Treatment of Francisella infections via PLGA- and lipid-based nanoparticle delivery of antibiotics in a zebrafish model.

We tested the efficiency of 2 different antibiotics, rifampicin and oxolinic acid, against an established infection caused by fish pathogen Francisella noatunensis ssp. orientalis (F.n.o.) in zebrafish. The drugs were tested in the free form as well as encapsulated into biodegradable nanoparticles, either polylactic-co-glycolic acid (PLGA) nanoparticles or nanostructured lipid carriers. The most promising therapies were PLGA-rifampicin nanoparticles and free oxolinic acid; the PLGA nanoparticles significantly delayed embryo mortality while free oxolinic acid prevented it. Encapsulation of rifampicin in both PLGA and nanostructured lipid carriers enhanced its efficiency against F.n.o. infection relative to the free drug. We propose that the zebrafish model is a robust, rapid system for initial testing of different treatments of bacterial diseases important for aquaculture.

The efficacy of a single intraperitoneal injection of oxolinic acid in the treatment of bacterial infections in goldsinny wrasse (Ctenolabrus rupestris) and corkwing wrasse (Symphodus melops) studied under field and laboratory conditions.

The efficacy of a single intraperitoneal injection of oxolinic acid to control an outbreak of atypical Aeromonas salmonicida infection in goldsinny wrasse (Ctenolabrus rupestris) and in the treatment of systemic vibriosis in corkwing wrasse (Symphodus melops) was examined. In addition a field study was performed to examine the effect of medication on the survival rate of goldsinny wrasse in Atlantic salmon cages. Four groups of wild caught goldsinny wrasse, each of 50 fish, were treated with an intraperitoneal injection of propylene glycol:saline (50:50) (control) or 50 mg/kg oxolinic acid at a concentration of 50 mg/mL. Three days after medication the fish in all groups were treated by an intraperitoneal injection of prednisolone acetate and an increase in seawater temperature from 9.0 to 11.5 degrees C. Cumulative mortalities were 18% in the two groups treated with oxolinic acid and 94 and 100% in the unmedicated control groups, giving a 'relative percentage survival' (RPS) value of 82%. A laboratory maintained population of originally wild caught corkwing wrasse experiencing high daily mortality was treated with oxolinic acid (50 mg/kg) or propylene glycol:saline (control). Cumulative mortalities were 84% (control) and 42% (oxolinic acid medicated group) giving an RPS value of 50%. In a field investigation using goldsinny wrasse approximately 30% were medicated with oxolinic acid (50 mg/kg) prior to stocking in cages with Atlantic salmon. In two of three cages the cumulative mortality was significantly lower (P = 0.025 and P < 0.001) in the medicated groups.

Efficacy of orally administered oxolinic acid and Vetoquinol, an oxolinic acid ester, for the treatment of furunculosis in Atlantic salmon Salmo salar held in seawater.

This study was performed to determine the efficacy of orally administered oxolinic acid and Vetoquinol, an oxolinic acid ester, in the treatment of experimental induced furunculosis in Atlantic salmon Salmo salar held in seawater. Two strains of the causative bacterium Aeromonas salmonicida subsp. salmonicida, 1 sensitive (VI-88/09/03175) and 1 resistant (3475/90) to oxolinic acid, were used. In 2 trials, cohabitational challenges were performed by introducing 8 fish challenged in advance by an intraperitoneal injection of 2.2 x 10(4) colony forming units of strain 3475/90 (Trial 1) or strain VI-88/09/03175 (Trial 2) to 10 aquaria each containing 40 healthy fish. The treatment groups in both trials consisted of 4 groups receiving either oxolinic acid (2 groups) or Vetoquinol (2 groups) and 1 control group. An unchallenged, unmedicated group was used to determine the natural mortality in the population. The recommended therapeutic dose of 25 mg oxolinic acid kg-1 fish at Days 1, 2, 4, 6, 8 and 10 following initiation of treatment was used. Oral medication initiated at Day 10 (Trial 1) or Day 11 (Trial 2) following challenge significantly (p < 0.05) lowered the specific mortality in all drug-treated groups compared to the untreated control groups. Mortality in Vetoquinol-treated groups was significantly (p < 0.05) lower than in oxolinic acid-treated groups in Trial 1 whereas no significant (p < 0.05) difference in survival rate was found between the medicated groups in Trial 2.

Therapeutic value of Gramurin (oxolinic acid) in Shigella infections and Shigella-negative dysentery syndrome.

