SEARCH · Search PubMed

Results for “Inflammatory pathways”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 559 records · Page 31Linked to original sources

PubMed1997

Biocompatibility in haemodialysis: fact and fiction.

Several of the pro-inflammatory pathways that are activated in patients during dialysis have the potential of producing many side effects. These occur three times a week, accompanying dialysis, and are particularly intense in patients dialysed with so-called 'bioincompatible' membranes. Despite the proven biological superiority of biocompatible membranes, we lack definitive evidence that complement and cell activation three times a week over a period of years is detrimental to patients, because the results of prospective randomized studies are conflicting. Although they do not lead to a decrease in acute clinical symptoms, epidemiological studies suggest that semi-synthetic and synthetic membranes may reduce morbidity and mortality in dialysis patients. Further large scale, prospective and randomized trials with a long follow-up are needed in order to clarify the clinical effects of biocompatibility per se, the increasingly recognized clinical importance of high-flux treatments and the possible interaction between biocompatibility and membrane flux.

Biocompatible Materials↗

PubMed2005

Factors associated with the development of post-infectious functional gastrointestinal diseases: does smoking play a role?

OBJECTIVES: Irritable bowel syndrome (IBS) is associated with psychological stress, alterations in gut motor function and/or visceral perception. Previous studies suggest 7-32% of people develop IBS after bacterial gastroenteritis but the exact mechanisms underlying post-infectious IBS are not clear. The present study's aim was to examine the role of possible causative factors in the development of post-infectious functional gastro-intestinal disorders (FGIDs), including IBS. METHODS: A prospective cohort study where 122 people without a prior FGID under study and with stool-positive bacterial gastroenteritis consented to participate. The presence or not of IBS, functional dyspepsia or functional diarrhoea was diagnosed at the start and on 6-month follow-up using self-complete Rome II modular questionnaires. Demographic data, smoking, alcohol use, anxiety and depression (using the Hospital Anxiety and Depression Scale), and life events and impact (using the Life Events Survey) were collected at the start of the study. RESULTS: One hundred and seven questionnaires were returned with 25 participants (23.4%) developing a FGID and 16 participants presenting symptoms consistent with IBS (15%). Smoking was significantly associated with the development of a post-infectious FGID (odds ratio = 4.8, 95% confidence interval = 1.5-15.2) on regression analysis. CONCLUSIONS: Post-infectious FGIDs appear to be associated with smoking. Smoking is known to moderate gut immunity in other disorders such as ulcerative colitis and Crohn's disease. This study adds to increasing evidence for an organic basis to post-infectious FGIDs, perhaps moderated via inflammatory pathways.

Adolescent↗

PubMed1997

Immune effector cells in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a poorly understood immunomediated disorder that is characterized by three major features; influx of inflammatory cells into the lower respiratory tract, alveolar epithelial or capillary cell injury, and release of cytokines that stimulate proliferation of fibroblasts and type II pneumocytes along with deposition of extracellular matrix proteins, notably collagen. In the past few years interest in the pathogenetic mechanisms taking place in IPF has focused on immune effector cells that are involved in pulmonary inflammatory pathways, cell-specific injury, and fibroblast activation. In particular, accumulating evidence indicates that a complex relationship exists between the macrophage/lymphocyte/neutrophil cellular axis and the local network of cytokines that, through paracrine and autocrine interactions, coordinate inflammation and fibrogenesis in the respiratory tract.

Cytokines↗

PubMed2005

Recent developments in immunomodulatory peptides in juvenile rheumatic diseases: from trigger to dimmer?

