Efficacy of the non-antibiotic paste Protexin Hoof-Care for topical treatment of digital dermatitis in dairy cows

In this study, the efficacy of the non-antibiotic paste Protexin Hoof-Care containing metallic salts and organic acids, was tested for local treatment of 26 acute digital dermatitis lesions. The control group (26 cases) was treated with local application of oxytetracycline spray. These 52 affected limbs with digital dermatitis were diagnosed in 47 dairy cows from eight different farms with slatted floors. The therapeutic effect was evaluated using a scoring system for weightbearing at stance, lameness at walk and pain of the digital dermatitis lesions. The pre-treatment and control examination scores were documented on days 0, 4, 10 and 28. Both treatment regimens were effective, no statistical differences regarding the examined parameters was found between the group treated with the non-antibiotic Protexin Hoof-Care paste and the group treated with oxytetracycline spray. Twenty-seven digital dermatitis lesions required only one treatment with one of these products. A second topical treatment was carried out on day 4 in 13 lesions of the study group and in 12 lesions of the control group. The data of this pilot study indicate that the non-antibiotic paste Protexin Hoof-Care could be a valuable alternative to topical antibiotic treatment for digital dermatitis in dairy cattle.     

Treatment of canine atopic dermatitis: 2010 clinical practice guidelines from the International Task Force on Canine Atopic Dermatitis

Atopic dermatitis (AD) is a common chronic relapsing pruritic skin disease of dogs for which treatment has varied over time and geographical location. Recent high quality randomized controlled trials and systematic reviews have established which drugs are likely to offer consistent benefit. The International Task Force for Canine AD currently recommends a multi‐faceted approach to treat dogs with AD. Acute flares should be treated with a combination of nonirritating baths and topical glucocorticoids, once an attempt has been made to identify and remove the suspected causes of the flare. Oral glucocorticoids and antimicrobial therapy must be added when needed. In dogs with chronic AD, a combination of interventions should be considered. Again, factors that trigger flares of AD must be identified and, if possible, avoided. Currently recognized flare factors include food, flea and environmental allergens, Staphylococcus bacteria and Malassezia yeast. Skin and coat hygiene and care must be improved by bathing with nonirritating shampoos and dietary supplementation with essential fatty acids. The severity of pruritus and skin lesions can be reduced with a combination of anti‐inflammatory drugs. Currently, medications with good evidence of high efficacy include topical and oral glucocorticoids, and calcineurin inhibitors such as oral ciclosporin and topical tacrolimus. The dose and frequency of administration of these drugs should be tailored to each patient considering each drug’s efficacy, adverse effects and cost. Allergen‐specific immunotherapy should be offered, whenever feasible, in an attempt to prevent recurrence of clinical signs upon further exposure to environmental allergens to which the patient is hypersensitive.     

An evaluation of the quality and physical properties of calf leather following topical application of eprinomectin

The gross and histological appearance of skins obtained from twelve 6–10 month-old Friesian × Hereford calves 14–15 days after they were treated with a topical formulation of 0.5% eprinomectin administered at 1 ml per 10 kg bodyweight was compared to that of skins from twelve untreated controls. No significant differences were observed and there were also no significant differences in the quality and physical properties of leather produced from the skins of treated and untreated groups, indicating that topical eprinomectin has no deleterious effects on the leather quality of calf skins.     

A multicentre placebo‐controlled clinical trial on the efficacy of oral ciclosporin A in the treatment of canine idiopathic sebaceous adenitis in comparison with conventional topical treatment

Canine idiopathic sebaceous adenitis (ISA) is an inflammatory reaction of sebaceous glands, potentially resulting in their complete loss. It is considered a T‐cell‐mediated disease, but its precise pathogenesis is still unknown. Topical treatment with oil soaks, humectants and shampoos is effective but laborious. Ciclosporin A (CsA), an immunomodulatory drug, has recently been shown to ameliorate the clinical picture of ISA and to reduce inflammation greatly. It is, however, an expensive treatment option. The objective of this multicentre, partly double‐blinded, randomized controlled study was to evaluate the efficacy of ciclosporin A, either alone or with topical therapy, in comparison to conventional topical treatment alone, as measured by the primary end‐points alopecia and scaling, and multiple histopathological secondary objectives. Thirty‐four dogs with an established diagnosis were treated for 4–6 months and were evaluated before, during and after therapy. Both CsA and topical therapy demonstrated efficacy in this study. Differences between the treatment protocols were marginal. Topical treatment, both alone and in combination with CsA, appeared to reduce scaling more effectively than CsA alone. Both therapies reduced alopecia. There is evidence of a synergistic benefit on both scaling and alopecia, if both treatment options are combined. Inflammation of the sebaceous glands is also best reduced by a combination of both CsA and topical therapy. There is evidence that regeneration of sebaceous glands is best achieved by CsA, either given alone or in combination with topical treatment.     

