Promutagenic methylation damage in liver DNA of mice infected with Schistosoma mansoni

Male and female BK-TO mice were infected with different numbersof Schistosoma mansoni cercariae under standard environmentalconditions. Promutagenic methylation damage (O⁶-methyldeoxyguanosine;O⁶-MedG) was detected in liver DNA, but not in kidney, spleenor bladder DNA of infected animals. It was shown that levelsof hepatic O⁶-MedG increased with increasing intensities ofschistosomal infection. Possible mechanisms of action are discussed.These include the activating effects of schistosomes and theirproducts on murine macrophages and subsequent endogenous formationof N-nitroso compounds by the activated macrophages.     

Rasterelektronenmikroskopische Untersuchungen der menschlichen Linsenkapsel nach Kapsulorhexis

Die Ophthalmologie - Fragestellung: Um das Reißverhalten der menschlichen Linsenkapsel bei der Kapsulorhexis besser zu verstehen, wurden rasterelektronenmikroskopische Untersuchungen der...     

ACETYLATION PHENOTYPING OF ISONIAZID USING A SIMPLE AND ACCURATE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY

A simple, specific, accurate and reproducible method for the analysis of isoniazid and its major metabolite, N-acetylisoniazid in urine using high-performance liquid chromatography (HPLC) is described. The assay is performed after extraction of isoniazid, N-acetylisoniazid and 5-(4-methylphenyl)-5-phenylhydantoin (internal standard) from urine using a mixture of chloroform:isopropanol (70:30, v/v) and eluted from a 5 microns C-18 reversed phase column at ambient temperature with a mobile phase consisting of 10 mM sodium acetate:methanol:acetonitrile (40:40:20, v/v) containing 10 mM dioctylsulphosuccinate sodium and adjusted to pH 2.9 with sulphuric acid (less than 1 ml), at a flow rate of 1 ml/min with u.v. detection at 266 nm. Quantification was achieved by the measurement of the peak height ratio, and the absolute recoveries ranged from 94 to 99%. Within-day coefficients of variation ranged from 2.81 to 4.54% for isoniazid and from 2.37 to 3.75% for N-acetylisoniazid. Between-day CVs varied from 3.27 to 5.62% and from 2.5 to 4.91% for isoniazid and N-acetylisoniazid, respectively. Preliminary stability tests using a urine sample from a subject showed an increase in mean isoniazid concentration of about 25% after 1 month storage at -20 degrees C. The method was used for acetylation phenotyping of five individuals.     

Kinetic model for surface-active enzymes based on the Langmuir adsorption isotherm: phospholipase C (Bacillus cereus) activity toward dimyristoyl phosphatidylcholine/detergent micelles.

A simple kinetic model for the enzymatic activity of surface-active proteins against mixed micelles has been developed. This model uses the Langmuir adsorption isotherm, the classic equation for the binding of gas molecules to metal surfaces, to characterize enzyme adsorption to micelles. The number of available enzyme binding sites is equated with the number of substrate and inhibitor molecules attached to micelles; enzyme molecules are attracted to the micelle due to the affinity of the enzyme active site for the molecules in the micelle. Phospholipase C (Bacillus cereus) kinetics in a wide variety of dimyristoyl phosphatidylcholine/detergent micelles are readily explained by this model and the assumption of competitive binding of the detergent at the enzyme active site. Binding of phospholipase C to pure detergent micelles is demonstrated by gel filtration chromatography. The experimentally determined enzyme-detergent micelle binding constants are used directly in the rate equation. The Langmuir adsorption model predicts a variety of the characteristics observed for phospholipase kinetics, such as differential inhibition by various charged, uncharged, and zwitterionic detergents and surface-dilution inhibition. The essential idea of this model, that proteins can be attracted and bound to bilayers or micelles by possessing a binding site for the molecules composing the surface, may have wider application in the study of water-soluble (extrinsic) protein-membrane interactions.     

A pilot study evaluating the safety and microbiologic efficacy of an economically viable antimicrobial lozenge in patients with head and neck cancer receiving radiation therapy.

