Oxidant stress: the role of nutrients in cell-lipoprotein interactions

Oxidant stress is increasingly becoming an important hypothesis to explain the genesis of several pathologies, including cancer, atherosclerosis and also ageing. Beside a few rare genetic defects, dietary factors are thought to play a key role in the regulation of the production of reactive oxygenated species. An imbalance between nutrients, and in particular those involved in antioxidant status, could explain the onset of an enhanced production of free radicals. We will briefly review information concerning oxidation of lipids and lipoproteins which lead to atherothrombosis. We also present new findings supporting a role for blood platelets in generating oxidant species. New data are also described concerning the role of oxygenated derivatives of cholesterol, oxysterols, in cellular cholesterol efflux and NO production. Also, new developments relating to the influence of direct effects of free radicals on cellular cholesterol homeostasis are presented. Finally, the in vitro effects of butyrate, a natural short-chain fatty acid produced by bacterial fermentation, in the protection against free radical-mediated cytotoxicity are discussed. These data provide information on the mechanisms of dietary antioxidants in preventing oxidant stress.     

Laboratory data in healthy volunteers: reference values, reference changes, screening and laboratory adverse event limits in Phase I clinical trials

Objective: Laboratory data are key evaluation procedures for Phase I clinical pharmacology for two reasons. Firstly, laboratory data are used within the screening process to exclude subjects with asymptomatic diseases, which could result in increased danger to themselves or confuse interpretation of the study results. Secondly, during study implementation, safety evaluation and in particular maximum tolerated dose determination have to be done by a case-by-case analysis, sometimes using laboratory adverse events (LAEs). Thus, relevant limits are needed to discriminate between a usual common variation and a significant abnormality, which is considered to be a LAE. This report presents laboratory data distribution, reference values and reference changes and, based on previously published new methods, suggests inclusion limits at screening and laboratory adverse event limits for analysis during study implementation. Subjects and methods: Nine hundred and twenty-seven young healthy male volunteers were recruited in one centre (Association de Recherche Thérapeutique). A standard screening process was carried out. Protocols were approved by the local ethics committee. Blood sampling was performed in the same conditions. Reference values (at screening and at baseline) were determined by a non-parametric procedure selecting 2.5% and 97.5% of the distribution of data. Reference changes were also defined as the 2.5–97.5% interval of distribution of the variations between the end of treatment and baseline. Inclusion limit and LAE limit methods of determination used had been specified in previous articles. Results: Detailed results of laboratory data distribution, reference values at screening and at baseline, reference changes, inclusion limits and LAE limits are presented in tables with number of subjects, mean, median, standard deviation, minimal and maximal values and the 2.5–97.5% interval for each laboratory parameter. Conclusion: The key aims of this paper are to provide clinical pharmacologists with data, reference values or changes obtained in the real conditions of Phase I study implementation, and to propose relevant limits, either for screening as inclusion limits, or during studies as LAE limits. Thus, these data, reference values and specific limits improve the capacity to screen healthy volunteers and to analyse LAEs during Phase I studies. Received: 30 July 1998 / Accepted in revised form: 25 November 1998     

Primary Bladder Neck Obstruction: Urodynamic Findings and Treatment Results in 36 Men

Purpose

We reviewed the urodynamic findings and treatment outcomes of a large series of men with primary bladder neck obstruction.

Materials and Methods

A retrospective review was done of the presenting symptoms and urodynamic findings of 36 men with primary bladder neck obstruction. Outcomes after treatment with alpha-blockers, transurethral incision of the bladder neck and prostate, or no long-term therapy were determined by chart review and patient survey in the majority of cases.

Results

Mean age of the men was 41 years. Patients had significant lower urinary tract symptoms, decreased peak urinary flow rates, elevated post-void residual, markedly elevated peak voiding pressures and poor funneling of the bladder neck during voiding. Although most patients initially chose alpha-blocker therapy, only 30 percent of those beginning alpha-blockers continued them long term, usually due to inadequate symptomatic improvement. A total of 18 men underwent transurethral incision, which resulted in significant improvements in symptom scores, peak urinary flow rates, post-void residual and peak voiding pressures. Patients reported a mean 87 percent overall improvement in symptoms after transurethral incision.

Conclusions

Video urodynamics facilitate diagnosis of primary bladder neck obstruction. Transurethral incision is the most effective therapy for primary bladder neck obstruction.     

Quantitation of adriamycin in plasma and urine: comparative study of radioimmunoassay and high-performance liquid chromatography methods

The response of tumours to adriamycin, and the cardiotoxicity of the drug, may be related to its pharmacokinetics and plasma levels. Rapid and sensitive methods of adriamycin determination in plasma and urine samples are thus needed. A comparative study shows that high-performance liquid chromatography with fluorimetric detection is a reliable and specific method, but it is relatively slow and sometimes lacks sensitivity. A commercially-available radioimmunoassay kit is convenient, but there is a cross reaction with the major metabolise adriamycinol and unless the assay is combined with an extraction step, it gives erroneously high results.     

Adriamycin: a possible indirect radiosensitizer of hypoxic tumor cells.

Multicellular spheroids grown in vitro provide a convenient model of nodular tumors for experimental tumor therapy studies. Adriamycin was found to inactivate cells grown as spheroids less efficiently than single cells, presumably due to enhanced cellular resistance analogous to the increased radioresistance observed when these cells are grown in close contact. Spheroid growth was retarded by a minimally toxic (0.005 mug/ml) chronic level of adriamycin; irradiation and exposure to that drug concentration were not found to be synergistic. Large adriamycin concentrations (0.5 mug/ml) present during radiation exposure produced a marked "radiosensitization," presumably due to the drug-inhibitng cellular oxygen consumption and thus permitting reoxygenation of the previously hypoxic spheroid cells.     

Residual nitrite and nitrate content in French cooked hams and shoulders]

The test laboratory of the "Centre technique de la salaison, de la charcuterie et des conserves de viandes" has evaluated the nitrite and nitrate salts contents of 1 468 cooked hams and shoulders. 90,5 p. 100 of sample have a sodium nitrite content of less than 150 mg/kg. 81,5 p. 100 have a potassium nitrate content of less than 500 mg/kg. The measured contents show a wide scattering. The nitrite mean content is of 61 mg/kg with a standard deviation of 95. The nitrate mean content is of 292 mg/kg with a standard deviation of 382. There were no significant variations between the various categories of cooked hams and shoulders.     

A training program on exclusive breastfeeding in maternity wards.

OBJECTIVES: To estimate whether a 3-day training program for health professionals was followed by changes in maternity ward practices and in the rate of exclusive breastfeeding. METHODS: A retrospective study in the maternity ward of a French university hospital involved two cross-sectional samples of 323 mother-infant pairs in 1997 and 324 in 2000. RESULTS: The rate of exclusive breastfeeding at discharge increased from 15.8% (12.0-20.2) in the before sample to 35.2% (30.0-40.6) in the after sample (P<0.01). This result persisted in the multivariable analysis [adjusted odds ratio, 2.74 (1.72-4.37)]. Infants in the before sample were less likely to be breastfed within 1 h of birth (9.2% vs. 16.9%, P=0.01), to room-in 24 h/day (56.6% vs. 72.6%, P<0.01), and were more likely to receive formula supplementation (77.6% vs. 54.0%, P<0.01). CONCLUSIONS: A training program for health professionals can be effective in improving maternity ward practices and increasing exclusive breastfeeding rate at discharge.