Oral pharmacokinetics of a pharmaceutical preparation of florfenicol in broiler chickens.

Introduction: The use of florfenicol must follow particular pharmacokinetic/pharmacodynamic (PK/PD) ratios, i.e., it requires achieving serum concentrations at or slightly above the pathogen's minimum inhibitory concentration (MIC) during the dosing interval and that the ratio of area under the concentration vs. time curve (AUC)/MIC should be as high as possible (still undetermined for poultry). As an alternative to the standard soluble florfenicol that is administered to the flock through drinking water, florfenicol premix is often recommended as feed medication in Latin America. However, no particular pharmaceutical design has been proposed. Methods: This study compared the PK of two preparations of florfenicol in broiler chickens and pondered the possibility of each covering the referred PK-PD ratios as predictors of clinical efficacy. The preparations comprise a pharmaceutical form as FOLA pellets (F = bioavailability; O = optimum; and LA = long-acting) and the premix formulation. The former are small colored pellets with vehicles and absorption enhancers of florfenicol designed for long action, and the latter is the reference premix of the antibiotic. First, these two pharmaceutical forms of florfenicol were administered as oral boluses (30 mg/kg), aided by a probe. In a second trial of the dosing form, both pharmaceutical preparations of florfenicol were administered in feed and ad libitum (110 ppm; ~30 mg/kg). Results: In both cases, FOLA-florfenicol presented much higher relative bioavailability (3.27 times higher) and mean better residence time than florfenicol premix (two times high when forced as bolus dose). Consequently, FOLA-florfenicol possesses better PK/PD ratios than less sensitive pathogens, i.e., E. coli. It is proposed that if a metaphylactic treatment of a bacterial outbreak in poultry is implemented with florfenicol prepared as FOLA, better PK/PD ratios will be obtained than those of standard florfenicol premix. Discussion: Clinicians must confirm that feed consumption in the flock has not been affected by the particular disease if FOLA pellets of florfenicol are used.

Comparative Efficacy of the Prokinetic Effects of Cisapride and Tegaserod in Equines.

The aim of this study was to compare the effects of cisapride and tegaserod on intestinal smooth muscle activity in equines. Efficacy was evaluated through measurement of gastrointestinal transit time, bowel movements per day, stool weight, and bowel sounds. Drug safety was evaluated via heart rate, respiratory rate, and rectal temperature. Records were obtained throughout three periods: a control phase without treatment, a period of cisapride administration at a dose of 0.22 mg/kg, and a period of tegaserod treatment at a dose of 0.27 mg/kg. Gastrointestinal transit time, bowel movements per day, and stool weight were significantly improved on administration of both cisapride and tegaserod, as compared with the control phase. With tegaserod administration, gastrointestinal transit time accelerates more than to cisapride administration; however, no significant difference was seen in bowel movements per day and stool weight. In terms of heart rate, respiratory rate, and rectal temperature, no significant variations were seen between the three sample phases. Because of the above findings, tegaserod can be considered an effective stimulant of intestinal smooth muscle, accelerating gastrointestinal transit time in healthy horses and representing a potential therapeutic agent similar to cisapride.

Oral Plus Topical Administration of Enrofloxacin-Hydrochloride-Dihydrate for the Treatment of Unresponsive Canine Pyoderma. A Clinical Trial.

An outpatient clinical trial on unresponsive deep-bacterial canine pyoderma (UDCP), without a control group, is presented. The chosen treatment was implemented with a new crystal-solvate of enrofloxacin (enrofloxacin HCl-2H2O or enro-C), in a dual scheme, i.e., 10 mg/kg/day PO, plus its topical administration, prepared as 0.5% in an alginate gel, thrice per day. Fifty-five cases that were unsuccessfully treated previously with another antibacterial drug, were selected and then classified as severe or very severe, according to a clinical score tailored for this trial. Aerobic bacteriological cultures of skin lesions and antibacterial sensitivity tests, were performed. Hematological status, liver, and kidney functions were determined before and after treatment. A complete success was obtained in 32 severe and 23 very severe, cases. The main bacterial isolates were: Staphylococcus intermedius (19/99), Staphylococcus pseudintermedius (16/99), Staphylococcus epidermidis (15/99), Staphylococcus pyogenes (14/99), Staphylococcus saprophyticus, Streptococcus sp., and others including Pseudomonas aeruginosa (6/99). The average duration of treatment was 8.03 days ± 2.1 SD and 12.0 ± 2.4 days, for dogs with severe or very severe UDCP, respectively. The adverse effects caused by enro-C were inconsequential and the hematological tests showed no deviations from normality. The use of enro-C administered dually to treat UDCP, is considered safe and highly effective.

