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91.
Margaret L Novak Eileen M Weinheimer‐Haus Timothy J Koh 《The Journal of pathology》2014,232(3):344-355
Following injury to different tissues, macrophages can contribute to both regenerative and fibrotic healing. These seemingly contradictory roles of macrophages may be related to the markedly different phenotypes that macrophages can assume upon exposure to different stimuli. We hypothesized that fibrotic healing after traumatic muscle injury would be dominated by a pro‐fibrotic M2a macrophage phenotype, with M1 activation limited to the very early stages of repair. We found that macrophages accumulated in lacerated mouse muscle for at least 21 days, accompanied by limited myofibre regeneration and persistent collagen deposition. However, muscle macrophages did not exhibit either of the canonical M1 or M2a phenotypes, but instead up‐regulated both M1‐ and M2a‐associated genes early after injury, followed by down‐regulation of most markers examined. Particularly, IL‐10 mRNA and protein were markedly elevated in macrophages from 3‐day injured muscle. Additionally, though flow cytometry identified distinct subpopulations of macrophages based on high or low expression of TNFα, these subpopulations did not clearly correspond to M1 or M2a phenotypes. Importantly, cell therapy with exogenous M1 macrophages but not non‐activated macrophages reduced fibrosis and enhanced muscle fibre regeneration in lacerated muscles. These data indicate that manipulation of macrophage function has potential to improve healing following traumatic injury. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
92.
93.
Felix Aberer MD Peter N. Pferschy MSc Norbert J. Tripolt PhD Caren Sourij MD Anna M Obermayer MD Florian Prüller MD Eva Novak MD Philipp Reitbauer Harald Kojzar BSc Barbara Prietl PhD Selina Kofler BSc Martina Brunner MSc Eva Svehlikova MD Tatjana Stojakovic MD Hubert Scharnagl MD Abderrahim Oulhaj PhD Faisal Aziz Msc Regina Riedl PhD Harald Sourij MD 《Diabetes, obesity & metabolism》2020,22(2):212-221
94.
Pancreatic cells contain specialised stores for ATP. Purinergic receptors (P2 and P1) and ecto-nucleotidases are expressed in both endocrine and exocrine calls, as well as in stromal cells. The pancreas, especially the endocrine cells, were an early target for the actions of ATP. After the historical perspective of purinergic signalling in the pancreas, the focus of this review will be the physiological functions of purinergic signalling in the regulation of both endocrine and exocrine pancreas. Next, we will consider possible interaction between purinergic signalling and other regulatory systems and their relation to nutrient homeostasis and cell survival. The pancreas is an organ exhibiting several serious diseases - cystic fibrosis, pancreatitis, pancreatic cancer and diabetes - and some are associated with changes in life-style and are increasing in incidence. There is upcoming evidence for the role of purinergic signalling in the pathophysiology of the pancreas, and the new challenge is to understand how it is integrated with other pathological processes. 相似文献
95.
96.
Pelikan Z 《Respiration; international review of thoracic diseases》2012,84(5):385-395
Background: Patients with allergic bronchial asthma can develop various types of asthmatic response to bronchial challenge with allergens, such as immediate (IAR), late (LAR) or delayed (DYAR) response, due to different immunological mechanisms. Objective: The DYAR, beginning within 26- 32 h after the challenge, reaching its maximum between 32 and 48 h and resolving within 56 h (p < 0.001), differs from IAR and LAR regarding the clinical features, diagnostic and immunological parameters. Methods: The repeated DYAR (p < 0.001) in 28 patients was supplemented with recording of cytokine concentrations in the serum before and up to 72 h after the bronchial challenge by means of enzyme-linked immunoassay. Results: The DYAR was accompanied by a significant increase in the serum concentration (p < 0.05) of IL-2 at 24, 36 and 48 h; IL-10 at 12, 24, 36 and 48 h; IL-18 at 12 and 24 h; IFN-γ at 24, 36, 48 and 56 h; G-CSF at 1 and 12 h; TNF-α at 12, 36 and 48 h and TGF-β at 12 and 36 h, and a significant decrease in the concentration (p < 0.05) of IL-7 at 36 and 48 h and IL-12p70 at 12 h, as compared both with the prechallenge and with PBS control values. No significant changes in the serum cytokines were recorded during the PBS controls (p > 0.2). Conclusions: These results support the evidence for an active involvement of the Th(1) cells, neutrophils, monocytes, macrophages, epithelial cells and endothelial cells, upon cooperation of other cell types, in the immunological mechanism(s) underlying the DYAR. 相似文献
97.
