ABSTRACT
Male and female F344 rats but not B6C3F1 mice exposed for 104 weeks to propiverine hydrochloride (1-methylpiperid-4-yl 2,2-diphenyl-2-(1-propoxy)acetate hydrochloride), used for treatment of patients with neurogenic detrusor overactivity (NDO) and overactive bladder (OAB), presented with an accumulation of proteins in the cytosol and nuclei of renal proximal tubule epithelial cells, yet despite this, no increased renal tumor incidence was observed. In order to provide an improved interpretation of these findings and a better basis for human health risk assessment, male and female F344 rats were exposed for 16 weeks to 1000 ppm propiverine in the diet, the accumulating protein was isolated from the kidneys via cytosolic and nuclear preparations or laser-capture microdissection and analyzed using molecular weight determination and mass spectrometry. The accumulating protein was found to be d-amino acid oxidase (DAAO), an enzyme involved in amino and fatty acid metabolism. Subsequent reanalysis of kidney homogenate and nuclear samples as well as tissue sections using western blot and DAAO-immunohistochemistry, confirmed the presence and localization of DAAO in propiverine-treated male and female F344 rats. The accumulation of DAAO only in rats, and the limited similarity of rat DAAO with other species, including humans, suggests a rat-specific mechanism underlying the drug-induced renal DAAO accumulation with little relevance for patients chronically treated with propiverine.
Subject(s)
Benzilates/adverse effects , Cell Nucleus/drug effects , Cholinergic Antagonists/adverse effects , Cytosol/drug effects , D-Amino-Acid Oxidase , Kidney/drug effects , Amino Acid Sequence , Animals , Benzilates/pharmacokinetics , Cell Nucleus/enzymology , Cell Nucleus/metabolism , Cholinergic Antagonists/pharmacokinetics , Cytosol/enzymology , Cytosol/metabolism , D-Amino-Acid Oxidase/isolation & purification , D-Amino-Acid Oxidase/metabolism , Electrophoresis, Polyacrylamide Gel , Female , Hyalin/metabolism , Immunohistochemistry , Kidney/enzymology , Kidney/metabolism , Kidney/pathology , Liver/drug effects , Liver/metabolism , Male , Molecular Sequence Data , Protein Conformation , Rats , Rats, Inbred F344 , Sex FactorsABSTRACT
BACKGROUND AND OBJECTIVE: The use of low-intensity laser therapy (LILT) as a therapeutic modality has become popular in a variety of clinical applications including the promotion of wound repair. Although the clinical evidence base for such application remains sparse, recent studies have demonstrated a number of quantifiable photobiological effects associated with such therapy. In the present study, the effect of laser irradiation at various radiant exposures on a radiation-impaired wound-healing model in murine skin was investigated. STUDY DESIGN/MATERIALS AND METHODS: The study included two phases; in phase one, male Balb/c mice (n = 36; age-matched at 10 weeks) were randomly allocated to three experimental groups (n = 12, each group). In all groups, a well-defined area on the dorsum was exposed to 20 Gy x-rays. Seventy-two hours postirradiation, all mice were anaesthetised and a 7 x 7 mm area wound was made on the dorsum. All wounds were videotaped alongside a marker scale (three times weekly) until closure was complete. In groups 2 and 3, mice were treated with laser irradiation (0.5 and 1.5 J/cm(2), respectively) three times weekly by using a 660-nm GaAlAs laser unit (5 kHz; 15 mW; Omega Laser Systems, London, UK). Wound areas were then calculated by using an image analysis system (Fenestra 2.1), and results were analyzed by using repeated measures and one-factor analysis of variance statistical tests. In phase two, two experimental groups were included (n = 12 each group); the protocol was identical to that described for phase 1; however, mice in group 2 were treated with a radiant exposure of 4 J/cm(2). RESULTS: Results from this investigation demonstrated that treatment with 0.5, 1.5. and 4 J/cm(2) had no beneficial effect on the rate of wound closure (P > 0.05). CONCLUSION: These findings provide little evidence of the putative stimulatory effects of LILT in vivo at the parameters investigated.
Subject(s)
Dermatologic Surgical Procedures , Lasers , Skin/radiation effects , Wound Healing/radiation effects , Animals , Male , Mice , Mice, Inbred BALB C , Radiation Dosage , Time FactorsABSTRACT
The problem of aflatoxin determination in processed cheese can be solved by the destruction of the emulsion with 6 m urea solution; the detection limit is 0.1-0.05 ppb B1 respectively G1. Examination of 115 trade samples resulted in 2 positive processed cheese samples only. This result cannot be reffered to the destruction of aflatoxins by the melting process, because neither at melting temperatures of 80-138 degrees C nor by melting salts and pH adjustments considerable losses could be observed, mostly below 5%.