BACKGROUND: Mucositis occurs in almost all radiotherapy-treated head and neck cancer patients, in approximately 75% of patients receiving hematopoietic marrow transplantation, and in approximately 40% of all patients who receive chemotherapy. Mucositis is painful, may affect all oral functions, and is a dose- and rate-limiting toxicity of therapy for cancer. Radiation-associated mucositis (onset, intensity, and duration) has been shown in recent clinical trials to be modified by the use of antibacterial/antifungal lozenges. PURPOSE: The aim of this collaborative two-center phase II study was to assess the toxicity and microbiologic efficacy of an economically viable antimicrobial lozenge in the management of patients receiving radiation therapy for head and neck cancer. MATERIALS AND METHODS: Seventeen patients scheduled to receive radical or postoperative radiotherapy were provided with bacitracin, clotrimazole, and gentamicin (BCoG) lozenges (one lozenge dissolved in the mouth qid from day 1 of radiotherapy until completion). Ease of use and palatability of the lozenges, patients' symptoms (swallowing and pain), and quantitative and qualitative microbiologic evaluation of an oral rinse collection was conducted at least once weekly during radiation therapy. RESULTS: No significant side effects were reported from the use of the lozenges. The lozenges were well tolerated at the beginning of treatment by all patients, with some minor difficulty associated with oral discomfort toward the end of the treatment. Microbiologic evaluation showed consistent elimination of yeast organisms in all patients. In four patients there was no growth of gram-negative bacilli on culture, whereas in two patients, fluctuating counts were seen, and one patient had increased counts. The remaining patients had significant reduction in the gram-negative bacilli counts. CONCLUSIONS: This study demonstrated that the BCoG lozenge is tolerable and microbiologically efficacious, achieving elimination of Candida in all patients and reduction in gram-negative flora in most patients. A phase III study is underway to evaluate the clinical efficacy of this lozenge.     

Topotecan in Platinum- and Paclitaxel-Resistant Ovarian Cancer

Objective:The purpose of this study was to define the response rate and toxicity of topotecan in patients with ovarian cancer resistant to first-line therapy.Methods:Twenty patients with advanced or recurrent ovarian cancer were enrolled in a phase I/II protocol, and an additional 16 patients were treated following protocol closure at Washington University Medical Center. The starting dose of topotecan was 1.25 mg/m²/day given intravenously over 30 min for 5 consecutive days. Patients were eligible for response evaluation if they completed more than one cycle of topotecan. All patients were evaluated for toxicity.Results:Of 28 patients eligible for response evaluation, 26 were resistant to both platinum and paclitaxel prior to treatment with topotecan. There were four partial responders and no complete responders for a total response rate of 14% (95% confidence interval: 4 to 33%). All responders had exhibited primary resistance to both platinum and paclitaxel. Myelotoxicity was the major toxicity, with 92% of patients experiencing Gynecologic Oncology Group (GOG) grade 3 or 4 neutropenia and 67% experiencing GOG grade 3 or 4 thrombocytopenia. Other toxicity was minimal and easily managed. Fifty percent of patients receiving more than one cycle of topotecan tolerated a dose equal or greater to the starting dose.Conclusions:Topotecan exhibits activity in patients with ovarian cancer resistant to both platinum and paclitaxel. Further study is warranted in less heavily pretreated patients and in combination with other chemotherapeutic agents.     

Solubilization and stabilization of an investigational antineoplastic drug (NSC no. 278214) in an intravenous formulation using an emulsion vehicle

The use of parenteral fat emulsions for development of an extemporaneous preparation of an intravenous formulation of a poorly water-soluble and unstable investigational anticancer agent (NSC no. 278214) is presented. The incorporation into a commercial fat emulsion of the drug, dissolved in dimethylacetamide-cremophor solution, results in a suitable parenteral formulation in which the drug is approximately 100-fold more stable than in simple aqueous solutions.     

Fetal ear length measurement: a useful predictor of aneuploidy?

OBJECTIVE: To determine the usefulness of short ear length (EL) measurement in the prenatal detection of fetuses with chromosomal abnormalities. DESIGN: Fetal EL measurements, routine biometry and complete anatomic survey for fetal abnormalities were prospectively performed by antenatal sonography. SUBJECTS: One thousand eight hundred and forty-eight patients with singleton pregnancies undergoing genetic amniocentesis in the second or third trimester. METHODS: Complete data for EL, biometry and anatomic survey for major structural abnormalities and minor sonographic markers of chromosomal abnormality were available in 1311 fetuses. Of these, 48 (3.7%) had an abnormal karyotype and 1263 (96.3%) had a normal karyotype. Using an EL measurement of < or = 10th percentile for corresponding gestational age in normal fetuses as abnormal cut-off values, detection rates for chromosomal abnormalities by short EL were determined. RESULTS: Among the 48 abnormal karyotypes, 34 were considered significant, and 11 of these 34 (32.4%) fetuses had short EL. In 14 cases, the karyotypic abnormality was considered non-significant and fetal EL was normal in all cases. Of the 34 fetuses with significant chromosomal abnormalities, six (17.6%) on antenatal sonography had no detectable abnormal findings, other than short EL. An increased biparietal diameter (BPD)/EL ratio of > or = 4.0 was also noted in fetuses with an abnormal karyotype, but the sensitivity and predictive value of increased BPD/EL ratio alone or increased BPD/EL ratio in combination with short EL was no better than the sensitivity and predictive value of short EL alone. A combination of short EL and abnormal ultrasound, however, gave a much higher positive predictive value (46%) for significant chromosomal abnormalities. CONCLUSIONS: Our findings suggest that in women at high risk for fetal chromosomal abnormality, a short fetal EL measurement on prenatal ultrasound, either alone or in combination with other sonographically detectable structural abnormalities, may be a useful parameter in predicting fetal aneuploidy.