Preliminary evaluation of cytosine-phosphate-guanine oligodeoxynucleotides bound to gelatine nanoparticles as immunotherapy for canine atopic dermatitis

2017 ◽  
Vol 181 (5) ◽  
pp. 118-118 ◽  
Author(s):  
I. Wagner ◽  
K. J. Geh ◽  
M. Hubert ◽  
G. Winter ◽  
K. Weber ◽  
...  

Cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN) are a promising new immunotherapeutic treatment option for canine atopic dermatitis (AD). The aim of this uncontrolled pilot study was to evaluate clinical and immunological effects of gelatine nanoparticle (GNP)-bound CpG ODN (CpG GNP) on atopic dogs. Eighteen dogs with AD were treated for 8 weeks (group 1, n=8) or 18 weeks (group 2, n=10). Before inclusion and after 2 weeks, 4 weeks, 6 weeks (group 1+2), 8 weeks, 12 weeks and 16 weeks (group 2) 75 µg CpG ODN/dog (bound to 1.5 mg GNP) were injected subcutaneously. Pruritus was evaluated daily by the owner. Lesions were evaluated and serum concentrations and mRNA expressions of interferon-γ, tumour necrosis factor-α, transforming growth factor-β, interleukin (IL) 10 and IL-4 (only mRNA expression) were determined at inclusion and after 8 weeks (group 1+2) and 18 weeks (group 2). Lesions and pruritus improved significantly from baseline to week 8. Mean improvements from baseline to week 18 were 23 per cent and 44 per cent for lesions and pruritus, respectively, an improvement of ≥50 per cent was seen in six out of nine and three out of six dogs, respectively. IL-4 mRNA expression decreased significantly. The results of this study show a clinical improvement of canine AD with CpG GNP comparable to allergen immunotherapy. Controlled studies are needed to confirm these findings.

2020 ◽  
Vol 20 ◽  
Author(s):  
Abbas Shapouri-Moghaddam ◽  
Seyed Jalil Tavakkol Afshari ◽  
Mohammad-Hadi Saeed Modaghegh ◽  
Hamid Reza Rahimi ◽  
Mahmoud Mahmoudi ◽  
...  

Background: Studies suggest that cytokines are involved in the development of both inflammatory disorders and vascular diseases. Objective: The changes in transforming growth factor β (TGFβ), interleukin 6 (IL6), tumor necrosis factor α (TNFα), and interferon γ (IFNγ) with the progression of the thromboangiitis obliterans (TAO) symptomswereinvestigated in this research. Methods: This study included 80 patients with TAO, who were selected from the Vascular and Endovascular Research Center in Alavi Hospital between 2012 and 2016. They were then categorized into three groups: mild (migratory thrombophlebitis, cold sensitivity or Raynaud's phenomenon, and skin discoloration), moderate (chronic ulcers, claudication, and burning pain of the feet at night), and severe (pain at rest and spontaneous gangrene) symptoms. The serum levels of TGFβ, IL6, TNFα, and IFNγwere determinedby the ELISA method and compared among the groups. Results: The first three predominant symptoms were pulse disorder (n = 76, 95.00%), cold intolerance (n = 61, 76.25%), and claudication (n = 59, 73.75%). A comparison of the analysis of covariance (ANCOVA) revealed that both TGFβ and IL6 were dysregulatedas the severity of the symptoms increased from the moderate to the severe stages; however, such changes were not significant(p > 0.05). In the multiple logistic regression model, increased TNFαlevelswere seen in the presence of the moderatesymptoms as compared to the severe ones (p < 0.05). Conclusion: It could be concluded that TNFα, as part of the defining cytokine-production profile of Thelper cells, can be significantly involved in the progression of TAO from the moderate to the severe stages.


2010 ◽  
Vol 30 (7) ◽  
pp. 603-615 ◽  
Author(s):  
Mikiya Fujieda ◽  
Taku Morita ◽  
Keishi Naruse ◽  
Yoshihiro Hayashi ◽  
Masayuki Ishihara ◽  
...  

