bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology of human atopic dermatitis – seven areas of notable progress and seven areas of notable ignorance
Authors: Williams Hywel C.
Published: January 2013

Background –  This narrative review highlights areas within the epidemiology of human atopic dermatitis (AD) where significant progress has been made and where considerable ignorance still exists. The review is supported by systematic reviews wherever possible, with the purpose of stimulating fresh approaches to human and veterinary research into AD.

Progress –  Areas of progress include valid and repeatable methods of disease definition, global documentation of disease prevalence and impact, clarification of the role of some genetic factors, such as filaggrin gene mutations, clear evidence that environmental factors are key, as demonstrated by the positive social class gradient and rising prevalence, a possible protective effect of infections in early life, documentation of comorbidities, such as a reduced risk of glioma, and mapping the evidence base through systematic reviews and an online global resource of clinical trials.

Ignorance –  Areas where significant uncertainty still exists include the question of whether AD is more than one disease, the tendency for researchers to look at the same old risk factors, lack of specific environmental risk factors that are amenable to manipulation, inconsistencies in the hygiene hypothesis, sparse knowledge about adult AD, lack of evidence that eczema can be prevented, and little scientific work exploring what causes flares in people with established AD.
Comparison of hair follicle histology between horses with pituitary pars intermedia dysfunction and excessive hair growth and normal aged horses
Authors: Innerå Marie , Petersen Annette D. , Desjardins Danielle R. , Steficek Barbara A. , Rosser Edmund J. , Schott Harold C.
Published: January 2013

Background – Pituitary pars intermedia dysfunction (PPID) in older equids is commonly recognized by a long hair coat that fails to shed.

Objective – The aim of this study was to compare hair follicle stages in PPID‐affected horses with excessively long hair coats with the stages of normal aged horses (controls) and to compare hair follicle stages in PPID‐affected horses after 6 months of treatment with pergolide mesylate with those of control horses.

Animals – Eight PPID‐affected horses and four normal, age‐matched, control horses.

Methods – Skin biopsies were collected from the neck and rump of PPID‐affected and control horses. A diagnosis of PPID was established based on hair coat changes and supportive overnight dexamethasone suppression test results. Skin biopsies were repeated after 6 months of treatment with pergolide. The number of hair follicles in anagen (A) or telogen (T) was counted for each skin biopsy using transverse sections.

Results – Pretreatment biopsies had a greater percentage of A follicles (neck 96%, rump 95%) and a lower percentage of T follicles (neck 4%, rump 5%) in PPID‐affected horses than in control horses (A, neck 15%, rump 25%; and T, neck 85%, rump 75%). After treatment with pergolide, all PPID‐affected horses had improved shedding, and the percentages of A follicles (neck 69%, rump 70%) and T follicles (neck 31%, rump 30%) were not different from untreated control horses (A, neck 68%, rump 82%; and T, neck 32%, rump 18%).

Conclusions – These findings document that excessive hair growth (hypertrichosis) in PPID‐affected horses is due to persistence of hair follicles in A. Furthermore, treatment with pergolide improved shedding and reduced the percentage of A follicles in PPID‐affected horses.
Kinase dysfunction and kinase inhibitors
Authors: London Cheryl A.
Published: January 2013

With recent advances in molecular biology, abnormalities in cancer cells that contribute to dysregulation of cell survival and proliferation are being characterized with greater precision. Through this process, key abnormalities in cancer cells involving proteins that regulate signal transduction, migration, mitosis and other critical processes have been identified. Such abnormalities often involve a class of proteins called kinases that act to phosphorylate other proteins in the cell, resulting in activation of these proteins in the absence of appropriate stimulation/regulation. Given their role in tumour biology, substantial effort has been directed at blocking the function of these proteins. Several approaches have been used, including monoclonal antibodies and small molecule inhibitors. While antibodies are primarily directed at cell surface proteins, small molecule inhibitors, also known as kinase inhibitors, target proteins throughout the cell.

A variety of kinase inhibitors have been approved for the treatment of human cancers. In some instances, these inhibitors have exhibited significant clinical efficacy, and it is likely that their biological activity will be further enhanced as combination regimens with standard treatment modalities are explored.

The use of kinase inhibitors in dogs and cats is relatively recent, although two inhibitors, toceranib (Palladia; Pfizer Animal Health, Madison, NJ, USA) and masitinib (Kinavet; Catalent Pharma Solutions, Somerset, NJ, USA) have been approved by the Federal Drug Administration (USA) for use in dogs. This article reviews the biology of protein kinase dysfunction in human and animal cancers, and the application of specific kinase inhibitors to veterinary cancer patients.
Innate immune defense system of the skin
Authors: Afshar Maryam , Gallo Richard L.
Published: January 2013

Background –  Antimicrobial peptides (AMPs) have a pivotal role in cutaneous innate immunity. They are present in the skin of many animals, including mammals, and are both constitutively present and inducible by infection and injury.

Functions –  Antimicrobial peptides exhibit antimicrobial activity against bacteria, viruses, fungi and parasites, with different potencies depending on their peptide structure. They also act as multifunctional effector molecules that influence diverse cellular processes, including cell migration, proliferation and differentiation, cytokine production, angiogenesis and wound healing. Suppressed AMP production has been associated with increased susceptibility to microbial insults and the pathogenesis of atopic dermatitis.

