Pruritic Skin Disease Research Articles

Convergent Synthesis, Kinetics, and Computational Studies of Indole(Phenyl)Triazole Bi-Heterocycles Modified With Propanamides as Elastase Inhibitors.

Biological screening combined with the synthesis of heterocyclic compounds with numerous functions is the most effective approach available for pharmacological assessment of potential future medications. In the under taken research that is presented here, 4-(1H-indol-3-yl)butanoic acid was sequentially converted into 4-(1H-indol-3-yl)butanoate, 4-(1H-indol-3-yl)butanohydrazide, and 5-[3-(1H-indol-3-yl)propyl]-1,2,4-triazole-2-thiol as a nucleophile. By treating aryl amines with 3-bromopropanoyl chloride in a series of parallel reactions, different electrophiles were created, leading to the formation of N-(aryl)-3-bromopropanamides. After that, several electrophiles were used in the nucleophilic substitution process of 5 to produce the final bi-heterocyclic derivative. The structural confirmation of all the synthesized compounds was done by IR, 1H-NMR, 13C-NMR, and CHN analysis data. The enzyme inhibitory effects of these bi-heterocyclic propanamides were evaluated against elastase, and all these molecules were identified as potent inhibitors relative to the standard oleanolic acid with IC50 value 13.453±0.015µM used. The kinetics mechanism was ascribed by evaluating the Lineweaver-Burk plots, which revealed that compound 9d inhibited elastase competitively to form an enzyme-inhibitor complex. The inhibition constant Ki calculated from Dixon plots for this compound was 0.51µM. Compound 9d's activity (IC50=0.142±0.014µM) significantly increased when a slightly bulky ethyl group was replaced for the solitary methyl group in 9c at the para-position. However, compound 9e's activity was significantly lower (IC50=38.338±0.993µM) when a more polar ethoxy group was replaced at the same para-position. This was likely because of electronic considerations. These molecules also exhibited mild cytotoxicity toward red blood cell membranes, when analyzing through hemolysis. So, these molecules might be deliberated as nontoxic medicinal scaffolds for dealing with the elastase-related ailments such as lung diseases, cyclic neutropenia, pruritic skin disease, and liver infection.

Efficacy and Safety of Ruxolitinib Cream by Anatomic Region in Children Aged 2 to 11 Years With Atopic Dermatitis: Results From TRuE-AD3

Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease. Ruxolitinib (Janus kinase [JAK]1/JAK2 inhibitor) cream has demonstrated efficacy and safety in patients aged ≥2 years with AD. In adolescents (aged ≥12 y) and adults with AD, application of ruxolitinib cream resulted in significant improvements across all anatomic regions vs vehicle. The objective of this analysis was to evaluate the efficacy and safety of ruxolitinib cream by anatomic region in the randomized, double-blind, phase 3 TRuE-AD3 study (NCT04921969). Children aged 2–11 years with AD for ≥3 months and an Investigator’s Global Assessment score of 2/3 were randomized 2:2:1 to apply 0.75% or 1.5% ruxolitinib cream twice daily (BID) or vehicle BID for 8 weeks. Efficacy was evaluated using the Eczema Area and Severity Index (EASI) subscores for head/neck, trunk, upper limbs, and lower limbs. Of 330 patients in TRuE-AD3, the mean (SD) age was 6.5 (2.9) years, and 179 patients (54.2%) were female; the mean (SD) EASI score was 8.6 (5.4). Improvements in EASI score were demonstrated with 0.75% and 1.5% ruxolitinib cream vs vehicle at first observation (Week 2), with statistically significant differences (at 0.05 alpha level and all P values below are nominal) at Week 8 in the head and neck (−0.63 [P=0.0108] and −0.70 [P=0.0011] vs −0.41), trunk (−0.98 [P=0.0310] and −1.18 [P=0.0003] vs −0.70), upper limbs (−1.81 [P<0.0001] and −2.06 [P<0.0001] vs −1.18), and lower limbs (−2.91 [P<0.0001] and −3.23 [P<0.0001] vs −1.43). Improvements in induration/papulation/edema, erythema, excoriation, and lichenification were observed for both strengths of ruxolitinib cream vs vehicle in all regions at Week 2, with statistical significance (at 0.05 alpha level) in nearly all AD signs and regions at Week 8. Ruxolitinib cream was well tolerated in both treatment groups (n=264), with 4.5% of patients experiencing application site reactions, which was similar to the frequency of application site reactions (4.3%) among patients with head/neck involvement (n=161) . In conclusion, ruxolitinib cream demonstrated significant improvements in AD vs vehicle in children with AD across anatomic regions, including on the head/neck, and was well tolerated. (Funding, Incyte Corporation)

