Cutaneous apocrine gland neoplasia in 16 captive African wild dogs (Lycaon pictus).

This retrospective study documents the occurrence of single and multiple cutaneous apocrine gland tumours (CATs) on the dorsal midline of 16 captive African wild dogs (AWDs, Lycaon pictus) derived from 161 submissions to diagnostic laboratories in South Africa, France and Germany between 1997 and 2022. Animals included in the study came from zoological institutions in South Africa (n = 2), France (n = 5) and Germany (n = 1) and ranged from 5 to 14 years of age. Fifteen affected animals were female (94%) and one was male. CATs presented as raised, hairless, multilobular, grey firm masses, consistently located along the dorsal midline. Apart from a single cutaneous apocrine adenoma and a cystadenoma occurring concurrently with two non-cystic adenocarcinomas, neoplasms were consistent with malignant cutaneous apocrine adenocarcinomas with lymphatic spread and visceral metastases. Advanced age and female sex were identified as risk factors. A genetic component or association with the increasing use of GnRH agonist contraceptives was suspected but could not be established. This study highlights the need for close clinical monitoring of AWDs over the age of 5 years for the development of CATs along the dorsal midline and supports early surgical intervention. More research is needed to determine the role of inbreeding, endocrine changes and husbandry factors that may play a role in the development of CATs on the dorsal midline of AWDs.

Macroscopic Skin Examination Can Determine the Number of Strips Necessary to Study the stratum corneum in Dogs.

To evaluate the skin barrier, the stratum corneum (SC) must be isolated and extracted. Currently, skin biopsy is the gold standard method to investigate skin immunology and the presence of biomarkers in dogs. However, a standardized, non-invasive tool to exclusively remove the SC would be of great interest to study healthy and atopic dogs. In this study, we performed D-squames® tape stripping with standardized pressure on seven healthy beagle dogs. A control site was defined and then 25 strips, 50 strips and as many strips as needed to achieve a shiny appearance of the skin were performed on three different experimental sites. After stripping, blinded histopathological examination of a skin biopsy from each site was performed. The number of tape strips required for the skin to become shiny varied between individuals, with a mean of 40 (29-50) strips. There was no significant difference in SC depth between the control site and the site that underwent 25 tape strips. In contrast, the use of 50 strips removed almost all of the SC, with a mean remaining SC depth of 7.82 µm. These data suggest that this non-invasive method can effectively remove the SC, with individual variability, and that a shiny appearance of the skin after stripping can be used as an accurate marker of SC removal.

Skin Barrier Reinforcement Effect Assessment of a Spot-on Based on Natural Ingredients in a Dog Model of Tape Stripping.

Skin barrier restoration is an important part of atopic dermatitis therapy. We investigated the effect of a spot-on containing plant-based essential fatty acids and essential oils on skin barrier parameters in a dog model of acute skin barrier disruption, using five healthy beagle dogs maintained in a laboratory setting. Four test sites on the dorsum and a control site on the abdomen were defined on each dog. Transepidermal water loss (TEWL) and skin surface hydration (SSH) were measured before and after tape stripping on the first day and then for three consecutive days, over four consecutive weeks. The spot-on was applied at the end of each of the first three weeks. The increase in TEWL after tape stripping was reduced after the spot-on application and reached control values in Weeks 3 and 4. SSH after tape stripping was reduced in Week 4 compared with the baseline. Thus, the ATOP 7® spot-on significantly reduced acute skin barrier impairment in a dog model. The use of this product should be further evaluated as a potential treatment for skin barrier defects such as canine atopic dermatitis.

Effect of an ear cleaner instillation containing lipacids in a model of re-acidification of the external auditory canal in dogs.

