Ex vivo nail infection as an effective preclinical method for screening of new topical antifungals.

Onychomycosis are fungal nail infections comprising of about 50% of onychopathies and are commonly caused by dermatophytes. The treatment of this dermatomycosis requires a long period of time and is associated with high rates of recurrence. In view of the need to evaluate the antifungal performance of promising preclinical compounds, we developed, in this study, a practical and accessibleex vivo model for establishing a Trichophyton rubrum onychomycosis framework using porcine hooves. This model has as its main advantage the similar structural and three-dimensional characteristics that the porcine hooves have with the human nail. The proposed model allowed to evaluate the antifungal activity of a new antifungal compound and a reference drug (terbinafine), both already incorporated into a nail lacquer for topical use. Treatments with compound 3-selenocyanate-indole (Se4a) and with terbinafine incorporated into this nail lacquer completely inhibited fungal growth, corresponding to the profile of in vitro activity observed against T. rubrum. This study concludes that the ex vivo porcine hoof model is an effective alternative method for preclinical screening of drugs or new topical compounds developed to combat onychomycosis. Further studies are needed to compare the permeability of porcine hooves with human nails permeability.

Influence of dietary zinc on the claw and interdigital skin of sheep.

Claw diseases like interdigital dermatitis and footrot threaten sheep health and are major welfare issues. Several studies mainly done in cattle suggested that zinc (Zn) supplementation may improve claw integrity. However, Zn supplements may differ markedly regarding Zn bioavailability. Zn bound to single amino acids has been shown to be more bioavailable than inorganic Zn sources. The aim of this study was to determine the effect of different Zn supplements on the integrity of the claw and interdigital skin of healthy sheep. At weaning 30 Merino lambs were randomly allocated to three different dietary treatments which were provided through the pelleted concentrates as follows: 1) no supplemental Zn (Zn0); 2) addition of 40 mg/kg Zn as Zn sulphate (ZnS); 3) addition of 40 mg/kg organic Zn as Zn amino acid complex (CZn). Barley straw and pelleted concentrates were given ad-libitum. The calculated Zn concentration of the total diet (roughage and concentrate) without supplemental Zn (Zn0) was 38 mg Zn/kg DM. The concentrates were formulated to meet the nutritional requirements for growing lambs and contained 207 g/kg DM crude protein and 12.4 MJ/kg DM metabolizable energy. After 8 weeks the lambs were slaughtered and the following specimens were collected: blood serum, liver, sole and coronary band of the claw, and interdigital skin. Serum and tissue Zn and copper (Cu) concentrations and claw hardness were determined. Routine pathohistology and electron microscopy were conducted. Franz diffusion cell system and Ki-67 immunostaining were used to determine the permeability of the interdigital skin and the keratinocyte proliferation in the basal layer of sole horn, coronary band and interdigital skin, respectively. The concentrations of Zn and Cu in serum and liver tissue as well as the Zn concentration in claw horn were not affected by dietary treatment. Zn0 lambs showed higher (p < 0.05) Cu concentrations in claw horn compared to both Zn supplemented groups. Routine pathohistology as well as electron microscopy did not show significant morphological differences between the three groups. Franz diffusion cell system proved to be a suitable method examining the interdigital skin permeability, but the group differences in this study were not significant. Dietary treatment did not affect keratinocyte proliferation in the coronary band. In the sole keratinocyte proliferation was significantly higher (p < 0.05) in the Zn0 group compared to CZn with ZnS being intermediate. Keratinocyte proliferation in the interdigital skin was significantly higher (p < 0.05) in the CZn group compared to the Zn0 with ZnS being intermediate. The results of the current experiment indicate that serum and tissue Zn concentrations and horn hardness are not affected by adding a moderate amount of Zn sulphate or Zn amino acid complex to a basal diet. However, supplemental Zn amino acid complex seems to affect keratinocyte proliferation of interdigital skin and sole horn of lambs. Effects on skin permeability should be retested using a higher number of animals prospectively.

Contracting for care - the construction of the farrier role in supporting horse owners to prevent laminitis.