Pharmacokinetics of enrofloxacin HCl-2H2O (Enro-C) in dogs and pharmacokinetic/pharmacodynamic Monte Carlo simulations against Leptospira spp.

Pharmacokinetic/pharmacodynamic (PK/PD) ratios of reference enrofloxacin (Enro-R) and enrofloxacin as HCl-2H2O (Enro-C), as well as Monte Carlo simulations based on composite MIC50 and MIC90 (MIC, minimum inhibitory concentration) vs. Leptospira spp., were carried out in dogs after their intramuscular (IM) or oral administration (10 mg/kg). Plasma determination of enrofloxacin was achieved by means of high-performance liquid chromatography. Maximum plasma concentration values after oral administration were 1.47 ± 0.19 µg/mL and 5.3 ± 0.84 µg/mL for Enro-R and Enro-C, respectively, and 1.6 ± 0.12 µg/mL and 7.6 ± 0.93 µg/mL, respectively, after IM administration. Areas under the plasma vs. time concentration curve in 24 h (AUC0-24) were 8.02 µg/mL/h and 36.2 µg/mL/h for Enro-Roral and Enro-Coral, respectively, and 8.55 ± 0.85 µg/mL/h and 56.4 ± 6.21 µg/mL/h after IM administration of Enro-R and Enro-C, respectively. The PK/PD ratios and Monte Carlo simulations obtained with Enro-C, not Enro-R, indicated that its IM administration to dogs will result in therapeutic concentrations appropriate for treating leptospirosis. This is the first time enrofloxacin has been recommended to treat this disease in dogs.

Development of an Aqueous Ophthalmic Solution with an Enhanced-Solubility Enrofloxacin Crystal, and its Clinical Evaluation in Dogs.

BACKGROUND: The concern about the frequent use of ciprofloxacin in veterinary medicine is linked to increased antimicrobial resistance. The corresponding fluoroquinolone for veterinary use is enrofloxacin. A new solvate form of enrofloxacin, as dihydrate-hydrochloride (enro-C) with higher water solubility than the parent compound, was formulated as an ophthalmic solution (pH 5). A multicentre, longitudinal, non-inferiority clinical study in a non-hospital environment was designed to treat 36 dogs affected by tobramycin-unresponsive conjunctivitis with either the experimental 0.5% enro-C ophthalmic preparation (enro-CG) or a commercial preparation of ciprofloxacin (cipro-G). Other causes of conjunctivitis were ruled out. Pathogens were isolated and minimum inhibitory concentration (MIC) studies of tobramycin were carried out. Three blocks of bacterial resistance were set up, beginning at the established breakpoint i.e., 4 µg/mL; 8 µg/mL and 16 µg/mL. Eighteen dogs were randomly assigned to each block. The enro-CG group was treated with two drops of the referred preparation (10 mg/eye) twice a day for 7 days, and the cipro-G group was treated with four drops of a 0.3% commercially available ciprofloxacin eye-drop preparation (9 mg/eye) twice a day, also for 7 days. Clinical and bacteriological cure rates were evaluated. RESULTS: Enro-C-treated dogs achieved a clinical cure one day earlier than ciprofloxacin-treated dogs, and unlike this latter group, enro-CG achieved bacteriological cure in all cases. No side effects were observed in either group, but dogs treated with enro-C showed no discomfort, allowing easier treatment-compliance. CONCLUSION: This is the first study reported on the successful formulation of enrofloxacin as an ophthalmic solution. Clinical assessment reveals outstanding clinical efficacy. It is necessary to conduct further research on clinical efficacy and toxicity, with the chronic use of this preparation under different clinical challenges.

