Physicochemical characterization and pharmacokinetics in broiler chickens of a new recrystallized enrofloxacin hydrochloride dihydrate.

Enrofloxacin, a key antimicrobial agent in commercial avian medicine, has limited bioavailability (60%). This prompted its chemical manipulation to yield a new solvate-recrystallized enrofloxacin hydrochloride dihydrate entity (enroC ). Its chemical structure was characterized by means of mass spectroscopy, Fourier transformed infrared spectroscopy, X-ray powder diffraction, and thermal analysis. Comparative oral pharmacokinetics (PK) of reference enrofloxacin (enroR ) and enroC in broiler chickens after oral administration revealed noticeable improvements in key parameters and PK/PD ratios. Maximum serum concentration values were 2.61 ± 0.21 and 5.9 ± 0.42 µg/mL for enroR and enroC , respectively; mean residence time was increased from 5.50 ± 0.26 h to 6.20 ± 0.71 h and the relative bioavailability of enroC was 336%. Considering Cmax /MIC and AUC/MIC ratios and the MIC values for a wild-type Escherichia coli O78/H12 (0.25 µg/mL), optimal ratios will only be achieved by enroC (Cmax /MIC = 23.6 and AUC/MIC = 197.7 for enroC ; vs. Cmax /MIC = 10.4 and AUC/MIC = 78.1 for enroR ). Furthermore, enroC may provide in most cases mutant prevention concentrations (Cmax /MIC ≥ 16). Ready solubility of powder enroC in drinking water at concentrations regularly used (0.01%) to provide an additional advantage of enroC in the field. Further development of enroC is warranted before it can be recommended for clinical use in veterinary medicine.

Novel inhibitors to Taenia solium Cu/Zn superoxide dismutase identified by virtual screening.

We describe in this work a successful virtual screening and experimental testing aimed to the identification of novel inhibitors of superoxide dismutase of the worm Taenia solium (TsCu/Zn-SOD), a human parasite. Conformers from LeadQuest(®) database of drug-like compounds were selected and then docked on the surface of TsCu/Zn-SOD. Results were screened looking for ligand contacts with receptor side-chains not conserved in the human homologue, with a subsequent development of a score optimization by a set of energy minimization steps, aimed to identify lead compounds for in vitro experiments. Six out of fifty experimentally tested compounds showed µM inhibitory activity toward TsCu/Zn-SOD. Two of them showed species selectivity since did not inhibit the homologous human enzyme when assayed in vitro.

Late-onset isolated gelastic epilepsy secondary to entrapment of the right temporal horn.

The case is reported of a 70 year-old woman with isolated gelastic seizures (GS) secondary to a rare form of focal obstructive hydrocephalus, called entrapment of the lateral horn. Laughing attacks started five years after conservative intracranial surgery for a giant basilar aneurysm. Serial neuro-imaging studies revealed a progressive cystic enlargement of the right temporal horn, damaging the baso-lateral temporal cortex. An ictal EEG recording confirmed the epileptic nature of laughing attacks, and showed that the epileptiform activity originated in the right temporal lobe. Complete seizure control was achieved with current doses of diphenilhydantoin. Analysis of this and other previously reported cases, indicate that symptomatic GS may originate in multiple sites of both cerebral hemispheres, although related to the limbic system. The fact that this case exhibited isolated GS stresses the importance of the baso-lateral temporal cortex in the genesis of this type of seizures.