We investigated whether pravastatin ameliorates renal damage induced by cisplatin (CP). Forty-three male Wistar rats were divided into four groups: rats treated with a control diet for 19 days and saline injection on day 14 (group1), group 1 with pravastatin treatment with 19 days (group 2), group 1 with CP injection on day 14 (group 3), and group 2 with CP injection (group 4). Renal function and serum lipids, renal malondialdehyde (MDA) and glutathione (GSH) levels, glutathione peroxidase (GPx) mRNA expression and activity, and kidney triglyceride (TG) concentrations were measured. Histology was evaluated by light microscopy with immunohistochemistry for p53, p53-upregulated modulation of apoptosis (PUMA), and terminal deoxynucleotide transferase dUTP nick end-labeling (TUNEL) staining. CP induced renal tubular damage with a higher MDA level, increased PUMA expression, p53- and TUNEL-positive cells counts, elevation of serum lipids, and decreased GSH level, GPx mRNA expression, and activity. Pravastatin partially ameliorated CP-induced renal injury, based on suppression of the renal MDA and TG levels, decreased p53 expression, and apoptosis in CP-treated rats. These findings suggest that pravastatin has a partial protective effect against CP nephrotoxicity via antioxidant activity as well as attenuation of the p53 response, and lipid-lowering effects.


2003 ◽  
Vol 198 (10) ◽  
pp. 1517-1525 ◽  
Author(s):  
Arihiro Kano ◽  
Michael J. Wolfgang ◽  
Qian Gao ◽  
Joerg Jacoby ◽  
Gui-Xuan Chai ◽  
...  

Endothelial cells (ECs) are believed to be an important component in the protection from lipopolysaccharide (LPS)-induced endotoxic shock. However, the cellular and molecular mechanism is not well defined. Here, we report that signal transducer and activator of transcription (STAT) 3 is an essential regulator of the antiinflammatory function of ECs in systemic immunity. Because STAT3 deficiency results in early embryonic lethality, we have generated mice with a conditional STAT3 deletion in endothelium (STAT3E−/−). STAT3E−/− mice are healthy and fertile, and isolated ECs initiate normal tube formation in vitro. Conditional endothelial but not organ-specific (i.e., hepatocyte or cardiomyocyte) STAT3 knockout mice show an increased susceptibility to lethality after LPS challenge. The LPS response in STAT3E−/− mice shows exaggerated inflammation and leukocyte infiltration in multiple organs combined with elevated activity of serum alanine aminotransferase and aspartate aminotransferase, indicating organ damage. Concomitantly, proinflammatory cytokines are produced at an exaggerated level and for a prolonged period. This defect cannot be explained by lack of antiinflammatory cytokines, such as interleukin 10 and transforming growth factor β. Instead, we have shown that a soluble activity derived from endothelia and dependent on STAT3 is critical for suppression of interferon γ. These data define STAT3 signaling within endothelia as a critical antiinflammatory mediator and provide new insight to the protective function of ECs in inflammation.


2020 ◽  
Vol 19 (6) ◽  
pp. 538-544
Author(s):  
Nikolay N. Murashkin ◽  
Svetlana G. Makarova ◽  
Stepan G. Grigorev ◽  
Dmitri V. Fedorov ◽  
Roman A. Ivanov ◽  
...  

Background. Malformations in epidermal barrier in children with atopic dermatitis (AD) can cause transcutaneous sensitization with further development of allergic diseases that can worsen the AD course and significantly reduces patients’ quality of life.Objective. The aim of the study was to determine the effect of topical treatment and maintenance therapy with pimecrolimus 1% cream (PIM) and topical glucocorticosteroids (tGCS) in infants with AD on reducing the risk of developing transcutaneous sensitization (due to the levels of specific IgE to the cow milk protein over time) and on reducing the disease severity (by the EASI scale).Methods. The study included children aged from 1 to 4 months with early manifestations of moderate and severe AD. The severity of AD was estimated via the EASI scale at start of observation, then at 6, 9 and 12 months of life. The class and level of specific IgE to cow milk proteins (CMP) were determined by the ImmunoCAP method at the point of enrolment and at the ages of 6 and 12 months. Statistical analysis of studied indicators dynamics and their comparison in research groups was carried out using multifactorial dispersion analysis.Results. The study included 36 patients. All patients have received standard tGCS therapy in combination with emollients (wet wrap) for 10 days. The maintenance therapy was prescribed in postacute period. It included topical calcineurin inhibitor PIM 2 times/day for 3 months, then double application (morning/evening) 3 times/week up to the age of 1 year old (group 1). Other group had maintenance therapy — tGCS2 times/week for 3 months, and then at AD aggravation (group 2). Group 1 has shown lower level of sensitization to CMP at the age of 6 and 12 months and more significant decrease in AD severity according to EASI scale compared to group 2.Conclusion. The treatment with PIM is effective in therapy of AD and prevention of transcutaneous sensitization in infants.