Fixing the skin barrier: past,present and future – man and dog compared

Skin barrier dysfunction exists in both human and canine atopic dermatitis, leading to increased water loss and potentially facilitating allergen penetration and sensitization. Both lipid (e.g. ceramides) and protein (e.g. filaggrin) abnormalities have been described. Some are genetically inherited (e.g. filaggrin mutations are one of the major risk factors in humans) and some are secondary and linked to inflammation. In humans, numerous studies have shown efficacy of emollients and moisturizers in barrier restoration, and this approach has been for years the mainstay of therapy. Recently, this strategy has shown promise as a preventative function. In veterinary medicine, evidence regarding skin barrier impairment is rapidly building. Decreased ceramides and filaggrin (in some subsets of dogs) have been described. Altered metabolism of ceramides has also been proposed. Despite these preliminary data and the availability of products marketed to improve the skin barrier, evidence regarding the clinical benefit of skin repair intervention is still limited. Preliminary studies have demonstrated that topical application of fatty acids and ceramides and systemic administration of fatty acids improve lipid deficiencies in the skin of dogs with atopic dermatitis, but limited clinical evidence exists. Disease remission in humans is paralleled by an improved skin barrier, both with calcineurin inhibitors and glucocorticoids. In veterinary medicine, a preliminary study on ciclosporin and prednisone failed to detect significant improvement of water loss, while successful immunotherapy correlated with an improved skin barrier. Controlled, large studies are needed to address the question of which skin repair approach is clinically most effective and whether this can be used as a preventative strategy.     

Evaluation of the Schirmer tear test in clinically normal rabbits

Mean (+/- SD) value for results of the Schirmer tear test without use of topical anesthesia on 142 rabbit eyes was 5.30 (+/- 2.96) mm/min; range was 15 mm/min, with low value of 0 and high value of 15 mm/min. Two SD from the mean provided a normal clinical range of 0 to 11.2 mm/min for inclusion of 95% of the population. Significant differences were not evident between eye (right vs left) or gender or among breeds; interaction among eye, gender, and breed also was not observed. Although mean values for 2 breeds were significantly different from values in the other 10 breeds and from each other, they were still within the proposed normal range of 2 SD. The Schirmer tear test without topical anesthesia may be useful in rabbits for evaluation of increased values correlated with ocular irritation, rather than for determination of decreased values associated with keratoconjunctivitis sicca.     

Evaluation of topically applied enilconazole for the treatment of dermatophytosis in a Persian cattery

Many Persian catteries have long-standing dermatophyte infections and are particularly difficult to treat. Enilconazole is a topical antifungal agent that has demonstrated good efficacy in recent studies. Twenty-two Persian cats naturally infected with Microsporum canis in a breeding cattery were treated with topical 0.2% enilconazole and monitored for 180 days. The treatments were repeated every 3 days for a total of eight applications. All the cats improved clinically and became culture negative by day 28. By day 180, four cats had developed clinical dermatophytosis and all cats had positive fungal cultures. In this study, topical 0.2% enilconazole was generally well tolerated but may have caused hypersalivation, idiopathic muscle weakness and slightly elevated serum alanine aminotransferase (ALT) concentrations. This study suggests that enilconazole may be used safely with little risk to the young, aged and gravid animals.     

Topical flea and tick pesticides and the risk of transitional cell carcinoma of the urinary bladder in Scottish Terriers

OBJECTIVE: To determine whether use of topical flea and tick products increases the risk of transitional cell carcinoma (TCC) of the urinary bladder in Scottish Terriers. DESIGN: Case-control study. ANIMALS: 87 adult Scottish Terriers with TCC (cases) and 83 adult Scottish Terriers with other health-related conditions (controls). PROCEDURE: Owners of study dogs were recruited through private veterinary practices and the Scottish Terrier Club of America. History of exposure to flea and tick products 1 year prior to diagnosis of TCC for case dogs and during a comparable period for control dogs was obtained through a questionnaire. Risk of TCC associated with exposure to flea and tick products was determined by means of univariate and multiple logistic regression analysis. RESULTS: After adjustment for host factors, Scottish Terriers treated with topical spot-on flea and tick products containing fipronil or imidacloprid did not have an increased risk of TCC, compared with Scottish Terriers that had never been exposed to any flea and tick products. The risk of TCC associated with use of older topical flea and tick products such as shampoos, dips, powders, sprays, and collars could not be evaluated because of the low number of owners in the study population that had used such products. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of topical spot-on flea and tick products does not increase the risk of TCC in Scottish Terriers.     

