well as 25 clinically healthy subjects. An activation of the sympathoadrenal system was revealed in the patients. This was ascertained on the basis of the data on vanillylmandelic acid excretion with the urine. The excretion of that acid is known to be dependent on the intensity of the paraesthesias, the duration of the ailment and the character of concurrent visceral diseases. The results obtained are regarded as evidences of the participation of the vegetative nervous system in the mechanism of the glossalgia syndrome development.     

A quantitative evaluation of the glycogen content of the hepatocytes from different lobular ares of the normal human liver and in chronic hepatitides of different etiologies

Investigation of glycogen function in hepatocytes of different liver lobule zones is particularly important in understanding glycogen metabolism in humans and animals in norm and pathology. The present study was done to investigate glycogen contents in hepatocytes of different lobule zones of human liver in norm, and in patients with chronic hepatitis of viral or alcohol etiology. Quantitative analysis of glycogen content in hepatocytes of portal and central lobule zones was conducted on slices of human liver (the material of series live punctional biopsies) stained using a quantitative variant of PAS-reaction (Kudryavtseva et al., 1970, 1974). The measurements were done by image analyzer , which allows to make jointly cytophotometric analysis of substance in cells and definition of cell localization in tissue. The results showed clear differences of glycogen contents in different lobule zones in normal liver and in liver during chronic viral and alcohol hepatitis. Glycogen contents in hepatocytes of portal lobule zone were significantly higher than in the central lobule zone in patients with chronic viral hepatitis. Opposite data were obtained in patients with chronic alcohol hepatitis. Significantly higher glycogen contents were found in hepatocytes of the central liver lobule zone. Possible mechanisms of such a phenomenon are discussed . Thus, if glycogen contents in hepatocytes may be taken as an indicator of liver chronic damage degree (as has been shown elsewhere: Kudryavtseva, 1987; Kudryavtseva et al., 1988) the pattern of distribution of hepatocytes with different glycogen content in the liver lobule can be used as an indicator of etiology of chronic hepatitis. The obtained data seem to be important and actual, particularly for diagnostic of subclinical and symptomless forms of these diseases. Further investigation is required to find out reasons and mechanisms of this phenomenon.     

Strategic questions for consumer-based health communications

Using the consumer-oriented approach of social and commercial marketers, this article presents a process for crafting messages designed to improve people's health behaviors. The process, termed consumer-based health communications (CHC), transforms scientific recommendations into message strategies that are relevant to the consumer. The core of CHC is consumer research conducted to understand the consumer's reality, and thereby allowing six strategic questions to be answered. The immediate result of the CHC process is a strategy statement--a few pages that lay out who the target consumer is, what action should be taken, what to promise and how to make the promise credible, how and when to reach him or her, and what image to convey. The strategy statement then guides the execution of all communication efforts, be they public relations, mass media, direct marketing, media advocacy, or interpersonal influence. It identifies the most important "levers" for contact with the consumer. Everyone from creative specialists through management and program personnel can use the strategy statement as a touchstone to guide and judge the effectiveness of their efforts. The article provides a step by step illustration of the CHC process using the 5 A Day campaign as an example.     

Factors affecting contrasting results between self-reported and performance-based levels of physical limitation

Molecular electrostatic potential (MEP) maps of certain 3-methoxy flavone derivatives having different anti-picornavirus activities have been studied. Geometries of the molecules were optimised and charge distributions computed using the AM1 molecular orbital method. Hybridization displacement charges (HDC) were combined with the L?wdin charge distributions to compute the MEP maps. Reliability of the method of computing MEP maps was tested by studying certain other molecules for which ab initio MEP results are available. The anti-picornavirus activities of the flavones have been shown to be related with negative MEP values in two regions, one near the 3-methoxy group and another in a diagonally opposite region near the substituent attached to the C7 atom of the molecules.     

The NS gene--a possible determinant of apathogenicity of a cold-adapted donor of attenuation A /Leningrad/134/47/57 and its reassortants

Phenotypical properties of single-gene reassortants of attenuated cold-adapted strain A/Leningrad/135/47/57 (H2N2) and strain A/PR8/34 virulent for laboratory animals were studied. Only the group of reassortants inheriting NS gene from cold-adapted virus was fully attenuated for various animals species, similarly as reassortants with 6/2 genomic formula containing all the 6 internal protein genes from strain A/Leningrad/134/47/57. Reassortant 25A-1 single-gene for NS was temperature-sensitive (ts) on mammalian cells but formed plaques at 40 degrees C on chicken kidney cells. Reassortants with genomic formula 6/2 were temperature-sensitive in all types of cells used. Reassortant 25A-1 could synthesize normal amounts of polypeptides in MDCK cells at 39 degrees C, whereas protein synthesis of reassortants with 6/2 genomic formula was noticeably reduced at this temperature. Hence, a similar level of attenuation of both reassortant groups appears to be due to various molecular mechanisms. Possible role of NS2 gene mutation in attenuation of strain A/Leningrad/134/47/57 and its reassortants is discussed.     

A safer and more effective treatment regimen for eclampsia

The purpose of our investigation was twofold: to provide normative data for the ratios between head circumference and cerebellum, abdominal circumference and cerebellum, and femur length and cerebellum; and to evaluate the predictive accuracy of an abnormal ratio in the detection of growth retardation and macrosomia. Data on 675 women with normal gestations between 14 and 42 weeks were used to estimate reference curves for the three ratios to be evaluated. We then compared the ratios of 34 fetuses with intrauterine growth retardation and 28 macrosomic fetuses to the control group. Of the three ratios that we investigated, abdominal circumference to transverse cerebellar diameter was the most efficacious. However, the sensitivity of this ratio for the detection of intrauterine growth retardation and macrosomia was only 52.9% and 46.6%, respectively. A ratio between head circumference, abdominal circumference, or femur length and the transverse cerebellar diameter cannot reliably distinguish between normally growing fetuses and those that are growth retarded or macrosomic.     

Relationship between lateral subluxation and widening of medial joint space in Legg-Calvé-Perthes disease

Fifty-five patients (61 affected hips and 49 unaffected hips) with Perthes disease were reviewed to evaluate the relationship between widening of medial joint space and lateral subluxation of the femoral head in radiographs. The components of the medial joint space were evaluated by using T1, T2, proton, and Gd-enhanced T1WI magnetic resonance images (MRI). The widened medial joint space in radiographs was filled with overgrown cartilage at the initial stage (27 hips) in MRI, with both overgrown cartilage and widened true medial joint space at the fragmentation stage (23 hips) and widened true medial joint space at the healing stage (11 hips). Between affected hips and unaffected hips, the mean difference of medial joint space in radiographs between hips at the initial stage and at the fragmentation stage was 2 and 4.5 mm, respectively; the mean difference in percentage of lack of coverage of the femoral head between hips at the initial stage and at the fragmentation stage was 3 and 15%, respectively. During the healing stage, widening of the medial joint space decreased or normalized because of ossification of overgrown cartilage despite the existence of lateral subluxation because of coxa magna. We concluded that widening of the medial joint space may be used as an index of lateral subluxation at only the fragmentation stage in Perthes disease.