BACKGROUND: Emerging research highlights how, due to demographic changes in horse owner populations in Western societies, complex owner-horse relationships are leading to inappropriate horse care, including overnutrition, which in turn can lead to laminitis. Farriers, due to their regular visits, may be in a position to support owners in dealing with this problem. OBJECTIVES: This study explored whether UK farriers have a role in working with horse owners to support horse welfare and prevent laminitis. STUDY DESIGN: Grounded theory analysis, a qualitative methodology. METHODS: Semi-structured interviews were conducted with 12 farriers and 11 horse owners. The interviews were transcribed verbatim and systematically analysed, using an inductive coding approach. RESULTS: The analysis of the farrier and horse owner interview data revealed farriers and horse owners undertake a contracting process leading to either a task-focussed or holistic care-focussed approach. Either approach can be satisfactory, but the evidence from this study suggests that when horses are at risk of laminitis, a task-focussed approach misses important opportunities to prevent it. MAIN LIMITATIONS: This analysis, based on a small sample of participants, was not able to identify the frequency of farriers or horse owners orientating towards different approaches in a way that can be generalised to a wider population. However, the power of grounded theory lies in its inductive design to develop new theory, which can be subsequently tested. CONCLUSIONS: Farriers are in a perfect position to support horse owners to prevent laminitis through providing feedback, guidance and advice. However, not all farriers adopt this role and it is not necessary in all contexts. The evidence presented in this study has implications for equine veterinarians and welfare officers in educating horse owners about the value of holistic care-focussed farriery.

Case-control study of mineral concentrations of hoof horn tissue derived from feedlot cattle with toe tip necrosis syndrome (toe necrosis).

This study determined whether mineral concentrations in the hooves of cattle with toe tip necrosis syndrome (cases) differed from those of cattle dying of all other causes (controls). Samples were collected over a 2-year period from 16 different feedlots and analyzed for 8 minerals [cobalt (Co), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), molybdenum (Mo), selenium (Se), and zinc (Zn)]. Mineral concentrations in the hoof wall and solar horn of the same hoof were poorly correlated; Se was the most correlated (ρ = 0.865; P < 0.001), while Mg (ρ = 0.465; P < 0.001) and Zn (ρ = 0.157; P = 0.053) were the least correlated. The cases had significantly lower Mg concentrations in both the hoof wall and solar horn tissue compared to the control subjects. For every 10 ppm decrease in Mg, the odds of a diagnosis of toe tip necrosis syndrome (TTNS) increased by 1.13 times for the hoof wall (P = 0.002) and 1.21 times for solar horn (P < 0.001).

Étude cas-témoin des concentrations de minéraux dans les tissus de la corne des sabots provenant de bovins en parc d'engraissement atteints du syndrome de nécrose du bout de l'onglon (nécrose de l'onglon). Cette étude a déterminé si les concentrations de minéraux dans les sabots des bovins atteints du syndrome de la nécrose du bout de l'onglon (cas) différaient de celles des bovins qui mouraient de toutes les autres causes (témoins). Des échantillons ont été prélevés pendant une période de 2 ans dans 16 parcs d'engraissement différents et analysés pour déceler la présence de 8 minéraux (cobalt [Co], cuivre [Cu], fer [Fe], magnésium [Mg], manganèse [Mn], molybdène [Mo], sélénium [Se] et zinc [Zn]). Il y avait une faible corrélation entre les concentrations des minéraux dans la paroi du sabot et la corne du même sabot. Le Se était le minéral avec la plus grande corrélation (ρ = 0,865; P < 0,001), tandis que le Mg (ρ = 0,465; P < 0,001) et le Zn (ρ = 0,157; P = 0,053) avaient la plus faible corrélation. Les cas présentaient des concentrations de Mg significativement inférieures dans la paroi du sabot et les tissus de la corne comparativement aux sujets témoins. Pour chaque diminution de 10 ppm en Mg, la probabilité d'un diagnostic du syndrome de nécrose du bout de l'onglon augmentait de 1,13 fois pour la paroi du sabot (P = 0,002) et de 1,21 fois pour la corne (P < 0,001).(Traduit par Isabelle Vallières).