Cytological Characteristics of the Eye Conjunctiva in Dogs with Atopic Dermatitis

Atopic dermatitis is a chronic, pruritic inflammatory skin disease affecting approximately 10% of dogs worldwide. The disease typically manifests at an early age, causing pruritus and secondary skin lesions in specific anatomical regions. The pathophysiology of canine atopic dermatitis (CAD) remains incompletely understood, but recent research suggests a complex interplay between skin barrier dysfunction, allergic sensitisation, and microbial dysbiosis. Despite the well-established association between atopic dermatitis and conjunctivitis, the prevalence of conjunctivitis in dogs with CAD is often underestimated in clinical practice due to inadequate recognition of symptoms and a lack of specific diagnostic protocols. This study aimed to analyse the cytological characteristics of the conjunctiva in dogs affected by atopic dermatitis. Samples were collected from 24 dogs diagnosed with CAD and treated at the University Veterinary Hospital, Faculty of Veterinary Medicine, University of Zagreb. Cytological analysis was performed on samples obtained using a cytobrush. The results revealed the presence of inflammatory cells in all samples, with lymphocytes most prevalent (87.5%). A mild degree of conjunctival metaplasia was observed in all dogs, regardless of the type of inflammatory cells and the severity of conjunctivitis. These findings suggest that atopic dermatitis may induce changes in the conjunctiva that are not necessarily correlated with the intensity of the inflammatory response. The presence of lymphocytes, along with eosinophils in some cases, underscores the diagnostic value of conjunctival cytology in dogs with CAD. Furthermore, the increased density of goblet cells suggests similarities in the pathophysiology of ocular allergies in dogs and humans, opening avenues for further research to better understand and treat these conditions. This study highlights the importance of an interdisciplinary approach in the diagnosis and treatment of atopic dermatitis, including regular ophthalmologic examinations as part of standard clinical practice.

Multi-step synthesis, kinetics and in silico explorations of indole-Phenyl-1,2,4-triazole Bi-heterocyclic hybrids unified with 3-substituted benzamides as elastase inhibitors

In the present research work, a library of unique indole-phenyltriazole hybrids comprising 3-substituted-benzamide moiety was synthesized through convergent multi-step strategy. The structural confirmation of all synthesized molecules was corroborated by IR, 1H NMR, 13C MMR, EI-MS and CHN analysis data. The results of in vitro inhibitory potential of novel benzamides against elastase enzyme revealed that all molecules were potent inhibitors and 10d was most active compound among them having IC50 value of (0.197 ± 0.027 µM), relative to the standard (13.421 ± 0.016 µM). The Kinetics mechanism analyzed by Lineweaver-Burk plots which exposed that 10d inhibited this enzyme competitively by forming an enzyme-inhibitor complex. The inhibition constant Ki determined from Dixon plot for compound 10d was 0.85 µM. Moreover, cytotoxicity of these compounds was also profiled by hemolytic activity and it was observed that almost all these benzamides compounds displayed low cytotoxicity. These molecules also exhibited mild cytotoxicity toward red blood cell membrane. In addition, the in silico computational explorations fully supported the in vitro enzyme inhibitory results. The binding energy ranges from -7.1 to -9.1 kcal/mol, which showed that compound possessed good interaction tendencies to the pancreatic elastase target protein. So, it was anticipated from the experimental results and computational investigations of the current research that these derivatives might lead to further research gateways for obtaining better and safe nontoxic medicinal scaffolds for dealing with the elastase related ailments such as lungs diseases, pruritic skin disease and liver infection.

