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The study aims to establish the plasma pharmacokinetic parameters of levofloxacin in mixed-breed dogs, at a single dose of 5 mg/kg, intravenously, orally only and orally with sucralfate pre-treatment (1 g per animal), to evaluate its influence on antimicrobial absorption. Concentrations of levofloxacin in plasma were determined using high-performance liquid chromatography (HPLC) with fluorescence detection. After iv of levofloxacin, the mean (±SD) of AUC0-24, Vz, t½λz and MRT, was 19.05 ± 6.4 µg-h/ml, 2.43 ± 0.5 L/kg, 7.93 ± 1.41 hours and 8.7 ± 1.5 hours, respectively. After oral administration, the C max, t½λz and bioavailability were 1.95 ± 0.7 µg/ml, 7.65 ± 1.38 hours and 71.93 ± 9.75%, respectively. In animals given an oral dose of levofloxacin with sucralfate pre-treatment, there was a significant decrease (p < 0.05) in C max (0.57 ± 0.23 µg/ml), AUC (5.73 ± 2.26 µg-h/ml) and bioavailability (31.92 ± 14.19%). In the dogs studied, it is suggested that the dose 5 mg/kg of levofloxacin for both routes is inadequate to meet PK-PD targets for susceptible bacteria using breakpoints established by the Institute of Clinical and Laboratory Standards (CLSI).

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Plasma pharmacokinetics (PK) and tissue disposition of enrofloxacin (EFX) was studied in rainbow trout (Oncorhynchus mykiss) after a single oral administration of 10 mg/kg, and by immersion baths of 20 ppm during 2.5 h and 100 ppm during 0.5 h, at water temperature of 16.3 ± 0.3 °C.Concentrations of EFX in plasma and tissues (skin, muscle, liver, kidney and gut) were determined using high performance liquid chromatography (HPLC) with fluorescence detection.Pharmacokinetic parameters were analyzed with a non-compartmental model. After oral administration, t½ß, AUC and AUCtissues/AUCplasma ratio were 42.98 h, 21.80µg-h/ml and ≤ 18.63, respectively.After immersion baths of 20 ppm during 2.5 h and 100 ppm during 0.5 h, the t½ß, AUC and AUCtissues/AUCplasma were 42.77 and 44.67, 9.83 and 12.83 µg-h/ml and ≤ 9.81 and ≤ 7.13, respectively.Therefore, oral (10 mg/kg) and bath administration in rainbow trout can provide AUC/MIC of ≥125 and Cmax/MIC of ≥10 to treat diseases caused by susceptible bacteria with MIC ≤ 0.04 µg/ml. This information can be helpful for the right use of EFX in rainbow trout. Also, this is the first study that determines the antibiotic tissue disposition in rainbow trout by using different administration routes.

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Early in postnatal life, the first wave of spermatogenesis is accompanied by an initial wave of germ cell apoptosis. This may reflect an adjustment in the number of germ cells that can be adequately maintained by Sertoli cells. Two major pathways (intrinsic and extrinsic) are involved in the process of caspase activation and apoptosis in mammalian cells. The extrinsic pathway is characterized by the oligomerization of death receptors such as FAS or tumor necrosis factor, followed by the activation of caspase-8 and caspase-3. The intrinsic pathway involves the activation of procaspase-9, which in turn activates caspase-3. Extensive information is available concerning apoptotic inducers and their possible mechanisms in the adult rat. However, no data exist regarding the molecular and cellular mechanisms governing physiological cell death during puberty in the male rat. We have studied caspase activation throughout the first wave of spermatogenesis in the rat under physiological conditions, by combining the TUNEL procedure with the localization of active caspases in germ cells. We observed TUNEL-positive germ cells in rats of 5-40 days of age, the highest number being found in 25-day-old rats. TUNEL-positive and caspase-3-positive germ cells appeared as long chains of interconnected germ cells in 25-day-old rats. Caspase activation was assayed by either immunohistochemistry with antibodies against active caspase-3, -8, and -9, or by determining enzymatic activity in seminiferous tubules extracts. Both techniques showed activation of caspase-3, -8, and -9 in 25-day-old rats and low enzymatic activity at other ages. Confocal scanning laser microscopy indicated that active caspase-3, -8, and -9 co-localized with TUNEL-positive cells. Thus, caspase-3, -8, and -9 are active in apoptotic germ cells during the first wave of rat spermatogenesis. The extrinsic pathway of apoptosis may therefore play an important role in germ cell apoptosis during puberty in the rat.

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