PURPOSE OF REVIEW: Current therapy for juvenile rheumatic diseases is based on general immune suppression or blocking inflammatory pathways. These treatments do not induce long-term disease remission and have a risk of side effects; this is especially unfavorable in children. It is better to focus on induction of tolerance mechanisms than on suppression of inflammation. This promotes epitope specific immunotherapy as a possible safe treatment option. RECENT FINDINGS: In the search for specific peptides for immunotherapy in autoimmunity, the focus is shifting from purported triggers of disease to peptides that regulate the ongoing inflammation. These so-called 'immunomodulatory peptides' are important in every healthy immune system. Several juvenile rheumatic diseases have been linked to certain immunomodulatory peptides. In juvenile dermatomyositis, peptides from human skeletal myosin play a role in the perpetuation of the disease. In systemic lupus erythematosus, the focus is mostly on DNA-derived peptides and peptides from anti-DNA antibodies. In juvenile idiopathic arthritis, heat shock proteins have been shown to contain important immunomodulatory epitopes. SUMMARY: Immunomodulatory peptides play an important role in juvenile rheumatic diseases. Promising candidates for immunotherapy have been identified. This opens the possibility of clinical testing in rheumatic diseases of childhood.

Arthritis, Juvenile↗

PubMed2006

Chronic pelvic pain and endometriosis in adolescents.

PURPOSE OF REVIEW: This review will provide a detailed account of chronic pelvic pain and endometriosis, two conditions that frequently occur in adolescents. Current approaches used to evaluate and treat these patients will be addressed. RECENT FINDINGS: Although previous investigations have established relative rates of disease and basic treatment algorithms for endometriosis in adolescents, its pathogenesis is yet to be explained. Recent scientific works have focused on the interplay of specific genes and the role of host immune response. Despite such progress, we have not yet learned how to apply this knowledge to clinical use. Most innovative treatment strategies are based on algorithms generated primarily for adults, with only a small percentage focusing on adolescents. SUMMARY: Treating pain associated with endometriosis may be facilitated by early intervention. Future study should focus on identifying adolescents with progressive disease and introducing less invasive therapies that could reverse inflammatory pathways and minimize subsequent morbidity.

Adolescent↗

PubMedDate not supplied

Genetic variation associated with preterm birth: a HuGE review.

Preterm birth (PTB) is a major public health concern because of its high prevalence, associated mortality and morbidity, and expense from both short-term hospitalization and long-term disability. In 2002, 11.9% of U.S. births occurred before 37 weeks gestation. Epidemiologic studies have identified many demographic, behavioral, and medical characteristics associated with PTB risk. In addition, recent evidence indicates a role for genetic susceptibility. We reviewed 18 studies published before June 1, 2004, that examined associations between polymorphisms in the maternal or fetal genome and PTB risk. Studies of a polymorphism in tumor necrosis factor-alpha, a proinflammatory cytokine, showed the most consistent increase in the risk of PTB. Environmental factors such as infection, stress, and obesity, which activate inflammatory pathways, have been associated with PTB, suggesting that environmental and genetic risk factors might operate and interact through related pathways. This review highlights maternal and fetal genetic susceptibilities to PTB, the potential relationships with environmental risk factors, and the need for additional well-designed studies of this critical public health problem.

Environmental Exposure↗

PubMed2006

Viral interaction and clinical implications of coinfection of hepatitis C virus with other hepatitis viruses.

Coinfection with other hepatitis viruses modifies the viral profile in serum and leads to more liver damage and more rapid progression during the course of hepatitis C virus infection. The viral interference is not only carried out by virus-virus or by virus-cell interactions but also by an enhanced immune response. A superinfecting viral infection does not crossactivate protective immune responses to the pre-existing virus albeit the latter can become undetectable. The induced cytokine stimulation might enhance the hepatic inflammation. Moreover, hepatitis B virus coinfection increases the risk of development of hepatocellular carcinoma in hepatitis C virus patients through common necro-inflammatory pathways or by direct oncogenic activity of hepatitis B virus. Viral interaction also complicates the management of the coinfection because hepatitis C virus impairs the humoral response to hepatitis A virus and hepatitis B virus vaccines, and because pharmacological suppression of hepatitis C virus endangers dually infected patients with reactivation of coinfected hepatitis B virus. Optimized strategies and follow-up are thus necessary in the treatment of infection with multiple viruses. It seems thus necessary to look for markers of hepatitis B virus and/or hepatitis D virus infection in chronic hepatitis patients positive for hepatitis C virus antibodies but negative for hepatitis C virus RNA, and equally well to search for hepatitis C virus RNA in HBsAg-negative/anti-HBc-positive patients with a low level of serum hepatitis B virus DNA.