Nguyen CT Jung W Kim J Chaney EJ Novak M Stewart CN Boppart SA 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(24):9529-9534
Otitis media (OM), a middle-ear infection, is the most common childhood illness treated by pediatricians. If inadequately treated, OM can result in long-term chronic problems persisting into adulthood. Children with chronic OM or recurrent OM often have conductive hearing loss and communication difficulties and require surgical treatment. Tympanostomy tube insertion, the placement of a small drainage tube in the tympanic membrane (TM), is the most common surgical procedure performed in children under general anesthesia. Recent clinical studies have shown evidence of a direct correspondence between chronic OM and the presence of a bacterial biofilm within the middle ear. Biofilms are typically very thin and cannot be recognized using a regular otoscope. Here we report the use of optical coherent ranging techniques to noninvasively assess the middle ear to detect and quantify biofilm microstructure. This study involves adults with chronic OM, which is generally accepted as a biofilm-related disease. Based on more than 18,537 optical ranging scans and 742 images from 13 clinically infected patients and 7 normal controls using clinical findings as the gold standard, all middle ears with chronic OM showed evidence of biofilms, and all normal ears did not. Information on the presence of a biofilm, along with its structure and response to antibiotic treatment, will not only provide a better fundamental understanding of biofilm formation, growth, and eradication in the middle ear, but also may provide much-needed quantifiable data to enable early detection and quantitative longitudinal treatment monitoring of middle-ear biofilms responsible for chronic OM. 相似文献
98.
Bruha R Vitek L Marecek Z Pospisilova L Nevsimalova S Martasek P Petrtyl J Urbanek P Jiraskova A Malikova I Haluzik M Ferenci P 《Journal of inherited metabolic disease》2012,35(3):541-548
Background &; Aims
Wilson disease (WD) is an inherited disorder of copper disposition caused by an ATP7B transporter gene mutation, leading to copper accumulation in predisposed tissues. In addition to a genetic predisposition, other factors are likely to contribute to its clinical manifestation. The aim of the study was to assess whether oxidative stress affects the phenotypic manifestation of WD.Methods
In 56 patients with WD (29 men; 26 with the hepatic form, 22 with the neurologic form, and eight asymptomatic; mean age 38.5?±?12 years), total serum antioxidant capacity (TAC) and inflammatory parameters (hs-CRP, IL-1??, IL-2, IL-6, IL-10, and TNF-??) were analyzed and related to the clinical manifestation, and mutations of the ATP7B gene. The control group for the TAC and inflammatory parameters consisted of 50 age- and gender-matched healthy individuals.Results
WD patients had a significantly lower TAC (p?0.00001), lower IL-10 levels (p?=?0.039), as well as both higher IL-1?? (p?=?0.019) and IL-6 (p?=?0.005) levels compared to the control subjects. TNF-??, hs-CRP, and IL-2 did not differ from the controls. Patients with the neurological form of WD had a significantly lower TAC than those with the hepatic form (p?0.001). In addition, the lower TAC was associated with the severity of the neurological symptoms (p?=?0.02). No relationship between the inflammatory parameters and clinical symptoms was found.Conclusions
Data from our study suggest that the increased oxidative stress contributes significantly to the clinical manifestation of WD; as a lower TAC is associated with the neurological symptoms in WD patients. 相似文献99.
Novak K Polic S Capkun V Fabijanic D Lukin A Dujic Z Rumboldt Z 《Archives of gerontology and geriatrics》2012,54(1):266-270
Previous studies have shown a paradoxical increase in early mortality in older patients (>70 years) with acute STEMI treated with fibrinolytic therapy (FT), which has been attributed to the development of free wall rupture (FWR). Our aim was to assess occurrence of FWR in STEMI patients receiving FT. In this 7-year prospective study, data from 1701 consecutive patients were obtained. We analyzed predictors of the in-hospital mortality in patients > 70 years old. The independent contribution of several variables to overall mortality and FWR development was assessed using multiple logistic regression analyses. The mortality of entire cohort was 18% (306/1701). Diabetes mellitus, anterior infarction, smoking, female gender and hypercholesterolemia were independent predictors of in-hospital mortality. FT was given to 18% of all patients (304/1701) of which 13% died (39/304). FWR was 18.4-times more often in patients who received FT. Among patients younger than 70 years who received FT there was no FWR, while in patients ≥70 years of age FWR was found in almost half of the deceased (30/68; 44%). Application of FT in STEMI patients is not associated with higher mortality, but significantly increases number of FWR, especially in patients over 70 years of age. 相似文献
100.
A reduction in calorie intake [caloric restriction (CR)] appears to consistently decrease the biological rate of aging in a variety of organisms as well as protect against age-associated diseases including chronic inflammatory disorders such as cardiovascular disease and diabetes. Although the mechanisms behind this observation are not fully understood, identification of the main metabolic pathways affected by CR has generated interest in finding molecular targets that could be modulated by CR mimetics. This review describes the general concepts of CR and CR mimetics as well as discusses evidence related to their effects on inflammation and chronic inflammatory disorders. Additionally, emerging evidence related to the effects of CR on periodontal disease in non-human primates is presented. While the implementation of this type of dietary intervention appears to be challenging in our modern society where obesity is a major public health problem, CR mimetics could offer a promising alternative to control and perhaps prevent several chronic inflammatory disorders including periodontal disease. 相似文献