Terbinafine hydrochloride nail lacquer for the management of onychomycosis: formulation, characterization and in vitro evaluation.

AIM: The present investigation's intention was to develop an optimized nail lacquer (NL) for the management of onychomycosis. MATERIALS & METHODS: The NL was optimized statistically adopting 32 full factorial design having different polymer ratios and solvent ratios. The formulations were assessed for drug permeation drying time and peak adhesive strength of the film. Characterization was done using techniques including attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), x-ray diffraction (XRD), etc. RESULTS & CONCLUSION: The formulation that had 1:1 polymer ratio and 80:20 solvent ratio was chosen as the optimized formulation. In vitro permeation studies showed better penetration (∼3.25-fold) as well as retention (∼11-fold) of the optimized NL formulation in the animal hoof as compared with the commercial formulation. The findings of in vitro and ex vivo studies elucidated the potential of the optimized formulation. [Formula: see text].

Response to acupuncture treatment in horses with chronic laminitis.

There is a need for evidence-based scientific research to address the question of the effectiveness of acupuncture in improving clinical signs of laminitis in horses. The objective of this study was to compare lameness levels before and after 2 acupuncture treatments in horses with chronic laminitis. Twelve adult horses with chronic laminitis received 2 acupuncture treatments 1 week apart. The points were treated using dry needling, hemo-acupuncture, and aqua-acupuncture. Lameness level was objectively evaluated using an inertial sensor-based lameness evaluation system (Lameness Locator), as well as routine examinations following American Association of Equine Practitioners scoring before the first and 1 week after the second acupuncture treatment. Data were analyzed using Wilcoxon signed-rank test and P-values < 0.05 were considered statistically significant. Both the Lameness Locator (P = 0.0269) and routine lameness examination (P = 0.0039) showed a significant reduction in lameness severity. Our results support using acupuncture, along with other treatment options, in treating chronic equine laminitis.

Réponse à un traitement à l'acupuncture chez des chevaux atteints de laminite chronique. Il existe un besoin de recherche scientifique factuelle afin d'aborder la question de l'efficacité de l'acupuncture pour améliorer les signes cliniques de la laminite chez les chevaux. L'objectif de cette étude consistait à comparer les niveaux de boiterie avant et après deux traitements d'acupuncture chez des chevaux atteints de laminite chronique. Douze chevaux adultes souffrant de laminite chronique ont reçu deux traitements d'acupuncture à 1 semaine d'intervalle. Les points ont été traités en utilisant des aiguilles, l'hémo-acupuncture et l'aqua-acupuncture. Le niveau de boiterie a été évalué objectivement en utilisant un système inertiel d'évaluation de la boiterie à base de sonde (repérage de la boiterie) ainsi qu'à l'aide d'examens de routine en se basant sur la notation de l'American Association of Equine Practitioners avant le premier traitement et 1 semaine après le deuxième traitement d'acupuncture. Les données ont été analysées en utilisant les tests de rang signés de Wilcoxon et des valeurs P < 0,05 étaient considérées comme étant significatives sur le plan statistique. Le repérage de la boiterie (P = 0,0269) et l'examen de routine de la boiterie (P = 0,0039) ont montré une réduction significative de la gravité de la boiterie. Nos résultats appuient l'utilisation de l'acupuncture, conjointement à d'autres options de traitement, pour traiter la laminite équine chronique.(Traduit par Isabelle Vallières).

Effect of rubber flooring on group-housed sows' gait and claw and skin lesions.