Animals↗

PubMed2005

Codetection of measles virus and tumor necrosis factor-alpha mRNA in otosclerotic stapes footplates.

HYPOTHESIS: Otosclerosis is a disease of unknown etiology causing conductive or sensorineural hearing loss. Persistent measles virus infection of the otic capsule is considered to be one of the etiologic factors in otosclerosis. BACKGROUND: Determinants of measles virus infection and reactive inflammation were studied in otosclerosis. The presence of measles virus was shown in otosclerotic patients by reverse-transcription polymerase chain reaction (RT-PCR) amplification of the viral RNA. No report is available, however, on the types and features of paracrine cytokines in otosclerosis. METHODS: Nucleic acid was extracted from stapes footplate samples of clinically otosclerotic patients. Measles virus nucleoprotein RNA was amplified by seminested RT-PCR. Tumor necrosis factor (TNF)-alpha mRNA expression was detected by RT-PCR in otosclerotic bone and was correlated with preoperative audiologic findings and measles virus positivity. RESULTS: Among 154 clinically otosclerotic patients, 99 stapes footplate specimens contained measles virus RNA. TNF-alpha mRNA was detectable in 88 virus-positive and in 6 virus-negative stapes footplates. There was no detectable TNF-alpha mRNA expression in virus negative cases. CONCLUSION: The etiologic role of measles virus in the pathogenesis of otosclerosis should be considered. Detection of TNF-alpha mRNA demonstrates activated osteoclast functions and inflammatory pathways in otosclerotic stapes footplates associated with measles virus presence. Virus-associated and virus-negative pathomechanisms of otosclerosis should be distinguished.

Adult↗

PubMed2006

Detection of osteoprotegerin and TNF-alpha mRNA in ankylotic Stapes footplates in connection with measles virus positivity.

HYPOTHESIS: Otosclerosis is a bone remodeling disorder of the otic capsule causing conductive and sensorineural hearing loss. Persistent measles virus infection of the temporal bone with increased tumor necrosis factor (TNF)-alpha and decreased osteoprotegerin mRNA expression is supposed to be the main etiologic factor in otosclerosis. BACKGROUND: Determinants of measles virus infection and reactive inflammation were studied in otosclerosis. The presence of measles virus was shown in otosclerotic patients by reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of the viral RNA. No report is available, however, about the role and interactions of bone-specific cytokines in otosclerosis. METHODS: : Nucleic acid was extracted from stapes footplates of clinically otosclerotic patients. Measles virus nucleoprotein RNA was amplified by seminested RT-PCR. TNF-alpha and osteoprotegerin mRNA coexpression was detected by RT-PCR in otosclerotic bone and was correlated to measles virus positivity. RESULTS: Among 154 clinically stapes fixation otosclerotic patients, 99 stapedes contained measles virus RNA. TNF-alpha mRNA was detectable in 88 virus-positive and in 6 virus-negative stapes footplates. Osteoprotegerin mRNA expression was significantly lower in the TNF-alpha-positive specimens (P < .0001) that was independent from virus positivity. CONCLUSION: Detection of TNF-alpha mRNA demonstrates activated osteoclast functions and inflammatory pathways in otosclerotic stapes footplates associated with measles virus presence. Increased expression of TNF-alpha and its action on RANK production inhibits the protective functions of osteoprotegerin on normal bone turnover in the otic capsule.

Adult↗

PubMed2006

Atherosclerotic process, renovascular disease and outcomes from bench to bedside.

