Pharmacokinetics of dextromethorphan after single or multiple dosing in combination with quinidine in extensive and poor metabolizers.

Dextromethorphan (DM) pharmacological properties predict that the widely used cough suppressant could be used to treat several neuronal disorders, but it is rapidly metabolized after oral dosing. To find out whether quinidine (Q), a CYP2D6 inhibitor, could elevate and prolong DM plasma profiles, 2 multiple-dose studies identified the lowest oral dose of Q that could be used in a fixed combination with 3 doses of DM. A multiple-dose study in healthy subjects with an extensive or a poor enzyme metabolizer phenotype evaluated the safety and pharmacokinetic profile of a selected fixed-dose combination (AVP-923).

Gliosarcoma: report of four cases with immunohistochemical findings.

Gliosarcoma (GSa) is a rare primary central nervous system neoplasm (CNS) characterized by biphasic histological pattern with both glial and sarcomatous components. Our objective is to describe the clinical, morphological and immunohistochemical features of four cases of GSa and to discuss its pathogenetic mechanisms. The male:female ratio was 3:1.

Influence of concomitant quinidine administration on dextromethorphan disposition in rats.

High doses of dextromethorphan (DM) have been clinically investigated for the treatment of multiple neuronal disorders including neuropathic pain. Several authors have suggested the concomitant administration of DM and a CYP2D6 reversible inhibitor in order to enhance the exposure of DM and limit the exposure to total dextrorphan (DX). The present study proposes to determine whether or not a single dose of quinidine is sufficient to enhance the plasma concentrations of DM in rats and keep those of DX at a minimal level.

Monitoring cyclosporine of pre-dose and post-dose samples using nonextraction homogeneous immunoassay.

A nonextraction homogeneous immunoassay (CEDIA Cyclosporine Plus Assay) has been developed for the measurement of cyclosporine in predose (trough) and post-dose (C2 to C8) whole-blood samples. The method includes a low-range assay that measures cyclosporine from 25 to 450 ng/mL in pre-dose samples and a high-range assay that detects cyclosporine from 450 to 2000 ng/mL in post-dose samples. The high-range assay allows a direct measurement of post-dose samples without a dilution step.

Optical tweezers stretching of chromatin.

Recently significant success has emerged from exciting research involving chromatin stretching using optical tweezers. These experiments, in which a single chromatin fibre is attached by one end to a micron-sized bead held in an optical trap and to a solid surface or second bead via the other end, allows manipulation and force detection at a single-molecule level. Through force-induced stretching of chromatin, mechanical properties, specific intermolecular bond strengths and DNA-protein association and dissociation kinetics have been determined.

Reliable microsatellite genotyping of the Eurasian badger (Meles meles) using faecal DNA.

The potential link between badgers and bovine tuberculosis has made it vital to develop accurate techniques to census badgers. Here we investigate the potential of using genetic profiles obtained from faecal DNA as a basis for population size estimation. After trialling several methods we obtained a high amplification success rate (89%) by storing faeces in 70% ethanol and using the guanidine thiocyanate/silica method for extraction.

Meningioma with extensive noncalcifying collagenous whorls and glial fibrillary acidic protein expression: new variant of meningioma diagnosed by smear preparation.

The purpose of this report is to describe the unique cytological findings of a new recently characterized type of meningioma that has extensive noncalcifying collagenous whorls and glial fibrillary acid protein (GFAP) expression. This new entity, described by Haberler and colleagues, was named whorling sclerosing variant of meningioma. The patient was a 34-yr-old white man with a large tumor in the brainstem.

Threonines 2638/2647 in DNA-PK are essential for cellular resistance to ionizing radiation.

DNA-dependent protein kinase (DNA-PK) is required for the repair of double-stranded DNA breaks through the nonhomologous DNA end joining pathway. DNA-PK activity is required for DNA repair, but kinase activity also appears to be attenuated through an autoregulatory feedback loop. We show that autophosphorylation of DNA-PK catalytic subunit occurs in trans at least three sites NH(2) terminal to the catalytic domain and that two sites, threonine 2638 and 2647, determine DNA-PK autophosphorylation in vitro.

The toxicity of behenyl alcohol. II. Reproduction studies in rats and rabbits.

Behenyl alcohol is a saturated 22-carbon, long-chain aliphatic alcohol, which has potential for use in foods as an oil-structuring and -solidifying agent in fats. Previously completed studies with behenyl alcohol indicated an absence of mutagenic or genotoxic potential. In addition, subchronic toxicity studies in rats and dogs reported no adverse effects following gross and histopathological examinations.

The toxicity of behenyl alcohol. I. Genotoxicity and subchronic toxicity in rats and dogs.

The genotoxic potential of behenyl alcohol, a saturated long-chain (C22:0) fatty alcohol, was examined in the Ames Salmonella typhimurium reverse mutation assay, the gene mutation, and chromosome aberrations assays in Chinese hamster V79 cells, and the micronucleus assay in NMRI mice. Behenyl alcohol did not increase the number of revertants per plate compared to controls in the S. typhimurium assay, with or without metabolic activation.

Primary epithelial malignant mesothelioma of the pericardium with deciduoid features: cytohistologic and immunohistochemical study.

Malignant mesothelioma with deciduoid features (MMWDF) is a recently characterized morphologic variant of epithelioid malignant mesothelioma, which frequently is misdiagnosed as peritoneal deciduosis or florid mesothelial hyperplasia. We report on the cytological, histological, immunohistochemical, and autopsy findings of a case of MMWDF arising in the pericardium of a 71-yr-old female patient. Cytology showed large, polygonal to round cells with pale to bright, eosinophilic cytoplasm, occasionally showing xantomatous pattern, containing a pleomorphic and vesicular nucleus with a single prominent nucleolus.

