Decreased Skin Thickness Research Articles

The AHR as a therapeutic target for inflammatory skin diseases

To investigate effect of Yupingfeng granules, prepared with Chinese Medicines, on the wound healing and on the expression of aquaporin 3 (AQP3) and the skin barrier in the animal models of atopic dermatitis (AD).Acute skin lesions of AD models were prepared using 2,4-dinitrochlorobenzo (DNCB) in mice and animals were treated with either Yupingfeng granules or placebo for two weeks. Skin wound healing outcome was assessed by measuring skin thickness, weight (quality) of the skin, and trans-epidermal water loss (TEWL). Expression of AQP3 mRNA and protein was assessed by reverse transcriotion polymerase chain reaction (RT-PCR) and immunoblotting, respectively.Yupingfeng granule treatment resulted in significant acceleration of wound healing with 63.64% efficiency, which was significantly higher than that of placebo granule treatment (31.82%, P < 0.01 by Wilcoxon Rank-sum test). Skin thickness, weight of the wounded skin, and TEWL were significantly higher in the AD models compared to that of normal animals. Treatment with Yupingfeng granules resulted in significant decrease in skin thickness [(937 ±31) vs (360 ±21) urn, P < 0.01], weight of the wounded skin [(42 ± 4) vs (24 ± 5) mg, P < 0.01], and TEWL [(30 ±4) vs (13 ± 4) g • h−1 • m−2, P < 0.01]. Yupingfeng granules also significantly down-regulated mRNA and protein expression of AQP3 in the animal models.Our findings suggested that Yupingfeng granules could be used in AD treatment.

Necrolytic Migratory Erythema in a Cat with Glucagonoma Syndrome

Background: Glucagonomas are very rare neuroendocrine tumors of pancreatic endocrine islets alpha cells and they produced excessive amount of glucagon hormone. Necrolytic migratory erythema (NME) is a rare dermatosis that characterized by erosive, ulcerative and crusted lesions in different sites of the skin and the common cause of this situation related to glucagon secreted tumors. NME can occur commonly in man but some rare and recent reports available the occurrence of this situation in pet animals especially dogs. Both gross and histological findings in both human and animals are similar. This paper reports a NME case with glucagonoma and diabetes mellitus (DM) by clinical, histopathological and immunohistochemical examinations.Case: A 12-year-old, cat presented with complaints of skin lesions in neck region, hyperglycemia, weight loss and history of anorexia during the 2 months. Biochemical analysis results revealed high glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and creatinine levels but decreased blood urea nitrogen (BUN), total protein and potassium levels. After 2 weeks of anti-diabetic drug treatment, the blood glucose level became normal and skin lesions ameliorated but anorexia and weight loss continued. The cat exhibited general weakness and pain in abdominal area. Although the clinical sings ameliorated and skin lesions and serum biochemical findings returned the relatively normal levels compared the admission, the cat died after 2 weeks of treatment and necropsy performed. At necropsy, marked cachexia, loss of skin elasticity and decreased skin thickness were observed. During the examination of abdominal cavity of the cat, there was a mass 0.5x0.5 cm in diameter, hard and grayish color was diagnosed at the pancreas. In addition, numerous whitish foci were also present the pancreatic tissue. Additionally, enlargement and paleness were noticed at the liver. Hemorrhages were observed at the liver, stomach and gut. Histopathologically pancreatic mass composed of polygonal neoplastic cells supported by thin, fibrovascular stroma characteristic for neuroendocrine tumor. But type of the cells undistinguished by histopathology for that reason immunohistochemistry performed for to evaluated insulin and glucagon secreting cells. Immunohistochemical examination revealed that only small number of insulin secreting but numerous glucagon secreting cells in the tumoral tissue and the tumor diagnosed as glucagonoma. Marked decrease were also noticed in insulin secretin cells in pancreas and together with high serum glucose levels diabetes mellitus (DM) also diagnosed to the cat. Histopathological examination of the skin revealed that decreased skin thickness, alopecia, slight inflammatory reaction and necrosis of the spinous layer.Discussion: Glucagonomas are rare tumors of pancreas even in human, and the incidence of this tumor is very rare in cat. They are usually silent tumors and they generally caused by paraneoplastic phenomena than primary clinical symptoms. The most prominent features of the “glucagonoma syndrome” are NME and DM. In human NME is commonly diagnosed in patient with glucagonoma syndrome. Very rare NME reports available in cats and dogs. The present cat had obvious clinical symptoms and typical skin lesions for NME. This report includes the very characteristic case of NME in a cat due to glucagonoma and DM, closely resembling the glucagonoma syndrome occurred in humans. Possible cause of the liver damage was also related the DM characterized high serum glucose level. We thought that liver lesions were also supported the occurrence of characteristic skin lesions.