Efecto del tratamiento de superficie en la fuerza de adhesión de postes de resina reforzados con fibras de cuarzo a los cementos de resina: Estudio in vitro

14. El propósito de este estudio fue determinar el efecto que ejercen distintos tratmientos de superficie en la fuerza de adhesión entre el cemento de resina y los postes de resina reforzados con fibras de cuarzo. Materiales y métodos: Sesenta postes de fibra de cuarzo (DT Light-Post™, Bisco™) se asignaron aleatoriamente a 12 grupos experimentales (n=5), según el cemento de resina utilizado (Biscem™ o Duolink™) y el tipo de tratamiento de superficie: limpieza con alcohol (grupo control), silanizado, primer, arenado, arenado+silanizado o arenado+primer. Se obtuvieron especímenes cilíndricos de resina utilizando resina nanohíbrida. Los postes se cementaron a los discos de resina y se sometieron a pruebas de push-out. Los datos se analizaron con ANOVA y prueba T para comparación de promedios y la prueba Tukey HSD con un nivel de significancia del 95%. Resultados: El cemento Biscem™ presentó, en general, una mayor fuerza de adhesión a los postes al compararse con el Duolink™. Se encontró diferencia significativa entre en grupo control y los grupos de arenado+silano y arenado+primer al utilizar el cemento Duolink™. Con el cemento Biscem™ no hubo diferencias entre grupos o con el grupo control. Conclusión: Los tratamientos de superficie en los postes de resina reforzados con fibra de cuarzo parecen no tener un efecto significativo en la fuerza de adhesión a los cementos de resina evaluados en este estudio, excepto al utilizar el cemento Duolink™ realizando el arenado y además se utilizando el silano o el primer.

18. The purpose of this study was to determine the effect of different surface treatments on the bond strength between resin cements and quartz fiber-reinforced resin posts. Materials and methods: Sixty quartz fiber-reinforced resin posts (DT Light-Post™, Bisco™) were randomly divided into 12 experimental groups (n=5), according to the resin cement used (Biscem™ or Duolink™) and the surface treatment: Alcohol (control group), silanized, primer, sandblasted, sandblasted + silanized or sandblasted + primer. Cylindrical resin specimens were obtained using nanohybrid resin. The posts were cemented to the resin discs and push-out tests were conducted. Data were analyzed with ANOVA and T test for averages comparison and the Tukey HSD test with a 95% level of significance. Results: Biscem™ cement generally showed higher bond strength when compared to Duolink™ Significant differences were found between the control group and the sandblasted + silane and sandblasted + primer groups when using Duolink™cement. With Biscem™ cement, no differences between groups or with the control group were found.. Conclusion: Surface treatments on quartz fiber-reinforced resin poles seem to have no significant effect on the bond strength to resin cements, except when using Duolink™ cement with sandblasted posts and using silane or primer.

Compact dual-view endoscope without field obscuration.

We have developed a compact dual-view endoscopic probe without field obscuration to address the need of simultaneously observing forward and backward fields of view (FOVs) in the colon. The objective is compact with the forward-view and rear-view optical paths sharing the same optical elements. The compact objective is new in that no FOV is blocked. The illumination for forward-view imaging is provided by the cylindrical light guide and backward illumination is achieved with a reflector. We have designed, prototyped, and tested the endoscope by comparing it to a standard clinical colonoscope. We will discuss the system concept, objective design, fabrication of the freeform lens, and test results.

Malformación linfática del omento menor / Lymphatic malformation of the lesser omentum

Introducción: Las malformaciones linfáticas se originan a partir de malformaciones de los vasos linfáticos durante el periodo embrionario, lo que condiciona sus características histopatológicas, el calibre de los vasos que lo componen, así como el sitio donde se localizan. Caso clínico: Se presenta el caso de un paciente masculino de un año 2 meses de edad, quien se diagnostica con una malformación linfática localizada en el omento menor. Esta localización es una de las menos frecuentes en este grupo de malformaciones. Conclusiones: Se expuso el abordaje diagnóstico y la resolución quirúrgica de una malformación linfática del omento menor, con resección completa del mismo, sin recidivas ni complicaciones.

Introduction: Lymphatic malformations are caused by malformations of the lymphatic vessels during embryonic life, conditioning their histopathological characteristics, the caliber of the vessels that compose it, and the site where they are located. Case report: We report the case of a male patient of 1 year and 2 months old who was diagnosed with a lymphatic malformation located in the lesser omentum, this localization being one of the least frequent of this group of malformations. Conclusion: We describe the diagnostic approach and surgical resolution of a lesser omentum lymphatic malformation with its complete removal and without complications or recurrence.

Efficacy of a pharmaceutical preparation based on glycyrrhizic acid in a challenge study of white spot syndrome in white shrimp (Litopenaeus vannamei).