BACKGROUND: In humans, the acidic pH of the ear canal plays a protective role against infection and a change towards alkalinity of the external auditory canal (EAC) is a local factor in the progression of acute to chronic otitis externa (OE). The use of acidic preparations alone for treatment of OE without concurrent antibiotic use is well-documented in humans. In dogs, only one study has investigated the EAC pH in healthy dogs and in dogs with OE, and investigations to understand the role of EAC pH in the pathogenesis of canine OE are lacking. HYPOTHESIS/OBJECTIVES: To obtain physiological EAC pH values in beagle dogs. To develop a model of re-acidification of the EAC in dogs and to investigate how an acidic solution may accelerate the return to a physiological pH. ANIMALS: Ten healthy beagle dogs in a laboratory setting. MATERIALS AND METHODS: A model of re-acidification of the EAC was developed by instillation of a pH 10.1 phosphate-buffered saline (PBS) solution and the subsequent acidic effect of an ear cleaner containing lipacids was evaluated in this model. RESULTS: Mean physiological EAC pH was 6.12 (± 0.36). EAC re-acidification took up to 9 h in this model. Mean pH values dropped immediately to 6.38 (± 0.27) on ears treated with an acidic ear cleaner. No abrupt drop was observed of the mean pH values for the control ears. CONCLUSION AND CLINICAL IMPORTANCE: This study confirms that physiological EAC pH in dogs is acidic. This model of re-acidification of the EAC pH allows investigations on acidic properties of topical ear products in healthy ears.

Contexte - Chez l'homme, le pH acide du conduit auditif joue un rôle protecteur contre l'infection et l'évolution vers l'alcalinité du conduit auditif externe (CAE) et est un facteur local de progression de l'otite externe (OE) aiguë à chronique. L'utilisation de préparations acides seules pour le traitement de l'OE sans utilisation concomitante d'antibiotiques est bien documentée chez l'homme. Chez les chiens, une seule étude a étudié le pH du CAE chez les chiens en bonne santé et chez les chiens atteints d'OE, et les recherches pour comprendre le rôle du pH du CAE dans la pathogenèse de l'OE canine font défaut. Hypothèses/objectifs - Obtenir des valeurs physiologiques de pH du CAE chez des chiens beagle. Développer un modèle de réacidification du CAE chez le chien et étudier comment une solution acide peut accélérer le retour à un pH physiologique. Animaux - Dix chiens beagle de laboratoire en bonne santé. Matériels et méthodes - Un modèle de réacidification du CAE a été développé par instillation d'une solution saline tamponnée (PBS) à pH 10,1 et l'effet acide ultérieur d'un nettoyant pour oreilles contenant des lipacides a été évalué dans ce modèle. Résultats - Le pH physiologique moyen du CAE était de 6,12 (± 0,36). La réacidification du CAE a pris jusqu'à 9 h dans ce modèle. Les valeurs moyennes du pH chutent immédiatement à 6,38 (± 0,27) sur les oreilles traitées avec un nettoyant auriculaire acide. Aucune chute brutale n'a été observée des valeurs moyennes de pH pour les oreilles témoins. Conclusion et importance clinique - Cette étude confirme que le pH physiologique du CAE chez le chien est acide. Ce modèle de réacidification du pH du CAE permet des investigations sur les propriétés acides des produits topiques auriculaires dans des oreilles saines.

Introducción; en humanos, el pH ácido del canal auditivo juega un papel protector contra la infección y un cambio hacia la alcalinidad del canal auditivo externo (EAC) es un factor local en la progresión de la otitis externa (OE) aguda a crónica. El uso de preparaciones ácidas solas para el tratamiento de la OE sin el uso concomitante de antibióticos está bien documentado en humanos. En perros, solo un estudio ha investigado el pH de EAC en perros sanos y en perros con OE, y faltan investigaciones para comprender el papel del pH de EAC en la patogenia de la OE canina. Hipótesis/objetivos - Obtener valores de pH fisiológico de EAC en perros beagle. Desarrollar un modelo de reacidificación del EAC en perros e investigar cómo una solución ácida puede acelerar el retorno a un pH fisiológico. Animales- diez perros beagle sanos en un laboratorio. Materiales y métodos- se desarrolló un modelo de reacidificación del EAC mediante la instilación de una solución salina tamponada con fosfato (PBS) de pH 10,1 y se evaluó en este modelo el efecto ácido subsiguiente de un limpiador de oídos que contenía lípidos. Resultados - El pH fisiológico medio del EAC fue de 6,12 (± 0,36). La reacidificación de EAC tomó hasta 9 h en este modelo. Los valores medios de pH cayeron inmediatamente a 6,38 (± 0,27) en los oídos tratados con un limpiador de oídos ácido. No se observó una caída abrupta de los valores medios de pH para los oíds de control. Conclusión e importancia clínica- este estudio confirma que el pH fisiológico de EAC en perros es ácido. Este modelo de reacidificación del pH de EAC permite realizar investigaciones sobre las propiedades ácidas de los productos tópicos para el oído en oídos sanos.