아로니아 및 모링가 종자 복합물의 항아토피 상승효과

Atopic dermatitis is a chronic, relapsing inflammatory skin disease. This study aimed to investigate the therapeutic benefits of Aronia melanocarpa (AM) and Moringa oleifera seed extract (MO) on experimental atopic dermatitis. We examined the effects of AM or MO and their combination on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in BALB/c mice as well as tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated HaCaT keratinocytes. Mice were orally treated with extract during repeated application of DNCB to shaved dorsal skin. Our results show that treatment with AM and MO in combination reduced histological manifestations such as epidermal hyperplasia and inflammatory cell infiltration. Furthermore, it significantly decreased skin thickness and serum immunoglobulin E (IgE) level compared to the AM or MO alone treated group. Combined extract of AM and MO suppressed expression of TNF-α/IFN-γ-induced T helper 2 (Th2) chemokines such as thymus and activation-regulated chemokine and macrophage-derived chemokine. To sum up, combination of AM and MO suppressed the inflammatory response and serum IgE as an indicator of several allergic diseases in DNCB-induced experimental atopic dermatitis and Th2 chemokine expression in HaCaT cells. This result suggests that combination of AM and MO could be a valuable strategy to improve atopic dermatitis.

Far-infrared suppresses skin photoaging in ultraviolet B-exposed fibroblasts and hairless mice.

Ultraviolet (UV) induces skin photoaging, which is characterized by thickening, wrinkling, pigmentation, and dryness. Collagen, which is one of the main building blocks of human skin, is regulated by collagen synthesis and collagen breakdown. Autophagy was found to block the epidermal hyperproliferative response to UVB and may play a crucial role in preventing skin photoaging. In the present study, we investigated whether far-infrared (FIR) therapy can inhibit skin photoaging via UVB irradiation in NIH 3T3 mouse embryonic fibroblasts and SKH-1 hairless mice. We found that FIR treatment significantly increased procollagen type I through the induction of the TGF-β/Smad axis. Furthermore, UVB significantly enhanced the expression of matrix metalloproteinase-1 (MMP-1) and MMP-9. FIR inhibited UVB-induced MMP-1 and MMP-9. Treatment with FIR reversed UVB-decreased type I collagen. In addition, FIR induced autophagy by inhibiting the Akt/mTOR signaling pathway. In UVB-induced skin photoaging in a hairless mouse model, FIR treatment resulted in decreased skin thickness in UVB irradiated mice and inhibited the degradation of collagen fibers. Moreover, FIR can increase procollagen type I via the inhibition of MMP-9 and induction of TGF-β in skin tissues. Therefore, our study provides evidence for the beneficial effects of FIR exposure in a model of skin photoaging.

Effects of Angelicae dahuricae Radix on 2, 4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions in mice model

BackgroundAtopic dermatitis (AD) is an inflammatory, chronically relapsing, and intensively pruritic skin disease that affect 10–30% of the global population. Angelicae dahuricae Radix (ADR) has been reported to be anti-inflammatory in Korean Medicine. In the present study, we investigated whether ADR suppresses the progression of AD in animal model.MethodsAD was induced by 2, 4-Dinitrochlorobenzene (DNCB). ADR was orally administered to mice to study the effect of ADR on AD. Histological Analysis, immunohistochemistry, blood analysis, RT-PCR, and ELISA assay were performed.ResultsADR significantly suppressed AD-like symptoms in BALB/c mice: ADR decreased skin thickness and spleen weight of mice. ADR reduced infiltration of mast cells, inflammatory cells and CD4+ cells into mouse skin. ADR lowered the number of WBCs in the blood of mice. ADR reduced the levels of IgE, IL-6, IL-10 and IL-12 in mice serum. ADR down-regulated mRNA expression of IL-4, IL-6 and TNF-α in mouse skin tissue.ConclusionOur present study clearly indicates that ADR suppresses the progression of AD induced by DNCB in BALB/c mice. This suggests that ADR might be a useful drug for the treatment of AD.