Discriminating small molecule DNA binding modes by single molecule force spectroscopy.

Drugs may interact with double stranded DNA via a variety of binding modes, each mode giving rise to a specific pharmacological function. Here we demonstrate the ability of single molecule force spectroscopy to discriminate between different interaction modes by measuring the mechanical properties of DNA and their modulation upon the binding of small molecules. Due to the unique topology of double stranded DNA and due to its base pair stacking pattern, DNA undergoes several well-characterised structural transitions upon stretching.

Primary fibromatosis of the breast in a patient with multiple desmoid tumors--report of a case with evaluation of estrogen and progesterone receptors.

Fibromatosis (or desmoid tumor) is an infiltrative fibroblastic/myofibroblastic lesion presenting a moderate risk for local recurrence and no metastatic potential. Classically, these lesions are classified whether in abdominal or extra-abdominal sites, and may be multicentric or familial. Primary fibromatosis of the breast (PFB) is an uncommon lesion that shows histological similarities with abdominal fibromatosis (AF), and frequently poses difficulties in the differential diagnosis with other spindle cell tumors of the breast.

Clinical efficacy of topical docosanol 10% cream for herpes simplex labialis: A multicenter, randomized, placebo-controlled trial.

Background: Recurrent herpes simplex labialis (HSL) occurs in 20% to 40% of the US population. Although the disease is self-limiting in persons with a healthy immune response, patients seek treatment because of the discomfort and visibility of a recurrent lesion.

Objective: Our purpose was to determine whether docosanol 10% cream (docosanol) is efficacious compared with placebo for the topical treatment of episodes of acute HSL.

Postabortion psychological adjustment: are minors at increased risk?

Purpose: To assess whether younger adolescents experience greater adverse psychological outcomes after abortion than those aged 18-21 years, whether abortion places all adolescents at risk for negative sequelae, and what factors predict negative outcomes.

Methods: A total of 96 young women aged 14-21 years seeking counseling for unwanted pregnancies at four clinics completed questionnaires after counseling. These included the Beck Depression Inventory (BDI), an emotion scale, questions regarding sociodemographic and reproductive background, feelings about pregnancy, and decision-making.

Force-induced melting of a short DNA double helix.

The dynamic behaviour of DNA is of fundamental importance to many cellular processes. One principal characteristic, central to transcription and replication, is the ability of the duplex to "melt". It has recently been shown that dynamic force spectroscopy provides information about the energetics of biomolecular dissociation.

The binding of Ku antigen to homeodomain proteins promotes their phosphorylation by DNA-dependent protein kinase.

The Ku antigen (70- and 80-kDa subunits) is a regulatory subunit of DNA-dependent protein kinase (DNA-PK) that promotes the recruitment of the catalytic subunit of DNA-PK (DNA-PKcs) to DNA ends and to specific DNA sequences from which the kinase is activated. Ku and DNA-PKcs plays essential roles in double-stranded DNA break repair and V(D)J recombination and have been implicated in the regulation of specific gene transcription. In a yeast two-hybrid screen of a Jurkat T cell cDNA library, we have identified a specific interaction between the 70-kDa subunit of Ku heterodimer and the homeodomain of HOXC4, a homeodomain protein expressed in the hematopoietic system.

The antiviral drug docosanol as a treatment for Kaposi's sarcoma lesions in HIV type 1-infected patients: a pilot clinical study.

Docosanol inhibits a broad spectrum of lipid-enveloped viruses in vitro including HSV-1, HSV-2, VZV, CMV, HHV-6, and HIV-1. These observations led us to conduct a pilot clinical study with docosanol 10% cream as a topical treatment for Kaposi's sarcoma (KS) in HIV-1-infected patients. In this open-label study 28 cutaneous KS lesions in 10 HIV-1-infected patients were treated topically five times daily for 4 weeks with evaluation of lesion characteristics of area, edema, and color.

Phylogeography and population structure of an ecotonal marsupial, Bettongia tropica, determined using mtDNA and microsatellites.

The northern bettong, Bettongia tropica, is an endangered species of Potoroidae with a restricted distribution in the wet tropics of north Queensland, Australia. The species is only found within a thin strip of sclerophyll forest along the western margin of rainforest. This tight association with rainforest boundaries is predicted to have resulted in population isolation as rainforest contracted during the Pleistocene, though some have proposed that the northern bettong was not present in the wet tropics until the late Pleistocene.

Topical application of docosanol- or stearic acid-containing creams reduces severity of phenol burn wounds in mice.

Because of their reported antiviral and anti-inflammatory activities, cream formulations containing n-docosanol (docosanol) or stearic acid were tested for effects on chemically-induced burns in mice. In this model, injury was induced by painting the abdomens of mice with a chloroform solution of phenol. This was followed by the topical application of test substances 0.

Atomic force microscopy studies of intercalation-induced changes in plasmid DNA tertiary structure.

Structural transitions in the tertiary structure of plasmid DNA have been investigated using atomic force microscopy. Changes in superhelical stress were induced by ethidium bromide intercalation, and conformational effects monitored by recording topographic images from DNA complexes of various ethidium bromide:base pair stoichiometry. Significant changes in the tertiary structure of individual DNA molecules were observed with increasing ethidium bromide concentration.