A total of 10 Shigella-positive and 10 Shigella-negative dysentery syndrome patients were treated with daily 2-g Gramurin doses for 3 days. Favourable clinical results could be obtained in response to the therapy. The complaints of the patients ceased within 48 hours. Bacterial negativity was recorded on days 3, 4, and 5 after cessation of therapy in Shigella flexneri-positive cases (5 cases), while in case of Shigella sonnei positivity bacterium negativity could be obtained within the abovementioned period in only 3 out of the 5 cases. The presented results of Gramurin therapy in Shigella infections and Shigella-negative dysentery syndrome are virtually congruent with the earlier reported favourable observations of the authors with the drug in these conditions.

[Modifying effect of oxolinic acid on the radiation-induced hemorrhagic syndrome]. / Modifitsiruiushchee vliianie oksolinovoi kisloty na luchevoi gemorragicheskii sindrom.

The radioprotective effect of oxolinic acid (200 mg/kg) was studied in irradiated guinea pigs (3 Gy, 0.83 cGy/min) by the following criteria: survival rate, hemorrhage severity, and homeostasis disturbance. Oxolinic acid was found to decrease the death rate, severity of hemorrhage and the degree of thrombo- and leukopenia, and to reduce the injury to blood coagulation and vascular wall of irradiated animals.

Evaluation of the release and efficacy of two new antibacterial agents from different ointment bases.

The in vitro release of rosoxacin (1) and oxolinic acid (2) from three different ointment bases including a revised water washable (NF), an oleaginous, and an O/W emulsion ointment base was studied. Among the bases evaluated, the revised water washable base provided the best release of the two drugs as revealed from the values of the release rate constant (K). The amounts released of both drugs from the revised water washable base showed direct relationship with the concentration of the drug in the ointment. In addition, the effect of some additives on the amount released of both drugs from the different bases has been investigated. The release of 1 from the revised water washable base had been enhanced by adding 0.2% Tween 80 or 10% ethanol, but addition of 10% of N,N-dimethylacetamide and polyvinylpyrrolidone (PVP) led to retardation of the release of the drug. Furthermore addition of 10% polyethylene glycol (PEG) 200, N,N-dimethylacetamide, or ethanol led to enhancement of the release of the drug from both the oleaginous and the emulsion bases. On the other hand, the release of 2 from the revised water washable base had been enhanced only on addition of 0.2% Tween 80 and been retarded by adding 10% ethanol, N,N-dimethylacetamide or PVP to the formula. The release of 2 from the oleaginous, as well as the emulsion bases had been enhanced by 10% PEG 200. However urea was found to show no pronounced effect on the release of the two drugs from the different ointment bases.(ABSTRACT TRUNCATED AT 250 WORDS)

[Radioprotective properties of oxolinic acid during long-term exposure to radiation]. / Protivoluchevye svoistva oksolinovoi kisloty pri prolongirovannom radiatsionnom vozdeistvii.

The antioxidant activity of oxolinic acid was studied in mongrel mice during the prolonged (6-8 hours) exposure to ionizing radiation. The drug administered before irradiation was shown to increase (by 7 to 33 per cent) the survival rate of mice. The effect was maximum after the subcutaneous injection. The results obtained on the effect of oxolinic acid on DNA synthesis by bone marrow karyocytes are submitted.

[Radioprotective properties of oxolinic acid]. / Protivoluchevye svoistva oksolinovoi kisloty.

Oxolinic acid was shown to produce a radioprotective effect on mice and a therapeutic radioprotective action on rats and hamsters. As to radioprotective efficiency, oxolinic acid is inferior to such known sulfur-containing agents as indolylalkylamines and alpha-adrenomimetics. But oxolinic acid has an important advantage over them, that is, the increase in radioresistance it induces persists for several hours. The radioprotective effectiveness of oxolinic acid prompts that it is expedient to search for new radioprotective preparations among specific inhibitors of DNA polymerase of replicative synthesis.

Experiences on the efficacy and safety of nalidixic acid, oxolinic acid, cinoxacin and norfloxacin in the treatment of urinary tract infections (UTI).

The purpose of this study was to determine the effectiveness and tolerability of norfloxacin, cinoxacin and oxolinic acid in the treatment of urinary tract infections (UTI) in comparison to nalidixic acid. 125 patients were given the drugs in the appropriate doses for 10-14 days and 30 patients were treated for six weeks. Clinical, bacteriological, hematological and chemical checks were made on all patients before and after treatment. It was found that norfloxacin, cinoxacin and oxolinic acid are safe and effective against Escherichia coli, Klebsiella and Proteus, the commonly encountered organisms in urinary tract infections. The cure rate for norfloxacin was 93%, for cinoxacin 83%, for oxolinic acid 80% and for nalidixic acid 70% in the short course. However, these differences were not statistically significant. Oxolinic acid, cinoxacin and norfloxacin have the advantage over nalidixic acid of being administered only twice daily.