This review highlights recent observations on the expression and role of AMPs, particularly the AMPs cathelicidin and β‐defensin, in healthy and diseased skin.
A systematic review of randomized controlled trials for prevention or treatment of atopic dermatitis in dogs: 2008–2011 update
Authors: Olivry Thierry , Bizikova Petra
Published: January 2013

Background –  The management of atopic dermatitis (AD) in dogs relies mainly on the use of interventions to reduce pruritus and skin lesions.

Objectives –  To provide a critical analysis of recent clinical trials reporting the efficacy and safety of interventions for canine AD.

Methods –  Systematic review of randomized controlled trials (RCTs) published, presented or completed between 2008 and 2011, which enrolled dogs with AD. The search was done using electronic databases, reviewing published meeting abstracts and sending queries to professional email lists. Trials reporting the efficacy of interventions aimed at treating, preventing or reducing glucocorticoid usage in atopic dogs were selected.

Results –  Twenty‐one RCTs were included. We found further moderate‐quality evidence of efficacy and safety of oral glucocorticoids and ciclosporin for treatment of canine AD. There was additional moderate‐quality evidence of the efficacy of a topical glucocorticoid spray containing hydrocortisone aceponate. Low‐quality evidence was found for the efficacy and safety of injectable recombinant interferons, a budesonide leave‐on conditioner, a ciclosporin topical nano‐emulsion and oral fexofenadine. There is low‐quality evidence of efficacy of oral masitinib, with a need for monitoring for protein‐losing nephropathy. Finally, we uncovered low‐quality evidence of efficacy of a commercial diet as a glucocorticoid‐sparing intervention and of a glucocorticoid spray as a flare‐delaying measure. Very low‐quality evidence was found for the efficacy of other interventions.

Conclusions and clinical importance –  Topical or oral glucocorticoids and oral ciclosporin remain the interventions with highest evidence for efficacy and relative safety for treatment of canine AD.
The stratum corneum: the rampart of the mammalian body
Authors: Nishifuji Koji , Yoon Ji Seon
Published: January 2013

Background –  The stratum corneum (SC) is the outermost region of the epidermis and plays key roles in cutaneous barrier function in mammals. The SC is composed of ‘bricks’, represented by flattened, protein‐enriched corneocytes, and ‘mortar’, represented by intercellular lipid‐enriched layers. As a result of this ‘bricks and mortar’ structure, the SC can be considered as a ‘rampart’ that encloses water and solutes essential for physiological homeostasis and that protects mammals from physical, chemical and biological assaults.

Structures and functions –  The corneocyte cytoskeleton contains tight bundles of keratin intermediate filaments aggregated with filaggrin monomers, which are subsequently degraded into natural moisturizing compounds by various proteases, including caspase 14. A cornified cell envelope is formed on the inner surface of the corneocyte plasma membrane by transglutaminase‐catalysed cross‐linking of involucrin and loricrin. Ceramides form a lipid envelope by covalently binding to the cornified cell envelope, and extracellular lamellar lipids play an important role in permeability barrier function. Corneodesmosomes are the main adhesive structures in the SC and are degraded by certain serine proteases, such as kallikreins, during desquamation.

Clinical relevance –  The roles of the different SC components, including the structural proteins in corneocytes, extracellular lipids and some proteins associated with lipid metabolism, have been investigated in genetically engineered mice and in naturally occurring hereditary skin diseases, such as ichthyosis, ichthyosis syndrome and atopic dermatitis in humans, cattle and dogs.
Evaluation of canine antimicrobial peptides in infected and noninfected chronic atopic skin
Authors: Santoro Domenico , Bunick David , Graves Thomas K. , Segre Mariangela
Published: January 2013

Background –  Antimicrobial peptides (AMPs) are small immunomodulatory peptides produced by epithelial and immune cells. β‐Defensins (BDs) and cathelicidins (Caths) are the most studied AMPs. Recently, increased cutaneous expression of AMPs was reported in atopic humans and in beagles with experimentally induced atopy.

Hypothesis/Objectives –  Our goal was to analyse mRNA expression and protein levels of canine (c)BD1‐like, cBD2‐like/122, cBD3‐like, cBD103 and cCath in healthy and naturally affected atopic dogs, with and without active skin infection, along with their distribution in the epidermis using indirect immunofluorescence.

Animals –  Skin biopsies were taken from 14 healthy and 11 atopic privately owned dogs.

Methods –  The mRNA levels of cBD1‐like, cBD2‐like/122, cBD3‐like, cBD103 and cCath were quantified using quantitative real‐time PCR. The protein levels of cBD3‐like and cCath were analysed by relative competitive inhibition enzyme‐linked immunosorbent assay, while the distributions of cBD2‐like/122, cBD3‐like and cCath were detected by indirect immunofluorescence.

Results –  Dogs with atopic dermatitis had significantly greater mRNA expression of cBD103 (P = 0.04) than control dogs. Furthermore, atopic skin with active infection had a higher cBD103 mRNA expression (P = 0.01) and a lower cBD1‐like mRNA expression (P = 0.04) than atopic skin without infection. No significant differences in protein levels (cBD3‐like and cCath) or epidermal distribution of AMPs (cBD2‐like/122, cBD3‐like and cCath) were seen between healthy and atopic dogs.

Conclusions and clinical importance –  Expression of cBD103 mRNA was greater, while expression of cBD1‐like mRNA was lower in dogs with atopic dermatitis that had active infections. Work is needed to clarify the biological mechanisms and possible therapeutic options to maintain a healthy canine skin.
The genomics revolution: will canine atopic dermatitis be predictable and preventable?
Authors: Nuttall Tim
Published: January 2013

Background – Heritability studies suggest that atopic dermatitis (AD) involves multiple genes and interactions with environmental factors. Advances in genomics have given us powerful techniques to study the genetics of AD.