This study evaluated the influence of floor type on sow welfare in terms of lameness, claw lesions, and skin lesions. In a 2 × 3 factorial design, we have investigated the effect of rubber coverings on concrete floors and the effect of 3 levels of dietary zinc supplementation on locomotion and claw and skin lesions in group-housed sows. Six groups of 21 ± 4 hybrid sows were monitored during 3 successive reproductive cycles. The sows were group housed from d 28 after insemination (d 0) until 1 wk before expected farrowing date (d 108) in pens with either exposed concrete floors or concrete floors covered with rubber in part of the lying area and the fully slatted area. During each reproductive cycle, locomotion and skin lesions were assessed 4 times (d 28, 50, 108, and 140) and claw lesions were assessed twice (d 50 and 140). Results are given as least squares means ± SE. Locomotion and claw scores were given in millimeters, on analog scales of 150 and 160 mm, respectively. Here, we report on the effect of floor type, which did not interact with dietary zinc concentration ( > 0.10 for all variables). At move to group (d 28) and mid gestation (d 50), no differences between floor treatments were seen in locomotion ( > 0.10). At the end of gestation (d 108), sows housed on rubber flooring scored 9.9 ± 4.1 mm better on gait ( < 0.001). Regarding claw disorders, both parameters "heel overgrowth and erosion" (difference of 4.6 ± 1.8 mm; = 0.01) and "heel-sole crack" (difference of 3.1 ± 1.5 mm; = 0.04) scores were better for sows on rubber flooring at mid gestation (d 50). However, sows on rubber flooring scored worse for "vertical cracks in the wall horn" (difference of 3.4 ± 1.7 mm; = 0.04). At the end of lactation (d 140), both "white line" (difference of 2.9 ± 1 mm; = 0.02) and "claw length" (difference of 4.7 ± 1.4 mm; < 0.001) had better scores on rubber flooring. No differences for skin lesions were observed between floor treatments. The improved scores for gait toward the end of gestation and some types of claw disorders at mid gestation suggest that rubber flooring in group housing has a beneficial effect on the overall leg health of sows. The documented increase in vertical cracks in the wall horn at d 50 requires further investigation.

Milk thistle extract and silymarin inhibit lipopolysaccharide induced lamellar separation of hoof explants in vitro.

The pathogenesis of laminitis is not completely identified and the role of endotoxins (lipopolysaccharides, LPS) in this process remains unclear. Phytogenic substances, like milk thistle (MT) and silymarin, are known for their anti-inflammatory and antioxidant properties and might therefore have the potential to counteract endotoxin induced effects on the hoof lamellar tissue. The aim of our study was to investigate the influence of endotoxins on lamellar tissue integrity and to test if MT and silymarin are capable of inhibiting LPS-induced effects in an in vitro/ex vivo model. In preliminary tests, LPS neutralization efficiency of these phytogenics was determined in an in vitro neutralization assay. Furthermore, tissue explants gained from hooves of slaughter horses were tested for lamellar separation after incubation with different concentrations of LPS. By combined incubation of explants with LPS and either Polymyxin B (PMB; positive control), MT or silymarin, the influence of these substances on LPS-induced effects was assessed. In the in vitro neutralization assay, MT and silymarin reduced LPS concentrations by 64% and 75%, respectively, in comparison PMB reduced 98% of the LPS concentration. In hoof explants, LPS led to a concentration dependent separation. Accordantly, separation force was significantly decreased by 10 µg/mL LPS. PMB, MT and silymarin could significantly improve tissue integrity of explants incubated with 10 µg/mL LPS. This study showed that LPS had a negative influence on the structure of hoof explants in vitro. MT and silymarin reduced endotoxin activity and inhibited LPS-induced effects on the lamellar tissue. Hence, MT and silymarin might be used to support the prevention of laminitis and should be further evaluated for this application.

A randomized trial to evaluate the effect of a trace mineral premix on the incidence of active digital dermatitis lesions in cattle.