Single-Cell RNA Sequencing Reveals Molecular Signatures that Distinguish Allergic from Irritant Contact Dermatitis

Allergic contact dermatitis (ACD) is a pruritic skin disease caused by environmental chemicals that induce cell-mediated skin inflammation within susceptible individuals. Irritant contact dermatitis (ICD) is caused by direct damage to the skin barrier by environmental insults. Diagnosis can be challenging as both types of contact dermatitis can appear similar by visual exam, and histopathological analysis does not reliably distinguish ACD from ICD. To discover specific biomarkers of ACD and ICD, we characterized the transcriptomic and proteomic changes that occur within the skin during each type of contact dermatitis. We induced ACD and ICD in healthy human volunteers and sampled skin using a non-scarring suction blister biopsy method that collects interstitial fluid and cellular infiltrate. Single cell RNA-sequencing analysis revealed that cell-specific transcriptome differences rather than cell type proportions best distinguished ACD from ICD. Allergy-specific genes were associated with upregulation of IFNG, and cell signaling network analysis implicated several other genes such as IL4, despite their low expression levels. We validated transcriptomic differences with proteomic assays on blister fluid and trained a logistic regression model on skin interstitial fluid proteins that could distinguish ACD from ICD and healthy control skin with 93% sensitivity and 93% specificity.

Sleep and quality of life in adults with atopic dermatitis: cross sectional study.

Background.Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease that causes sleep disturbances and worsens quality of life.However, few studies have been conducted on sleep in adults with atopic dermatitis. This study aimed to evaluate sleep and quality of life in adults with AD. Methods. A cross-sectional study was conducted with 36 adults diagnosed with AD and 21 healthy volunteers (controls), who completed questionnaires on sleep, itching, and quality of life. Disease severity was estimated using SCORing Atopic Dermatitis (SCORAD). All participants wore actigraphy watches for one week to objectively assess sleep quality. Results. Adults with AD slept worse than controls as measured by self-report (Global Pittsburgh Sleep Quality Index, mean ± SD, 9.33 ± 3.59 vs 5.00 ± 2.30, p < 0.001) and by actigraphy (sleep efficiency, SE), mean ± SD, 74.48 ± 11.63 vs 85.6 ± 6.53, p < 0.001). Actigraphy showed that adults with AD slept, on average, almost one hour less (p = 0.010), stayed awake during sleep for almost 44 minutes more (p < 0.001), and woke up 25% more than the controls (p = 0.047). In the AD group, SE and total sleep time were significantly inversely correlated with SCORAD (rs = -0.601, p < 0.001 and rs = -0.604, p < 0.001, respectively), but no significant correlation was found between itch and SE. A decreased quality of life was observed in adults with AD (DLQI, mean ± SD, 8.75 ± 6.7). Conclusions. Adults with AD slept worse than the controls and had a diminished quality of life. Actigraphy is a useful tool to objectively measure sleep quality in adults with AD especially those with moderate to severe disease.

Notoedres Cati Infestation in a Cat and its Management: A Case Report

Notoedric mange is a highly contagious and pruritic skin disease caused by burrowing mites Notoedres cati of family Sarcoptidae. Notoedric cati primarily affects cats, although it can also affect humans and other species. Present paper deals with clinical signs, diagnosis, and treatment of Notoedric mange in a kitten, aged about three and half months. In this case report, 1 kg male Persian kitten was presented to the Referral Veterinary Polyclinic of ICAR- Indian Veterinary Research Institute (IVRI), Izatnagar with a complaint of itching and alopecia for past 15 days. On physical examination skin thickening, dry crusty and scaly lesions on the face, neck and limbs could be noticed. The appetite and defecation was normal and all the clinical parameters (rectal temperature, pulse rate, heart rate etc.) were within the normal range. On laboratory examination, skin scraping was positive for Notoedres cati. Based on the history, clinical manifestations and skin scraping examination, the case was diagnosed as Notoedres cati infestation. Therapeutic management was done with Inj. ivermectin @ 200 μg/kg, b. wt, subcutaneously once in a week for four weeks along with supportive therapy by oral administration of antihistamine hydroxyzine hydrochloride @ 2.2 mg/kg b. wt thrice in a day and supplementation of multivitamin, minerals, omega 3 and omega 6 fatty acids. Owner was advised to give bath with benzyl peroxide shampoo twice in a week. Kitten showed some improvement following the second dose of ivermectin, and complete remission of clinical signs was noticed following the fourth treatment.