PURPOSE OF REVIEW: Atherosclerotic renal artery stenosis has become an important cause of secondary hypertension and renal dysfunction in the aging population. Its presence increases cardiovascular morbidity and mortality independent of other atherosclerotic risk factors. Therefore, novel renoprotective strategies are needed to decrease the impact of this disease. RECENT FINDINGS: Although medical therapy can be effective in patients with atherosclerotic renal artery stenosis and mild renal dysfunction, revascularization is desirable for patients with target-organ injury. Technical developments (such as drug-eluting or low-profile stents and distal protection devices) have increased the safety and effectiveness of renal revascularization, but in a significant proportion of patients renal function is not fully restored. Recent experimental evidence suggests that atherosclerotic renal artery stenosis is associated with the activation of intrarenal fibrogenic and inflammatory pathways, oxidative stress, and microvascular remodeling, and blocking these mechanisms can improve renal hemodynamics and function. SUMMARY: Despite significant advances in revascularization techniques, it remains unclear why the kidney affected by atherosclerotic renal artery stenosis often does not improve or even progressively deteriorates. In addition to the restoration of blood flow, targeted interventions to attenuate injurious intrarenal mechanisms should probably become part of a comprehensive management plan to preserve the ischemic kidney.

Atherectomy↗

PubMed2003

Predictive value of monocyte histocompatibility leukocyte antigen-DR expression and plasma interleukin-4 and -10 levels in critically ill patients with sepsis.

It has been suggested that excessive activation of the anti-inflammatory pathways in sepsis may lead to poor outcome of patients with sepsis. The aim of this study was to test the value of histocompatibility leukocyte antigen (HLA)-DR-expression on blood monocytes and plasma levels of interleukin (IL)-4 and -10 in prediction of hospital mortality in patients with sepsis. Sixty-one critically ill patients with sepsis were prospectively enrolled to this study in two university hospital intensive care units. Survivors (n = 41) and nonsurvivors (n = 20) differed significantly in HLA-DR expression at admission: survivors' median 84% (interquartile range 64%-98%) versus nonsurvivors' median 62% (interquartile range 47%-83%, P = 0.025 by Mann-Whitney test). Similarly, the analysis revealed statistically significant differences between survivors and nonsurvivors in admission plasma IL-10 levels and in admission Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores, but not in IL-4 levels. The areas under receiver operating curves (AUC) showed that both monocyte HLA-DR expression and plasma IL-4 level showed poor discriminative power in prediction of hospital mortality (AUC < 0.70). Only IL-10 levels on days 1 and 2 showed reasonable predictive power (AUCs 0.706 and 0.725, respectively). The highest AUC values were those of APACHE-II (0.786) and admission SOFA score (0.763). In conclusion, APACHE II and SOFA scores on admission showed better discriminatory power than HLA-DR expression and IL-10 and IL-4 levels in prediction of hospital mortality in critically ill patients with sepsis.

APACHE↗

PubMed2024

Omics studies in Behçet's disease.

PURPOSE OF REVIEW: In this review, we aimed to highlight recent findings from "-omics" studies in Behçet's disease. RECENT FINDINGS: Recent genomic studies in Behçet's disease identified possible risk loci associated with Behçet's disease related uveitis, neurologic involvement and gastrointestinal involvement. Additionally, sex-specific genetic effects were determined in Behçet's disease. Transcriptomic analyses of immune cells in Behçet's disease revealed that key inflammatory pathways such as NF-κB and MAPK have roles in Behçet's disease pathogenesis. Proteomic studies have highlighted the role of immune cell derived extracellular vesicles and identified potential biomarkers for vascular involvement and examined HLA I-bound immunopeptidomes. Metabolomics studies are still limited, but recent research has pointed to alterations in fatty acid metabolism and lipid profiles in Behçet's disease patient. SUMMARY: Omics studies have gained importance in the field of Behçet's disease through the generation of large data sets and efforts to extend their application are intensifying. These studies can provide opportunities for understanding Behçet's disease pathogenesis when they lead to testable hypotheses. Current challenges include the choice of appropriately homogeneous patient and control groups, effective data management and sharing, high cost and a rapidly increasing gap between the wealth of observational data generated and the relative paucity of controlled experimental efforts that could lead to mechanistic understanding.

Behcet Syndrome↗

PubMed2006

Novel therapeutic approaches to the treatment of chronic abdominal visceral pain.