Protective effects of ginsenoside F2 on 12-O-tetradecanoylphorbol-13-acetate-induced skin inflammation in mice

Topical use of ginsenosides, the major bioactive substances in Panax ginseng, has been used for the treatment of irritated skin complaints. However, the protective mechanisms of ginsenosides remain unclear. In the present study, we investigated the anti-inflammatory role of ginsenoside F2 (GF2) on the skin inflammation. To induce irritant dermatitis, 12-O-tetradecanoylphorbol-13-acetate (TPA) was applied on the surface of the mouse ears with or without treatments of GF2 and dexamethasone for 24 h. Protective effects of GF2 on edema and inflammation were assessed by measuring ear thickness, weights of skin punch, and inflammatory responses. In gross findings, treatments with GF2 significantly decreased skin thickness and weight compared to those of TPA-treated groups, which was comparable with the protective effects of dexamethasone. In addition, expression of inflammatory mediators was remarkably reduced in GF2-treated ears compared to that of vehicle-treated ears of mice. Interestingly, immunohistochemistry and flow cytometry analyses revealed that TPA treatment significantly increased infiltration of interleukin-17 (IL-17) producing dermal γδ T cells, while frequencies of γδ T cells was decreased by GF2 treatment, subsequently ameliorating inflammation in skin. Concomitantly, TPA-mediated skin inflammation was significantly ameliorated in IL-17A knock out mice. Furthermore, GF2 treatment inhibited infiltration and generation of reactive oxygen species (ROS) of neutrophils in damaged ears compared with vehicle-treated mice. These results clearly suggest that GF2 treatment ameliorates TPA-induced dermal inflammation by inhibiting production of IL-17 and ROS in γδ T cells and neutrophils, respectively. Therefore, as a natural compound, application of GF2 may be a novel therapeutic approach for treating skin inflammation.

Contra-lateral hip fracture in the elderly: are decreased body mass index and skin thickness predictive factors?

A correlation between soft tissue thickness and osteoporosis has been suggested. We aimed to estimate if a low body mass index (BMI) and/or a decrease of skin thickness could estimate the risk of contra-lateral hip fracture. First, we performed a retrospective analysis of 1268 patients treated for a hip fracture. The 146 patients who had a contra-lateral hip fractures-study group-were compared with the 1078 patients who did not-control group. Four BMI categories were considered: obese, overweight, normal weight and low weight. Second, we enrolled prospectively 1000 consecutive patients in the emergency department. History of fractures, BMI, and skin aspect on the dorsum of both hands-classified as severe decrease thickness, moderate decrease thickness or normal-were recorded. pt?>In the first part, we found that patients with contra-lateral fractures had a significantly lower BMI than those in the control group (22.2 Vs 26.5kg/m2, p = 0.01). In the second part, 48 on 1000 patients had a hip fracture. Among them, six had a contra-lateral fracture. BMI was 23.4kg/m2 in bilateral hip fractures, 33.68kg/m2 in the unilateral fracture group, and 28.04kg/m2 in the non-fracture group (p = 0.04). Finally, patients with contra-lateral hip fractures had a severe decrease thickness of the skin. A low BMI and a decreased skin thickness increase independently the risk of fractures by three times. When associated, they increase the risk of fracture risk by five times. This combination had a sensitivity at 71% and a specificity at 90% for predicting hip fracture.