Contexto - Em humanos, o pH ácido do conduto auditivo exerce uma grande função protetora contra infecções e a alcalinização do conduto auditivo externo (CAE) é um fator local de progressão de otite externa (OE) aguda para crônica. A utilização unicamente de formulações ácidas para o tratamento de OE sem a utilização concomitante de antibióticos é bem documentada em humanos. Em cães, apenas um estudo investigou o pH do CAE em cães saudáveis com OE, e são escassas as pesquisas investigando o papel do pH do CAE na patogênese da OE. Hipótese/objetivos - Se obter os valores fisiológicos do pH dos CAEs de cães Beagle. Desenvolver um modelo de re-acidificação do CAE em cães e investigar como uma solução ácida pode acelerar o retorno ao pH fisiológico original. Animais - Dez cães Beagle saudáveis de laboratório. Materiais e Métodos - Um modelo de re-acidificação do CAE foi desenvolvido por instilação de solução salina tamponada com fosfato (PBS) com um pH 10,1 e o efeito acidificante subsequente de um limpador de ouvido contendo ácidos lipídicos foi avaliado neste modelo. Resultados - O pH fisiológico médio do CAE foi de 6,12 (± 0,36). A re-acidificação do CAE levou até 9h neste modelo. Os valores médios de pH caíram imediatamente para 6,38 (± 0,27) nas orelhas tratadas com um limpador otológico ácido. Não foi observada queda abrupta dos valores médios de pH para as orelhas controle. Conclusão e importância clínica - Este estudo confirmou que o pH fisiológico do CAE de cães é ácido. Este modelo de re-acidificação do pH do CAE permite investigações sobre as propriedades acidificantes de produtos otológicos tópicos para orelhas saudáveis.

Ex-vivo study of the percutaneous absorption of a tramadol formulation through feline inner pinna skin.

OBJECTIVES: Oral medication of small animals, particularly cats, is often challenging. The transdermal route may provide an easier option for owners to administer chronic treatment. Tramadol is an analgesic mainly used in humans; it is also commonly used in dogs, despite some controversy over its clinical efficacy. Recent studies have suggested that tramadol is efficacious for pain management in cats. In cats, the inner pinna is the most commonly used site for transdermal drug therapy; the use of this site has been validated in experimental studies of methimazole and mirtazapine treatment. This ex vivo study aimed to characterise the percutaneous absorption pharmacokinetics of a formulation of tramadol in Pentravan through feline inner pinna skin. METHODS: High-performance liquid chromatography was used to assess the stability of the tramadol formulation (100 mg/ml in Pentravan) over three months at room temperature. Forced degradation was also assessed in neutral, acidic, alkaline, and oxidative conditions. A Franz cell system was employed to evaluate percutaneous absorption of a finite dose of tramadol. RESULTS: The tramadol formulation was stable for three months at room temperature. Tramadol penetrated through ex vivo feline inner pinna skin, but considerable intra- and inter-individual variability in kinetics was observed. Comparison with another vehicle, Lipoderm, revealed no significant difference in the percutaneous absorption of tramadol. CONCLUSIONS AND RELEVANCE: The Pentravan formulation assessed in this study supported tramadol absorption across the feline inner ear skin. In vivo studies are necessary to evaluate the pharmacokinetics and efficacy of this formulation.

Clinical Guidelines for the Use of Antipruritic Drugs in the Control of the Most Frequent Pruritic Skin Diseases in Dogs.

Pruritus is a common clinical sign in many skin disorders and is currently the main complaint in canine dermatology. Pruritic skin diseases can affect the quality of life of dogs and their owners. Several families of antipruritic drugs are available to help control pruritus in dogs. The aim of this review is to help practitioners select the most appropriate symptomatic treatment in the most frequent situations of dermatological pruritus in dogs. The molecules reviewed here are systemic and topical glucocorticoids, antihistamines, ciclosporin, oclacitinib and lokivetmab. A level of evidence (1, 2 or 3) has been established according to a detailed algorithm for each individual study in the literature published between 1990 and March 2021. The guidelines result from evidence grading using the strength of recommendation taxonomy (SoRT) and clinical recommendations using a thorough methodology.