A balanced, parallel-group, single-blinded randomized efficacy study divided into 2 periods was conducted to evaluate the effect of a premix containing higher than typically recommended levels of organic trace minerals and iodine (HOTMI) in reducing the incidence of active digital dermatitis (DD) lesions acquired naturally and induced by an experimental infection challenge model. For the natural exposure phase of the study, 120 healthy Holstein steers 5 to 7 mo of age without signs of hoof disease were randomized into 2 groups of 60 animals. The control group was fed a standard trace mineral supplement and the treatment group was fed the HOTMI premix, both for a period of 60 d. On d 60, 15 steers free of macroscopic DD lesions were randomly selected from each group for the challenge phase and transported to an experimental facility, where they were acclimated and then challenged within a DD infection model. The same diet group allocation was maintained during the 60 d of the challenge phase. The primary outcome measured was the development of an active DD lesion greater than 20mm in diameter across its largest dimension. No lesions were identified during the natural exposure phase. During the challenge phase, 55% (11/20) and 30% (6/20) of feet were diagnosed with an active DD lesion in the control and treatment groups, respectively. Diagnosis of DD was confirmed by histopathologic demonstration of invasive Treponema spp. within eroded and hyperplastic epidermis and ulcerated papillary dermis. All DD confirmed lesions had dark-field microscopic features compatible with DD and were positive for Treponema spp. by PCR. As a secondary outcome, the average DD lesion size observed in all feet was also evaluated. Overall mean (standard deviation) lesion size was 17.1 (2.36) mm and 11.1 (3.33) mm for the control and treatment groups, respectively, with this difference being driven by acute DD lesions >20mm. A trend existed for the HOTMI premix to reduce the total DD infection rate and the average size of the experimentally induced lesions. Further research is needed to validate the effect of this intervention strategy in the field and to generate prevention and control measures aimed at optimizing claw health based on nutritional programs.

Effect of a tea tree oil and organic acid footbath solution on digital dermatitis in dairy cows.

Copper sulfate is the industry gold standard footbath ingredient for controlling dairy cow digital dermatitis. However, when used footbath solutions are deposited on soil, high levels of copper in the soil may result, which can have toxic and negative effects on plant growth. An alternative to copper sulfate is Provita Hoofsure Endurance (Provita Eurotech Ltd., Omagh, UK), which is a biodegradable solution containing organic acids, tea tree oil, and wetting agents. The objective of this study was to quantify changes in digital dermatitis frequency when using Provita Hoofsure Endurance and copper sulfate in a split footbath in 3 commercial dairy herds. This study was conducted from January 5, 2012, to March 19, 2012, in 3 commercial Kentucky dairies with 120, 170, and 200 milking Holstein cows. None of the herds was using a footbath for digital dermatitis control before the study. Footbath solutions were delivered using a split footbath. During the study, a 3% Hoofsure Endurance solution for the left hooves and a 5% copper sulfate solution for the right hooves was used. Digital dermatitis was scored every 3wk using the M0 to M4 system, where M0=a claw free of signs of digital dermatitis; M1=a lesion <2cm that is not painful; M2=the ulcerative stage, with lesion diameter of >2cm, and painful to the touch; M3=the healing stage and covered by a scab; and M4=the chronic stage and characterized by dyskeratosis or proliferation of the surface that is generally not painful. McNemar's test statistic suggested that a statistically significant difference existed in the proportions of M1 and M2 lesions between the beginning and end of the study for both treatments. This indicates that each solution was effective in decreasing the proportion of M1 or M2 lesions from baseline to the last time point. A chi-square test calculated using PROC FREQUENCY of SAS (SAS Institute Inc., Cary, NC) indicated that no statistically significant relationship existed between the treatments among changes in digital dermatitis frequency from the baseline to the end of the study. Performance of the 2 footbath solutions was comparable throughout the study. No significant differences were observed between the copper sulfate and Provita Hoofsure Endurance.

Stryphnodendron adstringens extract associated with the hooves trimming surgical procedure for the treatment of bovine digital dermatitis.

Hoof care, lesion curettage, and application of 5 % Stryphnodendron adstringens bark extract (S. adstringens (Mart.) Coville) or 3 % copper sulfate on surgical wounds of cattle were carried out in this research. A total of 180 cattle with digital dermatitis were used. They were distributed into six groups of 30 animals each (GI, GII, GIII, GIV, GV, and GVI). In GI and GII, only the sick digit was trimmed; in GIII and GIV, both sick and healthy digits of the lesioned limb were trimmed; and in GV and GVI, all digits were trimmed. During the postoperative period, 5 % S. adstringens extract was applied in GI, GIII, and GV, and 3 % copper sulfate solution was applied in GII, GIV, and GVI. After 60 days of evaluation, the data were analyzed using the Chi-squared test (p ≤ 0.05). Both therapeutic protocols utilizing surgical curettage of the lesions were efficient for treating digital dermatitis. However, when the procedure is followed by the trimming of sick and healthy digits, the healing is optimized and a greater number of animals are rehabilitated.

