Fate of the anthelmintic,phenothiazine, in man

1. Radiolabelled [35 S]-phenothiazine has been administered orally to two healthy adult male volunteers (6mg kg -1 body weight). Faeces were the major route of excretion of radioactivity (68%), the remainder being eliminated via the urine (32%) with an estimated urinary half-life (biphasic) of 6-16 h. Over the 5 days of the study a complete recovery of radioactivity was achieved. 2. From urinary data, it was shown that metabolism occurred via ring carbon oxidation to form phenothiazone and thionol and via ring sulphur oxidation to form phenothiazine sulphoxide. The majority of urinary material (92%) was present in the form of conjugates of phenothiazine and phenothiazone. Only unchanged phenothiazine was detected in the faeces. Phenothiazine sulphoxide was reduced to phenothiazine during incubation with faecal homogenates.     

A novel approach to controlling bacterial contamination on toothbrushes: chlorhexidine coating

Abstract: Purpose: This project was conducted to determine the effectiveness of chlorhexidine‐coated toothbrush filaments in reducing quantities of bacteria. Materials and methods: An Institutional Review Board (IRB)‐approved, two‐group, double‐blind, randomized, post‐test only study was conducted. Sixty‐four individuals utilized control and experimental toothbrushes, for 30 days. At the end of the study toothbrushes were returned and transported to the laboratory for analysis. Microorganisms were detached from the filaments by sonification and vortexing then plated on Mitis Salivarius (MS) (selective) and trypticase soy agar (TSA) 5% Sheep Blood (non‐selective) media. Inoculated plates were incubated aerobically for 24 h at 37°C. After incubation, bacterial colony‐forming units (CFU) were determined. Data were analysed using Wilcoxon and Kruskal–Wallis tests. Results: Fifty‐nine toothbrushes were returned for analysis; experimental (n = 31) and control (n = 28). Data from TSA media revealed a mean CFU for the control group of 5.41 × 10⁵ compared with 6.28 × 10⁵ for the experimental group. Data from MS agar resulted in a mean CFU for the control group of 4.32 × 10⁵ compared with 4.20 × 10⁵ for the experimental group. Conclusion: Results revealed no statistically significant difference in the quantity of bacteria surviving on toothbrush filaments between control and experimental groups, on both selective and non‐selective media, after 30 days.     

The pharmacokinetics of orally administered S-carboxymethyl-l-cysteine in the dog,calf and sheep

The aim of this study was to investigate the feasibility of employing S-carboxymethyl-l-cysteine as a treatment of chronic obstructive pulmonary disease in dogs. To this end the pharmacokinetic parameters of orally administered S-carboxymethyl-l-cysteine were determined in the dog, cow and sheep. Six healthy beagle dogs, six endogenous Greek sheep and four Holstein Fresian calves were orally dosed with 10 mg/kg body weight of S-carboxymethyl-l-cysteine. No significant differences in T_max and T_1/2 were reported between the species. However, significantly higher AUC_(0–last), 21.56 ± 6.67 μg h ml^?1 and AUC_(0–∞), 21.63 ± 6.68 μg h ml^?1 were seen in the dogs compared to the sheep and calves. The calculated V_D was significantly higher in the sheep (10.4 ± 2.7 L kg^?1) and the calves (3.8 ± 0.7 L kg^?1) compared to the dogs (1.0 ± 0.6 L kg^?1). The rank order of increasing C_L was sheep (3.4 ± 2.7 L h^?1 kg^?1) > calves (2.7 ± 0.4 L h^?1 kg^?1) > dogs (0.5 ± 0.2 L h^?1 kg^?1). The result for the dogs was significantly lower that the calculated C_L for the sheep and calves.All these results indicate that the oral administration of S-carboxymethyl-l-cysteine may be useful during the therapeutic management of chronic obstructive pulmonary disease in dogs.     