Chronic abdominal visceral pain (CAVP) has a significant clinical impact and represents one of the most frequent and debilitating disorders in the general population. It also leads to a significant economic burden due to workdays lost, reduced productivity, and long-term use of medications with their associated side effects. Despite the availability of several therapeutic options, the management of patients with CAVP is often inadequate, resulting in frustration for both patients and physicians. This may in part be explained by the lack of understanding of the mechanisms underlying chronic pain; in contrast with acute pain in which the pathophysiology is relatively well known and has several satisfactory therapeutic options. Recently, the development of tools for brain investigation, such as functional magnetic resonance imaging, has provided new insights on the pathophysiology of chronic pain. These new data have shown that plastic changes in the central and peripheral nervous system might play an important role in the maintenance of chronic pain. Therefore, approaches aimed at the modulation of the nervous system, rather than the ones interfering with the inflammatory pathways, may be more effective for chronic pain treatment. We propose that noninvasive central nervous system stimulation, with transcranial magnetic stimulation (TMS), might be a novel therapeutic option for CAVP. This paper will present an overview of the pathophysiology and the available therapies for CAVP, focusing on the recent advances in the treatment of this pathology.

Abdominal Pain↗

PubMed1987

Recent investigations of mechanisms of chemically induced skin irritation in laboratory mice.

The time course, dose response, components of inflammation, and involvement of putative mediators of inflammation in irritation induced by different chemicals was compared using a mouse ear swelling technique. Differences in time courses of inflammation produced by the irritants were not solely due to differences in rates of penetration. Changes in blood flow and permeability of vessels were phasic with different numbers of phases induced by different irritants. Effects of antagonist, synthesis, inhibitors, and depleting agents of putative inflammatory mediators on intensity of inflammation varied for different irritants. These studies demonstrate that all chemicals do not produce skin irritation by a common inflammatory pathway.

Alkynes↗

PubMed2026

Spatial Transcriptomics Identifies Characteristic Immunological Niches in Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) is primarily driven by a Type 2 immune response, with T helper (TH2) cells producing IL-4 and IL-13, thereby promoting inflammation, itch, and a compromised skin barrier. Yet, the spatial organization of pathogenic immune cells and their interactions with stromal and epithelial compartments in human AD skin remain incompletely understood. METHODS: We performed 10× Genomics Visium spatial transcriptomics on FFPE skin biopsies from patients with AD (n = 6), psoriasis (n = 2), and healthy controls (n = 5). Data were integrated with AD single-cell RNA sequencing (scRNA-seq) datasets and complemented by imaging mass cytometry (IMC) and multiplex immunofluorescence (IF) to validate the spatial localization of immune cells. Cell-cell communication analysis revealed putative signaling interactions within immune niches. RESULTS: Spatial clustering resolved tissue compartments and demonstrated transcriptional dysregulation in keratinocytes in AD and psoriasis. AD lesions showed a conserved spatial organization of immune aggregates within the superficial dermis. Integration of scRNA-seq signatures revealed spatially organized co-localization of T cells and mature migratory dendritic cells (mmDCs). We developed a ring-based neighborhood analysis to characterize the cellular organization of the immune-stromal niches, revealing T cell-enriched regions surrounded by inflammatory fibroblasts and activated keratinocytes. Intercellular communication analysis further identified putative signaling within mmDC-T cell niches that may promote pathogenic T cell recruitment and activation. Application of tertiary lymphoid structure (TLS) signatures indicated the presence of TLS-like regions. IMC and IF validated the close spatial proximity between activated TH2 cells and mmDCs. CONCLUSION: AD lesions contain spatially organized TLS-like immune niches at the dermal-epidermal junction, characterized by the close association of T cells and mmDCs and coordinated interactions with surrounding stromal and epithelial compartments. These mmDC-T cell niches may represent potential targets for future therapeutic strategies aimed at disrupting persistent local inflammatory pathways and improving long-term disease control.

atopic dermatitis↗

PubMed2006

The effect of aprotinin on activated protein C-mediated downregulation of endogenous thrombin generation.

