Glutathione ester protects against hydroxynonenal-induced loss of auditory hair cells.

OBJECTIVE: Test the ability of glutathione monoethyl ester (GSH(e)) to protect auditory hair cells against the ototoxic effects of 4-hydroxy-2,3-nonenal (HNE). STUDY DESIGN AND SETTING: Organ of Corti explants were either untreated or treated with one of a series of four concentrations of GSH(e) for one day, then exposed to HNE. Counts of FITC-phalloidin-labeled hair cells determined both HNE ototoxicity and GSH(e) otoprotection. RESULTS: HNE was toxic to hair cells at physiologically relevant levels, eg, 400 muM, and GSH(e) provided a significant level of protection against HNE ototoxicity (P < 0.05) at all levels tested, ie, 1.16 to 9.3 mM. CONCLUSION: GSH(e) protects auditory hair cells from damage and loss initiated by a naturally occurring ototoxic molecule, ie, HNE (a by-product of oxidative stress). SIGNIFICANCE: Treatment with GSH(e) may be an effective therapy to protect the cochlea against the adverse effects of traumas (eg, electrode insertion) that generate oxidative stress.     

Keratinolytic fungi in sewage sludge applied to devastated urban soil. A preliminary experiment

The qualitative and quantitative (q/q) changes of keratinolytic fungi in soil mixtures with added sewage sludge were examined during a preliminary reclamation experiment. Sludge before land application was characterized by the weak growth of keratinolytic fungi. In devastated urban soil, abundant fungal growth was observed. Over a 19‐month reclamation period, decreasing frequency of Chrysosporium concurrent with the enrichment of the mixture with the geophilic dermatophytes Arthroderma quadrifidum and A. uncinatum were clearly seen. The results are discussed with respect to possible ecological factors influencing the occurrence of keratinolytic fungi in the materials examined. The public health risk associated with the application of sewage sludge for reclamation is also discussed.     

Treatment results of aseptic non-unions of long bones with medullary canal reaming followed by intramedullary nailing]

This paper presents results of treatment of 46 consecutive patients with pseudoarthroses of the long bones treated with closed intramedullary reaming followed by intramedullary nailing. There were 22 nonunions of the tibia, 15 of the femur, 3 of the humerus and 6 of the forearm. The union occurred in 40 cases, among them in 3 of 4 treated atrophic, that gives 87% success. None of treated pseudoarthrosis of the humerus united.     

Antidepressant-like effects of trazodone on a behavioral screen are mediated by trazodone, not the metabolite m-chlorophenylpiperazine

Trazodone is an atypical antidepressant drug (i.e. blocks neither monoamine uptake nor monoamine oxidase) which tests as an antidepressant drug on the differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule of reinforcement by increasing the reinforcement rate and decreasing the response rate. m-Chlorophenylpiperazine (m-CPP) is a 5-HT1B and 5-HT1C agonist, weak 5-HT2 antagonist, and trazodone metabolite. It has been suggested that formation of m-CPP is responsible for the antidepressant action of trazodone. Administration of m-CPP (1-10 mg/kg i.p.) 60, 30 or 10 min before the behavioral session did not mimic the reinforcement rate-increasing effects of trazodone (10-20 mg/kg i.p.) on rats performing under the DRL 72-s schedule of water reinforcement. Pretreatment with proadifen (50 mg/kg i.p.), an inhibitor of trazodone metabolism, caused a greater than 30-fold leftward shift in the dose-response curve for both the reinforcement rate and the response rate. These results suggest that the parent compound and not the trazodone metabolite m-CPP, mediates the antidepressant-like effects of trazodone on DRL 72-s behavior.     

Cytostatic and immunomobilizing activities of polymer-bound drugs: experimental and first clinical data.

An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carrier containing doxorubicin and human immunoglobulin as an actively/passively targeting moiety was used in four patients with generalized breast cancer resistant to standard cytotoxic chemotherapy. The dose and time schedule were deduced from a Phase I clinical trial in which doxorubicin bound to HPMA copolymer carrier (PK1) was tested. It was confirmed that the Dox-HPMA-HuIg conjugate is stable and doxorubicin remains in the peripheral blood with a small amount also in the urine, mostly in its polymer-bound form. More than 116 biochemical, immunological and hematological parameters were determined for blood samples taken from patients 24 h, 48 h, 72 h and 1 to 11 weeks after treatment. Depending on the patient, some parameters decreased permanently or temporarily to the normal level (CRP, C3, CA 72-4, beta(2)-microglobulin, ferritin, CEA, CA 125, CD4, CD8, CE19, CD16(+)56(+), leu, ery) and some moved markedly towards physiological values (AST, ALT, ALP, GMT, CA 15-3, NSE, AFP). While the number of peripheral blood reticulocytes was significantly decreased after treatment with the classical free drug, their number was not affected or was even elevated after treatment with Dox-HPMA-HuIg. Increased absolute numbers of CD16(+)56(+) and CD4(+) cells in the peripheral blood and activation of NK and LAK cells in all patients support data obtained in experimental animals, pointing to a dual, i.e. cytostatic and immunomobilizing character of Dox-HPMA conjugates containing a targeting immunoglobulin moiety.     

A Buprenorphine Stabilization and Rapid-Taper Protocol for the Detoxification of Opioid-Dependent Patients

Management of hospitalized opioid-dependent patients can be problematic at times, especially when patients are medically unstable, elderly, or have acute or chronic pain syndromes. The authors report a case series of 65 patients detoxified on 74 separate occasions with the use of the partial μ-agonist buprenorphine. The buprenorphine was administered subcutaneously as an initial stabilization dose, after which patients received a rapid taper over approximately 6 days. Ninety-seven percent (n = 72) of the 74 episodes of detoxification were successfully managed with buprenorphine; 62% (n = 40) of the patients bad no symptoms of opioid withdrawal. All patients reported that this detoxification protocol was as comfortable or more comfortable than any previously encountered withdrawal experience. The results of this case series provide strong support for further studies of the role of buprenorphine in the short-term detoxification of hospitalized opioid-dependent patients.