Objective – To review the application of these techniques to canine AD.

Results – Candidate genes can be studied using quantitative PCR and genomic techniques, but these are hypothesis‐dependent techniques and may miss novel genes. Hypothesis‐free techniques avoid this limitation. Microarrays quantify expression of large numbers of genes, although false‐positive associations are common. In the future, expression profiling could be used to produce a complete tissue transcriptome. Genome‐wide linkage studies can detect AD‐associated loci if enough affected dogs and unaffected relatives are recruited. Genome‐wide association studies can be used to discover AD‐associated single nucleotide polymorphisms without relying on related dogs. Genomic studies in dogs have implicated numerous genes in the pathogenesis of AD, including those involved in innate and adaptive immunity, inflammation, cell cycle, apoptosis, skin barrier formation and transcription regulation. These findings, however, have been inconsistent, and problems include low case numbers, inappropriate controls, inconsistent diagnosis, incomplete genome coverage, low‐penetrance mutations and environmental factors.

Conclusions – Canine AD has a complex genotype that varies between breeds and gene pools. Breeding programmes to eliminate AD are therefore unlikely to succeed, but this complexity could explain variations in clinical phenotype and response to treatment. Genotyping of affected dogs will identify novel target molecules and enable better targeting of treatment and management options. However, we must avoid misuse of genomic data.
Expression of thymic stromal lymphopoietin in canine atopic dermatitis
Authors: Klukowska‐Rötzler Jolanta , Chervet Ludovic , Müller Eliane J. , Roosje Petra , Marti Eliane , Janda Jozef
Published: January 2013

Background –  In humans, thymic stromal lymphopoietin (TSLP) plays a central role in the development of allergic inflammation, such as atopic dermatitis (AD), but it is unknown whether it is involved in the pathogenesis of canine AD (CAD).

Hypothesis/Objectives –  Our aim was to characterize canine TSLP and to assess its expression in CAD.

Methods –  Canine TSLP was identified based on sequence homology with human TSLP and the complementary DNA (cDNA) cloned by RT‐PCR. Real‐time quantitative RT‐PCR was established to assess the expression of canine TSLP in cultured canine keratinocytes and in skin biopsy specimens from lesional and nonlesional skin of 12 dogs with CAD and eight healthy control dogs.

Results –  Partial canine TSLP cDNA was cloned and characterized. It contained four exons that shared 70 and 73% nucleotide identity with human and equine TSLP, respectively, encoding the signal peptide and full‐length secreted protein. We found significantly increased TSLP expression in lesional and nonlesional skin of dogs with CAD compared with healthy control dogs (P < 0.05), whereas no difference was measured between lesional and nonlesional samples. In cultured primary canine keratinocytes, we found increased TSLP expression after stimulation with house dust mite allergen extract or Toll‐like receptor ligands lipopolysaccharide and poly I:C.

Conclusions and clinical importance –  Increased TSLP expression in the skin of dogs with CAD supports an involvement of TSLP in the pathogenesis of CAD similar to that in humans. Further studies should elucidate the function and therapeutic potential of TSLP in CAD.
Epidermal structure created by canine hair follicle keratinocytes enriched with bulge cells in a three‐dimensional skin equivalent model in vitro: implications for regenerative therapy of canine epidermis
Authors: Kobayashi Tetsuro , Enomoto Kaoru , Wang Yu Hsuan , Yoon Ji Seon , Okamura Ryoko , Ide Kaori , Ohyama Manabu , Nishiyama Toshio , Iwasaki Toshiroh , Nishifuji Koji
Published: January 2013

Background –  Keratinocytes in the hair follicle bulge region have a high proliferative capacity, with characteristics of epithelial stem cells. This cell population might thus be an ideal source for generating the interfollicular epidermis in a canine skin equivalent.

Hypothesis/Objectives –  This study was designed to determine the ability of canine hair follicle bulge cell‐enriched keratinocytes to construct canine living skin equivalents with interfollicular epidermis in vitro.

Animals –  Four healthy beagle dogs from a research colony.

Methods –  Bulge cell‐enriched keratinocytes showing keratin 15 immunoreactivity were isolated from canine hair follicles and cultured on dermal equivalent containing canine fibroblasts. Skin equivalents were subjected to histological, immunohistochemical, western blot and RT‐PCR analyses after 10–14 days of culture at the air–liquid interface.

Results –  The keratinocyte sheets showed an interfollicular epidermal structure comprising four to five living cell layers covered with a horny layer. Immunoreactivities for keratin 14 and desmoglein 3 were detected in the basal and immediate suprabasilar layers of the epidermis, while keratin 10 and desmoglein 1 occurred in more superficial layers. Claudin 1 immunoreactivity was seen in the suprabasalar layer of the constructed epidermis, and filaggrin monomers and loricrin were detected in the uppermost layer. Basal keratinocytes in the skin equivalent demonstrated immunoreactivity to antibodies against basement membrane zone molecules.

Conclusions and clinical importance –  A bulge stem cell‐enriched population from canine hair follicles formed interfollicular epidermis within 2 weeks in vitro, and thus represents a promising model for regenerative therapy of canine skin.
Interleukin‐31: its role in canine pruritus and naturally occurring canine atopic dermatitis
Authors: Gonzales Andrea J. , Humphrey William R. , Messamore James E. , Fleck Timothy J. , Fici Gregory J. , Shelly John A. , Teel Janet F. , Bammert Gary F. , Dunham Steven A. , Fuller Troy E. , McCall Robert B.
Published: January 2013

Background –  Interleukin‐31 (IL‐31) is a member of the gp130/interleukin‐6 cytokine family that is produced by cell types such as T helper 2 lymphocytes and cutaneous lymphocyte antigen positive skin homing T cells. When overexpressed in transgenic mice, IL‐31 induces severe pruritus, alopecia and skin lesions. In humans, IL‐31 serum levels correlate with the severity of atopic dermatitis in adults and children.