Thrombin plays a central role in coagulation and haemostasis. Binding of thrombin to thrombomodulin generates activated protein C (APC), which exerts a negative feedback on thrombin formation. Aprotinin, a natural proteinase inhibitor is used extensively during cardiac surgery because this procedure is often associated with profound activation of coagulation and inflammatory pathways. Some in vitro evidences suggest that aprotinin inhibits APC, but the clinical relevance is unclear. The recombinant human soluble thrombomodulin (rhsTM)-modified thrombin generation (TG) assay was used to investigate the effects of aprotinin on APC in plasma samples obtained from healthy volunteers, aprotinin-treated cardiac surgical patients and in protein C (PC)-depleted plasma. Based on the results of in vitro TG assay, addition of rhsTM (0.75-3.0 microg/ml) to volunteer or patient platelet-poor plasma significantly reduced (70.8 +/- 21.9 and 95.3% +/- 4.6%, respectively) thrombin formation when compared with PC-depleted plasma (8.3% +/- 5.2%). Aprotinin (100-200 KIU) caused a small, statistically insignificant decrease in the peak thrombin formation in normal and PC-deficient plasma (12.0 +/- 6.1%). In cardiac surgical patients, levels of functional PC, factor II, antithrombin and platelet significantly decreased after cardiopulmonary bypass (CPB). Soluble thrombomodulin concentrations were increased after CPB (3.5 +/- 2.2 to 5.0 +/- 2.2 ng/ml), but they were still within the normal range for human plasma. Our results showed that, even though endogenous PC level is decreased after CPB, it retains its activity in the presence of thrombomodulin, and aprotinin has limited inhibitory effect on APC generation.

Aged↗

PubMed2006

Cytokine production from sputum cells in eosinophilic versus non-eosinophilic asthmatics.

The inflammatory pathways involved in asthma are more complex than the sole Th2-mediated eosinophilic airway inflammation. Different phenotypes of asthma have been recently highlighted and are probably underlied by different immunological profiles. The aim of the study was to assess cytokine production from sputum cells in eosinophilic versus non-eosinophilic asthmatics. Induced sputum was obtained from 48 consecutive stable mild to moderate asthmatics (20 eosinophilic asthmatics, 28 non-eosinophilic asthmatics) and 31 healthy subjects. Cytokine released from sputum cells were measured by a home-made two-step sandwich immunoassay. Cytokines investigated were interleukin (IL)-4, IL-6, IL-10, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma. Sputum cells from eosinophilic asthmatics produced more IL-4 than those from both healthy subjects (P < 0.05) and non-eosinophilic asthmatics (P < 0.05). Conversely, sputum cells from eosinophilic asthma were found to release lower amounts of TNF-alpha than those from healthy subjects (P < 0.05). The group of non-eosinophilic asthmatics did not distinguish from healthy subjects with respect to any cytokines measured. Sputum cells from asthmatics exhibiting eosinophilic airway inflammation release more IL-4 and less TNF-alpha than those of healthy subjects. By contrast, non-eosinophilic asthmatics did not distinguish from healthy subjects by abnormal cytokine release from their sputum cells.

Adult↗

PubMed2006

Proteomic analysis of rat aorta during atherosclerosis induced by high cholesterol diet and injection of vitamin D3.

1. Atherosclerosis (AS) in rats displays important clinical similarities to human AS. 2. After the experimental model of AS in rat was established and using a proteomic approach, we compared the protein profiling of aorta tissues from healthy and AS rats. 3. Using two-dimensional electrophoresis (2-DE), over 1878 protein species were separated; among them, 1239 protein spots were matched between different gels with average matching rate of approximately 66%. Gel analysis and protein characterization have identified 58 protein spots whose abundance is significantly altered in AS rats. 4. By using matrix-associated laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS) and NCBInr database, 46 proteins were successfully identified. Among them, 18 proteins were of increased abundance in diseased tissues including a group of oxidization-related enzymes such as peroxiredoxin2 and NADH dehydrogenase Fe-S protein 6, components of inflammatory pathways such as lamin A, while 28 proteins were of decreased abundance in the diseased state, including CaM-KII inhibitory protein, transferring, fructose-bisphosphate aldolase. 5. We believe that these results would give insights into the cellular and molecular mechanisms involved in AS development and might lead to the discovery of novel diagnostic markers and new therapeutic opportunities.

Animals↗