Model Features of a Cardiac lontophoretic Drug Delivery Implant

Pharmaceutical Research -     

Occupational irritant contact dermatitis and fungal infection in construction workers

We have examined 6 construction workers who developed chronic skin diseases on their hands over a period of 15 years (1970–1985). 4 developed a Trichophyton rubrum infection, and the other 2 an irritant contact dermatitis. All of them carried out jobs which caused traumatization of the skin, due to the presence of ethylene glycol and mineral oils during operation of pneumatic hammers in winter. They also suffered other types of skin trauma during their work. Construction workers may be at risk of developing an occupational skin disease involving fungal infection.     

2-Aminofluorene-DNA adducts in mouse urinary bladder: effect of age, sex and acetylator phenotype.

Formation of urinary bladder DNA-2-aminofluorene adducts in inbred and acetylator congenic mice was measured 3 h after a 60 mg/kg dose of the arylamine carcinogen. The sensitivity of 32P-postlabeling with HPLC analysis permitted quantitation of adducts in individual mouse bladders. Acetylator phenotype was a significant determinant of DNA damage in female mice as slow acetylators had higher levels of bladder DNA adducts than rapids. This correlation is the reverse of that seen with hepatic DNA. Age was also a significant determinant of DNA damage as older mice (20-23 weeks) formed more bladder DNA adducts than young (7 week) mice. The age-related increase in bladder adduct formation was seen in both sexes of all mouse lines. Male B6 mice exposed to 2-aminofluorene at 20-23 weeks of age showed a 26-fold higher level of bladder DNA adducts than males exposed at 7 weeks. In addition to the large increase in total adduct level, the older male B6 mice produced significant amounts of an unidentified, early-eluting adduct peak that had chromatographic properties similar to an aminofluorene-DNA adduct produced through peroxidative activation. These results indicate that age, sex and acetylator phenotype are all important determinants of aromatic amine-bladder DNA adduct formation in mice.     

Spatial low frequency pattern analysis in positron emission tomography: a study between normals and schizophrenics.

Using the two-dimensional Fourier transform and the brain's centroidal principal axis, a method is developed for the analysis of PET metabolic brain images without the use of predefined anatomic regions of interest. We applied the method to images from a group of 11 normal and 12 medicated schizophrenics tested under resting conditions and under a visual task. A cortical/subcortical spatial pattern was found to be significant in two directions; anterior/posterior and chiasmatic (left-anterior/right-posterior). The best individual clinical classification (Jackknife classification) occurred under visual task at two axial brain levels: at the basal ganglia with correct classification rates of 91% and 84%, while the cerebellum had rates of 82% and 92%. These high classification rates were obtained using only the four coefficients of the lowest spatial frequency. These results point to the generalized brain dysfunction of regional glucose metabolism in chronic medicated schizophrenics both at rest and at a visual image-tracking task.     

Metabolic, molecular genetic and toxicological aspects of the acetylation polymorphism in inbred mice.

Over the past 10 years, much fascinating information has been obtained concerning the biochemistry, genetics, toxicological implications and molecular genetics of the N-acetylation polymorphism in mice. Using C57BL/6J (B6) mice as representative of rapid acetylation and A/J (A) mice as representing slow acetylation, it has been shown that the polymorphism observed in N-acetyltransferase (NAT) activity in liver also occurs in kidney, bladder, blood, and other tissues. The development of congenic acetylator mouse lines derived from B6 and A, have provided the necessary tools to study the role of the acetylation polymorphism, on either the B6 or A genetic background, free of nearly all other genetic differences between these strains. Eliminating genes which modify and complicate the differences due to the acetylator genes make the congenic lines very useful in toxicology studies, particularly those involving carcinogenesis. The molecular genetic basis of the acetylator polymorphism in B6 and A mice involves two Nat genes. Nat-1 encodes a protein termed NAT1 which is identical in rapid and slow acetylator strains. Nat-2, however, differs between rapid and slow strains by a single nucleotide change in the coding region. The corresponding NAT2 proteins differ by a single change at amino acid 99: an hydrophilic asparagine in rapid acetylator NAT2 to an hydrophobic isoleucine in NAT2 from slow acetylators. The mechanistic basis for the differences between rapid and slow acetylation in mice appears to be that NAT2 from the rapid B6 strain is 15-fold more stable at 37 degrees C and is transcribed/translated with a maximal efficiency twice that of the enzyme from slow acetylator A mice. Results discussed in this review indicate that mice provide an excellent system for studying the N-acetyltransferase polymorphism and also are useful for modelling several aspects of the human N-acetyltransferase polymorphism.     

Use of herbal supplements for chronic liver disease.

BACKGROUND & AIMS: Complementary and alternative medicine (CAM) is becoming popular among patients with liver disease. Although there is a growing body of evidence regarding potential mechanisms of action of these and other herbs, caution must be used to interpret the results of the few clinical trials available. Our goal was to discuss the biologic rationale for the use of specific herbs (silymarin, glycyrrhizin, sho-saiko-to, Phyllanthus amarus , Picrorrhiza kurroa , Compound 861, CH-100, and LIV.52) in the treatment of chronic liver diseases, as well as the evidence for their efficacy and adverse effects according to clinical trials. METHODS: Because of the relative paucity of clinical studies using herbs, every trial published in English was reviewed. RESULTS: Although many trials suggest that these herbs can decrease serum transaminase levels, the effects on hepatic histopathology and long-term survival are either poorly studied or conflicting. LIV.52 has been withdrawn from the market because of deleterious effects in patients with liver disease. CONCLUSIONS: Based on current evidence, we cannot recommend the use of herbal supplements for the routine treatment of any chronic liver disease and further well-designed clinical trials are necessary.