Strain specific response of mice to IMQ-induced psoriasis

Author(s):  
Murali Badanthadka ◽  
Lidwin D’Souza ◽  
Fathima Salwa

Abstract Objectives Psoriasis is an autoimmune, inflammatory disease that needs a reliable animal model. Imiquimod (IMQ)-induced psoriasis is a widely used preclinical tool for psoriasis research. However, this model is sensitive to the genetic variation of mice. The present study explores mice’s genetic background on disease stability and severity induced by IMQ. Methods Three distinct strains of mice (Balb/c, C57BL/6, and Swiss albino) were divided into four groups (Vaseline, IMQ, IMQ+Clobetasol, and IMQ+Curcumin). Psoriasis area severity index (PASI) score, ear/back skin thickness, body weight alterations, and histopathological examination were employed to analyze disease severity. The spleen index studied the systemic effect. Strain effect on oxidative stress induced by IMQ was evaluated by estimating antioxidant factors, superoxide dismutase (SOD), catalase, and glutathione (GSH). Results IMQ application resulted in increased PASI score, thickness, and alterations in body weight, confirming disease development in all the mice. However, the disease stability/severity between these strains was not identical. Although IMQ application caused splenomegaly, IMQ+curcumin treated C57BL/6 mice demonstrated a synergistic effect of IMQ and curcumin on the spleen resulting in increased splenomegaly. Decreased cellular enzyme activity in SOD, Catalase, and levels of GSH was observed in IMQ challenged mice, indicating the participation of the redox system in the genesis of the disease that was comparable among the strains. Conclusions These results indicate the existence of strain-dependent development of the disease. The Swiss model was found to be better in terms of disease severity and stability than other models. Further, a detailed mechanistic study might help to explain the pathological difference between these strains.

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Cristina Aguilar-Flores ◽  
Octavio Castro-Escamilla ◽  
Elizabeth M. Ortega-Rocha ◽  
César Maldonado-García ◽  
Fermín Jurado-Santa Cruz ◽  
...  

Psoriasis is an inflammatory autoimmune disease characterized by cutaneous lesions in plaques. It has been proposed that the immune response has a key role in the disease progression. Particularly, the Th17 cells through IL-17 can contribute to maintain the inflammatory process. The pathogenic Th17 phenotype has been described in human diseases and associated with high severity in inflammatory experimental models. However, it is not clear if the pathogenic phenotype could be present in the skin and peripheral blood as well as its possible association to severity in psoriasis. In the lesional skin, we found high infiltration of Th17 cells and the pathogenic phenotype, finding a correlation between the frequency of Th17 cells and the Psoriasis Area and Severity Index (PASI) score. In peripheral blood, we observed a pool of Th17 lymphocytes with potential to acquire pathogenic features. Interestingly, the percentage of pathogenic Th17 cells (CD4+ RORγt+ IFN-γ+) correlates with disease severity. Moreover, we distinguished three groups of patients based on their IL-17/IFN-γ production by Th17 lymphocytes, which seems to be related with a dynamic or stable potential to express these cytokines. Remarkably, we evaluated the cytokine production by Th17 cells as an immunological marker for the adequate selection of biologic therapy. We found that patients analyzed by this immunological approach and treated with antibodies against IL-17 and TNFα showed great improvement depicted by reduction in PASI and Dermatology Life Quality Index (DLQI) score as well as the percentage of Body Surface Area (BSA). Altogether, our results highlight the importance of the assessment of the pathogenic phenotype in Th17 cells as an immune personalized analysis with the potential to support the therapy choice in the clinical practice.


2015 ◽  
Vol 36 (6) ◽  
pp. 2307-2316 ◽  
Author(s):  
Xiaohui Xu ◽  
Tao Liang ◽  
Xing Lin ◽  
Qingwei Wen ◽  
Xingmei Liang ◽  
...  