Detection of calprotectin and apoptotic activity within the equine colon from horses with black walnut extract-induced laminitis.

The black walnut extract (BWE) model of equine laminitis is associated with a systemic inflammatory response manifest by increased expression of inflammatory cytokines in the lungs and liver as well as the laminae. The specific role of the gastrointestinal tract in development of this response is unclear and is of utmost importance, as gastrointestinal disease and laminitis are intimately related. We investigated calprotectin expression and epithelial and endothelial apoptosis in the colon of horses exposed to orally administered BWE. Sections of colon from 19 horses including 7 controls not exposed to BWE, 6 horses at the developmental time-point of leukopenia (DTP) and 6 at the onset of Obel grade 1 laminitis (LAM) after BWE-administration were histologically examined. Immunohistochemical evaluation for calprotectin expression with MAC 387 antibody was performed along with assessment of epithelial and endothelial apoptosis with caspase-3 active antibody. Calprotectin expression and percentage of apoptotic cells were compared between controls and the two treatment groups and presence of a correlation between calprotectin expression and apoptosis was evaluated. Histological findings from BWE-treated horses included eosinophil and lymphocyte epitheliotropism. The DTP group had a higher (p<0.01) calprotectin score with respect to the control group, while there was no significant difference in percentage of epithelial and endothelial apoptotic cells between groups (p=0.08 and p=0.48 respectively). No significant correlation was found between calprotectin score and epithelial or endothelial apoptosis (p=0.69 and p=0.29 respectively). There is preliminary evidence that exposure of horses to BWE results in an early inflammatory response in the colon. Further studies are needed to characterize the nature of the colonic injury in BWE-exposed horses and the link to the development of laminitis.

Curative effect of topical treatment of digital dermatitis with a gel containing activated copper and zinc chelate.

The efficacy of two topical treatments for painful ulcerative stage (M2) of bovine digital dermatitis (BDD) lesions was compared in a clinical trial conducted on five dairy farms in 2009 to 2010. The first treatment was a water-based gel with active components copper and zinc (Intra Hoof-fit gel [IHF]) and the second treatment was a topical chlortetracycline spray (CTC spray). The experimental unit for this study was the hindleg with the presence of a BDD lesion. Cure was defined as the transition of an M2 lesion into a healed (M0) or a non-painful chronic stage (M4) of BDD at D28. On day 0, cows with M2 BDD lesions were photographed and were treated with either IHF or CTC. Subsequently, feet were photographed and scored on D28. The cure rate of M2 BDD lesions treated with IHF at D28 was 0.92 (CI 0.84 to 0.96) and was significantly better than for M2 BDD lesions treated with CTC, which was 0.58 (CI 0.47 to 0.68).

Presence of mononuclear cells in normal and affected laminae from the black walnut extract model of laminitis.

REASONS FOR PERFORMING STUDY: There is increasing evidence of involvement of inflammatory cells in acute laminitis. OBJECTIVE: To immunolocalise monocytes/macrophages and B and T lymphocytes in the laminar tissue of normal horses and those with black walnut extract (BWE)-induced laminitis. METHODS: Immunohistochemistry was used in archived laminar tissue samples from 20 horses divided equally into 4 groups: control animals (CON), and those administered BWE at 1.5 h (1.5H DTP group), at the onset of leucopenia (3H DTP group) and at the onset of lameness (LAM group). Antibodies against CD3, CD20 and CD163 were used to recognise lymphocytes (T and B) and monocytes/macrophages, respectively. RESULTS: Mononuclear cells were present in laminar tissue of normal horses. The majority of CD3- and CD20-positive lymphocytes were localised around the deep dermal vessels but were also evident around vessels of the primary dermal laminae. CD163-positive macrophages were primarily perivascular in deep dermis or in dermal laminae. No changes in the number of laminar B or T lymphocytes occurred at any time point post BWE administration. However, increases (P=0.0016) in laminar CD163-positive cells occurred in the secondary dermal laminae (SDL) in the 1.5H DTP and 3H DTP groups, returning to basal values in LAM group. CONCLUSIONS: Lymphocyte and macrophage populations are present in the laminar tissue of clinically normal horses and BWE administration induces an increase in CD163-positive macrophages in SDL. POTENTIAL RELEVANCE: Both the host tissue population of mononuclear cells and the influx of monocytes may play an important role in the pathophysiological changes leading to laminar injury.