Systemic Collagen VII Replacement Therapy for Advanced Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic skin blistering disease associated with progressive multiorgan fibrosis. RDEB is caused by biallelic mutations in COL7A1 encoding the extracellular matrix protein collagen VII (C7), which is necessary for epidermal‒dermal adherence. C7 is not simply a structural protein but also has multiple functions, including the regulation of TGFß bioavailability and the inhibition of skin scarring. Intravenous (IV) administration of recombinant C7 (rC7) rescues C7-deficient mice from neonatal lethality. However, the effect on established RDEB has not been determined. In this study, we used small and large adult RDEB animal models to investigate the disease-modulating abilities of IV rC7 on established RDEB. In adult RDEB mice, rC7 accumulated at the basement membrane zone in multiple organs after a single infusion. Fortnightly IV injections of rC7 for 7 weeks in adult RDEB mice reduced fibrosis of skin and eye. The fibrosis-delaying effect was associated with a reduction of TGFß signaling. IV rC7 in adult RDEB dogs incorporated in the dermal‒epidermal junction of skin and improved disease by promoting wound healing and reducing dermal‒epidermal separation. In both species, IV C7 was well-tolerated. These preclinical studies suggest that repeated IV administration of rC7 is an option for systemic treatment of established adult RDEB.

The Linoleic Acid Content of the Stratum Corneum of Ichthyotic Golden Retriever Dogs Is Reduced as Compared to Healthy Dogs and a Significant Part Is Oxidized in Both Free and Esterified Forms.

Golden Retrievers may suffer from Pnpl1-related inherited ichthyosis. Our study shows that in the stratum corneum (SC) of ichthyotic dogs, linoleic acid (LA) is also present in the form of 9-keto-octadecadienoic acid (9-KODE) instead of the acylacid form as in normal dogs. The fatty acids purified from SC strips (LA, acylacids) were characterized by liquid chromatography-tandem mass spectrometry (LC-MS) and atmospheric pressure chemical ionization (APCI). Electrospray ionization (ESI) and MS2(MS/MS Tandem mass spectrum/spectra)/M3 (MS/MS/MS Tandem mass spectrum/spectra) fragmentation indicated the positions of the double bonds in 9-KODE. We showed that ichthyotic dogs have a threefold lower LA content in the form of acylacids. The MS2 fragmentation of acyl acids showed in some peaks the presenceof an ion at the m/z 279, instead of an ion at m/z 293 which is characteristic of LA. The detected variant was identified upon MS3 fragmentation as 9-keto-octadecadienoic acid (9-KODE), and the level of this keto-derivative was increased in ichthyotic dogs. We showed by the APCI that such keto forms of LA are produced from hydroperoxy-octadecadienoic acids (HpODE) upon dehydration. In conclusion, the free form of 9-KODE was detected in ichthyotic SC up to fivefold as compared to unaffected dogs, and analyses by HPLC (High performance liquid chromatography) and ESI-MS (Electrospray Ionization-Mass Spectrometry) indicated its production via dehydration of native 9-HpODE.

Extra-auricular lesions of proliferative and necrotizing otitis externa in three kittens.

BACKGROUND: Proliferative and necrotising otitis externa (PNOE) is a rare disorder in cats with poorly understood pathogenesis. Extra-auricular (EA) lesions recently have been mentioned in a textbook and in one case report. OBJECTIVES: To describe EA lesions associated with PNOE in three kittens. ANIMALS: A 6-month-old female domestic short hair (DSH) cat (Case 1), an 8-month-old female DSH cat (Case 2) and a 5-month-old female DSH cat (Case 3). METHODS AND RESULTS: All cases exhibited classical lesions of PNOE associated with EA lesions, generalised (cases 1 and 3) or limited to eyelids (Case 2). Lesions were characterised by thick, adherent, hyperkeratotic papules coalescing to plaques and attempts to remove the hyperkeratotic plaques resulted in erosions. Histopathological examinations revealed classical features of PNOE: severe acanthosis associated with a marked lymphocytic exocytosis, satellitosis and apoptotic keratinocytes at all levels of the epidermis and the outer root sheath of hair follicles. Cases 2 and 3 resolved spontaneously. Case 1 remained stable with topical tacrolimus and oral prednisolone after a short course of ciclosporin. CONCLUSIONS AND CLINICAL IMPORTANCE: This report describes EA lesions of PNOE in three kittens. Such lesions may be underdiagnosed, and this report emphasises the role of a thorough clinical inspection in PNOE cases.