Background: Averrhoacarambola L., which is a folk medicine used in diabetes mellitus (DM) in ancient China, has been reported to have anti-diabetic efficacy. Aims: The aim of this study was to evaluate the hypoglycemic effect of the extract of Averrhoacarambola L. root (EACR) on the regulation of the Toll-like receptor 4 (TLR4)-Nuclear-factor kappa B (NF-κB) pathway in B) pathway in streptozotocin (STZ)-induced diabetic mice. Methods: the mice were injected with STZ (120 mg/kg body weight) via a tail vein. After 72 h, the mice with FBG = 11.1 mmol/L were confirmed as having diabetes. Subsequently, the mice were treated intragastrically with EACR (300, 600, 1200 mg/kg body weight/d) and metformin (320 mg/kg body weight/d) for 14 days. Results: As a result the serum fasting blood glucose (FBG), interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) levels were decreased following EACR administration. Immunohistochemical analysis revealed that the pancreatic tissue expression levels of TLR4 and NF-κB were downregulated after EACR administration. EACR suppressed pancreatic mRNA expression level of TLR4 and blocked the downstream NF-κB pathway in the pancreas. According to Western blot analysis EACR suppressed pancreatic TLR4 and NF-κB protein expression levels. Histopathological examination of the pancreas showed that STZ-induced pancreas lesions were alleviated by the EACR treatment. Conclusion: These findings suggest that the modulation of the IL-6 and TNF-a inflammatory cytokines and the suppression of the TLR4-NF-κB pathway are most likely involved in the anti-hyperglycemic effect of EACR in STZ-induced diabetic mice.


2017 ◽  
Vol 20 (2) ◽  
pp. 417-420 ◽  
Author(s):  
M. Śmiałek ◽  
M. Gesek ◽  
A. Śmiałek ◽  
A. Koncicki

Abstract The aim of the study was to investigate the possibility of Transmissible Viral Proventriculitis (TVP) occurrence in broiler chickens in Poland. In march 2016 proventriculi samples were collected from broiler chickens showing poor uniformity and decreased body weight, accompanied by enlarged proventriculi. Histopathological examination of affected proventriculi revealed typical lesions associated with TVP (vacuolar degeneration and necrosis of glandular epithelium, replacement of glandular epithelium by hyperplastic ductal epithelium and moderate to severe lymphocytic infiltration). To our best knowledge, up to date there is no report indicating the presence of TVP in Poland nor in Central and Eastern Europe.


2019 ◽  
Vol 7 ◽  
pp. 2050313X1984519 ◽  
Author(s):  
Misha Zarbafian ◽  
Benoit Cote ◽  
Vincent Richer

Treatment of moderate-to-severe psoriasis in patients with HIV infection is a clinical challenge. We present the case of a patient with a longstanding history of well-controlled HIV. He had failed topical management, and his hypertriglyceridemia made use of acitretin potentially unsafe. He was unable to regularly attend a phototherapy unit. Physical examination revealed 12% total body surface area involvement with a Psoriasis Area Severity Index (PASI) of 10.2. His Dermatology Quality of Life Index (DLQI) was 20. After 3 months of apremilast treatment, his PASI decreased to 4.1. After 7 months, his PASI decreased to 2.7 and his DLQI to 1. Two years later, his PASI score was 2.4, with a stable CD4 count of 1200 cells/mm3 and an undetectable viral load. There were no serious opportunistic infections or laboratory abnormalities. To our knowledge, this represents the second reported case of psoriasis treatment with apremilast in a patient with HIV.


