Enhancement of transdermal delivery of phenylbutazone from liposomal gel formulations through deer skin

Phenylbutazone (PBZ) is a nonsteroidal anti‐inflammatory drug used in the treatment of chronic pain and arthritis. Topical and transdermal administration of PBZ would be beneficial in large animals in terms of minimizing gastro‐intestinal ulcerations and other side effects, easy administration to legs and joints and minimizing the dose to reduce systemic toxicity of the drug. A topical liposomal preparation with different concentrations of a mono‐substituted alkyl amide (MSA) and PBZ was formulated. The formulations were evaluated by in vitro skin‐permeation kinetics through deer skin using Franz diffusion cells. By increasing drug loading from 1% to 5% w/w, the steady‐state flux (μg/cm²/h) of PBZ was increased twofold (P < 0.001). Similarly, by increasing the MSA concentration from 0% to 4%, the steady‐state flux (μg/cm²/h) of PBZ was increased twofold (P < 0.001). Overall, by increasing the drug load and the use of an appropriate amount of the penetration enhancer, the steady‐state flux of PBZ through skin was increased fourfold (P < 0.001). MSA at both 2% and 4% w/w concentrations significantly increased the skin levels of PBZ as compared with control (P < 0.05). In conclusion, MSA served as an effective skin‐penetration enhancer in the liposomal gel of PBZ for deer.     

Biomechanical Comparison of Two Alternative Tibial Plateau Leveling Osteotomy Plates with the Original Standard in an Axially Loaded Gap Model: An In Vitro Study

Objective— To compare the axial compression stiffness of osteotomized canine tibiae stabilized with Slocum, Securos, or Synthes plates after a tibial plateau leveling osteotomy (TPLO) procedure. Study Design— In vitro, paired comparison of cadaveric tibial constructs subjected to mechanical testing under an axial load. Sample Population— Canine tibiae (n=16 pairs) from skeletally mature male and female dogs of various breeds (18–55 kg). Methods— Tibial pairs (n=16) were randomly assigned to 1 of 2 study cohorts (n=8 pairs/cohort): cohort 1, tibial osteotomy stabilization with a Slocum or a Securos plate, or cohort 2, tibial osteotomy stabilization with a Slocum or a Synthes plate. One tibia from each pair was stabilized with 1 of each plate design assigned to the cohort after TPLO. A 3.2 mm osteotomy gap was maintained during plate application in all constructs. Load and axial displacement were recorded while constructs were loaded to 2000 N in axial compression. Failure loads were not reported because no distinct yield point or failure point was evident within the load range for many specimens. Failure modes were recorded for each construct, and photographs of typical failures were obtained. Stiffness (N/mm) was calculated from load–displacement curves. Paired comparisons of mean stiffness were performed within study groups using a paired t‐test. Significance was set at P<.05. Results— The mean construct stiffnesses for the Slocum (383±183 N/mm) and Securos (258±64.1 N/mm) constructs were not significantly different (P=.164; power=0.566). The mean construct stiffness for the Synthes constructs (486±91.0 N/mm) was significantly greater than that of the Slocum constructs (400±117 N/mm); P=.0468. Modes of failure for the Slocum (16/16) and Securos (8/8) constructs included plastic deformation of the implant with valgus deformity combined with fibular luxation (2/16 Slocum; 1/8 Securos) or fibular fracture (2/16 Slocum; 4/8 Securos). Most Synthes constructs underwent elastic deformation (7/8). One Synthes construct fractured in the saggital plane through the tibial plateau depression at the point of load application. Conclusions— The Slocum and Securos plate/tibia construct have similar stiffness, whereas the Synthes/tibia constructs are significantly stiffer than the Slocum/tibia constructs. Modes of fixation failure observed in this model were consistent with TPLO fixation failures observed clinically. Clinical relevance— Construct stiffness in axial load varies with implant type. Implants that confer higher stiffness to the construct may result in greater fixation stability in tibial metaphyseal osteotomies.     