Hypothesis/Objective –  To determine the role of IL‐31 in canine pruritus and naturally occurring canine atopic dermatitis (AD).

Animals –  Purpose‐bred beagle dogs were used for laboratory studies. Serum samples were obtained from laboratory animals, nondiseased client‐owned dogs and client‐owned dogs diagnosed with naturally occurring AD.

Methods –  Purpose‐bred beagle dogs were administered canine interleukin‐31 (cIL‐31) via several routes (intravenous, subcutaneous or intradermal), and pruritic behaviour was observed/quantified via video monitoring. Quantitative immunoassay techniques were employed to measure serum levels of cIL‐31 in dogs.

Results –  Injection of cIL‐31 into laboratory beagle dogs caused transient episodes of pruritic behaviour regardless of the route of administration. When evaluated over a 2 h period, dogs receiving cIL‐31 exhibited a significant increase in pruritic behaviour compared with dogs that received placebo. In addition, cIL‐31 levels were detectable in 57% of dogs with naturally occurring AD (≥13 pg/mL) but were below limits of quantification (<13 pg/mL) in normal, nondiseased laboratory or client‐owned animals.

Conclusions –  Canine IL‐31 induced pruritic behaviours in dogs. Canine IL‐31 was detected in the majority of dogs with naturally occurring AD, suggesting that this cytokine may play an important role in pruritic allergic skin conditions, such as atopic dermatitis, in this species.
Small Demodex populations colonize most parts of the skin of healthy dogs
Authors: Ravera Iván , Altet Laura , Francino Olga , Sánchez Armand , Roldán Wendy , Villanueva Sergio , Bardagí Mar , Ferrer Lluís
Published: January 2013

Background – It is unproven that all dogs harbour Demodex mites in their skin. In fact, several microscopic studies have failed to demonstrate mites in healthy dogs.

Hypothesis/Objectives – Demodex canis is a normal inhabitant of the skin of most, if not all, dogs. This hypothesis was tested using a sensitive real‐time PCR to detect Demodex DNA in the skin of dogs.

Animals – One hundred dogs living in a humane society shelter, 20 privately owned and healthy dogs and eight dogs receiving immunosuppressive or antineoplastic therapy.

Methods – Hair samples (250–300 hairs with their hair bulbs) were taken from five or 20 skin locations. A real‐time PCR that amplifies a 166 bp sequence of the D. canis chitin synthase gene was used.

Results – The percentage of positive dogs increased with the number of sampling points. When a large canine population was sampled at five cutaneous locations, 18% of dogs were positive for Demodex DNA. When 20 skin locations were sampled, all dogs tested positive for mite DNA. Our study indicates that Demodex colonization of the skin is present in all dogs, independent of age, sex, breed or coat. Nevertheless, the population of mites in a healthy dog appears to be small. Demodex DNA was amplified from all 20 cutaneous points investigated, without statistically significant differences.

Conclusions and clinical importance – Using a real‐time PCR technique, Demodex mites, albeit in very low numbers, were found to be normal inhabitants of haired areas of the skin of healthy dogs.
Usefulness of cefovecin disk‐diffusion test for predicting mecA gene‐containing strains of Staphylococcus pseudintermedius and clinical efficacy of cefovecin in dogs with superficial pyoderma
Authors: Iyori Keita , Toyoda Yoichi , Ide Kaori , Iwasaki Toshiroh , Nishifuji Koji
Published: January 2013

Background –  Cefovecin has been widely used to treat skin infections in dogs. The relationship of the cefovecin disk‐diffusion test results to the presence of the mecA gene and the clinical efficacy of cefovecin have not been fully evaluated.

Hypothesis/Objectives –  To determine the usefulness of an in vitro cefovecin disk‐diffusion test in predicting the presence of the mecA gene in Staphylococcus pseudintermedius, as well as the in vivo efficacy of cefovecin therapy in dogs with superficial pyoderma.

Methods –  Twenty‐six S. pseudintermedius strains isolated from 22 dogs with pyoderma were used. In vitro disk‐diffusion test results of cefovecin were compared with agar‐dilution test results, the presence of the mecA gene, and the improvement in clinical scores of dogs with superficial pyoderma at 14 days post treatment.

Results –  There was a significant linear correlation (r = −0.83) between the diameter of the obvious zone of inhibition by disk diffusion and the minimal inhibitory concentration for cefovecin (P < 0.0001). Receiver operating characteristic analysis revealed that zone diameters between 25 and 27 mm exhibited better sensitivity (92.9%) and specificity (100.0%) for detection of strains carrying the mecA gene. The mean improvement in clinical scores in dogs carrying cefovecin‐resistant strains was significantly lower than in dogs carrying cefovecin‐susceptible strains (P < 0.01).

