The venotonic drug hydroxyethylrutosiden does not prevent or reduce docetaxel-induced fluid retention: results of a comparative study

PURPOSE: Fluid retention, which includes peripheral edema, ascites, pleural or pericardial effusion, or a combination of these that is sometimes associated with significant weight gain, is one of the most troublesome cumulative side effects of docetaxel. A suggestive observation from the data base available at the manufacturer (Rhone-Poulenc Rorer) was that patients who received venotonic drugs appeared to tolerate more courses of docetaxel. This prompted a comparative study to investigate whether the venotonic drug hydroxyethylrutosiden could reduce or delay docetaxel-related fluid retention. METHODS: A total of 85 patients with metastatic breast cancer who were treated with docetaxel at a dose of 100 mg/m2 with corticoid comedication were allocated to receive either 300 mg hydroxyethylrutosiden given orally four times daily (group A) or no hydroxyethylrutosiden (group B). The end point for analysis was the development of fluid retention of > or = grade 2. RESULTS: Fluid retention of > or = grade 2 was reported in 14 of 42 patients (33%) in group A and in 15 of 43 patients (35%) in group B and occurred after a median of 4 cycles of docetaxel in both groups. Weight gain was similar in groups A and B. CONCLUSION: We conclude that hydroxyethylrutosiden does not reduce or delay the incidence and severity of docetaxel-related fluid retention.     

Sensory and chemical analysis of cooked porcine meat patties in relation to warmed-over flavour and pre-slaughter stress

Two independent sensory profiles were carried out to evaluate warmed-over flavour (WOF) development in cooked, chill-stored and reheated pork patties. The patties were derived from the Musculus semimembranosus of animals subjected to different pre-slaughter stress treatments. All patties were stored in oxygen permeable bags at 4°C for 0, 1, 2, 3 and 5 days to facilitate WOF development. In addition, thiobarbituric acid reactive substances (TBARS), conjugated dienes, pH, water content, total lipids and the fatty acid compositions of phosphatidyl choline (PC), phosphatidyl ethanolamine (PE) and total lipids, were measured in the cooked meat patties. A data analytical strategy involving Analysis of Variance-Partial Least Squares Regression (ANOVA-PLSR), to determine relationships between the design variables (WOF and pre-slaughter stress) and the sensory-chemical data, and PLSR to elucidate predictive links between the sensory and chemical data was utilised. WOF was found to involve the development of lipid oxidation derived nuance off-flavour and odour notes, e.g. rancid-like flavour and linseed oil-like odour, in association with a concurrent decrease in cooked pork meat-like flavour. The reduction in "meatiness", over the initial days, 0-2 of WOF development was attributed to the degradation of both, unstable sulfur-containing amino acids in meat proteins and sulfur-containing "meaty" aroma compounds. Whereas, at the later days, 3-5 of WOF development the "meaty" loss was ascribed to perceptual masking by lipid oxidation products. TBARS and conjugated dienes were found to be significant (P<0.05) predictors of the sensory terms related to the lipid oxidation aspect of WOF. Whilst the polyunsaturated fatty acid (PUFAs) contents of PE, PC and the total lipids were found to decrease with WOF development, reflecting their loss in lipid oxidation reactions. The sensory variation related to pre-slaughter stress appeared to be distinct from WOF variation and was described by a sour to sweet taste continuum. However, interactions were noted that indicated increasing pre-slaughter stress resulted in a decreased sensory perception of WOF. Moreover, pH and water content were found to significantly (P<0.05) predict the sensory effects resulting from pre-slaughter stress.     

Involvement of intracellular calcium in morphine tolerance in mice

We attempted to mimic in small upflow anaerobic sludge bed (UASB) bioreactors the metabolic association found in nature between methanogens and methanotrophs. UASB bioreactors were inoculated with pure cultures of methanotrophs, and the bioreactors were operated by using continuous low-level oxygenation in order to favor growth and/or survival of methanotrophs. Unlike the reactors in other similar studies, the hybrid anaerobic-aerobic bioreactors which we used were operated synchronously, not sequentially. Here, emphasis was placed on monitoring various methanotrophic populations by using classical methods and also a PCR amplification assay based on the mmoX gene fragment of the soluble methane monooxygenase (sMMO). The following results were obtained: (i) under the conditions used, Methylosinus sporium appeared to survive better than Methylosinus trichosporium; (ii) the PCR method which we used could detect as few as about 2,000 sMMO gene-containing methanotrophs per g (wet weight) of granular sludge; (iii) inoculation of the bioreactors with pure cultures of methanotrophs contributed greatly to increases in the sMMO-containing population (although the sMMO-containing population decreased gradually with time, at the end of an experiment it was always at least 2 logs larger than the initial population before inoculation); (iv) in general, there was a good correlation between populations with the sMMO gene and populations that exhibited sMMO activity; and (v) inoculation with sMMO-positive cultures helped increase significantly the proportion of sMMO-positive methanotrophs in reactors, even after several weeks of operation under various regimes. At some point, anaerobic-aerobic bioreactors like those described here might be used for biodegradation of various chlorinated pollutants.     

Recommendations for toxicological investigations of drug-facilitated sexual assaults

The recent increase in reports of drug-facilitated sexual assaults has caused alarm in the general public and prompted forensic toxicologists from across North America to address the toxicological issues surrounding this matter. The authors have developed recommendations and guidelines to inform law enforcement, medical, and scientific personnel of the requirements for performing successful toxicological examinations in cases of drug-facilitated rape.