Epithelioid sarcoma with metastatic spread to the tongue

Epithelioid sarcoma (ES) is a rare tumour that seldom presents to the otolaryngologist. It typically occurs in the extremities of young adolescents; however, it has the capability of metastasizing, often to the lungs or skin. The diagnosis is by histopathological examination and immunohistochemistry. We present a case of metastatic ES occuring in the tongue, a tumour not reported previously in the English literature.     

Phenylalanine 4-monooxygenase and the S-oxidation of S-carboxymethyl-L-cysteine in HepG2 cells

The role of phenylalanine 4-monooxygenase (PAH) in the S-oxidation of S-carboxymethyl-L-cysteine (SCMC) in the rat has now been well established in rat cytosolic fractions in vitro. However, the role of PAH in the S-oxidation of SCMC in human cytosolic fractions or hepatocytes has yet to be investigated. The aim of this investigation was to analyse the kinetic parameters of PAH oxidation of both L-phenylalanine (Phe) and SCMC in the human HepG2 cell line in order to investigate the use of these cells as a model for the cellular regulation of SCMC S-oxidation. The experimentally determined Km and V(max) were 7.14 +/- 0.32 mM and 0.85 +/- 0.32 nmole Tyr formed min(-1) x mg protein(-1) using Phe as substrate. For SCMC the values were 25.24 +/- 5.91 mM and 0.79 +/- 0.09 nmole SCMC (RIS) S-oxides formed min(-1) x mg protein(-1). The experimentally determined Km and V(max) for the cofactor BH4 were 6.81 +/- 0.21 microM and 0.41 +/- 0.004 nmole Tyr formed min(-1) x mg protein(-1) for Phe and 7.24 +/- 0.19 microM and 0.42 +/- 0.002 nmole SCMC (R/S) S-oxides formed min(-1) x mg protein(-1) for SCMC. The use of various PAH inhibitors confirmed that HepG2 cells contained PAH and that the enzyme was capable of converting SCMC to its (R) and (S) S-oxide metabolites in an in vitro PAH assay. Thus HepG2 cells have become a useful additional tool for the investigation of the cellular regulation of PAH in the S-oxidation of SCMC.     

CYP1A2 in a smoking and a non-smoking population; correlation of urinary and salivary phenotypic ratios

The use of caffeine as a probe for CYP1A2 phenotyping has been extensively investigated over the last 25 years. Numerous metabolic ratios have been employed and various biological fluids analysed for caffeine and its metabolites. These investigations have used non-smoking, smoking and numerous disease populations to investigate the role of CYP1A2 in possible disease aetiology and for induction and inhibition studies in vivo using dietary, environmental and pharmaceutical compounds. This investigation found that the 17X/137X CYP1A2 metabolic ratio in a 5 h saliva sample and 0-5 h urine collection was not normally distributed in both a non-smoking and a smoking population. The urinary and salivary CYP1A2 metabolic ratio was log normally distributed in the non-smoking population but the smoking population showed a bi- (or tri-)modal distribution on log transformation of both the urinary and salivary CYP1A2 metabolic ratios. The CYP1A2 metabolic ratios were significantly higher in the smoking population compared to the non-smoking population when both the urinary and salivary CYP1A2 metabolic ratios were analysed. These results indicate that urinary flow rate was not a factor in the variation in CYP1A2 phenotype in the non-smoking and smoking populations studied here. The increased CYP1A2 activity in the smoking population was probably due to induction of the CYP1A2 gene via the Ah receptor causing an increase in the concentration of CYP1A2 protein.     

Development of a clockwork light source to enable cervical inspection by village health workers

Background  

Cervical cancer can often be prevented by screening and may be curable if identified and treated in its early stages. However, 80% of new cases occur in less-developed countries where cervical cancer screening programmes are small-scale or non-existent. This is a human tragedy of great proportion, with many of those affected being young mothers. There is some evidence that cancerous or precancerous lesions may be detected by visual inspection with acetic acid (VIA) and field studies indicate that this technique is effective, safe and acceptable to women. However, the provision of a light source for inspection of the cervix presents a major problem in less-developed countries, where candles and torches often provide the only means of illumination. Our objective was to develop a light source based on clockwork technology, that required no batteries or external power source.