2018 ◽  
Vol 2018 ◽  
pp. 1-6
Author(s):  
Mayuresh Naik ◽  
Anuj Mehta ◽  
Neha Mehrotra ◽  
Anil Solanki

A 2-year-old male child presented with a painless progressive mass in the inferolateral aspect of right orbit of three-month duration. Differential leucocyte count revealed raised eosinophil count (13%). On radiological examination, CT scan showed 25 × 27 mm round well-defined smooth-outlined homogenously enhancing extraconal mass arising from the zygomatic bone at the inferotemporal periorbital area of right orbit with bone erosion. Histopathological examination of the incision biopsy revealed characteristic Langerhans cells and immunohistochemical studies were positive for S-100 protein and adenosine deaminase. A diagnosis of Langerhans Cell Histiocytosis (LCH) was made and PET-CT revealed no other foci of uptake anywhere else in the body. The patient received 12 cycles of vinblastine, 0.2 mg/kg body weight, along with oral prednisolone, 1 mg/kg body weight. On completion of three cycles of chemotherapy, a reduction in size of the mass was noticed. A repeat PET scan was done 3 months after completion of chemotherapy did not reveal any activity noted previously.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Bruna L. S. Picciani ◽  
Thays T. Souza ◽  
Vanessa de Carla B. Santos ◽  
Tábata A. Domingos ◽  
Sueli Carneiro ◽  
...  

Geographic tongue (GT) and fissured tongue (FT) are the more frequent oral lesions in patients with psoriasis. The aims of this study were to compare the prevalence of GT/FT between psoriasis group (PG) and healthy controls (HC) and investigate the correlation between GT/FT and psoriasis severity using the PASI and age of psoriasis onset. Three hundred and forty-eight PG and 348 HC were selected. According to the age of psoriasis onset, the individuals were classified as having early psoriasis and late psoriasis. The severity of vulgaris psoriasis was determined according to PASI. A follow-up was conducted in patients with psoriasis vulgaris (PV) with GT to evaluate the progression of oral and cutaneous lesions. The FT and GT were more frequent in PG than in HC. The incidence of GT was higher in patients with early psoriasis and that of FT in late-psoriasis. There is association between psoriasis intensity and GT; and a higher monthly decrease of PASI score in patients without GT. The presence of GT and FT is higher in PG than in the HC. GT is associated with disease severity and may be a marker of the psoriasis severity.


1987 ◽  
Vol 45 (3) ◽  
pp. 477-491 ◽  
Author(s):  
A. W. Stott ◽  
J. Slee

ABSTRACTThe resistance to body cooling of 594 newborn Scottish Blackface lambs was measured in a water bath during a programme of upwards and downwards genetic selection. Cold resistance was defined as the time taken for rectal temperature to fall to 35°C in the water bath.Upwards selection produced increased cold resistance which was genetically associated with increased skin thickness, increased total body insulation and greater persistence of high metabolic rate during cold exposure. The first two correlated responses to selection were more pronounced in twins than in singles.High cold resistance was phenotypically, but not genetically, associated with greater body weight, increased coat depth and higher levels of cold-induced metabolic rate (heat production). Single lambs showed higher weight-adjusted metabolic rates and higher cold resistance than twins. Singles recovered from hypothermia faster than twins in the low selection line only.Female lambs showed higher metabolic rate (whether weight-adjusted or not) and greater total body insulation than males. Their greater cold resistance was not quite significant. Increasing age (range 0·3 to 36 h) was associated with a small but significant decline in cold resistance.Thermoneutral metabolic rate was proportional to body surface area, whereas peak metabolic rate was proportional to body weight such that peak metabolic rate per unit body weight was independent of changes in body weight. These findings are discussed in relation to lamb survival.


2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Kingsley C. Patrick-Iwuanyanwu ◽  
Iniobong A. Charles