The effects of seed mix and management on the abundance of desirable and pernicious unsown species in arable buffer strip communities

Buffer strips are refuges for a variety of plants providing resources, such as pollen, nectar and seeds, for higher trophic levels, including invertebrates, mammals and birds. Margins can also harbour plant species that are potentially injurious to the adjacent arable crop (undesirable species). Sowing perennial species in non‐cropped buffer strips can reduce weed incidence, but limits the abundance of annuals with the potential to support wider biodiversity (desirable species). We investigated the responses of unsown plant species present in buffer strips established with three different seed mixes managed annually with three contrasting management regimes (cutting, sward scarification and selective graminicide). Sward scarification had the strongest influence on the unsown desirable (e.g. Sonchus spp.) and unsown pernicious (e.g. Elytrigia repens) species, and was generally associated with higher cover values of these species. However, abundances of several desirable weed species, in particular Poa annua, were not promoted by scarification. The treatments of cutting and graminicide tended to have negative impacts on the unsown species, except for Cirsium vulgare, which increased with graminicide application. Differences in unsown species cover between seed mixes were minimal, although the grass‐only mix was more susceptible to establishment by C. vulgare and Galium aparine than the two grass and forb mixes. Annual scarification can enable desirable annuals and sown perennials to co‐exist, however, this practice can also promote pernicious species, and so is unlikely to be widely adopted as a management tool in its current form.     

Is there an association between ossification of the cartilages of the foot and collateral desmopathy of the distal interphalangeal joint or distal phalanx injury?

Reasons for performing study: Associations between degree of ossification of the cartilages of the foot and injuries to other structures of the foot have been suggested, but have not been investigated by large scale studies. Objectives: To describe the frequency of grade >3 ossification of the cartilages of the foot (possibly significant ossification, PSO), mediolateral symmetry of ossification and left‐right symmetry between feet; and to investigate associations between PSO and injury of either the collateral ligaments (CLs) of the distal interphalangeal (DIP) joint or the distal phalanx. Hypotheses: Possibly significant ossification of the cartilages of the foot is associated with CL and distal phalanx injury. Distal phalanx injury is associated with a mediolateral difference in ossification grade of ≥2. Methods: Horses were examined for lameness localised to the foot by perineural analgesia, and underwent radiographic and magnetic resonance imaging examinations. Age, breed, occupation, duration of lameness, lame(st) limb, primary cause of lameness, and presence or absence of CL injury were recorded. Dorsopalmar (dorsoplantar) radiographs were examined and ossification of the cartilages of the foot graded using a modification of a previously published scale. Results: One foot from each of 462 horses was included for analysis. There was left‐right symmetry of ossification between feet, and significant association between grades of each foot, with lateral ≥medial cartilages. Possibly significant ossification occurred in the maximally ossified cartilage in 59 (12.8%) feet. There were significant associations between PSO of the maximally ossified cartilage of the foot and injuries of both the CLs of the DIP joint and the distal phalanx. There was no association between distal phalanx injury and marked asymmetry of the ossified cartilages of the foot. Conclusions and clinical relevance: Extensively ossified cartilages of the foot are significantly associated with CL or distal phalanx injury. Markedly asymmetric ossification did not increase the likelihood of distal phalanx injury and should be considered at a prepurchase examination.     