Conclusions and clinical importance –  The cefovecin disk‐diffusion test with a cut‐off value estimated in this study was valuable for predicting mecA gene carriage in S. pseudintermedius, as well as the in vivo efficacy of cefovecin therapy in dogs with superficial pyoderma caused by S. pseudintermedius.
The contribution of stem cells to epidermal and hair follicle tumours in the dog
Authors: Brachelente Chiara , Porcellato Ilaria , Sforna Monica , Lepri Elvio , Mechelli Luca , Bongiovanni Laura
Published: January 2013

Background –  Although cutaneous stem cells have been implicated in skin tumourigenesis in humans, no studies have been conducted to elucidate the presence and the possible role of stem cells in hair follicle tumours in the dog.

Hypothesis –  Stem cell markers are expressed in canine epidermal and follicular tumours and can be used to better understand the biology and origin of these tumours.

Animals and Methods –  In the present study, normal skin sections and 44 follicular tumours were retrospectively investigated for the immunohistochemical expression of keratin 15 (K15) and nestin. In addition, 30 squamous cell carcinomas were evaluated for K15 expression.

Results –  In normal skin, K15 and nestin were expressed in the outer root sheath cells of the isthmic portion of the hair follicle (bulge region), and K15 expression was also scattered in the basal cell layer of the epidermis. Infundibular keratinizing acanthomas, pilomatricomas and squamous cell carcinomas were mostly negative for K15, trichoblastomas were moderately to strongly positive, tricholemmomas were either negative or strongly positive, and trichoepitheliomas had heterogeneous staining. Nestin expression was generally faint in all follicular tumours.

Conclusions and clinical importance –  Our results show that K15 can be a reliable marker for investigating the role of stem cells in hair follicle tumours of the dog, while nestin was judged to be a nonoptimal marker. Furthermore, our study suggests that hair follicle stem cells are present in the bulge region of hair follicles and could possibly play a role in tumourigenesis of canine tumours originating from this portion of the follicle, namely trichoblastomas, tricholemmomas and trichoepitheliomas. The loss of K15 expression in squamous cell carcinomas compared with normal skin suggests that this event could be important in the malignant transformation.
Skin lipid profiling in normal and seborrhoeic shih tzu dogs
Authors: Yoon Ji‐Seon , Nishifuji Koji , Ishioroshi Sinpei , Ide Kaori , Iwasaki Toshiroh
Published: January 2013

Background –  Seborrhoea is a clinical condition resulting in excessive lipid and/or scale on the skin and is a common and important skin disease of dogs. However, there is little information on the skin surface lipid composition of dogs with seborrhoea.

Hypothesis/Objectives –  To compare skin surface lipid profiles in normal and seborrhoeic shih tzu dogs.

Methods –  Fourteen client‐owned dogs (seven seborrhoeic and seven normal) were investigated. Lipids in sebaceous glands (SGs) were extracted from homogenized tissues of SG hyperplasia. Surface lipid was collected by tape stripping [stratum corneum (SC)‐enriched fraction] and acetone‐wetted cotton swab (acetone‐extracted fraction). Lipids in SGs, SC‐enriched fractions and acetone‐extracted fractions were evaluated by high‐performance thin‐layer chromatography.

Results –  Lipids in SGs mainly consisted of cholesterol esters, wax esters and triglycerides, whereas lipids in the SC‐enriched fraction mainly consisted of ceramides. The acetone‐extracted fraction contained a mixture of lipid classes recognized in SG‐ and SC‐enriched fractions. In seborrhoeic dogs, concentrations of wax esters and triglycerides in the acetone‐extracted fraction were significantly higher than in control dogs (P = 0.0285). Amounts of total ceramides (in micrograms) per milligram of SC were not significantly different between the two groups (P = 0.5204). Interestingly, two unknown ceramide fractions, which accounted for 20% of the total ceramides, were recognized exclusively in seborrhoeic dogs.

Conclusions and clinical importance –  These results provide evidence that the skin surface lipid profiles are altered in shih tzu dogs with seborrhoea.
In vitro antiseptic susceptibilities for Staphylococcus pseudintermedius isolated from canine superficial pyoderma in Japan
Authors: Murayama Nobuo , Nagata Masahiko , Terada Yuri , Okuaki Mio , Takemura Noriyuki , Nakaminami Hidemasa , Noguchi Norihisa
Published: January 2013

Background –  Topical therapy, particularly with chlorhexidine, is becoming increasingly common as a treatment option for canine pyoderma; however, there are limited studies on the susceptibility of Staphylococcus pseudintermedius to chlorhexidine compounds.

Objectives –  To determine the in vitro susceptibility of both meticillin‐resistant and meticillin‐susceptible S. pseudintermedius isolates to chlorhexidine and other antiseptic agents and the presence of multidrug efflux pump genes.

Samples –  One hundred S. pseudintermedius isolates from 23 initial and 77 recurrent cases of canine pyoderma.

Methods –  After bacterial identification and mecA testing, minimal inhibitory concentrations (MICs) of antiseptic agents were determined. Multidrug efflux pump genes, including qacA, qacB and smr, were identified.

Results –  Of the 100 isolates, 57 were identified as meticillin‐resistant S. pseudintermedius. The MIC90 of chlorhexidine acetate, chlorhexidine gluconate, acriflavine, ethidium bromide and benzalkonium chloride were 1, 1, 2, 0.5 and 2 μg/mL, respectively. Multidrug efflux pump genes qacA, qacB and smr were not detected in any of the isolates.