The present investigation was aimed to determine the effect of sub-chronic exposure to Solignum<sup>®</sup>, a permethrin-containing wood preservative on biochemical and histological changes in liver and kidneys of male Wistar albino rats. Thirty-two male rats were randomly divided into four groups: control and three treatment concentrations containing 8 rats each. The treatment groups were exposed to Solignum<sup>®</sup> at dose rates of 100, 200 and 400 mg/kg body weight (BW) respectively per day orally for four weeks. Data obtained from the study showed a progressive increase in the body weight of rats in control whereas, rats treated with different concentrations (100, 200 and 400 mg/kg BW) of Solignum<sup>®</sup> decreased significantly (≤0.05) especially at the end of the second and fourth week when compared with control. On the other hand, there was a significant decrease in the relative liver weights of rats treated with 100 and 200 mg/kg BW Solignum<sup>®</sup> while rats treated with 400 mg/kg BW showed a significant increase when compared with control. The relative weight of kidneys in experimental groups increased significantly when compared with control. Biochemical analysis results illustrated that there was a significant increase in marker enzymes namely alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activity at the end of the fourth week. Similarly, total bilirubin, serum urea, creatinine and electrolytes (Na<sup>+</sup>, K<sup>+</sup> and Cl<sup>-</sup>) levels increased in a dose dependent manner in treated rats when compared with untreated control group. Serum total protein decreased significantly in experimental rats when compared with control. However, cholesterol and triglycerides showed no significant difference when compared with control. Histopathological examination of hepatocytes in treated rats was characterized by mild periportal inflammatory cells and cytoplasmic degeneration. Furthermore, histopathological examination of rat kidneys revealed inflammatory cells, congested vessel and interstitial hemorrhage in rats treated with Solignum<sup>®</sup>. Therefore, this present study is aimed to evaluate the hepatotoxic and nephrotoxic potentials associated with sub-chronic exposure to the commercial pesticide Solignum<sup>®</sup>.


2012 ◽  
Vol 2012 ◽  
pp. 1-11
Author(s):  
Tony Yuqi Tang

Mono- or combine immunosuppressants are commonly used for psoriasis; however the side effect caused by potent systemic immunosuppressants frequently incurred; moreover the inflammation flares up shortly after immunosuppressants are discontinued. An alternative nonimmunosuppressive therapy was introduced to psoriasis subjects. A retrospective observational study consisted of 1583 psoriasis patients who were treated with Herose Psoria capsule 1440 mg three times daily at two clinical centres, one in China, the other in Singapore, from 1 January 2000 to 1 January 2011. Psoriasis lesion evolution was photographed at monthly visit, and efficacy and safety were assessed using psoriasis area severity index PASI score grading, renal and liver function testing, and adverse event reporting and supplemented by information obtained during targeted telephone interviews. The effectiveness of Herose on psoriasis was inversely associated to prior immunosuppressants exposure (r=0.9154), significant improvements occurred in non-immunosuppressants subjects, and complete clearance was achieved in 8 months (87.5%, 14 of 16); the wavelike evolution of psoriatic lesion appeared in prior immunosuppressants subjects.


Author(s):  
Bob A. Ukonu ◽  
Perpetua U. Ibekwe

<p class="abstract"><strong>Background:</strong> Psoriasis is a common chronic cutaneous inflammatory disorder of the skin which presents as sharply demarcated scaly erythematous papules or plaques. The level of its clinical severity at presentation largely determines the cost implications and economic burden on the patient. The study aimed to determine the direct cost of treating various clinical severity of psoriasis and its economic consequences to our healthcare system.</p><p class="abstract"><strong>Methods:</strong> This is a retrospective study that was conducted between May 2016 and October 2019 at the Dermatology Unit of University of Abuja Teaching Hospital. Data was retrieved from patient’s folder into a designed proforma, noting their biodata, clinical level of severity using psoriasis area severity index (PASI) score, amount of money spent on drugs, laboratory test, nursing time and consultation fees. <strong></strong></p><p class="abstract"><strong>Results:</strong> Out of 82 psoriasis patients seen during the study period, 66 fulfilled the inclusion criteria. About 51.5% of them had severe psoriasis with a mean PASI score 33.2. The annual cost of treating mild, moderate and severe psoriasis was N198,900.00, N261,633.00 and N323,708.00 respectively. This accounted for 1.77% of the national annual healthcare spending within the years under review.</p><p class="abstract"><strong>Conclusions:</strong> The cost of treating psoriasis and its economic burden is largely determined by the level of its clinical severity.</p>


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