Understanding canine atopic dermatitis

It is important for veterinary nurses to understand that canine apotic dermatitis is a disease that can resemble many other pruritic skin diseases and to be aware of the many skin issues that can occur when carrying out consultations, conducting telephone triages and booking consultations, as first opinion practices are inundated with itchy dog phone calls. Research has found that pruritic skin disease accounts for just under half of dermatological problems in first opinion practice. Canine apotic dermatitis can very easily be misdiagnosed and mistreated for other skin issues or diseases.

Vinpocetine, a phosphodiesterase 1 inhibitor, mitigates atopic dermatitis-like skin inflammation.

Atopic dermatitis (AD) is the most common inflammatory pruritic skin disease worldwide, characterized by the infiltration of multiple pathogenic T lymphocytes and histological symptoms such as epidermal and dermal thickening. This study aims to investigate the effect of vinpocetine (Vinp; a phosphodiesterase 1 inhibitor) on a 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like model. DNCB (1%) was administered on day 1 in the AD model. Subsequently, from day 14 onward, mice in each group (Vinp-treated groups: 1 mg/kg and 2 mg/kg and dexamethasone- treated group: 2 mg/kg) were administered 100 µl of a specific drug daily, whereas 0.2% DNCB was administered every other day for 30 min over 14 days. The Vinp-treated groups showed improved Eczema Area and Severity Index scores and trans-epidermal water loss, indicating the efficacy of Vinp in improving AD and enhancing skin barrier function. Histological analysis further confirmed the reduction in hyperplasia of the epidermis and the infiltration of inflammatory cells, including macrophages, eosinophils, and mast cells, with Vinp treatment. Moreover, Vinp reduced serum concentrations of IgE, interleukin (IL)-6, IL-13, and monocyte chemotactic protein-1. The mRNA levels of IL-1β, IL-6, Thymic stromal lymphopoietin, and transforming growth factor-beta (TGF-β) were reduced by Vinp treatment. Reduction of TGF-β protein by Vinp in skin tissue was also observed. Collectively, our results underscore the effectiveness of Vinp in mitigating DNCB-induced AD by modulating the expression of various biomarkers. Consequently, Vinp is a promising therapeutic candidate for treating AD.

Prevalence, incidence and treatment patterns of prurigo nodularis in England: a retrospective database analysis.

Prurigo nodularis (PN) is a pruritic skin disease characterized by multiple intensely itchy skin nodules in symmetrically distributed areas of the extremities. There are limited studies on the epidemiology and treatment pathways of PN, especially moderate-to-severe PN, from England. To assess the epidemiology and treatment pathways of mild and moderate-to-severe PN in England. This retrospective cohort study used data from the Clinical Practice Research Datalink and Hospital Episode Statistics in England. Adult patients (aged ≥ 18 years) with a PN-specific diagnosis code allocated any time between 1 April 2007 and 1 March 2019 (patient identification period) were selected. Patients were included if their first PN diagnostic code (index diagnosis date; IDD) was recorded during the identification period, with data available 6 months before and ≥ 12 months after the IDD. Patients were classified as having moderate-to-severe PN (MSPN) or mild PN (MiPN), based on the presence or absence of a prescription record, post-IDD, for either a systemic immunosuppressant or a gabapentinoid. Patients with MSPN and MiPN were matched 1 : 1 according to age, sex and IDD. Prevalence and incidence were calculated for each year from 2007 to 2019. Drugs prescribed post-IDD were analysed. A total of 8933 patients (MSPN, n = 2498; MiPN, n = 6435) were included in the study; 2462 patients with MiPN and 2462 with MSPN were included for the comparative analysis. The presence of atopic dermatitis, asthma and eosinophilic oesophagitis were significantly higher (all P < 0.001) in patients with MSPN compared with those with MiPN. The overall prevalence of cases of PN increased during the study period. The incidence rate also showed a similar trend. The rates of prescription of potent and super-potent topical corticosteroids (TCS), topical calcineurin inhibitors, first- and second-generation antihistamines, oral and injectable systemic corticosteroids, methotrexate, antidepressants and tacrolimus were significantly higher (all P < 0.001) in patients with MSPN compared with those with MiPN. The epidemiology of PN was consistent with that found in other European studies. Patients with MSPN received a significantly higher number of prescriptions for potent TCS and systemic drugs compared with patients with MiPN.

Exploring the Potentiality of a Plant Platform for Monoclonal Antibody Production in Veterinary Medicine.

