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.     

Effect of magnitude and direction of force on laryngeal abduction: Implications for the nerve‐muscle pedicle graft technique

Reasons for performing study: The nerve‐muscle pedicle graft technique is a treatment for recurrent laryngeal neuropathy (RLN), but the optimal placement of the pedicles within the cricoarytenoideus dorsalis (CAD) muscle is unknown. Hypothesis: The magnitude and direction of force placed on the muscular process of the left arytenoid cartilage affects the magnitude of laryngeal abduction. Methods: Five larynges were harvested from cadavers. Using increments of 0.98 N, a dead‐weight force generator applied a force of 0–14.7 N for 1 min each to the left muscular process at 0, 10, 20, 30, 40, 50, 60 and 70° angles. The rima glottis was photographed digitally 1 min after each force had been applied. Distances between biomarkers (Lines 1–4) and right to left angle quotient (RLQ) were used to assess the degree of left arytenoid abduction. Results: Increasing force from 0–14.7 N progressively and significantly increased the length of all lines and RLQ, indicating abduction. Furthermore, there was a significant interaction between force and angles. Applying forces of 7.84 N or greater (Lines 2–4 and RLQ) or 11.76 N or greater (Line 1) at angles 0, 10, 20 and 30° resulted in significantly greater abduction than applying the same forces at 40, 50, 60 and 70°. Angles of 0–30° correspond with the direction of pull exerted by the lateral compartment of the CAD muscle. Conclusion: In RLN, nerve‐muscle pedicle grafts should be placed preferentially in the lateral rather than in the medial compartment of the CAD muscle. Potential relevance: The information presented can be used to assist surgeons in the planning and application of the nerve‐muscle pedicle graft procedure.     

Cutaneous neoplasms in pet rabbits: a retrospective study

Over a 16-year period, 190 tumors and tumorlike lesions from 179 pet rabbits were submitted for histopathologic examination. A total of 23 different tumor types and 1 tumorlike lesion were diagnosed. The most common diagnoses were trichoblastoma, collagenous hamartoma, and Shope fibroma. Viral-induced tumors were Shope fibroma (19) and Shope papilloma (2). Common nonviral epithelial tumors included trichoblastoma (59), squamous cell carcinoma (5), squamous papilloma (4), trichoepithelioma (3), and apocrine carcinoma (3). Common mesenchymal tumors were lipoma (10), liposarcoma (3), myxosarcoma (9), malignant peripheral nerve sheath tumor (8), fibrosarcoma (7), and leiomyosarcoma (4). Malignant melanoma was diagnosed in 8 rabbits. Collagenous hamartomas were diagnosed in 26 rabbits. Mesenchymal proliferations occurred significantly more often in male rabbits than in females. Collagenous hamartomas and myxosarcomas occurred exclusively in male animals, and 3 rabbits had multiple collagenous hamartomas. Immunohistochemistry was applied in cases in which a definite diagnosis could not be reached on hematoxylin and eosin slides. Follow-up information was received in 19 cases. Carcinomas recurred (2 of 3) or metastasized (1 of 3), whereas sarcomas frequently recurred (7 of 12). One malignant melanoma (1 of 3) and one poorly differentiated round cell neoplasm recurred (1 of 1). This is the first comprehensive retrospective analysis on skin neoplasia in pet rabbits.     

Sialidase activity in Mycoplasma synoviae

Eleven strains of the avian pathogen Mycoplasma synoviae were evaluated for the presence of sialidase activity with the use of the fluorogenic substrate 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid and the sialidase inhibitor 2-deoxy-2,3- didehydro-N-acetylneuraminic acid. The kinetics of in vitro growth in modified Frey medium were also assessed for each strain. Five strains had been isolated from clinically symptomatic chickens, and strains WVU 1853T and K3344 have been demonstrated to be capable of reproducing disease in specific-pathogen-free chickens. All strains exhibited sialidase activity, although the amount varied 65-fold among strains (P < 0.0001) from 1.3 x 10(-7) to 2.0 x 10(-9) activity units per colony-forming unit. Strains originally isolated from clinically symptomatic birds had more (P < 0.05) sialidase activity than strains from asymptomatic birds. Strain WVU1853T exhibited the most sialidase activity (P < 0.0001) and grew to the highest culture density (P < 0.0001) among strains, but across strains, the rank correlation of growth rate with sialidase activity was not significant. Negligible activity was detected in conditioned culture supernatant fluid. This is the first report of sialidase activity in pathogenic strains of M. synoviae, which suggests a potential enzymatic basis for virulence of the organism.     