Cutaneous and systemic granulomatous disease associated with hairy vetch toxicosis in a French Holstein dairy herd.

This report describes an outbreak of hairy vetch toxicosis afflicting a herd of cattle with a fatal cutaneous and systemic granulomatous disease. It highlights how this condition remains poorly recognized by cattle production professionals in Europe and the need for communication about vetch-associated diseases.

Cet article décrit une épidémie de toxicose due à la vesce velue touchant un troupeau de bovins se manifestant par une maladie granulomateuse systémique et cutanée fatale. Ceci illustre comment cette atteinte reste peu connue par les professionnels de l'élevage en Europe et le besoin de communiquer sur les maladies associées à la vesce velue.

Este artículo describe un brote de toxicosis de veza vellosa (Vicia villosa) que afectó a un rebaño de ganado con una enfermedad granulomatosa cutánea y sistémica mortal. Destaca cómo esta condición sigue siendo poco reconocida por los profesionales de la producción ganadera en Europa y la necesidad de comunicación sobre las enfermedades asociadas al consumo de veza.

Este relato descreve um surto de intoxicação por ervilhaca peluda em um rebanho de gado com uma doença granulomatosa cutânea e sistêmica. Destaca-se como essa enfermidade continua pouco reconhecida pelos profissionais de bovinocultura na Europa, e a necessidade de comunicação sobre doenças associadas à ervilhaca.

A moisturizer formulated with glycerol and propylene glycol accelerates the recovery of skin barrier function after experimental disruption in dogs.

BACKGROUND: Moisturizers are foundational therapies for human atopic dermatitis. In veterinary medicine, the use of moisturizers has been recommended by an expert committee to alleviate skin dryness that would occur, for example, in canine atopic dermatitis (cAD). However, little is known regarding the effects of moisturizers on the skin barrier. HYPOTHESIS/OBJECTIVES: To investigate the effects of a moisturizer on skin barrier recovery in a canine model of chronic mechanical barrier disruption. ANIMALS: Six healthy beagle dogs maintained in a laboratory setting. METHODS AND MATERIALS: A model of chronic skin barrier disruption was simulated by tape stripping on both sides of the thorax. The moisturizer then was applied twice daily for one week to one side of the thorax, while the other hemithorax was left untreated. The effects were evaluated by measurement of transepidermal water loss (TEWL) at various times during skin barrier recovery, and by histological assessment of the disrupted skin one week after moisturizer application. RESULTS: Overall, TEWL was reduced, epidermal thickness was lower, stratum corneum thickness was greater and the intensity of the dermal inflammatory infiltrate was reduced for treated sites. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest a potential benefit of the moisturizer for improving skin barrier function, which is frequently altered in chronic inflammatory dermatoses such as cAD.

Long-term successful treatment of a donkey with cutaneous lupus erythematous with methotrexate.

Cutaneous lupus erythematosus (CLE) is a rare immune-mediated dermatitis. To the best of the authors' knowledge it has not been described in donkeys. A 5-year-old male neutered donkey, living in south-east France, was diagnosed with CLE. Clinical signs included generalized symmetrical areas of alopecia, erythema, crusting and scales. Diagnostic tests included examination of skin biopsy samples by histopathological and immunohistochemical analysis which demonstrated an interface dermatitis with CD8+ T cells. The skin condition was successfully treated initially with glucocorticoids and methotrexate; successful long-term maintenance was associated with administration of methotrexate.

