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Despite the chicken being one of the most genetically mapped of all animals, its karyotype remains poorly defined. This is primarily due to microchromosomes that belie assignment by conventional methods. To address this problem, we have developed chromosome-specific paints using flow cytometry and microdissection. For the microchromosomes it was necessary to amplify and label DNA from single microdissected chromosomes. Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Uric acid is a major antioxidant in the blood of humans that can protect cultured neurons against oxidative and metabolic insults. However, uric acid has a very low solubility which compromises its potential clinical use for neurodegenerative disorders. Here we describe the synthesis, characterization and preclinical development of neuroprotective methyl- and sulfur-containing analogs of uric acid with increased solubility. In vitro and cell culture screening identified 1,7-dimethyluric acid (mUA2) and 6,8-dithiouric acid (sUA2) as two analogs with high antioxidant and neuroprotective activities. When administered intravenously in mice, uric acid analogs mUA2 and sUA2 lessened damage to the brain and improved functional outcome in an ischemia-reperfusion mouse model of stroke. Analogs sUA2 and mUA2 were also effective in reducing damage to the cerebral cortex when administered up to 4 h after stroke onset in a permanent middle cerebral artery occlusion mouse model. These findings suggest a therapeutic potential for soluble analogs of uric acid in the treatment of stroke and related neurodegenerative conditions.

Individuals with elevated homocysteine levels are at increased risk for cardiovascular disease and stroke, and neurodegenerative disorders such as Alzheimer's and Parkinson's diseases Homocysteine is a modified form of the amino acid methionine that is tightly regulated by enzymes requiring folate. By impairing DNA repair mechanisms and inducing oxidative stress, homocysteine can cause the dysfunction or death of cells in the cardiovascular and nervous systems. Dietary folate stimulates homocysteine removal and may thereby protect cells against disease processes. The enzymes involved in homocysteine and folate metabolism provide novel targets for drug discovery.

Administration of morphine exerts many effects on the immune system. On the other hand little attention has been paid to the fact, that endogenous morphine and codeine exists in mammals, including man. This raises the question, whether or not endogenous opiate alkaloids play some role in immunoregulation. In addition muramyl-dipeptide (MDP), product of bacterial cell wall degradation and a potent immunomodulatory agent exhibits a broad spectrum of effects including effects on CNS functions. The present study investigated whether or not the endogenous levels of morphine and codeine are affected by administration of MDP in mice. Marked variation was found in spleen, brain, small intestine and heart in morphine and codeine concentrations. The intraperitoneal administration of MDP produced a significant increase in tissue morphine levels 30 minutes after injection.

The partial molal volumes, V2, at infinite dilution of atropine and hyoscine were determined in each of eight different solvents having cohesive energy densities in the range 64 to 144 cal cm-3. V2 for hyoscine in a given solvent was invariably and significantly smaller than that of atropine in the same solvent. The difference being 1.58 cm3 mol-1 in the least polar solvent (n-propylbenzene) and 4.29 cm3 mol-1 in the most polar one (acetonitrile) in the series studied. It is proposed that the lower affinity of atropine relative to that of hyoscine for the muscarinic cholinoceptor could be accounted for by the relative increase in enthalpy in the adsorption of atropine to the receptor with respect to the same process with hyoscine.

The partial molal volume at infinite dilution, V2, was determined in toluene, benzene and acetonitrile for fifteen different drug molecules comprising muscarinic agonists, partial agonists and antagonists. The difference in V2 between a given drug, X, and hyoscine, expressed as (V2x - V2h) was then multiplied by the internal pressure of the holding phase (Pi approximately cohesive energy density) in order to obtain an estimate of the excess enthalpy (delta H) over hyoscine in the interaction of drug molecule X with a common cholinoceptor. As a working hypothesis, delta H for hyoscine is taken as zero, hyoscine having the lowest V2/affinity ratio of any drug in the series investigated. The corresponding change in entropy (delta S) was then calculated from the relationship: RT ln Kx = Pi(V2x - V2h) - T delta S, where Kx is the affinity constant of drug molecule X to the common cholinoceptor, obtained independently. Linear regression of Pi (V2x - V2h) congruent to delta H from the data in acetonitrile over delta S gave a satisfactory isoequilibrium plot, r2 = 0.954, slope (beta) = 231 degrees K. The present approach offers a new course for the study of the enthalpy-entropy relationship in the interaction of drug molecules in a given series with a common receptor. It could provide an alternative to the Van't Hoff procedure for the estimation of relative delta H, and is independent of the free energy of binding (delta G).

We encountered three women from three generations of the same family with features of focal dermal hypoplasia (FDH). Two of the patients, the proposita and her mother, demonstrated severe manifestations, including skin, dental, skeletal, and visceral abnormalities. The proposita's grandmother, the first family member affected, had very mild expression, with aplasia cutis congenita and dental caries as the only features expressed. This family illustrates both the marked variability of expression and the proposed X-linked dominant mode of inheritance of FDH. We postulate that early embryologic random inactivation of the X chromosome bearing the mutant gene responsible for FDH is the cause of the variable expression.

An open, multicenter study was conducted to evaluate the efficacy and adverse effects of ketoconazole in patients with cutaneous fungal infections seen in typical dermatology practices. One hundred twelve American investigators entered 954 patients into this trial. Responses based on clinical and mycologic assessments were available on 672 patients. Mycologic evaluations were conducted using pre- and post-therapy wet mounts in potassium hydroxide. Eighty percent of these patients were mycologically clear and clinically rated as either excellent (cured) or marked improvement. Adverse effects were mild to moderate in severity and only rarely caused therapy to be interrupted. Gastrointestinal effects were the most frequently reported complaints.