Topical tacrolimus (FK506) for the treatment of feline idiopathic facial dermatitis

A 3-year-old, neutered male Persian cat with chronic ulcerative facial dermatitis was diagnosed with feline idiopathic facial dermatitis based on signalment, clinical history and diagnostic test results, including dermatohistopathological evaluation. Initial treatment started with 4 weeks of oral antifungal/antibiotic medication for severe secondary infectious dermatitis of Malassezia and bacteria. As the lesions gradually improved, the oral medication was withdrawn, leaving only 0.1% topical FK506 (tacrolimus) ointment for the remaining lesions. Topical treatment was administered just in case any new lesions developed. The patient has been managed effectively with topical tacrolimus and no side-effects were observed during treatment. Feline idiopathic facial dermatitis is known as a difficult dermatosis to manage successfully, but our experience suggests that it may respond to topical tacrolimus.     

Transdermal drug delivery: basic principles for the veterinarian

The use of topical pharmaceutical formulations is increasingly popular in veterinary medicine. A potential concern is that not all formulations are registered for the intended species, yet current knowledge strongly suggests that simple extrapolation of transdermal drug pharmacokinetics and pharmacodynamics between species, including humans, cannot be done. In this review, an overview is provided of the underlying basic principles determining the movement of topically applied molecules into and through the skin. Various factors that may affect transdermal drug penetration between species, between individuals of a particular species and regional differences in an individual are also discussed. A good understanding of the basic principles of transdermal drug delivery is critical to avoid adverse effects or lack of efficacy when applying topical formulations in veterinary medicine.     

The influence of topical unsaturated fatty acids and essential oils on normal and atopic dogs

Seven dogs with atopic dermatitis and six normal dogs were treated with a spot-on product containing essential oils and unsaturated fatty acids q 7 days for 8 wk. Seven additional atopic dogs received a daily spray containing similar ingredients to the spot-on. In all dogs, transepidermal water loss (TEWL) was measured before and after treatment using a closed chamber device. In atopic dogs, a validated lesion score (canine atopic dermatitis extent and severity index, CADESI) was determined and pruritus was assessed with a visual analog scale before and after treatment. The mean CADESI scores in atopic dogs decreased with the spot-on (P=0.0043) and with the spray (P=0.0366). Similarly, the pruritus scores decreased with the spot-on (P=0.266) and with the spray (P=0.0177). There was a significant difference between the TEWL values of healthy and atopic dogs on the abdomen (P=0.0181) and back (P=0.0123). TEWL decreased significantly on the back after treatment with the spray (P=0.016), but not on the abdomen (P=0.078). Adverse effects were not observed. The results of this pilot study indicate that topical fatty acids and essential oils are a useful treatment option for canine atopic dermatitis.     

The clinical efficacy of topical and systemic therapy for the treatment of feline ocular chlamydiosis

Twenty-four specific-pathogen-free-derived cats aged four to 11 months were challenged by ocular application of a field isolate of Chlamydia psittaci to evaluate the effect of topical and systemic therapy on the course of disease. The cats were monitored for 35 days post-challenge, with severity of clinical signs being measured using a scoring system, and ocular shedding of the organism monitored by culture of conjunctival swabs. All cats developed active C psittaci infection, and after 7 days the cats were randomly assigned to one of four treatment groups: Group P (placebo) was given twice-daily ophthalmic tear-replacement ointment; group F was given twice-daily topical 1% fusidic acid ophthalmic viscous drops; group C was given twice-daily topical 1% chlortetracycline ophthalmic ointment; and group D was given doxycycline at 10 mg/kg daily per os in addition to twice-daily topical 1% fusidic acid ophthalmic ointment. Within 24 h of commencement of therapy, group D had significantly lower median clinical scores than group P, and with the exception of day 16, this trend was maintained throughout the observation period. Median clinical scores of cats in group F were not appreciably different to those in group P, whereas the median scores of cats in group C generally fell between those of groups P and D. The median duration of C psittaci shedding was 10 and 15 days for groups D and C respectively, but four of the six cats in groups F and P were still shedding organisms at the end of the study (day 35). In this study, systemic therapy with doxycycline proved superior to topical therapy in the treatment of feline chlamydiosis.     