Le lupus cutané érythémateux (CLE) est une dermatite à médiation immune rare. A la connaissance des auteurs, il n'a pas été décrit chez le singe. Un singe mâle castré de 5 ans, vivant dans le sud-est de la France a été diagnostiqué avec CLE. Les signes cliniques incluaient des zones symétriques généralisées d'alopécie, d'érythème, de croûtes et de pellicules. Les tests diagnostics comprenaient un examen histopathologique et immunohistochimique de biopsies cutanées qui ont révélé une dermatite d'interface avec cellules T CD8+. La dermatose a été traitée avec succès initialement avec des corticoïdes et du méthotrexate; un traitement efficace au long cours a été associé avec l'administration de méthotrexate.

El lupus eritematoso cutáneo (CLE) es una rara dermatitis inmunomediada. A entender de los autores, esta enfermedad no se ha descrito en burros. Un burro castrado macho de 5 años de edad, que vive en el sureste de Francia fue diagnosticado con CLE. Los signos clínicos incluyeron áreas simétricas generalizadas de alopecia, eritema, costras y escamas. Las pruebas de diagnóstico incluyeron el examen de muestras de biopsia de piel mediante análisis histopatológico e inmunohistoquímico que demostró una dermatitis de interfase con células T CD8+. La condición de la piel se trató con éxito inicialmente con glucocorticoides y metotrexato; el control exitoso a largo plazo de la enfermedad se obtuvo con la administración de metotrexato.

O lúpus eritematoso cutâneo (LEC) é uma dermatite imunomediada rara. De acordo com os conhecimentos do autor, a doença ainda não foi descrita em jumentos. Um jumento macho castrado de cinco anos de idade, habitante do sul da França, foi diagnosticado com LEC. Os sinais clínicos incluíram alopecia, eritema, crostas e descamação generalizadas e simétricas. Os testes diagnósticos utilizados foram avaliação de amostras de biópsia por análise histopatológica e imunohistoquímica, que demonstraram dermatite de interface com células T CD8+. A dermatopatia foi tratada satisfatoriamente inicialmente com glicocorticoide e metotrexato; a manutenção satisfatória a longo prazo foi associada à administração de metotrexato.

Pharmacokinetics of low-dose methotrexate in horses.

This study aimed to investigate both the pharmacokinetic behavior and tolerance of methotrexate (MTX) in horses to design a specific dosing regimen as a new immunomodulatory drug for long-term treatment. To determine the primary plasma pharmacokinetic variables after single intravenous, subcutaneous or oral administration, six horses were administered 0.3 mg/kg MTX in a crossover design study. After a 10-week washout, MTX was administered subcutaneously to three of the six previously treated horses at a dose of 0.3 mg/kg once per week for 3 months. In both studies, MTX and metabolite concentrations were measured using LC-MS/MS. The absolute bioavailability of MTX was 73% following subcutaneous administration but less than 1% following oral administration. The plasma clearance was 1.54 ml min-1  kg-1 (extraction ratio = 2%). After 24 hr, plasma concentrations were below the LOQ. No adverse effects were noted except for a moderate reversible elevation in liver enzymes (GLDH). With regards to the main metabolites of MTX, very low concentrations of 7-hydroxy-MTX were found, whereas polyglutamated forms (mainly short chains) were found in red blood cells. A subcutaneous dose of 0.2 mg kg-1  week-1 may be safe and relevant in horses, although this has yet to be clinically confirmed.

Equine pastern vasculitis in a horse associated with a multidrug-resistant Pseudomonas aeruginosa isolate.

BACKGROUND: Equine pastern vasculitis is an uncommon disorder in horses. Underlying causes are difficult to assess, especially bacterial infections. CLINICAL SUMMARY: A 13-year-old French saddle gelding horse presented for evaluation of a six weeks history of pastern dermatitis. Histopathological examination of skin biopsy samples revealed small vessel vasculitis. A pure growth of a multidrug-resistant Pseudomonas aeruginosa (MRPA) was obtained from a deep skin biopsy. Clinical remission was observed after a six week course of enrofloxacin and lesions did not recur. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first report of a pastern vasculitis associated with MRPA and successfully treated with a six week course of enrofloxacin.

In situ synthesis of Fe3O4 nanoparticles coated by chito-oligosaccharides: physico-chemical characterizations and cytotoxicity evaluation for biomedical applications.

