Catalase inhibition by amino triazole induces oxidative stress in goldfish brain

The effects of in vivo inhibition of catalase by 3-amino 1,2,4-triazole (AMT) on the levels of damage products resulting from reactive oxygen species attack on proteins and lipids as well as on the activities of five antioxidant and associated enzymes were studied in the brain of goldfish, Carassius auratus. Intraperitoneal injection of AMT at a concentration of 0.1 mg/g wet weight caused a gradual decrease in brain catalase activity over 72 h, whereas higher AMT concentrations (0.5 or 1.0 mg/g) reduced catalase activity by about two-thirds within 5-10 h. AMT effects on antioxidant enzyme activities and oxidative stress markers were studied in detail using fish treated with 0.5 mg/g AMT for 24 or 168 h. The levels of thiobarbituric acid-reactive substances (a lipid damage product) increased 6.5-fold by 24 h after AMT injection but fell again after 168 h. The content of carbonylproteins (CP) also rose within 24 h (by approximately 2-fold) and remained 1.5-fold higher compared with respective sham-injected fish after 168 h. CP levels correlated inversely with catalase activity (R(2) = 0.83) suggesting that catalase may protect proteins in vivo against oxidative modification. The activities of both glutathione peroxidase and glutathione-S-transferase increased by approximately 50% and 80%, respectively, in brain of AMT-treated fish and this might represent a compensatory response to lowered catalase activity. Possible functions of catalase in the maintenance of prooxidant/antioxidant balance in goldfish brain are discussed.     

Human mini-antibodies to orthopoxviruses

A library of human scFv antibodies displayed on the surface of bacteriophages (MRC, Cambridge, England) was panned against the Elstree strain of vaccinia virus (VACV), which resulted in the phage repertoire enriched with clones positive to the strain. Individual clones from the repertoire were screened for binding, independently, to the vaccinia and ectromelia viruses; phage antibodies to the orthopoxviruses were selected. Ten unique antibodies were identified after their Vh- and Vl-genes were sequenced. All selected antibodies were assayed by ELISA for binding to the vaccinia, cowpox and ectromelia viruses. Furthermore, all selected antibodies were assayed for binding with major alastrim strains of the live variola virus. According to the results, the above phage antibodies recognized genus-specific epitopes, some of which differed in their conformation.     

Developmental changes in GABAergic actions and seizure susceptibility in the rat hippocampus

The immature brain is prone to seizures but the underlying mechanisms are poorly understood. We explored the hypothesis that increased seizure susceptibility during early development is due to the excitatory action of GABA. Using noninvasive extracellular field potential and cell-attached recordings in CA3 of Sprague-Dawley rat hippocampal slices, we compared the developmental alterations in three parameters: excitatory actions of GABA, presence of the immature pattern of giant depolarizing potentials (GDPs) and severity of epileptiform activity generated by high potassium. The GABA(A) receptor agonist isoguvacine increased firing of CA3 pyramidal cells in neonatal slices while inhibiting activity in adults. A switch in the GABA(A) signalling from excitation to inhibition occurred at postnatal day (P) 13.5 +/- 0.4. Field GDPs were present in the form of spontaneous population bursts until P12.7 +/- 0.3. High potassium (8.5 mm) induced seizure-like events (SLEs) in 35% of slices at P7-16 (peak at P11.3 +/- 0.4), but only interictal activity before and after that age. The GABA(A) receptor antagonist bicuculline reduced the frequency or completely blocked SLEs and induced interictal clonic-like activity accompanied by a reduction in the frequency but an increase in the amplitude of the population spikes. In slices with interictal activity, bicuculline typically caused a large amplitude interictal clonic-like activity at all ages; in slices from P5-16 rats it was often preceded by one SLE at the beginning of bicuculline application. These results suggest that, in the immature hippocampus, GABA exerts dual (both excitatory and inhibitory) actions and that the excitatory component in the action of GABA may contribute to increased excitability during early development.     