Morphological, physical and mechanical properties of nanocrystalline cellulose filled Nylon 6 foams

Nanocomposite foams based on Nylon 6 and nanocrystalline cellulose were prepared via extrusion and injection molding to study the effect of nanocrystalline cellulose concentration (0 to 5%), chemical foaming agent content (0, 1%, and 2%), and mold temperature (30℃ and 80℃) on the morphological, physical, and mechanical properties of the samples. Nanocrystalline cellulose content, especially between 1 and 3 wt%, was very effective in reducing the cell size and increasing the cell density of the foam structure. Nanocrystalline cellulose addition (0–5%) was found to increase density (4% for composites and 20% for foams), tensile strength (10% for composite and 13% for foams), tensile modulus (20% for composites and 34% for foams), and flexural modulus (37% for composites and 29% for foams), but decreased the impact strength (35–40% for composites and 20–40% for foams). Foaming agent addition (1%) was able to improve the specific tensile (10%) and flexural (12%) moduli, tensile strength (14%), elongation at break (6%), and impact strength (27%). Finally, higher mold temperature decreased skin thickness and, consequently, decreased the mechanical properties, mostly tensile strength of the foam samples (1% for composites and 18% for foams).

Incubation Temperature during Fetal Development Influences Morphophysiological Characteristics and Preferred Ambient Temperature of Chicken Hatchlings.

Skin and feather characteristics, which play a critical role in body temperature maintenance, can be affected by incubation circumstances, such as incubation temperature. However, no study to date has assessed the influence of incubation temperature during the fetal stage on morphometric characteristics and vascular development of the skin, feather characteristics, and their relationship to hormone levels and preferred temperature in later life in chickens. Broiler breeder eggs were exposed to low (36°C), control (37.5°C), or high (39°C) temperatures (treatments LT, CK, and HT, respectively) from day 13 of incubation onward, because it is known that the endocrine axes are already established at this time. During this period, eggshell temperature of HT eggs (38.8±0.33°C) was higher than of LT (37.4±0.08°C) and CK eggs (37.8 ±0.15°C). The difference between eggshell and incubator air temperature diminished with the increasing incubation temperature, and was approximately zero for HT. HT hatchlings had higher surface temperature on the head, neck, and back, and thinner and more vascularized skin than did CK and LT hatchlings. No differences were found among treatments for body weight, total feather weight, number and length of barbs, barbule length, and plasma T4 concentration. LT hatchlings showed lower plasma T3 and GH, as well as lower T3/T4 ratio and decreased vascularity in the neck, back, and thigh skin compared to CK hatchlings. On the other hand, HT hatchlings had decreased skin thickness and increased vascularity, and preferred a higher ambient temperature compared to CK and HT hatchlings. In addition, for all treatments, surface temperature on the head was higher than of the other body regions. We conclude that changes in skin thickness and vascularity, as well as changes in thyroid and growth hormone levels, are the result of embryonic strategies to cope with higher or lower than normal incubation temperatures. Additionally exposure to increased temperature during incubation is an environmental factor that can exert early-life influence on ambient temperature preference of broiler hatchlings in later life.

Human adipose mesenchymal stem cells as potent anti-fibrosis therapy for systemic sclerosis

ObjectivesDisplaying immunosuppressive and trophic properties, mesenchymal stem/stromal cells (MSC) are being evaluated as promising therapeutic options in a variety of autoimmune and degenerative diseases. Although benefits may be expected in systemic sclerosis (SSc), a rare autoimmune disease with fibrosis-related mortality, MSC have yet to be evaluated in this specific condition. While autologous approaches could be inappropriate because of functional alterations in MSC from patients, the objective of the present study was to evaluate allogeneic and xenogeneic MSC in the HOCl-induced model of diffuse SSc. We also questioned the source of human MSC and compared bone marrow- (hBM-MSC) and adipose-derived MSC (hASC). MethodsHOCl-challenged BALB/c mice received intravenous injection of BM-MSC from syngeneic BALB/c or allogeneic C57BL/6 mice, and xenogeneic hBM-MSC or hASC (3 donors each). Skin thickness was measured during the experiment. At euthanasia, histology, immunostaining, collagen determination and RT-qPCR were performed in skin and lungs. ResultsXenogeneic hBM-MSC were as effective as allogeneic or syngeneic BM-MSC in decreasing skin thickness, expression of Col1, Col3, α-Sma transcripts, and collagen content in skin and lungs. This anti-fibrotic effect was not associated with MSC migration to injured skin or with long-term MSC survival. Interestingly, compared with hBM-MSC, hASC were significantly more efficient in reducing skin fibrosis, which was related to a stronger reduction of TNFα, IL1β, and enhanced ratio of Mmp1/Timp1 in skin and lung tissues. ConclusionsUsing primary cells isolated from 3 murine and 6 human individuals, this preclinical study demonstrated similar therapeutic effects using allogeneic or xenogeneic BM-MSC while ASC exerted potent anti-inflammatory and remodeling properties. This sets the proof-of-concept prompting to evaluate the therapeutic efficacy of allogeneic ASC in SSc patients.