There is a lack of preventive and therapeutic drug-based treatments for the shrimp viral disease known as white spot syndrome (WSSV). Thus a challenge study inducing WSSV in juvenile white shrimp (Litopenaeus vannamei) was established, setting 4 groups: challenged - not treated and unchallenged, untreated control groups and two experimental ones (E1 and E2) both treated with diammonium glycyrrhizic acid, extracted from licorice with added vitamins and oligoelements, and as in-feed medication. Group E1 received diammonium glycyrrhizic acid included in their daily feed, starting 17 days before challenge with WSSV and maintaining the treatment for further 5 days after the end of the trial, which was set on day 18. Group E2 received this medication as group E1 throughout the trial, but starting 1 day before the challenge with WSSV. The group with highest surviving median values was E1, amounting two times the survival median in comparison with the control groups (P = 0.007). Also a statistical difference was found in terms of survival means in favor of group E1 as compared to group E2. Macroscopic and histopathological findings revealed lesions compatible with WSSV and similar mortality in the challenged untreated group. These findings were highly reduced or inexistent in mortality analyzed from groups E1 as well as in the unchallenged - untreated control group and greatly reduced in group E2. Considering the apparent high efficacy observed and that glycyrrhizic acid and mineral and vitamin components added as treatment, and taking as an advantage that this preparation has been regarded as nutraceuticals, it is here proposed that large scale trials should be conducted to evaluate the effects here observed in commercial and larger scale shrimp farms.

In vitro activity of the nisin dehydratase NisB.

The biosynthesis of several classes of ribosomally synthesized and posttranslationally modified peptides involves dehydration of serine and threonine residues. For class I lantibiotics, thiopeptides, and goadsporin, this dehydration is catalyzed by lanthionine biosynthetic enzyme B (LanB) or LanB-like proteins. Although LanB proteins have been studied since 1992, in vitro reconstitution of their dehydration activity has been elusive. We show here the in vitro activity of the dehydratase involved in the biosynthesis of the food preservative nisin (NisB). In vitro, NisB dehydrated its substrate peptide NisA eight times in the presence of glutamate, ATP, Mg(2+), and the ribosomal/membrane fraction of bacterial cell extract. Mutation of 23 highly conserved residues of NisB identified a number of amino acids that are essential for dehydration activity. In addition, these mutagenesis studies identified three mutants, R786A, R826A, and H961A, that result in multiple glutamylations of the NisA substrate. Glutamylation was observed during both Escherichia coli coexpression of NisA with these mutants and in vitro assays. Treatment of the glutamylated substrate with WT NisB results in dehydrated NisA, suggesting that the glutamylated peptide is an intermediate in dehydration. Collectively, these studies suggest that dehydration involves glutamylation of the side chains of Ser and Thr followed by elimination. The latter step has precedent in the virginiamycin resistance protein virginiamycin B lyase. These studies will facilitate investigation of other LanB proteins involved in the biosynthesis of lantibiotics, thiopeptides, and goadsporin.

Melengestrol acetate as a tool for inducing early ovulation in transitional mares.

The efficacy of melengestrol acetate (MGA) to shorten the vernal transition of mares by synchronising and accelerating the first ovulation of the year after 60 days of phototherapy was determined by ultrasonographic monitoring. Sixteen mares in late transition were fed two doses of MGA (150 mg/mare/day and 100 mg/mare/day, respectively) for 10 days. A luteolytic dose of prostaglandin was administered to each mare one day after the end of MGA treatment. The presence and duration of oestrus, follicular growth, uterine oedema and presence of ovulation were monitored by ultrasonography and the cervical tone was evaluated by rectal palpation. Ovulation was detected in 87.5% of the mares treated with 150 mg MGA/mare/day for 10 days, and in 62.5% of the mares receiving 100 mg MGA/mare/day for 10 days. This was statistically different (P = 0.03) from the untreated control mares having an ovulation rate of 20%. Mares that received 150 mg MGA/day for 10 days had a mean treatment to ovulation interval of 13.1 +/- 5.97 days after the end of treatment, while mares that received 100 mg MGA/day for 10 days had a mean of 25.6 +/- 10.50 days (P = 0.01) to ovulation. These results suggest that MGA can be used for synchronising and hastening the first ovulation of the year in mares.

The genome of deep-sea vent chemolithoautotroph Thiomicrospira crunogena XCL-2.