[Feed-related selenium poisoning in swine]. / Fütterungsbedingte Selen-Vergiftung beim Schwein.

The following case report describes a selenium toxicosis in a pig-fattening farm of two finisher groups. The diseased animals partly showed ataxia and paresis or intense lameness in connection with band-like ablation of the epidermis at the coronary band. Some of them suffered from alopecia. Foot-and-mouth disease and swine vesicular disease were excluded by serological tests. Dissection revealed a multifocal bilateral symmetric poliomyelomalacia. Histological changes in the claws ranged from severe cell-decay in the germinative layer to distinctive decay of the stratum corneum. Due to damage of the claw epidermis the corium was partly exposed. Feed analysis revealed 100-fold increased selenium content in the finishing premix from the feed mill and as a result 20- to 60-fold increased selenium values in feed samples from the farm-made finisher mixture. Selenium concentration in the blood of diseased animals was 4- to 10-fold higher than normal values, which confirmed the tentative diagnosis of a selenium toxicosis.

Acute laminitis: medical and supportive therapy.

Acute laminitis is a serious complication of many primary conditions in the horse. This article summarizes the most appropriate approach to management of the horse with acute laminitis, based on current information.

Evaluation of the possible role of prostaglandin F(2 alpha) in laminitis induced in horses by nasogastric administration of black walnut heartwood extract.

OBJECTIVE: To provide insights into the role of prostaglandin F(2 alpha) (PGF(2 alpha)) in the developmental stages of laminitis induced in horses by ingestion of black walnut heartwood extract (BWHE). SAMPLE POPULATION: 10 adult mixed-breed horses. PROCEDURES: Horses were separated into 2 groups and were euthanatized at 12 hours after placebo (water) administration (control horses) or after BWHE administration and development of Obel grade 1 laminitis. Blood samples were obtained to determine plasma PGF(2 alpha) concentrations hourly for the first 4 hours and subsequently every 2 hours after substance administration. Laminar arteries and veins were isolated, and responses to increasing concentrations of PGF(2 alpha) were measured before and after preincubation of blood vessels with prostanoid and thromboxane receptor antagonists SQ 29,548, SC-19220, and AH 6809. RESULTS: Plasma PGF(2 alpha) concentrations increased in horses given BWHE; the WBC count decreased concurrently. In control horses, PGF(2 alpha) was a potent contractile agonist for laminar veins but not for laminar arteries. In horses given BWHE, PGF(2 alpha) was similarly selective for laminar veins; however, the magnitude of PGF(2 alpha)-induced venoconstriction was less than that in control horses. After preincubation with SQ 29,548, laminar veins from control horses responded to PGF(2 alpha) with a small degree of dilation, whereas laminar veins from horses given BWHE did not. CONCLUSIONS AND CLINICAL RELEVANCE: PGF(2 alpha) may play a role in the inflammatory and vascular dysfunction associated with the prodromal stages of laminitis. Prostanoids such as PGF(2 alpha) may be viable targets for the prevention of acute laminitis in horses.

Comparison of characteristics and enzymatic products of leukocytes in the skin and laminar tissues of horses administered black walnut heartwood extract or lipopolysaccharide.