Pigeon paramyxovirus: association with common avian pathogens in chickens and serologic survey in wild birds

Pigeon paramyxovirus-1 (PPMV-1) was isolated from pigeons from east-central Alabama and used in association with chicken anemia virus (CAV), infectious bursal disease virus (IBDV), or finch Mycoplasma gallisepticum (MG) in specific-pathogen-free chickens to assess dinical disease and pathology. PPMV-1 infection in all groups was conducted at day 10 of age via the ocular route. The low passage PPMV-1 isolate was inoculated into chickens in different groups at 10 days post-CAV infection, 6 days post-IBDV infection, and 6 days post-finch MG infection, respectively. Additionally, to obtain information on the status of paramyxovirus infection in the wild bird population of the region, we used a multispecies competitive enzyme-linked immunosorbent assay kit to assess serum samples from 180 wild birds representing 24 species obtained throughout 2001. Mild respiratory signs characterized by sneezing were observed in PPMV-1-infected chicks. In the brain, PPMV-1 caused disseminated vasculitis in the neuropile and meninges, sometimes with small foci of gliosis. Most brains had only mild lesions. In the upper respiratory tract, lesions were confined to the larynx and proximal trachea as hyperplasia of laryngeal mucosa-associated lymphoid tissue. In the lung, PPMV-1 caused minimal to moderate multifocal interstitial pneumonia. Lymphocytic expansion occurred in the interstitium of the Harderian gland. PPMV-1 in the spleen caused expansion of the white pulp as a result of hypertrophy of the macrophages in the periarteriolar sheaths accompanied by lymphocytic hyperplasia at the periphery. No severe aggravation of either signs or lesions could be attributed to any of the avian pathogens used in association with PPMV-1. The serologic survey in wild birds showed antibody levels that were considered negative or doubtful. Interestingly, significantly (P < 0.05) higher mean titers were observed during the months of October and November 2001, following closely multiple PPMV-1 episodes of mortality in wild collard doves in northwestern Florida.     

Persistence of Salmonella Typhimurium DT120 in abattoir paddocks holding sheep

In the summer of 1999 there was an outbreak of Salmonella Typhimurium DT120 in people in the north of England which was unusual in being sensitive to antimicrobial drugs. The outbreak was linked to mutton and lamb from a local abattoir, and attention focused on four holding paddocks used to retain sheep before slaughter. In November 1999, samples of soil and faeces were taken from these paddocks and samples of faeces were taken from the concrete race leading from them. Salmonella Typhimurium was isolated from 59 of the 100 samples. Between January 2000 and October 2000 seven visits were made to the abattoir at each of which 100 samples were taken from the paddocks and concrete race and examined for the presence of Salmonella. The paddocks remained heavily contaminated with S Typhimurium DT120 until April when there was a marked reduction in the recovery of the organism. By June the contamination was minimal and by August it had disappeared, and the organism was not recovered in September or October.     

Surgical advancement of the larynx (laryngeal tie-forward) as a treatment for dorsal displacement of the soft palate in horses: a prospective study 2001-2004

