scholarly journals Combination Therapy of Acarbose and Cyclosporine a Ameliorates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1822 ◽  
Author(s):  
Hsin-Hua Chen ◽  
Chi-Chien Lin ◽  
Yu-Tang Tung ◽  
Ya-Hsuan Chao ◽  
Wen-Ching Huang ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Low Dose ◽  
Skin Lesions ◽  
Treg Cells ◽  
Psoriatic Skin ◽  
Th22 Cells ◽  
Immune Mediated ◽  
Cytokine Tumor Necrosis Factor ◽  
High Doses ◽  
Factor Α

Moderate to severe psoriasis, an immune-mediated inflammatory disease, adversely affects patients’ lives. Cyclosporin A (CsA), an effective immunomodulator, is used to treat psoriasis. CsA is ineffective at low doses and toxic at high doses. Acarbose (Acar), a common antidiabetic drug with anti-inflammatory and immunomodulatory effects, reduces imiquimod (IMQ)-induced psoriasis severity. Combinations of systemic drugs are generally more efficacious and safer than higher doses of single drugs. We observed that mice treated with a combination of Acar (250 mg/kg) and low-dose CsA (10 or 20 mg/kg) exhibited significantly milder IMQ-induced psoriasis-like dermatitis and smoother back skin than those treated with Acar (250 mg/kg), low-dose CsA (10 or 20 mg/kg), or IMQ alone. The combination therapy significantly reduced serum and skin levels of Th17-related cytokines (interleukin (IL)-17A, IL-22, and IL-23) and the Th1-related cytokine tumor necrosis factor-α (TNF-α) compared with Acar, low-dose CsA, and IMQ alone. Additionally, the combination therapy significantly reduced the percentages of IL-17- and IL-22-producing CD4+ T-cells (Th17 and Th22 cells, respectively) and increased that of Treg cells. Our data suggested that Acar and low-dose CsA in combination alleviates psoriatic skin lesions by inhibiting inflammation. The findings provide new insights into the effects of immunomodulatory drugs in psoriasis treatment.

Cutaneous Autoimmune Phenomena of the Anti-TNFa Biosimilars. Casebased Review

2020 ◽  
Vol 16 ◽  
Author(s):  
Eleftherios Pelechas ◽  
Alexandra Papoudou-Bai ◽  
Paraskevi V Voulgari ◽  
Alexandros A. Drosos
Keyword(s):  
Tumor Necrosis ◽  
Relevant Literature ◽  
Topical Steroid ◽  
Skin Lesions ◽  
Chronic Inflammatory Disease ◽  
Psoriatic Skin ◽  
Erythematous Skin ◽  
Factor Α ◽  
Autoimmune Phenomena ◽  
Necrosis Factor

: Psoriasis (Pso) is a common chronic inflammatory disease affecting the skin, both sexes and all ages. It can be associated with other chronic inflammatory musculoskeletal disorders and certain drugs, including tumor necrosis factor α (TNFα) antagonists. A 64-years-old man with seronegative rheumatoid arthritis (RA) refractory to leflunomide and prednisone was treated with SB-4 (Benepali), an etanercept biosimilar 50mg/week subcutaneously. He responded well to the treatment but a year later, he developed erythematous skin eruptions affecting mainly the palms of both hands. Skin biopsy showed a picture compatible with Pso. SB-4 was discontinued and the skin lesions disappeared with the addition of topical steroid therapy. This is the only case of psoriatic skin lesions associated with SB-4 treatment. Thus, we review and discuss the relevant literature of Pso cases related to SB-4 and other anti-TNFα biosimilars. Rheumatologists dealing with patients on anti-TNFα biosimilars should be aware and recognize these complications.

scholarly journals Overexpression of Hepatocyte growth factor in dental pulp stem cells ameliorates the severity of psoriasis by downregulating Th1 and Th17 cells and upregulating Treg cells

2021 ◽  
Author(s):  
Hongfang Meng ◽  
Fen Wei ◽  
Ying Zhou ◽  
Zhiqiang Ge ◽  
Jide Jin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Th17 Cells ◽  
Skin Lesions ◽  
Treg Cells ◽  
Psoriatic Skin ◽  
T Helper ◽  
Ifn Γ ◽  
Hepatocyte Growth