Conclusions and clinical importance –  The MICs for chlorhexidine and other antiseptics remain low, and multidrug efflux pump genes were not found in the tested isolates.
Ulcerated and nonulcerated nontuberculous cutaneous mycobacterial granulomas in cats and dogs
Authors: Malik Richard , Smits Bronwyn , Reppas George , Laprie Caroline , O’Brien Carolyn , Fyfe Janet
Published: January 2013

Background –  Mycobacterial granulomas of the skin and subcutis can be caused by one of a number of pathogens. This review concentrates on noncultivable species that cause diseases characterized by focal granuloma(s), namely leproid granuloma (in dogs) and feline leprosy (in cats). Clinically indistinguishable lesions can be caused by tuberculous organisms (Mycobacterium bovis and Mycobacterium microti) and members of the Mycobacterium avium complex. Rapidly growing mycobacterial species that cause infection of the subcutaneous panniculus associated with draining tracts are not discussed. Disease caused by Mycobacterium ulcerans is an important emerging differential diagnosis for ulcerated cutaneous nodules in certain localized regions.

Clinical lesions –  Lesions comprise one or multiple nodules in the skin/subcutis. These are generally firm and well circumscribed, and typically become denuded of hair. They may or may not ulcerate, depending on the virulence of the causal organisms and the immune response of the host.

Diagnosis –  The most inexpensive, noninvasive means of diagnosis is by submission of methanol‐fixed, Romanowsky‐stained smears to a Mycobacterium Reference Laboratory after detecting negatively stained or acid‐fast bacilli on cytological smears. Scrapings of material from slides usually provide sufficient mycobacterial DNA to enable identification of the causal organism using sequence analysis of amplicons after PCR using specific mycobacterial primers.

Therapy –  Therapy relies upon a combination of marginal resection of easily accessible lesions and treatment using two or three drugs effective against slowly growing mycobacteria, choosing amongst rifampicin, clarithromycin, clofazimine and pradofloxacin/moxifloxacin.
Characterization of canine filaggrin: gene structure and protein expression in dog skin
Authors: Kanda Satoko , Sasaki Takashi , Shiohama Aiko , Nishifuji Koji , Amagai Masayuki , Iwasaki Toshiroh , Kudoh Jun
Published: January 2013

Background –  Filaggrin (FLG) is a key protein for skin barrier formation and hydration of the stratum corneum. In humans, a strong association between FLG gene mutations and atopic dermatitis has been reported. Although similar pathogenesis and clinical manifestation have been argued in canine atopic dermatitis, our understanding of canine FLG is limited.

Hypothesis/Objectives –  The aim of this study was to determine the structure of the canine FLG gene and to raise anti‐dog FLG antibodies, which will be useful to detect FLG protein in dog skin.

Methods –  The structure of the canine FLG gene was determined by analysing the publicly available canine genome DNA sequence. Polyclonal anti‐dog FLG antibodies were raised based on the canine FLG sequence analysis and used for defining the FLG expression pattern in dog skin by western blotting and immunohistochemistry.

Results –  Genomic DNA sequence analysis revealed that canine FLG contained four units of repeated sequences corresponding to FLG monomer protein. Western blots probed with anti‐dog FLG monomer detected two bands at 59 and 54 kDa, which were estimated sizes. The results of immunohistochemistry showed that canine FLG was expressed in the stratum granulosum of the epidermis as a granular staining pattern in the cytoplasmic region.

Conclusions and clinical importance –  This study revealed the unique gene structure of canine FLG that results in production of FLG monomers larger than those of humans or mice. The anti‐dog FLG antibodies raised in this study identified FLG in dog skin. These antibodies will enable us to screen FLG‐deficient dogs with canine atopic dermatitis or ichthyosis.
Canine inflamed nonepitheliotropic cutaneous T‐cell lymphoma: a diagnostic conundrum
Authors: Moore Peter F. , Affolter Verena K. , Keller Stefan M.
Published: January 2013

Background –  Cutaneous T‐cell lymphoma (CTCL) in dogs is a heterogeneous disease complex, which consists of nonepitheliotropic (NE) and epitheliotropic forms. These lymphomas are readily recognized by the presence of dominant populations of cytologically atypical lymphocytes.

Objective –  The objective of this study was to introduce the key features of inflamed NE‐CTCL, which is easily confused with reactive, inflammatory histiocytic disease.

Animals –  Twenty‐four dogs (mean age 7.5 years) presented with inflamed NE‐CTCL. Lesions presented as nodules, plaques or masses. An initial diagnosis of cutaneous reactive histiocytosis (11 dogs) or histiocytic neoplasia (three dogs) was made by primary pathologists.

Methods –  Lesions were assessed by histology and immunohistochemistry to detect canine leukocyte antigens. Lesional genomic DNA was extracted and gene rearrangement analysis of the T‐cell receptor γ locus was assessed.

Results –  The cutaneous lesions consisted of pleocellular infiltration of the dermis with variable extension into the subcutis. The lesions often surrounded vessels and adnexae. Epitheliotropism was minimal or lacking. Small lymphocytes, plasma cells and intermediate to large, cytologically atypical lymphocytes were scattered between prominent histiocytic infiltrates. Atypical lymphocytes often had marked variation in the intensity of CD3 expression. Molecular clonality analysis of the T‐cell receptor γ locus revealed clonal expansion of T cells in 22 of 23 dogs tested.

Conclusion –  The recognition of inflamed NE‐CTCL and its differentiation from cutaneous reactive histiocytosis depends on careful assessment of lymphocyte morphology and immunostaining patterns. Confirmation of the diagnosis is best accomplished by T‐cell antigen receptor gene rearrangement analysis.
Advances in the management of skin cancer
Authors: Martin Pamela D. , Argyle David J.
Published: January 2013

Skin cancer is one of the most commonly diagnosed cancers in the world today in both humans and our pet population. Advances in molecular techniques are now affording us an opportunity to develop therapeutics targeted at specific cancer‐related cellular pathways. However, despite progress in conventional treatments, such as chemotherapy and radiation, and the new targeted therapies, some cancers, such as melanoma and cutaneous lymphoma, continue to cause significant mortality and morbidity.