Canine atopic dermatitis (CAD) is an allergic, inflammatory, and pruritic skin disease associated with the production of IgE antibodies against environmental allergens and mainly house dust mite allergens. This complex dermatological pathology involves Interleukin 31 (IL-31) as a central itch mediator. One of the most effective CAD treatments is a caninized monoclonal antibody (mAb) called Lokivetmab. It is produced in CHO cells and targets specifically canine IL-31 (cIL-31) and blocks its cellular messaging. This treatment has undoubtedly contributed to a breakthrough in dermatitis-related pruritus. However, its production in mammalian cells requires time-consuming procedures, high production costs, and investment. Plants are considered an emerging protein production platform for recombinant biopharmaceuticals due to their cost-effectiveness and rapidity for production. Here, we use transient expression in Nicotiana benthamiana plants to produce recombinant canine Interleukin 31 (cIL-31) and an anti-IL-31 monoclonal antibody (M1). First, we describe the production and characterization of M1 and then its activity on an IL-31-induced pruritic model in dogs compared to its commercial homolog. Dogs treated with the plant-made M1 mAb have shown similar improvements to Lokivetmab-treated ones after different challenges using canine IL-31. Furthermore, M1 injections were not associated with any side effects. These results demonstrate the safety and efficacy of this plant-made Lokivetmab biosimilar to control dogs' pruritus in a well-established model. Finally, this study shows that the plant-production platform can be utilized to produce rapidly functional mAbs and bring hope to the immunotherapy field of veterinary medicine.

Therapeutic management of atopic dermatitis.

Atopic dermatitis (AD), a chronic inflammatory, pruritic skin disorder, is seen primarily in the pediatric population but can be found among all age groups. The symptoms of AD can cause embarrassment in patients and can interrupt daily activities and productivity, potentially resulting in avoidance of social situations. In addition to nonpharmacologic management, mainstay pharmacologic treatments for AD are topical medications including corticosteroids, calcineurin inhibitors, phosphodiesterase-4 inhibitors, and topical Janus kinase (JAK) inhibitors. Promising new drugs-oral JAK inhibitors and monoclonal antibodies-have emerged as new treatment options for moderate-to-severe AD.

PDE4D and miR-203 are promising biomarkers for canine atopic dermatitis

BackgroundCanine atopic dermatitis (CAD) is a common genetically predisposed, inflammatory, and pruritic skin disorder that affects dogs globally. To date, there are no specific biomarkers available to diagnose CAD, and the current diagnosis is based on a combination of criteria including patient history, clinical signs, and exclusion of other relevant differential diagnoses.Methods and resultsWe examined the gene expression of phosphodiesterase 4D (PDE4D) in peripheral blood mononuclear cells (PBMCs), as well as miR-203 and miR-483 in plasma, in three groups: healthy dogs, CAD dogs, and other inflammatory pruritic skin diseases (OIPSD) such as pemphigus foliaceus, scabies, cutaneous lymphoma, and dermatophytosis. Our results showed that PDE4D gene expression in the CAD group is statistically higher compared to those in the healthy and OIPSD groups, suggesting PDE4D may be a specific marker for CAD. Nevertheless, no correlation was found between PDE4D gene expression levels and the lesion severity gauged by CAD severity index-4 (CADESI-4). We also showed that miR-203 is a generic marker for clinical dermatitis and differentiates both CAD and OIPSD inflammatory conditions from healthy controls.ConclusionsWe show that PDE4D is a potential marker to differentiate CAD from non-atopic healthy and OIPSD while miR-203 may be a potential marker for general dermatologic inflammation. Future study of PDE4D and miR-203 on a larger scale is warranted.

Dietary Galacto-oligosaccharides Ameliorate Atopic Dermatitis-like Skin Inflammation and Behavioral Deficits by Modulating Gut Microbiota-Brain-Skin Axis.

