Old and new approaches to the interpretation of acid-base metabolism, starting from historical data applied to diabetic acidosis.

The approach to acid-base chemistry in medicine includes several methods. Currently, the two most popular procedures are derived from Stewart's studies and from the bicarbonate/BE-based classical formulation. Another method, unfortunately little known, follows the Kildeberg theory applied to acid-base titration. By using the data produced by Dana Atchley in 1933, regarding electrolytes and blood gas analysis applied to diabetes, we compared the three aforementioned methods, in order to highlight their strengths and their weaknesses. The results obtained, by reprocessing the data of Atchley, have shown that Kildeberg's approach, unlike the other two methods, is consistent, rational and complete for describing the organ-physiological behavior of the hydrogen ion turnover in human organism. In contrast, the data obtained using the Stewart approach and the bicarbonate-based classical formulation are misleading and fail to specify which organs or systems are involved in causing or maintaining the diabetic acidosis. Stewart's approach, despite being considered 'quantitative', does not propose in any way the concept of 'an amount of acid' and becomes even more confusing, because it is not clear how to distinguish between 'strong' and 'weak' ions. As for Stewart's approach, the classical method makes no distinction between hydrogen ions managed by the intermediate metabolism and hydroxyl ions handled by the kidney, but, at least, it is based on the concept of titration (base-excess) and indirectly defines the concept of 'an amount of acid'. In conclusion, only Kildeberg's approach offers a complete understanding of the causes and remedies against any type of acid-base disturbance.

Short term inhalation toxicity of a liquid aerosol of glutaraldehyde-coated CdS/Cd(OH)2 core shell quantum dots in rats.

Quantum dots exhibit extraordinary optical and mechanical properties, and the number of their applications is increasing. In order to investigate a possible effect of coating on the inhalation toxicity of previously tested non-coated CdS/Cd(OH)2 quantum dots and translocation of these very small particles from the lungs, rats were exposed to coated quantum dots or CdCl2 aerosol (since Cd(2+) was present as impurity), 6h/d for 5 consecutive days. Cd content was determined in organs and excreta after the end of exposure and three weeks thereafter. Toxicity was determined by examination of broncho-alveolar lavage fluid and microscopic evaluation of the entire respiratory tract. There was no evidence for translocation of particles from the respiratory tract. Evidence of a minimal inflammatory process was observed by examination of broncho-alveolar lavage fluid. Microscopically, minimal to mild epithelial alteration was seen in the larynx. The effects observed with coated quantum dots, non-coated quantum dots and CdCl2 were comparable, indicating that quantum dots elicited no significant effects beyond the toxicity of the Cd(2+) ion itself. Compared to other compounds with larger particle size tested at similarly low concentrations, quantum dots caused much less pronounced toxicological effects. Therefore, the present data show that small particle sizes with corresponding high surfaces are not the only factor triggering the toxic response or translocation.

Reproducibility over time of the urinary diclofenac/4'-OH diclofenac ratio among different CYP2C9 genotypes.

Diclofenac has been used for the evaluation of CYP2C9 activity in vitro as well as in vivo with varying results. The present study was aimed at evaluating the reproducibility of the urinary diclofenac/4'-OH diclofenac ratio among different CYP2C9 genotypes in healthy volunteers. The study of CYP2C9 genotypes in the family of a CYP2C9*3/*3 subject is also reported. The urinary diclofenac/4'-OH diclofenac ratio was determined on two occasions within a period of 9-12 months, and was found to be correlated (r = 0.83, p < 0.05). The mean (+/- SD) of diclofenac/4'-OH diclofenac ratio was 1.5 times higher among subjects carrying CYP2C9*3 allele (CYP2C9*1/*3 and CYP2C9*2/*3 genotypes) (0.91 +/- 0.28), compared to CYP2C9*1/*1 subjects (0.60 +/- 0.11). The results show that the urinary diclofenac/4'-OH diclofenac ratio might be used to study CYP2C9 in humans. The data agree with previous studies showing that the CYP2C9*3 allelic variant seems to cause a decreased CYP2C9 hydroxylation capacity.

Detectability of phencyclidine and 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid in adulterated urine by radioimmunoassay and fluorescence polarization immunoassay.

The ability to alter immunoassay test results by the addition of some commonly available chemicals to drug-positive and drug-negative urine specimens was investigated. Urine specimens containing either phencyclidine (PCP) or 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (9-THC-COOH) were adulterated with sodium chloride, bleach, vinegar, potassium hydroxide, liquid soap, 2-propanol, and ammonia. Subsequent analyses by radioimmunoassay (RIA) and fluorescence polarization immunoassay (FPIA) demonstrated false positive and false negative results with some adulterants. Radioimmunoassay false positives occurred with potassium hydroxide (PCP and THC-COOH assays) and bleach (THC-COOH assay) adulterants. Bleach (PCP assay) and soap (THC-COOH assay) additives resulted in false negative analyses by RIA. No adulterant caused FPIA false positives. FPIA false negatives occurred with bleach (PCP and THC-COOH assays) and potassium hydroxide (PCP assay) adulterants.

Time course and dose dependence of antacid effect on urine pH.

Daily administration of a proprietary magnesium and aluminum hydroxides suspension, 15 ml four times a day, to normal adult volunteers resulted in a statistically significant increase in urine pH on the 1st day of treatment. The urine pH's on the 2nd and subsequent days of treatment were statistically significantly higher than on the 1st day. A 7.5-ml dose of the antacid suspension, taken four times a day, had only a small and not statistically significant effect on urine pH, while 30 ml four times a day increased urine pH by approximately the same magnitude as the 15-ml doses. The effect of the antacid on urine pH persisted for at least 1 day after discontinuation of dosing.