This short synopsis is not complete but is aimed at providing an insight into current advanced treatments and horizon therapies for cutaneous malignancies in dogs and cats with comparative aspects.
Equine sarcoidosis: clinical signs, diagnosis, treatment and outcome of 22 cases
Authors: Sloet van Oldruitenborgh‐Oosterbaan Marianne M. , Grinwis Guy C. M.
Published: January 2013

Background – Equine sarcoidosis may present as a generalized or localized exfoliative dermatitis and/or as a granulomatous inflammation of multiple organs.

Objectives – To report the clinical signs, diagnosis, treatment and outcome for 22 horses with histologically confirmed sarcoidosis.

Animals – Twenty‐two horses of different breeds, between 3 and 17 years of age.

Methods – Diagnosis was based on clinical signs and histopathological findings.

Results – The following three forms of equine sarcoidosis were identified: generalized (13.6%), partially generalized (18.2%) and localized (68.2%). High‐dose systemic corticosteroids were used as the initial treatment in all three forms, followed by lower doses for a variable number of weeks. No local treatment was prescribed. Case outcome was variable; one of three cases of generalized sarcoidosis was euthanized immediately and the remaining two were euthanized after 2–3 months of unsuccessful treatment; all four cases of partially generalized sarcoidosis deteriorated despite treatment and were euthanized after 3.5–12 months; two cases with localized disease showed no response or insufficient response to treatment and were euthanized; four cases recovered fully with or without treatment, and one showed partial recovery without treatment; and eight cases improved whilst receiving prednisolone but required continuous low doses to maintain remission.

Conclusions and clinical importance – Recognition of the different forms of sarcoidosis based on history, clinical appearance and histopathology assisted in making an informed choice between treatment and euthanasia and prevented unnecessary local treatment. Equine sarcoidosis should be included in the differential diagnosis of a localized exfoliative dermatitis of unknown origin.
Serum anti‐Staphylococcus pseudintermedius IgE and IgG antibodies in dogs with atopic dermatitis and nonatopic dogs
Authors: Bexley Jennifer , Nuttall Timothy J. , Hammerberg Bruce , Fitzgerald J. Ross , Halliwell Richard E.
Published: January 2013

Background –  Dogs and humans with atopic dermatitis (AD) are predisposed to colonization and recurrent infection with Staphylococcus spp. Studies in humans suggest that staphylococcus‐specific immunoglobulin E (IgE) plays a key role in disease pathogenesis. Few such studies have been undertaken in dogs.

Hypothesis/Objectives –  The aim of this study was to compare levels of staphylococcus‐specific IgE and immunoglobulin G (IgG) in dogs with AD, nonatopic dogs with staphylococcal pyoderma, and nonatopic and noninfected control dogs.

Animals –  Sera were collected from 108 dogs with AD, 39 nonatopic dogs with staphylococcal pyoderma secondary to different underlying conditions, 67 age‐matched nonatopic control dogs, and nine control dogs reared in minimal disease conditions.

Methods –  Serum Staphylococcus pseudintermedius‐specific IgE and IgG antibodies were measured by enzyme‐linked immunosorbent assay.

Results –  Dogs with AD had significantly higher levels of anti‐staphylococcal IgE than nonatopic dogs with staphylococcal pyoderma and the two groups of control dogs. Levels of anti‐staphylococcal IgG were significantly higher in atopic dogs and nonatopic dogs with pyoderma compared with nonatopic control dogs and control dogs reared in minimal disease conditions, but there was no significant difference in levels of anti‐staphylococcal IgG between dogs with AD and nonatopic dogs with pyoderma.

Conclusions and clinical importance –  A significantly increased IgE response to S. pseudintermedius antigens in atopic dogs suggests an immunopathogenic role for anti‐staphylococcal IgE. The finding of elevated IgE and IgG in atopic dogs is also important as a prelude to studies on antigenic specificity and possible correlations with disease phenotype.
Photodynamic therapy for pythiosis
Authors: Pires Layla , Bosco Sandra de M. G. , da Silva Junior Nelson F. , Kurachi Cristina
Published: January 2013

Background –  Pythiosis is a life‐threatening disease caused by Pythium insidiosum. Photodynamic therapy (PDT) is an alternative treatment to surgery that uses the interaction of a photosensitizer, light and molecular oxygen to cause cell death.

Objectives –  To evaluate the effect of PDT on the in vitro growth of P. insidiosum and in an in vivo model of pythiosis.

Methods –  For in vitro studies, two photosensitizers were evaluated: a haematoporphyrin derivative (Photogem®) and a chlorine (Photodithazine®). Amphotericin B was also evaluated, and the control group was treated with sterile saline solution. All experiments (PDT, porphyrin, chlorine and light alone, amphotericin B and saline solution) were performed as five replicates. For in vivo studies, six rabbits were inoculated with 20,000 zoospores of P. insidiosum, and an area of 1 cm3 was treated using the same sensitizers. The PDT irradiation was performed using a laser emitting at 660 nm and a fluence of 200 J/cm2. Rabbits were clinically evaluated daily and histopathological analysis was performed 72 h after PDT.

Results –  For in vitro assays, inhibition rates for PDT ranged from 60 to 100% and showed better results in comparison to amphotericin B. For the in vivo assays, after PDT, histological analysis of lesions showed a lack of infection up to 1 cm in depth.