Abstract Background Psoriasis is a kind of autoimmune disease still lacking standard treatment. Recently, it was demonstrated that mesenchymal stem cells (MSCs) are capable of immunoregulation. The underlying mechanism might involve the secretion of soluble cytokines, such as hepatocyte growth factor (HGF). This study aims to investigate the therapeutic effect of dental pulp stem cells (DPSCs), and hepatocyte growth factor (HGF) overexpressed DPSCs (HGF-DPSCs) on psoriatic mice and the underlying mechanisms. Methods DPSCs were isolated and transfected by adenovirus vector carrying human HGF cDNA (Ad-HGF). DPSCs and HGF-DPSCs were transplanted into the psoriatic mice model. On 7th day of post-transplantation, the mice were euthanized and sacrificed. The psoriatic skin lesions were analyzed by hematoxylin-eosin (H&E) and immunohistochemical staining for histopathological changes, and quantitative real time-polymerase chain reaction (Q-PCR) was applied to detect the expression levels of T-bet, IFN-γ, GATA3, IL-4, RORγt, IL-17A, IL-17F, IL-23, Foxp3 and IL-10. The concentrations of IFN-γ, TNF-α, and IL-17A in the mice blood serum were measured by MILLIPLEX analysis. Human peripheral blood mononuclear cells (PBMCs) were cocultured with DPSCs or HGF-DPSCs under appropriate stimulations. The proliferation index and quantity of T helper 1 (Th1) cells, T helper 2 (Th2) cells, interleukin 17 (IL-17)-secreting helper T (Th17) cells, and regulatory T (Treg) cells were analyzed by flow cytometry. The concentrations of IFN-γ, IL-4, TGF-β1, and IL-6 in the coculture supernatants were quantitated by enzyme linked immunosorbent assay (ELISA) analysis. Results In psoriatic mice, HGF overexpression enhanced the amelioration of epidermal thickening, inflammation infiltration and keratinocyte differentiation by DPSCs treatment. In the psoriatic skin lesions, HGF overexpression enhanced the downregulation of T-bet, IFN-γ, RORγt, IL-17A, IL-17F, IL-23, and upregulation of Foxp3 and IL-10 by DPSCs treatment. When cocultured with PBMCs, HGF overexpression significantly enhanced the downregulation of Th1 and Th17 cells and upregulation of Treg cells by DPSCs, but did not affect their suppression effect on lymphocyte proliferation. Conclusion HGF overexpression enhanced the treatment effect of DPSCs on psoriasis by downregulating Th1 and Th17 cells’ activity and upregulating Treg cells’ activity.

Combination therapy for obesity

2017 ◽  
Vol 31 (11) ◽  
pp. 1503-1508 ◽  
Author(s):  
John PH Wilding
Keyword(s):  
Bariatric Surgery ◽  
Combination Therapy ◽  
Low Dose ◽  
Lifestyle Modification ◽  
Gut Hormones ◽  
First Line ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
High Doses

Obesity is a chronic disease with serious consequences and although lifestyle modification is considered first line treatment, it is often ineffective, especially in the long term. Relatively few people with obesity will undergo the most effective currently available treatment of bariatric surgery. Pharmacotherapy can bridge the gap between lifestyle modification and surgery, but many monotherapies have only modest efficacy or require high doses with unacceptable side effects. As with many other areas of medicine, combination therapy is now becoming accepted as a way of optimising efficacy for weight management, whilst minimising adverse effects. Combinations may use different medications with complementary modes of action. Currently available combination therapies are low-dose phentermine and sustained release topiramate and naltrexone/bupropion. Many other possibilities exist and promising options include combination of phentermine with a sodium glucose co-transporter 2 inhibitor or combination of a glucagon-like peptide 1 agonist with other gut hormones or with a sodium glucose co-transporter 2 inhibitor. The ultimate aim is to match the efficacy of bariatric surgery with a combination of medicines, but this remains an elusive goal.

Use of Propentofylline in Feline Bronchial Disease: Prospective, Randomized, Positive-Controlled Study

2010 ◽  
Vol 46 (5) ◽  
pp. 318-326 ◽  
Author(s):  
Ulrike Stursberg ◽  
Isabella Zenker ◽  
Silke Hecht ◽  
Katrin Hartmann ◽  
Bianka S. Schulz
Keyword(s):  
Combination Therapy ◽  
Low Dose ◽  
Respiratory Pattern ◽  
Controlled Study ◽  
Control Group ◽  
Bronchial Disease ◽  
Observation Period

Propentofylline is a methylxanthine derivative with bronchodilating actions similar to those of theophylline. Nineteen cats with bronchial disease were enrolled in this study. All cats received a low dose of prednisolone; 10 of the cats additionally received propentofylline. Propentofylline-treated cats significantly improved in their auscultation scores, respiratory pattern scores, and radiological bronchial markings score over the observation period, and they coughed less and slept less at the end of the study. No significant changes were noted in the control group. This study provides evidence that a combination therapy with prednisolone and propentofylline in cats with bronchial disease might be superior over monotherapy with prednisolone.

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