Fe3O4 nanoparticles coated with chito-oligosaccharides (COS) were prepared in situ by a simple co-precipitation method through a mixing of iron ions (Fe3+ and Fe2+) and COS aqueous solutions followed by precipitation with ammonia. The impact of COS with different degree of polymerization (DP 10, 24 and 45) and degree of N-acetylation (DA) âˆ¼ 24% and 50% (exhibiting high solubility) on the synthesis and physical properties of the coated magnetic nanoparticles was evaluated. Several advantages were found when the magnetic nanoparticles were prepared in the presence of the studied COS, such as: preparation of functionalized magnetic nanoparticles with narrower size distributions and, consequently, higher saturation magnetization (an increase of up to 22%); and an expressive increasing in the concentration of COS-coated magnetic nanoparticles (up to twice) in the cell viability test in comparison with pure Fe3O4 nanoparticles. Furthermore, among the analyzed samples, the magnetic nanoparticles coated by COS with DA âˆ¼ 50% present a higher cytocompatibility. Our results allow envisioning various biomedical applications, valorizing the use of coated-magnetic nanoparticles for magnetic-field assisted drug delivery, enzyme or cell immobilization, or as a marker for specific cell tracking, among others.

Granulomatous mural folliculitis in a dog treated with ciclosporin and methotrexate.

BACKGROUND: Canine granulomatous mural folliculitis is a very rare cause of scarring alopecia with unknown pathogenesis. HYPOTHESIS/OBJECTIVES: To report a case of granulomatous mural folliculitis in a dog treated with ciclosporin (Cs) and methotrexate (MTX). ANIMAL: A 13-year-old spayed female Pyrenean shepherd dog with a one month history of scarring alopecia. METHODS AND RESULTS: Histopathological examination revealed a granulomatous and lymphocytic mural and necrotizing folliculitis and furunculosis. Immunochemistry, using antibodies for CD3, CD204, CD206, IBA-1 and CD208, revealed that CD3+ lymphocytes were infiltrating the outer root sheath along with IBA-1+ or CD204+ cells. Ciclosporin (5 mg/kg once daily) and MTX (0.25 mg/kg once weekly then 0.5 mg/kg once weekly) were initiated simultaneously, and Cs was stopped after stabilization of the lesions. The dog's skin disease was stable for six months. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first report of the long-term management of a granulomatous mural folliculitis in a dog. Ciclosporin and MTX appeared to be an effective treatment option. Additional treated cases are needed to assess the effectiveness of MTX in canine immune-mediated diseases.

Refined Immunochemical Characterization in Healthy Dog Skin of the Epidermal Cornification Proteins, Filaggrin, and Corneodesmosin.

Filaggrin (FLG) and corneodesmosin (CDSN) are two key proteins of the human epidermis. FLG loss-of-function mutations are the strongest genetic risk factors for human atopic dermatitis. Studies of the epidermal distribution of canine FLG and CDSN are limited. Our aim was to better characterize the distribution of FLG and CDSN in canine skin. Using immunohistochemistry on beagle skin, we screened a series of monoclonal antibodies (mAbs) specific for human FLG and CDSN. The cross-reactive mAbs were further used using immunoelectron microscopy and Western blotting. The structure of canine CDSN and FLG was determined using publicly available databases. In the epidermis, four anti-FLG mAbs stained keratohyalin granules in the granular keratinocytes and corneocyte matrix of the lower cornified layer. In urea-extracts of dog epidermis, several bands corresponding to proFLG and FLG monomers were detected. One anti-CDSN mAb stained the cytoplasm of granular keratinocytes and cells of both the inner root sheath and medulla of hair follicles. Dog CDSN was located in lamellar bodies, in the extracellular parts of desmosomes and in corneodesmosomes. A protein of 52 kDa was immunodetected. Genomic DNA analysis revealed that the amino acid sequence and structure of canine and human CDSN were highly similar.

Highly Reduced Genome of the New Species Mycobacterium uberis, the Causative Agent of Nodular Thelitis and Tuberculoid Scrotitis in Livestock and a Close Relative of the Leprosy Bacilli.