Abstract P4-02-08: MRI changes in breast skin following preoperative therapy for inflammatory breast cancer (IBC)

Abstract Purpose: Standard treatment for IBC includes preoperative systemic therapy (PST), followed by mastectomy (M) and adjuvant radiation (R). Determining the optimal sequencing of M and R after PST may be difficult when clinical changes suggest residual disease within breast skin. With the goal of selecting appropriate patients (pts) for M prior to R, we correlated pathologic disease response in breast skin with changes in skin thickness and enhancement determined by MRI. Methods: An IRB approved database of IBC pts evaluated at Dana Farber Cancer Institute (DFCI) from 1997-2013 was used for retrospective analysis. 40 pts met criteria: confirmed diagnosis of IBC, completed PST followed by M without preoperative R. Baseline and post-PST breast MRI imaging was reviewed. Using the ACR BI-RADS lexicon, we recorded skin thickness, qualitative enhancement and kinetic analysis using computer-aided detection post-processing software. Findings were correlated with pathologic response in skin found at M. Results: MRI showed baseline skin thickening in all 40 pts (median 6mm, range 3-13mm). Although 34 (85%) had persistent skin thickening post-PST (median 4 mm, range &amp;lt;3-13 mm), there was a significant overall reduction in skin thickness (p&amp;lt;0.001); median decrease =2mm, range 1-7mm. MRI showed qualitative skin enhancement at baseline in 39/40 pts. 29 (73%) had medium/fast initial phase kinetics: 25 persistent delayed phase kinetics, 2 wash-out, 2 plateau. 20 pts had residual qualitative skin enhancement post-PST; 11 pts (28%) had medium/fast initial phase kinetics, all persistent delayed kinetics. The decrease in skin thickness was significantly greater among the 19 pts achieving resolution of skin enhancement post-PST compared with the decrease in skin thickness among the 20 pts with residual skin enhancement (p=0.02). 8 pts (20%) had residual tumor within the skin at M. All 8 pts had thicker skin on post-PST MRI (median 5 mm, range 3-13mm) compared with pts without residual disease in the skin (median 3.5mm, range &amp;lt;3-11 mm). Qualitative skin enhancement post-PST was seen in 63% of pts (5/8) with residual skin disease compared with 47% of pts (15/32) without disease. Conclusion: Although IBC pts have skin thickening demonstrated by MRI at baseline, there is a statistically significant reduction in the skin thickness following successful PST. This correlates with a reduction in enhancement of the skin shown by MRI imaging. More substantial and persistent skin thickening with enhancement was seen in the setting of residual dermal lymphatic involvement following the completion of PST, though this study is too small to detect any significant correlation. Since an accurate assessment of residual disease in breast skin is vital in determining the optimal sequencing of M and R following PST in IBC pts, MRI evaluation of skin thickness and enhancement may be a useful tool to predict residual disease and guide surgical management of IBC. Citation Format: Yeh E, Rives A, Guo H, Regan M, Birdwell R, Nakhlis F, Bellon J, Warren L, Hirshfield-Bartek J, Jacene H, Dominici L, Overmoyer B. MRI changes in breast skin following preoperative therapy for inflammatory breast cancer (IBC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-02-08.

Effect of Dangguibohyul-Tang, a Mixed Extract of Astragalus membranaceus and Angelica sinensis, on Allergic and Inflammatory Skin Reaction Compared with Single Extracts of Astragalus membranaceus or Angelica sinensis