蟋蟀粉替代鱼粉对黄颡鱼幼鱼生长性能、肌肉氨基酸组成和血清生化指标的影响

为研究蟋蟀(Gryllus bimaculatus)粉替代鱼粉对黄颡鱼(Pelteobagrus fulvidraco)幼鱼生长性能、肌肉成分和血清生化指标的影响,以黄颡鱼幼鱼[(2.0±0.13) g]为研究对象,分别使用蟋蟀粉替代0 (对照组)、15%、30%、45%和60%的鱼粉配制成5组等氮等能的实验饲料,分别记为T0、T15、T30、T45和T60组。实验幼鱼在室内循环水系统进行为期10周的养殖实验。结果显示,随着蟋蟀粉替代量的增加,黄颡鱼幼鱼生长呈先增加后降低的趋势;T30组的终末均重(FBW)、增重率(WGR)和特定生长率(SGR)最高,且均显著高于T0组;T30组的饲料系数(FCR)显著低于T0和T15组;T30的肝体比(HSI)显著高于T0和T15,而与T45和T60组无显著差异。与T0组相比,各替代组的脏体比(VSI)、摄食量(FI)、肥满度(CF)和成活率(SR)均无显著差异。黄颡鱼幼鱼肌肉必需氨基酸(EAA)含量中,T60组肌肉中精氨酸(Arg)和缬氨酸(Val)含量显著高于T0组;且蟋蟀粉替代不同比例的鱼粉对黄颡鱼幼鱼肌肉中的总呈味氨基酸(TFAA)含量均未产生显著影响。T30、T45和T60组血清中的葡萄糖(GLU)含量显著高于T0组;相反,其总胆固醇(TCHO)含量显著低于T0组。在本研究条件下,蟋蟀粉替代不同比例的鱼粉不影响黄颡鱼幼鱼的生长性能和肌肉氨基酸含量,且能增加血清GLU和降低TCHO含量,以30%的蟋蟀粉替代鱼粉比例能生长最佳,且优于对照组。本研究对揭示蟋蟀粉在黄颡鱼饲料中替代鱼粉应用的可行性、为今后昆虫蛋白源在水产饲料中的开发提供科学依据。     

Detection of the source of infection of apple trees by Cylindrocarpon heteronema using DNA polymorphisms

Restriction fragment length polymorphisms (RFLPs) of the ribosomal DNA (rDNA) and mitochondrial DNA (mtDNA) of isolates of Cylindrocarpon heteronema were analysed using rDNA from Saccharomyces carlsbergensis and mtDNA from C. heteronema as probes. These analyses revealed intraspecific heterogeneity; four rDNA and six mtDNA restriction pattern categories were observed among the isolates tested. The two main rDNA RFLP categories, both of which subdivided into two mtDNA categories, detected within the UK isolates could not be associated with the localities from which they were obtained, but the majority of isolates originating from trees produced in the same nursery, irrespective of where they were finally planted, belonged to the same category.     

Fluoroquinolones in animal health

The fluoroquinolones are a series of synthetic antibacterial agents that are undergoing extensive investigation for both human and veterinary use in the treatment of a variety of bacterial infections. These agents work through the inhibition of DNA gyrase, interfering with the supercoiling of bacterial chromosomal material. As a result, these agents are rapidly bactericidal primarily against gram-negative bacteria, mycoplasma, and some grampositive bacteria, with most having little to no activity against group D streptococci and obligate anaerobic bacteria. Resistance develops slowly and is almost always chromosomal and not plasmid-mediated. However, development of resistance to the fluoroquinolones and transfer of that resistance among animal and human pathogens have become a hotly debated issue among microbiologists. The fluoroquinolones are a current antimicrobial class whose use in veterinary medicine is being scrutinized. From a pharmacokinetic perspective, these agents are variably but well absorbed from the gastrointestinal tract and almost completely absorbed from parenteral injection sites, and they are well distributed to various tissues in the body. The fluoroquinolones are metabolized and renally excreted, with many of them having approximately equal excretion by the hepatic and the renal excretory systems. The primary toxicity observed at therapeutic doses involves the gastrointestinal system and phototoxicity, although at higher doses central nervous system toxicity and ocular cataracts are observed. Administration to immature animals may result in erosive arthropathies at weight-bearing joints, and administration of high doses to pregnant animals results in maternotoxicity and occasionally embryonic death. The fluoroquinolones are approved for indications such as urinary tract infections and soft tissue infections in dogs and cats and colibacillosis in poultry. Approval for bovine respiratory disease in the United States is being sought. Other indications for which the fluoroquinolones have been used in animal health include deep-seated infections, prostatitis, and other bacterial infections resistant to standard antimicrobial therapy.     