A pilot study of the efficacy of topical ivermectin against lungworm in young red deer (Cervus elaphus)

Three groups of ten 4-month-old red deer (Cervus elaphus) calves naturally infected with lungworm (Dictyocaulus viviparus) were treated with either oral ivermectin (200 microg/kg), topical (pour-on) ivermectin (500 microg/kg) or oral oxfendazole (5 mg/kg). Faecal larval counts for lungworm were undetectable or very low for 14 days after treatment with oxfendazole, 28 days after treatment with oral ivermectin and for 49 days after treatment with topical ivermectin. This pilot study suggests that the topical formulation of ivermectin was very effective against lungworm and had a more persistent action than the oral ivermectin formulation in young red deer.     

A novel transcutaneous plasmid-dimethylsulfoxide delivery technique for avian nucleic acid immunization

In this report, we show that dimethylsulfoxide (DMSO) enhances liposome-mediated transfection of nucleic acid in chicken macrophage cells and that this could be exploited for the transcutaneous delivery of naked DNA through the intact skin of chickens. We found that DMSO enhanced transfection efficiencies of lipofectamine and polyethyleneimine in HD-11 chicken macrophage cells. Based on this principle, we showed that transcutaneous delivery of a DNA plasmid-dimethylsulfoxide mixture (1:1) to untreated skin of chickens results in a wide distribution of the plasmid in the body. Distribution studies were done using plasmids encoding enhanced green fluorescent protein (EGFP) reporter gene and a bivalent DNA vaccine coding for infectious bursal disease virus (IBDV) and Newcastle disease virus (NDV) immunogenic protein genes. This bivalent vaccine induced mucosal and systemic immune responses, as evidenced by IgA and IgM production in the tears and serum of vaccinated chickens. Mucosal immune responses in the tears after topical vaccination were significantly higher (P < 0.05) than after i.m. delivery of the same DNA vaccine and were characterized by the absence of an IgG response. The biodistribution of plasmid indicated that topical delivery with DMSO resulted in a wide distribution and persistence of the plasmid until 15 weeks post-primary vaccination. Both delivery methods resulted in insert-specific message being made in several body tissues, but after topical delivery the virus-specific mRNA could be detected in the bone marrow of one out of three chickens until 15 weeks post-primary vaccination. Furthermore, transcutaneous delivery of this DNA vaccine using DMSO conferred protection from challenge with virulent IBDV (86% survival) and NDV (86% survival). This novel transcutaneous method of delivery of a DNA vaccine shows promise as being an easy and effective way to deliver nucleic acids through intact skin for vaccination or therapeutic purposes.     

A review of the role of acid-base balance in amino acid nutrition

Acid-base balance and amino acid metabolism are intimately related. Changes in acid-base balance influence the metabolic fate of many amino acids. Also, acid-base homeostasis is achieved in part by alteration of amino acid metabolism, not only in the kidney, but also in liver, muscle and splanchnic tissue. Glutamine is the primary amino acid involved in renal ammonia-genesis, a process intimately related to acid excretion. The metabolism of other amino acids, such a serine, glycine and the branched-chain amino acids, also appears to be influenced by acid-base balance. Conversely, the metabolic fate of various amino acids will influence the daily acid load experienced by the animal. Oxidation of amino acids contributes to the total acid and base load imposed on the pig. The basic (cationic) amino acids (lysine, arginine and histidine) yield neutral end-products plus a proton; sulfur (methionine and cysteine) amino acids are also acidogenic because they generate sulfuric acid when oxidized. The dicarboxylic (anionic) amino acids (aspartate and glutamate, but not asparagine and glutamine) consume acid when oxidized and thus reduce the acid load of the diet. Acid-base balance and related phenomena are discussed in the context of practical and metabolic aspects of amino acid nutrition.     

Topical treatment of non-healing corneal epithelial ulcers in dogs with aminocaproic acid

The potential efficacy of topical epsilon-aminocaproic acid, an antiplasmin agent, in the treatment of persistent corneal epithelial defects was evaluated in a study of the medical records of 44 dogs, in which 51 eyes had been diagnosed with a corneal epithelial defect lasting more than 10 days, with no apparent underlying cause. At an initial examination all the affected eyes had had non-adherent epithelium removed. Thirty-four of the eyes in 28 dogs examined between January 2000 and March 2003 were also treated by the topical application of a solution of 35.7 mg/ml ophthalmic aminocaproic acid three times a day; the other 17 eyes in 16 dogs treated between October 1997 and March 1999 had received only topical treatment with gentamicin in addition to the debridement. Both groups were assessed clinically at weekly intervals for a maximum of three weeks. The two groups had approximately the same breed distribution, and there were no statistically significant differences between them in terms of their age, sex, affected side or duration of the corneal erosions. After three weeks, 32 of the 34 eyes treated with aminocaproic acid (94.1 per cent) had been cured, compared with seven of the 17 eyes treated with gentamicin (41.2 per cent) (P=0.0001). No adverse drug reactions were reported.     