REASONS FOR PERFORMING STUDY: Correct placement of sutures ('laryngeal tie-forward') in experimentally created dorsal displacement of the soft palate (DDSP) has been observed to replace the function of the thyrohyoideus muscles and prevent DDSP. HYPOTHESIS: The 'laryngeal tie-forward' procedure would prevent or delay the occurrence of DDSP during exercise in horses with naturally occurring DDSP and therefore improve performance. METHODS: A clinical population (n = 116), mainly of racehorses was presented for treatment of naturally occurring exercise-induced DDSP. All horses underwent the 'laryngeal tie-forward' procedure. The relative position of the thyroid and cricoid cartilage in relation to the caudal aspect of the basihyoid bone was recorded; follow-up was obtained by telephone communication with trainers, owners and/or referring veterinarians. In addition, a performance index and earnings were determined using race records. RESULTS: Preoperatively, the median distance between the caudal aspect of the basihyoid bone and rostral aspect of the thyroid cartilage was 3.5 cm. Post operatively, the thyroid cartilage was moved a median distance of 4 cm rostrally and the larynx was shown to be in a position more rostral and dorsal than in preoperative radiographs. Of 98 horses for which follow-up was available, the performance of 87% was classified as improved, 12% as unchanged and 2% as worse. In 20 horses in which the diagnosis had been confirmed by treadmill videoendoscopy, 80% had a significantly increased performance index and earnings (P = 0.007). For the entire population, there was a significant improvement in performance index and earnings after surgery (82%) (P = 0.0001). CONCLUSIONS: Placing the larynx in a more rostral and dorsal position may have improved the performance in 80-82% of the horses affected with naturally-occurring DDSP. POTENTIAL RELEVANCE: 'Laryngeal tie-forward' is a surgical technique that has a measurable effect on the position of the larynx and offers an alternative therapy for treating horses affected with DDSP. More experience may be needed with this technique prior to its widespread use in horses with a clinical diagnosis of DDSP.     

Evaluation of genetic and metabolic predispositions and nutritional risk factors for pasture-associated laminitis in ponies

OBJECTIVE: To evaluate genetic and metabolic predispositions and nutritional risk factors for development of pasture-associated laminitis in ponies. DESIGN: Observational cohort study. ANIMALS: 160 ponies. PROCEDURES: A previous diagnosis of laminitis was used to differentiate 54 ponies (PL group) from 106 nonlaminitic ponies (NL group). Pedigree analysis was used to determine a mode of inheritance for ponies with a previous diagnosis of laminitis. In early March, ponies were weighed and scored for body condition and basal venous blood samples were obtained. Plasma was analyzed for glucose, insulin, triglycerides, nonesterified fatty acids, and cortisol concentrations. Basal proxies for insulin sensitivity (reciprocal of the square root of insulin [RISQI]) and insulin secretory response (modified insulin-to-glucose ratio [MIRG]) were calculated. Observations were repeated in May, when some ponies had signs of clinical laminitis. RESULTS: A previous diagnosis of laminitis was consistent with the expected inheritance of a dominant major gene or genes with reduced penetrance. A prelaminitic metabolic profile was defined on the basis of body condition, plasma triglyceride concentration, RISQI, and MIRG. Meeting > or = 3 of these criteria differentiated PL- from NL-group ponies with a total predictive power of 78%. Determination of prelaminitic metabolic syndrome in March predicted 11 of 13 cases of clinical laminitis observed in May when pasture starch concentration was high. CONCLUSIONS AND CLINICAL RELEVANCE: Prelaminitic metabolic syndrome in apparently healthy ponies is comparable to metabolic syndromes in humans and is the first such set of risk factors to be supported by data in equids. Prelaminitic metabolic syndrome identifies ponies requiring special management, such as avoiding high starch intake that exacerbates insulin resistance.     

Mycobacterium bovis cultured from commercially pasteurized cows' milk: laboratory cross-contamination

The ability of Mycobacterium paratuberculosis to survive the commercial pasteurization process of raw milk remains controversial. In a study undertaken in Venezuela to culture M. paratuberculosis from commercially pasteurized cows' milk, 83-200 ml containers of milk were processed and cultured on Herrold's egg yolk slants. No M. paratuberculosis was cultured but a total of six colonies of Mycobacterium bovis were isolated from one container each from two different milk providers. Because laboratory cross-contamination was suspected, the laboratory records were reviewed and spoligotyping was carried out on the isolated individual colonies. On the day before these milk specimens were processed, the biological safety cabinet had been used for the isolation of M. bovis from lymph nodes from infected cattle. Spoligotyping showed that that the colonies isolated from the milk all had the same pattern as the strains isolated from the lymph nodes that were processed the previous day. As far as we know, this is the first report of cross-contamination in a veterinary mycobacterial laboratory. False-positive cultures in the mycobacterial laboratory are not rare. In this setting M. bovis was isolated because it is the most common manipulated organism in this laboratory. We believe that reports on the isolation of M. paratuberculosis from commercially pasteurized milk should exclude cross-contamination before reporting, especially when this organism is routinely isolated from animal material in the same lab.