Pharmacokinetics of gemcitabine and its primary metabolite in dogs after intravenous infusion

Gemcitabine is a relatively new chemotherapeutic compound used to treat a variety of cancers in dogs. Previous work presented in a companion paper explored the plasma kinetics of gemcitabine and its inactive metabolite, 2',2'-difluorodeoxyuridine (dFdU), in dogs after an intravenous bolus gemcitabine dose and demonstrated the saturation of intracellular dFdCTP (2',2'-difluorodeoxycytidine 5'-triphosphate) occurs in vitro with increasing extracellular gemcitabine exposure in canine melanoma cells. In this study, the plasma pharmacokinetics (PKs) of gemcitabine and dFdU are further explored after gemcitabine doses of 10, 30, and 60 mg/kg administered by intravenous infusion with a loading dose. Gemcitabine displayed linear PKs, while the kinetics of dFdU were not dose proportional. The overall clearance, volume of distribution at steady-state, and terminal elimination half-life (t(1/2)) for gemcitabine were 0.421 L/h.kg, 0.822 L/kg, and 1.49 h, respectively. Plasma concentrations of dFdU peaked at approximately 2 h postdosing and had a t(1/2) of 14.9 h.     

Compensation for changes in hoof conformation between shoeing sessions through the adaptation of angular kinematics of the distal segments of the limbs of horses

OBJECTIVE: To determine the mechanism that enables horses to partially counteract the shift of the center of pressure under the hoof induced by changes in hoof morphology attributable to growth and wear during a shoeing interval. ANIMALS: 18 clinically sound Warmblood horses. PROCEDURES: Horses were evaluated 2 days and 8 weeks after shoeing during trotting on a track containing pressure-force measuring plates and by use of a synchronous infrared gait analysis system set at a frequency of 240 Hz. All feet were trimmed toward straight alignment of the proximal, middle, and distal phalanges and shod with standard flat shoes. Results-Temporal characteristics such as stance time and the time between heel lift and toe off (ie, breakover duration) did not change significantly as a result of shoeing interval. Protraction and retraction angles of the limbs did not change. Compensation was achieved through an increase in the dorsal angle of the metacarpohalangeal or metarsophalangeal (fetlock) joint and a concomitant decrease of the dorsal angle of the hoof wall and fetlock. There was an additional compensatory mechanism in the hind limbs during the landing phase. CONCLUSIONS AND CLINICAL RELEVANCE: Horses compensate for changes in hoof morphology that develop during an 8-week shoeing interval such that they are able to maintain their neuromuscular pattern of movement. The compensation consists of slight alterations in the angles between the distal segments of the limb. Insight into natural compensation mechanisms for hoof imbalance will aid in the understanding and treatment of pathologic conditions in horses.     

Muscle reorganisation through local injection of stem cells in the diaphragm of mdx mice

Background

The diaphragm is the major respiratory muscle affected by Duchenne muscular dystrophy (DMD) and is responsible for causing 80% of deaths. The use of mechanical forces that act on the body or intermittent pressure on the airways improves the quality of life of patients but does not prevent the progression of respiratory failure. Thus, diseases that require tissue repair, such as DMD, represent a group of pathologies that have great potential for cell therapy. The application of stem cells directly into the diaphragm instead of systemic application can reduce cell migration to other affected areas and increase the chances of muscle reorganisation. The mdx mouse is a suitable animal model for this research because its diaphragmatic phenotype is similar to human DMD. Therefore, the aim of this study was to assess the potential cell implantation in the diaphragm muscle after the xenotransplantation of stem cells.

Methods

A total of 9 mice, including 3 control BALB/Cmice, 3 5-month-old mdx mice without stem cell injections and 3 mdx mice injected with stem cells, were used. The animals injected with stem cells underwent laparoscopy so that stem cells from GFP-labelled rabbit olfactory epithelium could be locally injected into the diaphragm muscle. After 8 days, all animals were euthanised, and the diaphragm muscle was dissected and subjected to histological and immunohistochemical analyses.

Results

Both the fresh diaphragm tissue and immunohistochemical analyses showed immunopositive GFP labelling of some of the cells and immunonegativity of myoblast bundles. In the histological analysis, we observed a reduction in the inflammatory infiltrate as well as the presence of a few peripheral nuclei and myoblast bundles.

Conclusion

We were able to implant stem cells into the diaphragm via local injection, which promoted moderate muscle reorganisation. The presence of myoblast bundles cannot be attributed to stem cell incorporation because there was no immunopositive labelling in this structure. It is believed that the formation of the bundles may have been stimulated by cellular signalling mechanisms that have not yet been elucidated.     