Dangguibohyul-tang (DBT), herbal formula composed of Astragalus membranaceus (AM) and Angelica sinensis (AS) at a ratio of 5 : 1, has been used for the treatment of various skin diseases in traditional medicine. We investigated the effect of DBT on allergic and inflammatory skin reaction in atopic dermatitis-like model compared to the single extract of AM or AS. DBT treatment showed the remission of clinical symptoms, including decreased skin thickness and scratching behavior, the total serum IgE level, and the number of mast cells compared to DNCB group as well as the single extract of AM- or AS-treated group. Levels of cytokines (IL-4, IL-6, IFN-γ, TNF-α, and IL-1β) and inflammatory mediators (NF-κB, phospho-IκBα, and phospho-MAPKs) were significantly decreased in AM, AS, and DBT groups. These results demonstrated that AM, AS, and DBT may have the therapeutic property on atopic dermatitis by inhibition of allergic and inflammatory mediators and DBT formula; a mixed extract of AM and AS based on the herb pairs theory especially might be more effective on antiallergic reaction as compared with the single extract of AM or AS.

Evidence Suggesting a Role of Iron in a Mouse Model of Nephrogenic Systemic Fibrosis.

Nephrogenic systemic fibrosis is associated with gadolinium contrast exposure in patients with reduced kidney function and carries high morbidity and mortality. We have previously demonstrated that gadolinium contrast agents induce in vivo systemic iron mobilization and in vitro differentiation of peripheral blood mononuclear cells into ferroportin (iron exporter)-expressing fibrocytic cells. In the present study we examined the role of iron in a mouse model of nephrogenic systemic fibrosis. Chronic kidney disease was induced in 8-week-old male Balb/C mice with a two-step 5/6 nephrectomy surgery. Five groups of mice were studied: control (n = 5), sham surgery control (n = 5), chronic kidney disease control (n = 4), chronic kidney disease injected with 0.5 mmol/kg body weight of Omniscan 3 days per week, for a total of 10 injections (n = 8), and chronic kidney disease with Omniscan plus deferiprone, 125 mg/kg, in drinking water (n = 9). Deferiprone was continued for 16 weeks until the end of the experiment. Mice with chronic kidney disease injected with Omniscan developed skin changes characteristic of nephrogenic systemic fibrosis including hair loss, reddening, ulceration, and skin tightening by 10 to 16 weeks. Histopathological sections demonstrated dermal fibrosis with increased skin thickness (0.25±0.06 mm, sham; 0.34±+0.3 mm, Omniscan-injected). Additionally, we observed an increase in tissue infiltration of ferroportin-expressing, fibrocyte-like cells accompanied by tissue iron accumulation in the skin of the Omniscan-treated mice. The deferiprone-treated group had significantly decreased skin thickness (p<0.05) and significantly decreased dermal fibrosis compared to the Omniscan-only group. In addition, iron chelation prevented tissue infiltration of ferroportin-expressing, fibrocyte-like cells. Our in vitro experiments demonstrated that exposure to Omniscan resulted in the release of catalytic iron and this was prevented by the iron chelator deferiprone. Deferiprone inhibited the differentiation of human peripheral blood mononuclear cells into ferroportin-expressing cells by immunohistochemical staining and western blot analysis. Our studies support an important role of iron in the pathophysiology of gadolinium chelate toxicity and nephrogenic systemic fibrosis.

Antioxidant and anti-ageing activities of citrus-based juice mixture

The production of excessive reactive oxygen species by exposure to oxidative stress and solar radiation are primary factors in skin damage. We examined the effects of a citrus-based juice mixture and its bioactive compounds on antioxidant and anti-ageing activities in human dermal fibroblasts and hairless mice via the regulation of antioxidant enzymes and the mitogen-activated protein kinase pathway. The citrus-based juice mixture reduced H2O2-induced cell damage and intracellular reactive oxygen species production in human dermal fibroblasts. Citrus-based juice mixture pretreatment suppressed the activation of the H2O2-mediated mitogen-activated protein kinase pathway by activating the expression of activator protein 1 and matrix metalloproteinases. Moreover, it increased the expression levels of antioxidant enzymes such as glutathione reductase, catalase and manganese superoxide dismutase. In addition, oral administration of the citrus-based juice mixture decreased skin thickness and wrinkle formation and increased collagen content on an ultraviolet light B-exposed hairless mouse. These results indicate that the citrus-based juice mixture is a potentially healthy beverage for the prevention of oxidative stress-induced premature skin ageing.

