Current Issue : October - December Volume : 2016 Issue Number : 4 Articles : 6 Articles
Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by highly pruritic\neczematous lesions that are commonly treated with topical corticosteroids and calcineurin inhibitors. Side-effects\nand safety concerns associated with these agents restrict their use, and new, safe treatment options are therefore\nneeded. Recent reports suggest that serotonin, i.e. 5-hydroxytryptamine (5-HT) and the 5-HT2 receptor family may\ncontribute to inflammation and pruritus in the skin. The objective of this particular study was to investigate the\n5HT2B receptor antagonist AM1030 with respect to its anti-inflammatory profile and potential.\nMethods: AM1030 was tested in a set of distinct human and rodent in vitro and in vivo models, differing with\nrespect to e.g. T cell involvement, triggering stimulus, main read-outs and route of drug administration. The in vitro\nsystems used were staphylococcal enterotoxin A (SEA)-stimulated human peripheral blood mononuclear cells,\nlipopolysaccharide (LPS)-stimulated human primary monocytes, LPS-stimulated human THP-1 monocytes and\nLPS-stimulated mouse primary macrophages. The in vivo systems used were LPS- and SEA-induced cytokine\nproduction in the mouse, antigen-induced arthritis in the rat, glucose-6-phosphate isomerase-induced arthritis in\nthe mouse and delayed-type hypersensitivity reaction in the mouse. In addition, different cell populations were\nanalyzed with respect to their expression of the 5-HT2B receptor at the mRNA level.\nResults: AM1030 significantly reduced both T cell-dependent and T cell-independent inflammatory responses, in\nvivo and in vitro. Due to the low or absent expression of the 5-HT2B receptor on T cell populations, the influence of\nAM1030 in T cell-dependent systems is suggested to be mediated via an indirect effect involving\nantigen-presenting cell types, such as monocytes and macrophages.\nConclusion: Based on the wide range of model systems used in this study, differing e.g. with respect to species,\nT cell involvement, triggering stimuli, route of drug administration and read-outs, our results suggest a broad\nanti-inflammatory effect of AM1030 and identify the 5-HT2B receptor as a promising future target for\nanti-inflammatory intervention, e.g. in AD....
Background: In the absence of a validated animal model and/or an immune correlate which predict vaccinemediated\nprotection, large-scale clinical trials are currently the only option to prove efficacy of new tuberculosis\ncandidate vaccines. Tools to facilitate testing of new tuberculosis (TB) vaccines are therefore urgently needed.\nMethods: We present here an optimized ex vivo mycobacterial growth inhibition assay (MGIA) using a murine\nMycobacterium tuberculosis infection model. This assay assesses the combined ability of host immune cells to inhibit\nmycobacterial growth in response to vaccination. C57BL/6 mice were immunized with Bacillus Calmette-GuÃ?©rin\n(BCG) and growth inhibition of mycobacteria by splenocytes was assessed. Mice were also challenged with\nMycobacterium tuberculosis Erdman, and bacterial burden was assessed in lungs and spleen.\nResults: Using the growth inhibition assay, we find a reduction in BCG CFU of 0.3ââ?¬â??0.8 log10 after co-culture with\nmurine splenocytes from BCG vaccinated versus naÃ?¯ve C57BL/6 mice. BCG vaccination in our hands led to a reduction\nin bacterial burden after challenge with Mycobacterium tuberculosis of approx. 0.7 log10 CFU in lung and approx. 1\nlog10 CFU in spleen. This effect was also seen when using Mycobacterium smegmatis as the target of growth inhibition.\nAn increase in mycobacterial numbers was found when splenocytes from interferon gamma-deficient mice were used,\ncompared to wild type controls, indicating that immune mechanisms may also be investigated using this assay.\nConclusions: We believe that the ex vivo mycobacterial growth inhibition assay could be a useful tool to help assess\nvaccine efficacy in future, alongside other established methods. It could also be a valuable tool for determination of\nunderlying immune mechanisms....
The potential effects of the quinoline on pubertal development and thyroid function were quantified in the peripubertal male Wistar rats. Vehicle control (corn oil - 0 mg/kg), positive control – vinclozolin (VCZ - 100 mg/kg) and two groups of quinoline (QNL - 100 and 150/200 mg/kg) were treated from postnatal day (PND) 23–53 at the dose volume of 2.5 ml/kg. Two mortalities, weakness, lethargy and significant reduction in body weight were observed at 200 mg/kg of QNL treated group hence dose was reduced to 150 mg/kg from PND 25. Body weight, body weight gain and feed consumption of the 100 and 150/200 mg/kg QNL groups were significantly decreased compared to the control group. Increase in urea and BUN was observed in all test dose levels of VCZ and QNL as compared to the control group. Decrease inseminal vesicle coagulating gland with and without fluid, ventral prostate, LABC, epididymes was observed in QNL at 150/200 mg/kg as compared to the vehicle control group. Thyroid hormone (T4, T3 and TSH) and testosterone analysis were not affected by treatment of QNL. Results of present study revealed that QNL showed no evidence of endocrine disruptor activity....