Atopic dermatitis (AD), a chronic, highly pruritic, and inflammatory skin disorder, often coexists with psychiatric comorbidities including anxiety and depression, posing considerable challenges for treatment. The current research aims at evaluating the efficacy and potential therapeutic mechanism of galacto-oligosaccharides (GOS) on AD-like skin lesions and comorbid anxiety/depressive disorders. Macroscopical and histopathological examination showed that GOS could markedly relieve skin inflammation by decreasing the production of IgE, IL-4, IL-13, IFN-γ, and TNF-α and regulating the PPAR-γ/NF-κB signaling in DNFB-induced AD mice. Moreover, GOS significantly improved the anxiety- and depressive-like symptoms as mirrored by the behavior tests including FST, TST, OFT, and EZM through normalizing the neurotransmitter levels of 5-HT, DA, NE, and CORT in the brain. Mechanistically, by virtue of the high-throughput 16S rRNA gene sequencing and GC-MS techniques, GOS restructured the gut microbiota and specifically induced the proliferation of Lactobacillus and Alloprevotella, leading to an increase in the total content of fecal SCFAs, in particular acetate and butyrate. Pearson correlation analysis found a marked correlation among the altered gut microbiota/SCFAs, AD-associated skin manifestations, and comorbid behavioral phenotypes. Collectively, this work highlights that GOS is a promising strategy against both AD and associated depressive symptoms by modulating the gut microbiota-brain-skin axis.

Should Emollients Be Recommended for the Prevention of Atopic Dermatitis?—New Evidence and Current State of Knowledge

Introduction: Atopic dermatitis (AD) is a chronic, pruritic skin disease with complex pathogenesis, which affects about 43 million children aged 1–4 years. One of the most known methods of alleviating symptoms of AD is emollient treatment, which varies depending on formulation and additional active ingredients. There is some evidence that emollients could be used in AD prevention in high-risk children. Materials and methods: A search of the literature from Cochrane Library, PubMed and Medline was conducted between August and September 2023 with the following keywords: “atopic dermatitis”, “emollients”, and “prevention”. Only randomised clinical trials published in the last 5 years were included into the meta-analysis. Results: Considering the inclusion criteria only 11 randomized clinical trials were taken into account, and six of them proved lack of effect of emollients in the prevention of atopic dermatitis among neonates from AD risk groups. Conclusions: Emollient treatment has a good safety profile and most of the ingredients used in formulations are nonirritant for sensitive newborn and infant skin. There is some evidence of the positive effects of emollient treatment in prevention of AD in predisposed populations. The relatively high cost of emollient treatment (vs regular infant skin-care routine) would support the necessity for further evaluation of their effectiveness in nonpredisposed populations.

Canine Atopic Dermatitis: Prevalence, Impact, and Management Strategies.

Atopic dermatitis (AD) is a common inflammatory and pruritic allergic skin disease in humans and dogs worldwide. The pathogenesis of AD is multifactorial, immunologically complex, and may involve genetic factors, epidermal barrier dysfunction, microbiome changes, immune dysregulation, and allergic sensitization. Across species, prevalence of AD is on the rise. At present, there is no cure for canine AD (CAD). The treatment for CAD is multifaceted and aimed at controlling the pruritus, associated inflammation, and infections, repairing the skin barrier function, and dietary management. This review presents data on prevalence, impact, and complex immunological interactions in AD with a focus on subsequent management of the disease in the canine population. A multimodal approach for management of CAD to address varying clinical signs and responses to therapies is discussed.

MANAGEMENT OF LICHEN AMYLOIDOSIS THROUGH AYURVEDA: A CASE STUDY

Lichen Amyloidosis is a chronic pruritic skin disorder of unknown origin characterized by Amyloid deposition in skin. Excessive scratching and consistent friction between skin can damage the epidermis of skin leading to extracellular protein accumulation which creates papules and rashes. A case of 74-year male patient presented with blackish papules associated with itching in bilateral shin region with no relevant family history and was diagnosed as Lichen Amyloidosis. As per Ayurveda on basis of Dosha, Kaphavataja Kushta i.e., Kitibha Kusta can be corelated to Lichen Amyloidosis. In conventional treatment as there is no known cure for amyloidosis, in the present case, treatment was planned based on the principles of Kusta chikitsa depending on Dosha dominence. Snehana, Swedana, Virechana and Shamana treatment was followed. Treatment shows marked improvement from symptoms which proves that Dosha/Lakshana based approach has good outcomes in chronic disorders of unknown origin also.

Efficacy of Allogeneic and Xenogeneic Exosomes for the Treatment of Canine Atopic Dermatitis: A Pilot Study.