Effects of topical application of realgar on pruritus and inflammation of atopic dermatitis

Objectives: Realgar has been frequently used for skin disorders in history of herbal medicine. However, the efficacy of realgar has not been examined in atopic dermatitis(AD). In this study, the effects of realgar on AD were investigated, especially on pruritus and inflammation. Methods: AD lesions were induced in the shaved backs of BALB/c mice through repeated application of DNCB. The mice were treated for 11 days with 1% realgar (100 μL/day). Histological changes in skin thickness were observed. The anti-pruritic effects of realgar were evaluated by the change in numbers of scratching behavior of mice and expression of substance P. The expressions of cytokines IL-4 and IL-6 were measured. Also, anti-inflammatory effects of realgar were examined on expressions of NF-κB, phospho-IκBα and mitogen-activated protein kinases (MAPKs).Realgar decreased skin thickness (both dermal and epidermal) 38% and 17% respectively, compared to positive control, DNCB group. The scratching behavior of mice was reduced by 42% and expression of substance P was significantly less. Cytokines IL-4 and IL-6 were significantly reduced by 52.6% and 77.6%, respectively. The expressions of NF-κB, phospho-IκBα and MAPKs (phospho-ERK1/2, -p38 and -JNK) were significantly suppressed with marked effects on phospho-ERK1/2. Conclusions: The collective results suggest that realgar shows anti-pruritic and anti-inflammatory effects on AD. And realgar might be a potential therapeutic candidate for treatment of atopic dermatitis.

MIF Antagonist (CPSI-1306) Protects against UVB-Induced Squamous Cell Carcinoma

Macrophage migration inhibitory factor (MIF) is a homotrimeric proinflammatory cytokine implicated in chronic inflammatory diseases and malignancies, including cutaneous squamous cell carcinomas (SCC). To determine whether MIF inhibition could reduce UVB light-induced inflammation and squamous carcinogenesis, a small-molecule MIF inhibitor (CPSI-1306) was utilized that disrupts homotrimerization. To examine the effect of CPSI-1306 on acute UVB-induced skin changes, Skh-1 hairless mice were systemically treated with CPSI-1306 for 5 days before UVB exposure. In addition to decreasing skin thickness and myeloperoxidase (MPO) activity, CPSI-1306 pretreatment increased keratinocyte apoptosis and p53 expression, decreased proliferation and phosphohistone variant H2AX (γ-H2AX), and enhanced repair of cyclobutane pyrimidine dimers. To examine the effect of CPSI-1306 on squamous carcinogenesis, mice were exposed to UVB for 10 weeks, followed by CPSI-1306 treatment for 8 weeks. CPSI-1306 dramatically decreased the density of UVB-associated p53 foci in non-tumor-bearing skin while simultaneously decreasing the epidermal Ki67 proliferation index. In addition to slowing the rate of tumor development, CPSI-1306 decreased the average tumor burden per mouse. Although CPSI-1306-treated mice developed only papillomas, nearly a third of papillomas in vehicle-treated mice progressed to microinvasive SCC. Thus, MIF inhibition is a promising strategy for prevention of the deleterious cutaneous effects of acute and chronic UVB exposure. Macrophage migration inhibitory factor is a viable target for the prevention of UVB-induced cutaneous SSCs.

Knockout of Endothelial Cell-Derived Endothelin-1 Attenuates Skin Fibrosis but Accelerates Cutaneous Wound Healing

Endothelin (ET)-1 is known for the most potent vasoconstrictive peptide that is released mainly from endothelial cells. Several studies have reported ET-1 signaling is involved in the process of wound healing or fibrosis as well as vasodilation. However, little is known about the role of ET-1 in these processes. To clarify its mechanism, we compared skin fibrogenesis and wound repair between vascular endothelial cell-specific ET-1 knockout mice and their wild-type littermates. Bleomycin-injected fibrotic skin of the knockout mice showed significantly decreased skin thickness and collagen content compared to that of wild-type mice, indicating that bleomycin-induced skin fibrosis is attenuated in the knockout mice. The mRNA levels of transforming growth factor (TGF)-β were decreased in the bleomycin-treated skin of ET-1 knockout mice. On the other hand, skin wound healing was accelerated in ET-1 knockout mice, which was indicated by earlier granulation tissue reduction and re-epithelialization in these mice. The mRNA levels of TGF-β, tumor necrosis factor (TNF)-α and connective tissue growth factor (CTGF) were reduced in the wound of ET-1 knockout mice. In endothelial ET-1 knockout mouse, the expression of TNF-α, CTGF and TGF-β was down-regulated. Bosentan, an antagonist of dual ET receptors, is known to attenuate skin fibrosis and accelerate wound healing in systemic sclerosis, and such contradictory effect may be mediated by above molecules. The endothelial cell-derived ET-1 is the potent therapeutic target in fibrosis or wound healing, and investigations of the overall regulatory mechanisms of these pathological conditions by ET-1 may lead to a new therapeutic approach.