Heat-Treated Fungizone Retains Amphotericin B Antifungal Activity Without Renal Toxicity in Rats Infected with Aspergillus Fumigatus

PURPOSE: The purpose of this study was to assess the antifungal activity and renal and hepatic toxicity of amphotericin B (AmpB) following administration of Fungizone (FZ) and a heat-treated form of FZ (HFZ) to rats infected with Aspergillus fumigatus. METHODS: Infected rats were administered FZ and HFZ at a dosing regimen of 1 mg/kg i.v. once daily for 4 consecutive days. Following administration the number of colony forming units (CFUs) of Aspergillus fumigatus in different organs and serum creatinine concentrations were determined. RESULTS: FZ and HFZ had similar overall effectiveness in decreasing the total number of Aspergillus fumigatus CFUs found in all organs analyzed compared to controls. Except for the serum creatinine concentrations reported in the nontreated infected control rats, none of the treatment groups tested displayed a greater than 50% increase in serum creatinine. CONCLUSIONS: Taken together, these findings suggest that HFZ at 1 mg/kg once daily x 4 days appears to be as effective as FZ as an antifungal agent without renal toxicity.     

Unidirectional Inhibition of Lipid Transfer Protein I-Mediated Transfer of Cholesteryl Esters Between High-Density and Low-Density Lipoproteins by Amphotericin B Lipid Complex

No HeadingPurpose. The purpose of this study was to determine whether Fungizone or amphotericin B lipid complex (ABLC; ABELCET^®) affects the transfer of cholesteryl ester (CE) by lipid transfer protein I (LTP I; also known as cholesteryl ester transfer protein) between HDL and LDL (bidirectional transfer HDL to LDL and LDL to HDL).Methods. Increasing concentrations of either Fungizone or ABELCET^® (1.25–12.5 g AmpB/ml) were incubated with HDL and [3H]CE-LDL or [3H]CE-HDL and LDL (the amount of each fraction added was equivalent to 10 g of cholesterol) and LTP I in delipidated human plasma at 37C for 90 min. As a positive control, TP2, a monoclonal antibody directed against LTP-1, was added instead of drug. After incubation, manganese and phosphate reagents were then added to precipitate out all of the LDL. The supernatant, consisted of only HDL, was counted for radioactivity to determine the amount of CE transferred from LDL. Similarly, the precipitate consisted of only LDL, was counted for radioactivity to determine the amount of CE transferred from HDL.Results. For Fungizone, the transfer of cholesteryl ester (CE) between HDL and LDL were not significantly different compared to nontreated controls. For ABELCET^®, CE transfer from HDL to LDL was significantly decreased at 12.5 g AmpB/ml compared to control. However, transfer from LDL to HDL was not significantly different compared to non-treated controls. Similar results were observed with the major lipid component of ABELCET^®, dimyristoylphosphatidylcholine. CE transfer from HDL to LDL and LDL to HDL was significantly decreased when using the positive control (TP2).Conclusions. Fungizone does not affect LTP I–mediated transfer of CE between HDL and LDL. ABELCET^® inhibits transfer from HDL to LDL, but has no effect on CE transfer from LDL to HDL. This uni-directional inhibition may contribute to the high recovery of AmpB in HDL but the very low presence of drug in the LDL fraction following ABELCET^® incubation.     

Alternative methods for prevention and treatment of dental caries using laser and magnetic laser exposure

Alternative methods for prevention and treatment of dental caries are presented, based on the use of laser and magnetic laser exposure (patent No. 2053818, in Russia) with a new generation laser device with Optodan microprocessor monitoring (patent No. 2014107, Russia). The methods are intended for wide clinical application in children and adolescents in pedodontic departments and outpatient centers and particularly for group and individual use in dental rooms at school.     

The economic costs of child sexual abuse in Canada: a preliminary analysis

This paper describes a study of the economic costs attributable to child sexual abuse in Canada for the 1997-98 fiscal year. The preliminary cost estimate of child sexual abuse in Canada exceeds $3.6 billion dollars annually. This includes both public and private costs across four policy areas: health, social/public services, justice, and education/research and employment. These estimates have important policy implications in the area of child sexual abuse. The effectiveness of remedies, and options for new initiatives, policies and programs can be further evaluated using these economic calculations.