Elution of antimicrobials from a cross‐linked dextran gel: In vivo Quantification

Reasons for performing study: Use of a novel, biodegradable, antimicrobial‐impregnated gel provides an alternative method of local treatment of infections in horses. Objectives: To determine in vivo elution of antimicrobial medications from antimicrobial‐impregnated cross‐linked dextran gel and to evaluate the effect on wound healing when implanted subcutaneously in horses. Methods: Amikacin‐, vancomycin‐ or amikacin/clindamycin‐impregnated gel was placed subcutaneously in 11 horses' necks, using 6 replicates with a 3 month washout between experiments. Capillary ultrafiltration probes for collection of interstitial fluid were placed 0 cm and 1.5 cm from the gel‐filled incisions. Samples were collected at 0, 4, 8 and 12 h, and on Days 1–10. Blood was collected on Days 0, 1 and 7. Amikacin and vancomycin samples were analysed via fluorescence polarisation immunoassay, and clindamycin samples via high‐performance liquid chromatography. Histology of biopsy samples was performed at the completion of the study. Differences in mean histomorphological scores between groups were assessed using Wilcoxon's signed ranks test. Results: Maximum antimicrobial concentrations were detected at 4 h (amikacin), and 8 h (vancomycin, and amikacin and clindamycin from the combination gel). Mean ± s.d. peak concentrations for amikacin, vancomycin, amikacin (amikacin/clindamycin) and clindamycin were 6133 ± 1461, 7286 ± 2769, 3948 ± 317 and 985 ± 960, respectively. Median number of days for which antimicrobial concentration remained above minimum inhibitory concentration for target microorganisms at implantation was ≥10 days for vancomycin, 9 days (± 1) for amikacin and 8 days (± 1) for clindamycin. Mean plasma amikacin and vancomycin concentrations were lower than detectable limits; mean serum clindamycin concentrations were 0.52 µg/ml and 0.63 µg/ml at 24 h and 7 days, respectively. There were no significant differences in histomorphological scores between treatment and control incisions (P≥0.22). Conclusions and potential relevance: Cross‐linked dextran gel is a safe, effective alternative local antimicrobial delivery method.     

Effect of Late-season Top-dressings of N (and K) applied to Conifer Transplants in the Nursery on their Survival and Growth on British Forest Sites

At two English forest nurseries, transplants of five coniferspecies—Picea sitchensis, Picea abies, Tsuga heterophylla,Abies grandis, and Pinus contorta—were grown with fertilizersupplying N, P, K, and Mg in amounts intended to be adequatefor producing healthy green trees with nutrient concentrationsin the ‘sufficiency range’ as determined by earlierexperiments. ‘Luxury uptake’ of nitrogen was obtainedwith top-dressings of ‘Nitro-Chalk’ applied in thenursery during early September, when top growth had nearly ceased.Tests of the effect of this extra N on forest establishmentwere repeated in four successive years under a wide range ofsoil and climatic conditions, keeping the trees in a cold storeduring each winter and planting them on forest sites in England,Scotland, or Wales during the following spring. Except for Grandfir, nitrogen advanced bud-break of all species during the firstsummer after planting and had no deleterious influence on survival.It tended to increase growth of Sitka spruce during the seasonafter planting, but in later years the differences became smallin relation to tree size. The effects on other species weresmall, except for one considerable decrease in the growth responseof Grand fir at a single site. Frost damage of Sitka spruce of Washington origin was severeon a Welsh and a Scottish site where this frost-sensitive provenancewould not normally be grown. At the Welsh, but not the Scottishsite, the nitrogen treatment increased the damage. In the few experiments (confined to Picea sitchensis) whichtested late-season potassium in the nursery, K concentrationswere increased from deficiency to barely sufficiency level;growth in the forest was increased in two of the four experiments.The extra K had no effect on frost damage.