Immuno Modulatory Effects of Hot Aqueous Extract of Ocimum sanctum and Argemone mexicana Leaves in Chicken Model

800x600 The present study was undertaken to study the immuno modulatrory effects of leaves of Ocimum santum (OS) and Argemone mexiana (AM) plants in chicken model. 250 mg/kg body weight oral dose of OS and AM was found ideal and nontoxic in chickens and experimental chickens were fed this dose. Humoral immune response to S. enterica serovar Typhimurium ‘O’ antigen was measured by quantitating the serum antibody level of immunized chickens by ELISA test. There was a significant rise in antibody titre of OS and AM fed chickens in comparison to control group. The antibody titre in the serum samples of HAE of OS and AM fed chickens were (5333.33±674.62) and (4266.67±674.62) respectively, whereas in control group it was 3733.33±533.33. This study indicated that the extract of both plants enhanced the antibody level and acted as a humoral immuno stimulant. Cell mediated immune response (CMI) was assayed by differential lymphocyte count (DLC) and DNCB sensitized hypersensitivity test. DLC revealed increase in lymphocyte count in OS fed group and decrease in lymphocyte count in AM fed group as compared to control group. DNCB test demonstrated 29.89% increase in skin thickness in OS fed group and 34.02% decrease in skin thickness in AM fed group as compared to control group at 24 hour interval. Present study indicated the T cell suppressive impact of hot aqueous extract of AM and stimulator effect of OS. Normal 0 7.8 pt 0 2 false false false EN-US ZH-CN X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:Table Normal; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:Times New Roman,serif;}

Large increases in adipose triacylglycerol flux in Cushingoid CRH-Tg mice are explained by futile cycling

Glucocorticoids are extremely effective anti-inflammatory therapies, but their clinical use is limited due to severe side effects, including osteoporosis, muscle wasting, fat redistribution, and skin thinning. Here we use heavy water labeling and mass spectrometry to measure fluxes through metabolic pathways impacted by glucocorticoids. We combine these methods with measurements of body composition in corticotropin-releasing hormone (CRH)-transgenic (Tg)(+) mice that have chronically elevated, endogenously produced corticosterone and a phenotype that closely mimics Cushing's disease in humans. CRH-Tg(+) mice had increased adipose mass, adipose triglyceride synthesis, and greatly increased triglyceride/fatty acid cycling in subcutaneous and abdominal fat depots and increased de novo lipogenesis in the abdominal depot. In bone, CRH-Tg(+) mice had decreased bone mass, absolute collagen synthesis rates, and collagen breakdown rate. In skin, CRH-Tg(+) mice had decreased skin thickness and absolute collagen synthesis rates but no decrease in the collagen breakdown rate. In muscle, CRH-Tg(+) mice had decreased muscle mass and absolute protein synthesis but no decrease in the protein breakdown rate. We conclude that chronic exposure to endogenous glucocorticoid excess in mice is associated with ongoing decreases in bone collagen, skin collagen, and muscle protein synthesis without compensatory reduction (coupling) of breakdown rates in skin and muscle. Both of these actions contribute to reduced protein pool sizes. We also conclude that increased cycling between triglycerides and free fatty acids occurs in both abdominal and subcutaneous fat depots in CRH-Tg(+) mice. CRH-Tg mice have both increased lipolysis and increased triglyceride synthesis in adipose tissue.

Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial

ObjectiveTo assess the safety and effectiveness of imatinib mesylate in the treatment of diffuse cutaneous systemic sclerosis (dcSSc).MethodsIn this phase IIa, open-label, single-arm clinical trial, 30 patients with dcSSc were...