Conclusions and clinical importance –  In vitro and in vivo studies showed that PDT was effective in the inactivation of P. insidiosum and may represent a new approach to treating pythiosis.
Epithelial‐to‐mesenchymal transition: immunohistochemical investigation of related molecules in canine cutaneous epithelial tumours
Authors: Bongiovanni Laura , D’Andrea Alessandra , Romanucci Mariarita , Malatesta Daniela , Candolini Melissa , Salda Leonardo D. , Mechelli Luca , Sforna Monica , Brachelente Chiara
Published: January 2013

Background –  Epithelial‐to‐mesenchymal transition (EMT) is a multistep process, important in tumour invasion and metastasis, characterized by loss of epithelial markers, redistribution of β‐catenin and gain of mesenchymal markers.

Hyposthesis/Objectives –  Our aim was to investigate the immunohistochemical aberrant expression of cytokeratin, vimentin, survivin and heat shock protein 72 (Hsp72) in canine cutaneous epithelial tumours, to understand the association of expression of these molecules with features of malignancy and their role in the EMT phenotype.

Methods –  Ten canine squamous cell carcinomas (SCCs; one with lymph node metastasis), 30 canine hair follicle tumours (six pilomatricomas, eight infundibular keratinizing acanthomas, six trichoepitheliomas and 10 trichoblastomas) and five normal skin samples were investigated by immunohistochemistry using specific anti‐vimentin, ‐cytokeratin, ‐survivin and ‐Hsp72 antibodies. A semi‐quantitative method was used to analyse the results, as follows: 0 to <5%; ≥5 to <10%; ≥10 to <25%; and ≥25% of positive cells. Immunofluorescence was performed to investigate survivin–vimentin and survivin–Hsp72 colocalization in selected SCCs.

Results –  In malignant hair follicle tumours and SCCs, a reduced intensity of cytokeratin and increased survivin and Hsp72 expression were observed. In SCCs, loss of cytokeratin expression and vimentin immunolabelling, suggestive of the EMT phenotype, were evident in <5% of neoplastic cells in the front of tumour invasion. In the same areas, strong nuclear survivin and cytoplasmic Hsp72 staining was evident, often colocalizing. Only a few neoplastic cells in the front of tumour invasion showed vimentin–survivin colocalization.

Conclusions and clinical importance –  A possible simultaneous involvement of survivin and Hsp72 in tumour invasion and the multistep process of EMT of cutaneous epithelial tumours of dogs is suggested.
Non‐surgical periodontal therapy decreases serum elastase levels in aggressive but not in chronic periodontitis
Authors: Eickholz Peter , Siegelin Yasemin , Scharf Susanne , Schacher Beate , Oremek Gerhard M. , Sauer‐Eppel Hildegund , Schubert Ralf , Wohlfeil Martin
Published: January 2013

Aim

Assessment of the effect of non‐surgical periodontal therapy (SRP) on serum inflammatory parameters in patients with untreated aggressive (AgP) and chronic (ChP) periodontitis.

Methods

Overall, 31 ChP and 29 AgP were examined clinically prior to and 12 weeks after SRP (subgingival scaling of all pockets within 2 days) with systemic antibiotics for patients positive for Aggregatibacter actinomycetemcomitans (14 AgP, 9 ChP). Blood was sampled prior to, one day, 6, and 12 weeks after the first SRP visit. Serum elastase, C‐reactive protein (CRP), lipopolysaccharide‐binding protein (LBP), interleukin (IL) 6, 8, and leukocyte counts were assessed.

Results

At baseline, serum elastase, CRP, and LBP were significantly (p < 0.01) higher in AgP than ChP. Serum elastase, CRP, LBP, and IL‐6 were significantly (p < 0.001) elevated one day after scaling in both groups. Both groups showed significant clinical improvement (p < 0.001). A significant difference was observed regarding change of serum elastase 12 weeks after SRP between AgP and ChP (p = 0.015). Multiple regression analysis revealed AgP, African origin, and bleeding on probing to be associated with more pronounced elastase reduction. CRP reduction was associated with African origin, systemic antibiotics, and baseline probing pocket depth.

Conclusion

SRP results in serum elastase reduction in AgP but not in ChP.
Biologic width dimensions – a systematic review
Authors: Schmidt Julia C. , Sahrmann Philipp , Weiger Roland , Schmidlin Patrick R. , Walter Clemens
Published: January 2013

Background

Consideration of the biologic width in restorative dentistry seems to be important for maintaining periodontal health.

Objective

To evaluate the dimensions of the biologic width in humans.

Materials and Methods

A systematic literature search was performed for publications published by 28 September 2012 using five different electronic databases; this search was complemented by a manual search. Two reviewers conducted the study selection, data collection, and validity assessment. The PRISMA criteria were applied. From 615 titles identified by the search strategy, 14 publications were included and six were suitable for meta‐analyses.

Results

Included studies were published from the years 1924 to 2012. They differed with regard to measurements of the biologic width. Mean values of the biologic width obtained from two meta‐analyses ranged from 2.15 to 2.30 mm, but large intra‐ and inter‐individual variances (subject sample range: 0.2 – 6.73 mm) were observed. The tooth type and site, the presence of a restoration and periodontal diseases/surgery affected the dimensions of the biologic width. Pronounced heterogeneity among studies regarding methods and outcome measures exists.

Conclusions

No universal dimension of the biologic width appears to exist. Establishment of periodontal health is suggested prior to the assessment of the biologic width within reconstructive dentistry.