The most widespread animal model to investigate Duchennemuscular dystrophy is the mdx-mouse. In contrast to humans, phases\nof muscle degeneration are replaced by regeneration processes; hence there is only a restricted time slot for research. The aim\nof the study was to investigate if an intramuscular injection of BTX-A is able to break down muscle regeneration and has direct\nimplications on the gene expression ofmyosin heavy chains in the corresponding treated and untreatedmuscles. Therefore, paralysis\nof the right massetermuscle was induced in adult healthy and dystrophic mice by a specific intramuscular injection of BTX-A. After\n21 days themRNA expression and protein content ofMyHC isoforms of the right and leftmasseter, temporal, and the tonguemuscle\nwere determined using quantitative RT-PCR andWestern blot technique.MyHC-IIa andMyHC-I-mRNA expression significantly\nincreased in the paralyzed masseter muscle of control-mice, whereas MyHC-IIb and MyHC-IIx/d-mRNA were decreased. In\ndystrophic muscles no effect of BTX-A could be detected at the level of MyHC. This study suggests that BTX-A injection is a\nsuitable method to simulate DMD-pathogenesis in healthy mice but further investigations are necessary to fully analyse the BTX-A\neffect and to generate sustained muscular atrophy in mdx-mice....
Renal fibrosis is the principal pathological process underlying the progression of chronic\nkidney disease that leads to end-stage renal disease. Melittin is a major component of bee venom,\nand it has anti-bacterial, anti-viral, and anti-inflammatory properties in various cell types. Thus,\nthis study examined the therapeutic effects of melittin on the progression of renal fibrosis using the\nunilateral ureteral obstruction (UUO) model. In addition, the effects of melittin on inflammation\nand fibrosis in renal fibroblast cells were explored using transforming growth factor-�²1 (TGF-�²1).\nHistological observation revealed that UUO induced a considerable increase in the number of\ninfiltrated inflammatory cells. However, melittin treatment markedly reduced these reactions\ncompared with untreated UUO mice. The expression levels of inflammatory cytokines and pro-fibrotic\ngenes were significantly reduced in melittin-treated mice compared with UUO mice. Melittin also\neffectively inhibited fibrosis-related gene expression in renal fibroblasts NRK-49F cells. These findings\nsuggest that melittin attenuates renal fibrosis and reduces inflammatory responses by the suppression of\nmultiple growth factor-mediated pro-fibrotic genes. In conclusion, melittin may be a useful therapeutic\nagent for the prevention of fibrosis that characterizes the progression of chronic kidney disease....
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by elevated immunoglobulin\nE (IgE), mast cell infiltration and skin lesions including pruritus, erythema and eczema.\nCudrania tricuspidata extracts have been clinically administered for a long time in the East Asia\nincluding Korean and China as a home-remedy to diminish the inflammation of gastritis and hepatitis.\nTo examine whether it works on AD or not, an AD-like animal model was experimented in\nthis study. AD was induced by applying Dermatophagoides farinae (D. farinae) extract to the backs\nof 9-week old NC/Nga mice for 21 days. Following this, an ethanol extract of C. tricuspidata stems\n(EECT) was applied topically for 14 days to the sensitized skin, while distilled water was used as a\ncontrol (EECT0 mice). Anti-AD effects of EECT were evaluated using scores for AD-like skin lesions,\nserum IgE levels and mast cell counts in the skin dermal layers to assess inflammation. Topically\napplied ethanol extract of Cudrania tricuspidata stems (EECT 7.5, 25 and 75 mg/mL) markedly\nreduced AD-like skin lesions after 4 days (by 30.1%, 31.4% and 38.5%, respectively) and also after 14 days (by 63.6%, 66.1% and 49.6%, respectively), while distilled water improved AD by 17.8%\nand 38.7%, respectively (p < 0.05). Serum IgE production was reduced in the EECT7.5, EECT25 and\nEECT75 groups after 4 days (by 57.6%, 65.9% and 59.3%, respectively) and after 14 days of the\ntreatment (by 82.0%, 79.6% and 75.3%, respectively), while distilled water decreased it by 38.8%\nand 62.3% (p = 0.0001 and p = 0.0001, respectively). Mast cell counts increased after sensitization\nby D. farinae extract (p = 0.003) and EECT attenuated the mast cell overproduction, and reduced\nmast cell degranulation markedly. Attenuation was most obvious in the early stage of EECT treatment\nwhen the AD was most acute....
Loading....