Nodular thelitis is a chronic enzootic infection affecting dairy cows and goats. The causative agent was recently shown to be related to the leprosy-causing bacilli Mycobacterium leprae and Mycobacterium lepromatosis In this study, the genome of this pathogen was sequenced and analyzed. Phylogenomic analyses confirmed that the pathogen present in nodular thelitis and tuberculoid scrotitis is a distinct species related to the leprosy bacilli and Mycobacterium haemophilum Because the pathogen was originally isolated from a bovine udder, it was named "Mycobacterium uberis" The genome of "M. uberis" is only 3.12 Mb in length, which represents the smallest mycobacterial genome identified so far but which is close to that of leprosy bacilli in size. The genome contains 1,759 protein-coding genes and 1,081 pseudogenes, indicative of extensive reductive evolution and likely the reason that M. uberis cannot be grown axenically. The pseudogenization and genome reduction in M. uberis seem to have been to some extent independent from the results determined for the genomes of the leprosy bacilli.IMPORTANCEM. uberis is an emerging skin pathogen in dairy animals. Its genome underwent massive reduction and gene decay, leading to a minimal set of genes required for an obligatory intracellular lifestyle, which highly resembles the evolution of the leprosy agents M. leprae and M. lepromatosis The genomic similarity between M. uberis and the leprosy bacilli can help in identifying key virulence factors of these closely related species or in identifying genes responsible for the distinct differences between thelitis or scrotitis and leprosy with respect to clinical manifestations. Specific DNA markers can now be developed for quick detection of this pathogen.

Efficacy of two formulations of afoxolaner (NexGard® and NexGard Spectra®) for the treatment of generalised demodicosis in dogs, in veterinary dermatology referral centers in Europe.

BACKGROUND: A multi-centre field trial was conducted to evaluate the efficacy of afoxolaner based chewables (NexGard® or NexGard Spectra®) for the treatment of generalised demodicosis caused by Demodex canis in dogs under field conditions in France, Italy and Poland. METHODS: Client-owned dogs, diagnosed positive for Demodex mites by pre-treatment skin scrapings and presenting clinical signs of generalised demodicosis were included. Dogs were orally treated with afoxolaner three times at monthly intervals. Of the 50 dogs enrolled, 48 completed the whole study. Efficacy of the treatments was assessed monthly by Demodex mite counts and physical examination with special regard to the severity and extension of skin lesions. RESULTS: Treatments were well tolerated in all dogs and resulted in a rapid reduction of mites, with all post-treatment mite counts significantly lower than baseline. The number of mites was reduced by 87.6%, 96.5% and 98.1% on Days 28, 56 and 84, respectively. In addition, the skin lesion severity and extent scores as well as the pruritus were all significantly lower at all post-treatment visits compared to the pre-treatment assessment. CONCLUSIONS: This clinical field study demonstrated that monthly administrations of afoxolaner in NexGard® or NexGard Spectra®, offered a convenient and reliable solution for the treatment of canine generalised demodicosis.

Pharmacokinetics of low-dose methotrexate in healthy beagle dogs.

Methotrexate may be an alternative to ciclosporin in the treatment of canine atopic dermatitis (cAD) as suggested by recent data. The aim of the study was to investigate both the tolerance and the pharmacokinetic behavior of methotrexate (MTX) in plasma, following intravenous (i.v.), subcutaneous (s.c.) or oral (OR) administration over several weeks. Six healthy dogs were given oral MTX once a week, respectively, per dog at 2.5 mg/1 week, 5 mg/4 weeks, 7.5 mg/3 weeks, 10 mg/6 weeks and 12.5 mg/5 weeks. No clinically relevant abnormalities of laboratory parameters were noticed. A high inter-individual variation of MTX plasma concentration was observed with a suspicion of saturation phenomenon in absorption. To compare with other routes of administration, six healthy beagle dogs followed a crossover design study at 7.5 mg per dog MTX. The absolute bioavailability was 93% for SC injection and 30% for the oral route. The inter-individual variability was quite low following SC administration compared to oral route. Just as in human, given the substantial variability of oral absorption, clinicians cannot assume consistent oral bioavailability of MTX. Therefore, they may consider switching dogs to the SC route in case of absence of clinical response with a weekly oral dose.