Author(s):  
Yi-Wen Huang ◽  
Chao-Wei Hsu ◽  
Sheng-Nan Lu ◽  
Ming-Lung Yu ◽  
Chien-Wei Su ◽  
...  

Abstract Background Ropeginterferon alfa-2b is a novel mono-pegylated interferon that has only one major form as opposed to 8–14 isomers of other on-market pegylated interferon, allowing injection every two or more weeks with higher tolerability. It received European Medicines Agency and Taiwan marketing authorization in 2019 and 2020, for treatment of polycythemia vera. This phase I/II study aimed to have preliminary evaluation of safety and efficacy in chronic hepatitis B. Methods Thirty-one HBeAg-positive and 31 HBeAg-negative were stratified by HBeAg status and randomized at 1:1:1 ratio to q2w ropeginterferon alfa-2b 350 μg (group 1), q2w 450 μg (group 2) or q1w PEG-IFN alfa-2a 180 μg (group 3). Each patient received 48-week treatment (TW48) and 24-week post-treatment follow-up (FW24). Results The baseline demographics were comparable among the three groups, except for mean HBeAg in HBeAg-positive patients (2.90, 2.23, 2.99 log10 S/CO, respectively). Cumulative HBeAg seroconversion rate at follow-up period was 27.3% (3/11), 36.4% (4/11), and 11.1% (1/9) with time to HBeAg seroconversion starting from TW24, TW16, and TW48 in group 1, 2, and 3, respectively. The rate of HBV DNA < 2000 IU/mL and HBsAg levels < 1500 IU/mL at FW24 were comparable in all groups. Ropeginterferon alfa-2b (group 1 & 2) had numerically lower incidence of rash (9.5% and 4.5%) as compared to PEG-IFN alfa-2a (36.8%). Ropeginterferon alfa-2b 350 μg (group 1) had more ALT elevation (38.1%), however the rate was comparable in group 2 (9.1%) and group 3 (10.5%). Conclusion In this preliminary study, ropeginterferon alfa-2b, although in only half the number of injections, is as safe and effective as pegylated interferon alfa-2a for chronic hepatitis B. Graphic abstract


2008 ◽  
Vol 19 (2) ◽  
pp. 59-66 ◽  
Author(s):  
Annemarie E. Merryman-Simpson ◽  
Shona H. Wood ◽  
Neale Fretwell ◽  
Paul G. Jones ◽  
William M. McLaren ◽  
...  

2015 ◽  
Vol 35 (5) ◽  
pp. 506-516 ◽  
Author(s):  
Keiichi Wakabayashi ◽  
Chieko Hamada ◽  
Reo Kanda ◽  
Takanori Nakano ◽  
Hiroaki Io ◽  
...  

BackgroundPreventing peritoneal damage during peritoneal dialysis is critical. Reactive oxygen species (ROS) have an important role in peritoneal damage; however, few studies have investigated this. We aimed to determine the effects of oral astaxanthin (AST) supplementation in a peritoneal fibrosis (PF) rat model.MethodsThirty-seven Sprague-Dawley rats were divided into 5 groups: Control 1 (fed a normal diet without stimulation), Control 2 (fed an AST-supplemented diet without stimulation), Group 1 (fed a normal diet with 8% chlorhexidine gluconate [CG] stimulation for 3 weeks), Group 2 (fed a 0.06% AST-supplemented diet with CG stimulation), and Group 3 (fed a 0.06% AST-supplemented diet that was initiated 4 weeks before CG stimulation). Peritoneal fibrosis, vascular proliferation, and fibrosis-related factor expression were examined.ResultsPeritoneal thickness was significantly suppressed by AST supplementation. Astaxanthin diminished the number of CD68-, 8-hydroxy-2'–deoxyguanosine (8-OHdG)-, and monocyte chemoattractant protein-1 (MCP-1)-positive cells. Type 3 collagen, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and MCP-1 mRNA expression was significantly lower in Group 3 than in Group 1. Increased transforming growth factor-β (TGF-β) and Snail mRNA expression, vascular density, and the number of α–smooth muscle actin (α–SMA)-positive cells were also decreased in Group 3.ConclusionAstaxanthin suppressed PF development through the inhibition of inflammation and oxidation in PF rats. It appears that the anti-oxidative agent AST may be useful for the prevention of peritoneal damage.


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