Inhibitory effect of 9-(2-phosphonylmethoxyethyl)adenine on visna virus infection in lambs: a model for in vivo testing of candidate anti-human immunodeficiency virus drugs

The acyclic nucleoside phosphonate analog 9-(2-phosphonylmethoxyethyl)adenine (PMEA) was recently found to be effective as an inhibitor of visna virus replication and cytopathic effect in sheep choroid plexus cultures. To study whether PMEA also affects visna virus infection in sheep, two groups of four lambs each were inoculated intracerebrally with 10(6.3) TCID50 of visna virus strain KV1772 and treated subcutaneously three times a week with PMEA at 10 and 25 mg/kg, respectively. The treatment was begun on the day of virus inoculation and continued for 6 weeks. A group of four lambs were infected in the same way but were not treated. The lambs were bled weekly or biweekly and the leukocytes were tested for virus. At 7 weeks after infection, the animals were sacrificed, and cerebrospinal fluid (CSF) and samples of tissue from various areas of the brain and from lungs, spleen, and lymph nodes were collected for isolation of virus and for histopathologic examination. The PMEA treatment had a striking effect on visna virus infection, which was similar for both doses of the drug. Thus, the frequency of virus isolations was much lower in PMEA-treated than in untreated lambs. The difference was particularly pronounced in the blood, CSF, and brain tissue. Furthermore, CSF cell counts were much lower and inflammatory lesions in the brain were much less severe in the treated lambs than in the untreated controls. The results indicate that PMEA inhibits the propagation and spread of visna virus in infected lambs and prevents brain lesions, at least during early infection. The drug caused no noticeable side effects during the 6 weeks of treatment.     

Optimization techniques for curved path computing

Participating media with an inhomogeneous index of refraction make light follow curved paths. Simulating this in a global illumination environment has usually been neglected due to the complexity of the calculations involved, sacrificing accurate physical simulations for efficient visual results. This paper aims to simulate non-linear media in a more reasonable time than previous works without losing physical correctness. Accuracy is achieved by solving the Eikonal equation of geometrical optics, which describes the path followed by a light beam that traverses a non-linear medium. This equation is used in the context of a photon mapping extension.     

Short-term handling of the slimming agent oleoyl-estrone in liposomes (Merlin-2) by the rat

Female adult rats were injected in the jugular vein with oleoyl-3H-estrone incorporated into liposomes. The label rapidly disappeared from the blood, being taken up by the tissues, mainly liver, spleen and lung, which filtered most of the label. However, many other tissues, such as the heart, brown adipose tissue, adrenals and visceral fat incorporated significant amounts of oleoyl-estrone. The analysis of the form in which the label remained 10 min after the injection showed that it was hydrolysed in a large proportion even in liver and lungs. However, in most tissues (brain, brown and white - periovaric - adipose tissues and ovaries), intact oleoyl-estrone accounted for less than one quarter of all tissue label, and less than 10% in the case of subcutaneous adipose tissue and uterus. This rapid destruction of oleoyl-estrone is in agreement with the active role of this compound in the control of body weight.     

Should patients with sleep apnoea/hypopnoea syndrome be diagnosed and managed on the basis of home sleep studies?

The purpose of this study was to analyse the validity and the economic efficiency of a portable monitor of respiratory parameters (PMRP), used in a home setting for the diagnosis of sleep apnoea/hypopnoea syndrome (SAHS). Eighty nine patients with suspected SAHS were studied in two settings: in the sleep laboratory using full-polysomnography (full-PSG); and at the patient's home using a PMRP. In the home setting, 50 patients were assisted by a technician and 39 set up the equipment themselves. SAHS (apnoea/hypopnoea index (AHI) >10 events x h(-1) by means of full-PSG) was diagnosed in 75 of the 89 patients. An acceptable agreement was obtained between the AHI measured by full-PSG and PMRP, according to the Bland and Altman method of concordance (mean bias 2.56; 95% confidence interval 3.25). Sensitivity and specificity of PMRP were adequate for diagnostic purposes; however, their values rely on the prior PMRP-AHI cut-off point selected with reference to full-PSG-AHI >10. The clinical therapeutic decision taken after PMRP agreed with that taken with full-PSG in 79 patients (89%). Although 10% of the studies with an individual set-up needed repetition, both of the domiciliary modalities (with and without a technician's intervention) were, economically, about three times more efficient than full-PSG. In conclusion, we believe that patients with a suspected sleep apnoea/hypopnoea syndrome should initially be studied in a home setting with a portable monitor of respiratory parameters, since it is a reliable method with an acceptable cost-effective profile.     