Canine atopic dermatitis (CAD) is a genetically predisposed inflammatory pruritic skin disease. The available treatments for CAD have several adverse effects and vary in efficacy, indicating the need for the development of improved treatments. In this study, we aimed to elucidate the therapeutic effects of allogeneic and xenogeneic exosomes on CAD. Six laboratory beagle dogs with CAD were randomly assigned to three treatment groups: control, canine exosome (cExos), or human exosome (hExos) groups. Dogs in the cExos and hExos groups were intravenously administered 1.5 mL of cExos (5 × 1010) and hExos (7.5 × 1011) solutions, respectively, while those in the control group were administered 1.5 mL of normal saline three times per week for 4 weeks. Skin lesion score and transepidermal water loss decreased in cExos and hExos groups compared with those in the control group. The exosome treatments decreased the serum levels of inflammatory cytokines (interferon-γ, interleukin-2, interleukin-4, interleukin-12, interleukin-13, and interleukin-31) but increased those of anti-inflammatory cytokines (interleukin-10 and transforming growth factor-β), indicating the immunomodulatory effect of exosomes. Skin microbiome analysis revealed that the exosome treatments alleviated skin bacterial dysbiosis. These results suggest that allogeneic and xenogeneic exosome therapy may alleviate CAD in dogs.

Nutritional composition of plants and preliminary assessment of nutrition in free-ranging bare-nosed wombats (Vombatus ursinus)

Nutrition is essential for not only survival but also successful growth and reproduction. Dietary demands are increased in a diseased state due to the increased energy and nutritional requirements associated with immune response, inflammation and convalescence. The herbivorous bare-nosed wombat (Vombatus ursinus) is notably susceptible to sarcoptic mange, a disease caused by the mite, Sarcoptes scabiei, which causes debilitating pruritic skin disease and leads to secondary bacterial infections and increased wombat morbidity and mortality, as well as regionally variable population declines. It is unknown why wombats are so susceptible to sarcoptic mange and if nutrition may play a role in disease expression, particularly relating to seasonality. The objective of this study was to quantify the differences in the nutritive value, over four seasons, of plants (mostly grasses and sedges) that are available as food items for bare-nosed wombats. We collected plants over four seasons from five wombat habitats that were known to have wombats affected by sarcoptic mange. We found seasonal and site differences for macro and micronutrients in the plants analysed. Monitoring the diet quality of wombats in the wild is useful for managing their populations and understanding population dynamics in relation to food resource quality.

Seladelpar treatment reduces IL-31 and pruritus in patients with primary biliary cholangitis.

Pruritus is a debilitating symptom for many people living with primary biliary cholangitis (PBC). In studies with seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist, patients with PBC experienced significant improvement in pruritus and reduction of serum bile acids. Interleukin-31 (IL-31) is a cytokine known to mediate pruritus, and blocking IL-31 signaling provides relief in pruritic skin diseases. This study examined the connection between seladelpar's antipruritic effects and IL-31 and bile acid levels in patients with PBC. IL-31 levels were quantified in serum samples from the ENHANCE study of patients with PBC receiving daily oral doses of placebo (n = 55), seladelpar 5mg (n = 53) or 10mg (n = 53) for 3 months, and for healthy volunteers (n = 55). IL-31 levels were compared with pruritus using a numerical rating scale (NRS, 0-10) and with bile acid levels. Baseline IL-31 levels closely correlated with pruritus NRS ( r = 0.54, p < 0.0001), and total ( r = 0.54, p < 0.0001) and conjugated bile acids (up to 0.64, p < 0.0001). Decreases in IL-31 were observed with seladelpar 5mg (-30%, p = 0.0003) and 10mg (-52%, p < 0.0001) versus placebo (+31%). Patients with clinically meaningful improvement in pruritus (NRS ≥ 2 decrease) demonstrated greater dose-dependent reductions in IL-31 compared to those without pruritus improvement (NRS < 2 decrease). Strong correlations were observed for the changes between levels of IL-31 and total bile acids ( r = 0.63, p < 0.0001) in the seladelpar 10mg group. Seladelpar decreased serum IL-31 and bile acids in patients with PBC. The reductions of IL-31 and bile acids correlated closely with each other and pruritus improvement, suggesting a mechanism to explain seladelpar's antipruritic effects.