The pharmacokinetics of transdermal flunixin meglumine in Holstein calves

This study describes the pharmacokinetics of topical and intravenous (IV) flunixin meglumine in Holstein calves. Eight male Holsteins calves, aged 6 to 8 weeks, were administered flunixin at a dose of 2.2 mg/kg intravenously. Following a 10‐day washout period, calves were dosed with flunixin at 3.33 mg/kg topically (transdermal). Blood samples were collected at predetermined times from 0 to 48 h for the intravenous portions and 0 to 72 h following topical dosing. Plasma drug concentrations were determined using liquid chromatography with mass spectroscopy. Pharmacokinetic analysis was completed using noncompartmental methods. The mean bioavailability of topical flunixin was calculated to be 48%. The mean AUC for flunixin was determined to be 13.9 h × ug/mL for IV administration and 10.1 h × ug/mL for topical administration. The mean half‐life for topical flunixin was 6.42 h and 4.99 h for the intravenous route. The C_max following topical application of flunixin was 1.17 μg/mL. The time to maximum concentration was 2.14 h. Mean residence time (MRT) following IV injection was 4.38 h and 8.36 h after topical administration. In conclusion, flunixin when administered as a topical preparation is rapidly absorbed and has longer half‐life compared to IV administration.     

Advances in topical glaucoma therapy

Significant advances have recently been achieved in the development of topical glaucoma medications. The primary advantage of a topical preparation is the reduced incidence of adverse systemic effects attributable to a given drug compared to its systemically administered counterpart. However, the strong protective barrier of the eye forces topical ophthalmic preparations to be highly concentrated and in some cases, they have the potential to produce unwanted systemic effects, particularly in smaller animals. Oral carbonic anhydrase inhibitors are commonly associated with adverse effects in both humans and animals. Two recently developed topical carbonic anhydrase inhibitors, dorzolamide and brinzolamide, have shown promise in reducing intraocular pressure in animals and systemic side effects are apparently limited with their use. The topical alpha2-agonist apraclonidine, on the other hand, effectively reduces intraocular pressure in cats and dogs, but in its currently available form is likely to induce unwanted systemic effects. Latanoprost is a topical prostaglandin F2alpha analog that has proven effective in reducing intraocular pressure in dogs and horses, but while systemic side effects have not yet been reported, this topical preparation may exacerbate pre-existing or concurrent ocular inflammatory disease.     

Aspects of pharmacodynamics and biotransformation of the glucocorticoid resocortol butyrate

Aspects of the biotransformation and pharmacodynamics of the novel glucocorticoid resocortol butyrate (RCB) and its metabolites were assessed in vitro and in vivo in comparison with selected reference compounds. The main route of biotransformation of ((3)H)-RCB in the skin and the liver was 5alpha-reduction of the A-ring followed by reduction of the 3-carbonyl group. In the liver, metabolism was much more rapid than in the skin and 5beta-reduction also occurred. RCB had a relative binding affinity for the glucocorticoid receptor similar to that of triamcinolone acetonide, about 1.5 times that of dexamethasone, three times that of betamethasone valerate (BMV) and 10-14 times that of cortisol. The metabolites of RCB displayed only low to very low affinities for the receptor. The suppression of the hypothalamic-pituitary-adrenal axis was investigated in placebo- and positive-controlled studies in dogs by measurement of basal and corticotrophin-releasing hormone (CRH) stimulated plasma cortisol concentrations. The AUC of the plasma cortisol vs. time curve following CRH stimulation, a measure of adrenal suppression, was reduced significantly after topical application of BMV compared with the pretreatment values. The AUC in the RCB group was not reduced significantly. Adrenocorticotrophic hormone concentrations were not affected. Oral administration of RCB did not suppress adrenocortical function, whereas BMV induced almost complete suppression of basal and CRH-induced cortisol concentrations. The pharmacodynamics of RCB makes it a relatively safe glucocorticosteroid for topical application.     

An evaluation of the quality and physical properties of calf leather following topical application of eprinomectin

The gross and histological appearance of skins obtained from twelve 6-10 month-old Friesian X Hereford calves 14-15 days after they were treated with a topical formulation of 0.5% eprinomectin administered at 1 ml per 10 kg bodyweight was compared to that of skins from twelve untreated controls. No significant differences were observed and there were also no significant differences in the quality and physical properties of leather produced from the skins of treated and untreated groups, indicating that topical eprinomectin has no deleterious effects on the leather quality of calf skins.