Presented here is the complete genome sequence of Thiomicrospira crunogena XCL-2, representative of ubiquitous chemolithoautotrophic sulfur-oxidizing bacteria isolated from deep-sea hydrothermal vents. This gammaproteobacterium has a single chromosome (2,427,734 base pairs), and its genome illustrates many of the adaptations that have enabled it to thrive at vents globally. It has 14 methyl-accepting chemotaxis protein genes, including four that may assist in positioning it in the redoxcline. A relative abundance of coding sequences (CDSs) encoding regulatory proteins likely control the expression of genes encoding carboxysomes, multiple dissolved inorganic nitrogen and phosphate transporters, as well as a phosphonate operon, which provide this species with a variety of options for acquiring these substrates from the environment. Thiom. crunogena XCL-2 is unusual among obligate sulfur-oxidizing bacteria in relying on the Sox system for the oxidation of reduced sulfur compounds. The genome has characteristics consistent with an obligately chemolithoautotrophic lifestyle, including few transporters predicted to have organic allocrits, and Calvin-Benson-Bassham cycle CDSs scattered throughout the genome.

Effects of alpha2-adrenergic receptor agonists on urine production in horses deprived of food and water.

OBJECTIVE: To quantitate the dose- and time-related effects of IV administration of xylazine and detomidine on urine characteristics in horses deprived of feed and water. ANIMALS: 6 horses. PROCEDURE: Feed and water were withheld for 24 hours followed by i.v. administration of saline (0.9% NaCI) solution, xylazine (0.5 or 1.0 mg/kg), or detomidine (0.03 mg/kg). Horses were treated 4 times, each time with a different protocol. Following treatment, urine and blood samples were obtained at 15, 30, 60, 120, and 180 minutes. Blood samples were analyzed for PCV and serum concentrations of total plasma solids, sodium, and potassium. Urine samples were analyzed for pH and concentrations of glucose, proteins, sodium, and potassium. RESULTS: Baseline (before treatment) urine flow was 0.30 +/- 0.03 mL/kg/h and did not significantly change after treatment with saline solution and low-dose xylazine but transiently increased by 1 hour after treatment with high-dose xylazine or detomidine. Total urine output at 2 hours following treatment was 312 +/- 101 mL versus 4,845 +/- 272 mL for saline solution and detomidine, respectively. Absolute values of urine concentrations of sodium and potassium also variably increased following xylazine and detomidine administration. CONCLUSIONS AND CLINICAL RELEVANCE: Xylazine and detomidine administration in horses deprived of feed and water causes transient increases in urine volume and loss of sodium and potassium. Increase in urine flow is directly related to dose and type of alpha2-adrenergic receptor agonist. Dehydration in horses may be exacerbated by concurrent administration of alpha2-adrenergic receptor agonists.

Actividad antibacteriana in vitro y biodisponibilidad en vacas de Actividad antibacteriana in vitro y biodisponibilidad en vacas de varios preparados de benzilpenicilina G, sola o combinada con sulfato de dihidroestreptomicina / In vitro antibacterial activity and bioavailability of various commercial preparations of benzylpenicillin-G, alone or combined with dihydrostreptomycin sulphate

Los fabricantes de benzilpenicilina G (BP-IG) buscan competitividad, no sólo mediante el costo/UI de actividad, sino también modificando las presentaciones tradicionales en polvo, generando suspensiones estables, preconstituidas. Considerando la falta de estabilidad de los b -lactámicos cuando se les suspende, así como los diferentes tipos de sales de BP-G presentes en un determinado preparado, se considera relevante realizar estudios comparativos de actividad in vitro (concentración mínima inhibitorio) y biodisponibilidad (por difusión en agar) de tres preparados en polvo de BP-G y tres preparados similares pero preconstituidos, así como un preparado de BP-G procaínica en polvo. Para determinar la biodisponibilidad de los preparados mencionados de BP-G se realizaron curvas de concentración-actividad de BP-G versus tiempo y se determinaron las variables de concentración plasmática máxima (CPmáx.) y tiempo para llegar a CPmáx (tmáx), después de una dosis bolo por vía IM. Los resultados muestran que los preparados de BP-G en polvo tuvieron una mayor potencia in vitro, al menos el doble de lo observado para los preconstituidos. Los valores de CPmáx fueron mayores cuando se utilizó BP-G procaínica y mínimos en los preparados que contenían BP-G benzatínica. Los preparados que contenían sulfato de dihidroestreptomicina mostraron mayor concentración-actividad antibacteriana que los preparados sin ella. Sin embargo, las diferencias no fueron estadísticamente significativas (P < 0.05). Se considera que esta información puede ser relevante al clínico, en particular cuando la susceptibilidad de un agente infeccioso a la BP-G está en los límites. Estos resultados cuestionan el valor de agregar dihidroestreptomicina a los preparados de BP-G y ponderan a la BP-G procaínica como la penicilina de elección para el ganado bovino.