OBJECTIVE: To compare characteristics and enzymatic products of leukocytes detected in the skin and laminar tissues of horses administered black walnut heartwood extract (BWHE) and horses administered purified lipopolysaccharide (LPS). ANIMALS: 25 healthy 5- to 15-year-old horses. PROCEDURES: Horses were randomly assigned to receive LPS (20 ng of O55:B5 Escherichia coli endotoxin/kg; n = 5) IV or 6 L of BWHE (10) or water (control group; 10) via nasogastric intubation. Horses were euthanatized 12 hours after treatment or at onset of Obel grade 1 lameness. Laminar tissue samples and skin samples from the middle region of the neck were harvested at the time of euthanasia. Leukocyte emigration (determined via CD13 immunohistochemical analysis) and matrix metalloproteinase (MMP)-2 and MMP-9 gene expressions and activities (determined via reverse transcription PCR assay and gelatin zymography, respectively) were measured in skin and laminar tissue samples. RESULTS: Tissues of horses receiving BWHE contained significantly higher numbers of CD13-positive cells and increased MMP-9 gene expression and activity, compared with findings in the other 2 groups. Values for laminar tissue and skin from LPS-treated horses were not increased, compared with findings in the control group, in any experiment. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that BWHE administration causes increases in CD13-positive leukocyte numbers and MMP-9 expression and activity in laminar tissue and skin in horses; similar effects were not detected following LPS administration. Leukocyte emigration in horses with experimentally induced endotoxemia and in horses administered BWHE differed markedly, thereby providing additional evidence that the development of laminitis involves more complex mechanisms than endotoxemia-induced leukocyte activation alone.

Symmetrical onychomadesis in Norwegian Gordon and English setters.

This study reports the condition onychomadesis affecting multiple claws in Norwegian Gordon and English setters. Medical records of and claw biopsies from 18 Gordon and four English setters with onychomadesis of multiple claws were obtained from July 2005 to January 2007. Only dogs with symmetrical onychomadesis and no signs of concurrent disease were included. Histopathological features varied between dogs, but typically included interface dermatitis with subepidermal cleft formation, pigment incontinence, basal cell vacuolization and necrosis, spongiosis and lymphocytic exocytosis, a lymphocytic, plasmacytic subepidermal inflammation, and fibroplasia. In two dogs, histopathological signs of a superficial infection were present. The age of onset of disease varied between 2 and 7 years with a mean of 3.9 years, and was not correlated with vaccination time. Six of the affected dogs also had siblings with the disease. Due to the close relationship of the affected dogs, pedigree map analysis was not possible. Three dogs were euthanized because of the disease and two had regrowth of normal claws. Seventeen dogs had persistent onychodystrophy that typically was nonpainful during therapy which in most dogs consisted of fatty acid supplementation or prednisolone.

Nail swelling as a pre-formulation screen for the selection and optimisation of ungual penetration enhancers.

INTRODUCTION: Targeting drug treatment to fungal infections that reside within or below the nail plate is problematic due to the highly restrictive barrier of the human nail. To optimise topical formulations for ungual drug delivery, inclusion of an effective penetration enhancer (PE) is imperative. At present, in vitro nail permeation studies can take weeks or months in order to obtain any meaningful data because the lack of a simple in vitro model to identify and develop nail PEs makes the selection and optimisation of novel PEs an empirical and inefficient process. The aim of this study was to compare three methods for pre-formulation screening of putative ungual PEs and then to select the most suitable technique for screening candidates that may enhance the permeation of therapeutic agents through the human nail. METHODS: Three screening techniques were evaluated; nail swelling (weight increase of human nail clippings), horse hoof swelling (weight increase of horse hoof clippings) and nail penetration of a radiolabelled permeability probe. Four test PEs were evaluated using each screening method and nail swelling was identified as a simple, rapid, economic, relevant and reliable technique. This screen was then used to evaluate 20 potential PEs. Thioglycolic acid (TA), hydrogen peroxide (H(2)O(2)) and urea H(2)O(2) produced the greatest nail weight increases; 71.0+/-4.6%, 69.2+/-6.6%, and 69.0+/-9.9 respectively. To confirm the relationship between human nail swelling and altered ungual barrier function, a permeation study was performed in human nails using caffeine as a model penetrant. RESULTS AND DISCUSSION: Human nails pre-treated with TA in vitro had a 3.8-fold increase in caffeine flux compared to the control (TA-free solution). This study illustrated the potential to use human nail clipping swelling as a surrogate marker of PE activity for topical ungual drug delivery.