Estimates by computer simulation of genetic distances from comparisons of RNAse A mismatch cleavage patterns

The RNAse A mismatch cleavage method was used to analyze genomic variability in RNA and DNA systems. However, there is no method which relates the digestion patterns observed to the extent of genetic variation. Here we report computer simulations which provide a simple estimator of genetic distances from the comparison of RNAse A digestion patterns. The results show that the number of non-shared fragments is proportional to the number of mutations between each pair of sequences compared. This prediction is supported by the comparison of the RNAse A mismatch patterns and the nucleotide sequences of a set of influenza A (H3N2) hemagglutinin genes. The procedure allows a quantitative and reliable use of the RNAse A mismatch cleavage method.     

Spontaneous mutation for a quantitative trait in Drosophila melanogaster. II. Distribution of mutant effects on the trait and fitness

Exposure of the Chinese hamster ovarian AuxB1 cell line in vitro to fractionated X-irradiation generated sublines designated DXR-10, which proved resistant to multiple drugs and overexpressed P-glycoprotein (Pgp), as judged by Western blotting using the C219 monoclonal antibody. Further characterization of these irradiated DXR-10 sublines has provided evidence for: (i) the expression of cross-resistance to gramacidin D, taxol, puromycin and Navelbine, but not to daunomycin or mitoxantrone; (ii) overexpression of the class I Pgp, as judged by Western blotting using the C494 monoclonal antibody; (iii) decreased accumulation of 3H-vincristine, which could be enhanced by verapamil addition; (iv) unaltered accumulation and subcellular distribution of adriamycin; (v) significantly increased rhodamine 123 accumulation in the presence of verapamil; (vi) plasma-membrane ultrastructural modifications resulting in a significantly increased surface area; (vii) numerous clonal karyotypic alterations, with abnormalities involving the long arm of chromosome 1 being consistently identified; (viii) a lack of overexpression of sorcin; (ix) increased total glutathione levels and overexpression of glutathione S-transferase pi. The fact that only certain of these features are considered characteristic of the 'classic' multidrug-resistant CHRC5 cell line supports our earlier proposal that exposure to fractionated X-irradiation results in the expression of a unique drug-resistance phenotype.     

Utility of Albicans ID plate for rapid identification of Candida albicans in clinical samples. Rapid identification of Candida albicans

A clinical study was carried out in an attempt to assess the efficacy of a newly designed electric toothbrush compared to a conventional manual toothbrush using the American Dental Association's protocol for evaluating toothbrushes. An Oral-B 35 manual toothbrush, which served as the control, was compared to the Plaq & White125 electric toothbrush. Examinations were performed by two calibrated examiners at baseline, day 15 and day 30. Examinations included the gingival index, plaque index and bleeding index. Mean indices were calculated and compared between the two brushes using the repeated measures multiple analysis of variance. No statistically significant differences between the mean indices on the three examination days were observed following the use of the manual or the electric toothbrushes. The results of this study demonstrate that the electric toothbrush was numerically more effective than the manual toothbrush in reducing supragingival plaque levels, either before or after brushing, at each examination date compared to baseline plaque values. However, this difference was not statistically significant. This and other findings concluded that the Plaq & White toothbrush is comparable to the control ADA-accepted toothbrush.