猪的回肠炎及其控制

猪的增生性回肠病 (回肠炎 )最早在 1 931年被发现 ,但直到约 60年后 ,本病的病原体由爱丁堡大学的 lawson等人命名为 lawsonia intracellu-laris。随后的 1 0年中由于许多特有技术的发展 ,使得人们可进一步研究这种细菌感染的流行病学和它的各种临床表现 -即地方性回肠炎 ( RI)、增生性肠病 ( PE)、坏死性肠炎 ( NE)和急性出血增生性肠病 ( AHPE)。所有疾病的控制方案都是以流行病学为基础的。有关病原体和传播方式的许多问题仍待解决。1　流行病学分子诊断技术可用于整个畜群抽查并可检测它们粪便中的 L intracellularis。西班牙对 7…     

Protecting effect of vitamin E supplementation on submaximal exercise-induced oxidative stress in sedentary dogs as assessed by erythrocyte membrane fluidity and paraoxonase-1 activity

The aim of this placebo-controlled study was to investigate the effects of oral vitamin E supplementation for 10 weeks on exercise-induced oxidative damage in untrained dogs. Eight dogs were randomly assigned to a supplementation (n = 4) or control (n = 4) group and underwent two isolated submaximal exercise sessions, 10 weeks apart. Blood was collected during each session to measure erythrocyte membrane fluidity (EMF), paraoxonase-1 (PON1) activity, plasma malondialdehyde (MDA) and vitamin E concentrations. These biomarkers were measured in venous blood samples collected before (t₀), just after (t, EMF only) and 1 d (t + 1 d) and 7 d (t + 7 d) after the dogs ran on a treadmill.Prior to vitamin E supplementation, exercise induced a significant decrease in PON1 activity, EMF, vitamin E concentration and a significant increase in MDA concentration at t + 1 d. After a 10 week vitamin E supplementation period, these exercise-induced changes in PON1 activity, EMF and MDA concentration were still significant in the control group, but not in the supplemented group. These results suggested that vitamin E supplementation had a protective effect on submaximal exercise-induced oxidative damage in sedentary dogs.     

Sheep fed with banana leaf hay reduce ruminal protozoa population

A ciliate protozoa suppression can reduce methane production increasing the energy efficiency utilization by ruminants. The physicochemical characteristics of rumen fluid and the profile of the rumen protozoa populations were evaluated for sheep fed banana leaf hay in replacement of the Cynodon dactylon cv. vaqueiro hay. A total of 30 male sheep were raised in intensive system during 15 days of adaptation and 63 days of experimental period. The animals were distributed in a completely randomized design that included six replicates of five treatments with replacement levels (0, 25, 50, 75, and 100%) of the grass vaquero for the banana leaf hay. Samples of fluid were collected directly from the rumen with sterile catheters. Color, odor, viscosity, and the methylene blue reduction potential (MBRP) were evaluated and pH estimated using a digital potentiometer. After decimal dilutions, counts of genus protozoa were performed in Sedgewick Rafter chambers. The averages of pH, MBRP, color, odor, and viscosity were not influenced by the inclusion of the banana leaf hay. However, the total number of protozoa and Entodinium spp. population significantly decreased at 75 and 100% inclusions of banana leaf hay as roughage.     

Black yeast-like fungi associated with Lethargic Crab Disease (LCD) in the mangrove-land crab, Ucides cordatus (Ocypodidae)

Lethargic Crab Disease (LCD) caused extensive epizootic mortality of the mangrove land crab Ucides cordatus (Brachyura: Ocypodidae) along the Brazilian coast, mainly in the Northeastern region. The disease was named after the symptoms of slow movement of infected crabs. Causative agents were suspected to be two black yeast-like fungi of the family Herpotrichiellaceae (ascomycete order Chaetothyriales), judged by infected tissue biopsies from moribund U. cordatus. The aim of the present study is to prove that two species are involved in the disease: the recently described black yeast Exophiala cancerae, but also a less virulent, hitherto undescribed fonsecaea-like species, introduced here as the novel species Fonsecaea brasiliensis. Strains were identified by ITS rDNA sequencing, and species borderlines were established by multilocus sequencing and AFLP analysis. Fonsecaea brasiliensis proved to be closely related to the pathogenic species Cladophialophora devriesii which originally was isolated from a systemic infection in a human patient. The virulence of F. brasiliensis is lower than that of E. cancerae, as established by artificial inoculation of mangrove crabs.