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Inflammatory Mechanisms (inflammatory + mechanism)

Distribution by Scientific Domains

Medical Sciences	86%

Selected Abstracts

Viral ssRNA Induces First Trimester Trophoblast Apoptosis through an Inflammatory Mechanism

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010
Paulomi B. Aldo
Citation Aldo PB, Mulla MJ, Romero R, Mor G, Abrahams VM. Viral ssRNA induces first-trimester trophoblast apoptosis through an inflammatory mechanism. Am J Reprod Immunol 2010; 64: 27,37 Problem, Infection during pregnancy represents a significant cause of mobility and mortality. While viruses pose a major threat, little is known about their effect on early pregnancy, or the mechanisms involved. The objective of this study was to characterize the trophoblast response following exposure to viral ssRNA. Method of study, First trimester trophoblast cells were treated with or without viral ssRNA. Cytokine production was measured using multiplex analysis and ELISA. Apoptosis was determined using Hoechst staining, cell viability, and caspase activity assays. Results, Treatment of trophoblasts with viral ssRNA increased their secretion of IL-8, IL-6, and IFN,. However, the ssRNA also induced trophoblast apoptosis. To test whether the viral ssRNA-induced inflammatory response was responsible for this induction of apoptosis, conditioned media (CM) from trophoblasts were added to a fresh culture of cells. The CM from viral ssRNA-treated induced higher levels of trophoblast apoptosis than the control CM. Moreover, recombinant IFN, induced trophoblast apoptosis. Conclusion, We demonstrate that viral ssRNA induces a pro-inflammatory and type I interferon response in the trophoblast and this inflammatory process may indirectly induce trophoblast apoptosis. These results provide a novel mechanism by which certain viral infections might compromise placental integrity and function, and therefore, pregnancy outcome. [source]

Development of antiinflammatory therapy for Alzheimer's disease

DRUG DEVELOPMENT RESEARCH, Issue 3 2002
Paul S. Aisen
Abstract Inflammatory mechanisms are active in the Alzheimer's disease (AD) brain. Studies that range from epidemiological surveys to therapeutic trials in transgenic mice provide growing support for the theory that antiinflammatory drugs may be useful in the prevention and/or treatment of the disease. Randomized controlled trials in humans have not yet confirmed this theory. However, prevention and treatment trials continue to test specific antiinflammatory strategies for AD. Drug Dev. Res. 56:421,427, 2002. © 2002 Wiley-Liss, Inc. [source]

What Is the mechanism of SIDS?

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2009
Clues from epidemiology
Abstract The cause of sudden infant death syndrome (SIDS) is unknown. Many mechanisms have been postulated, although thermal stress, rebreathing of expired gases and infection/inflammation seem the most viable hypotheses for the causation of SIDS. Deaths from SIDS have reduced dramatically following the recommendation not to place infants to sleep prone. Epidemiological data have shown that prone sleeping position is more risky in winter, colder latitudes, higher altitudes, if the infant is unwell or has excessive bedding or clothing. This suggests prone sleeping position involves either directly or indirectly a thermal mechanism. SIDS caused by an infective/inflammatory mechanism might be associated with deaths occurring during the night. Rebreathing of expired gases, airway obstruction, long QT syndrome and other genetic conditions may explain a small number of sudden unexpected deaths in infancy. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 215,222, 2009 [source]

Viral ssRNA Induces First Trimester Trophoblast Apoptosis through an Inflammatory Mechanism

Dramatic efficacy of infliximab in cauda equina syndrome complicating ankylosing spondylitis

ARTHRITIS & RHEUMATISM, Issue 6 2009
Divi Cornec
Cauda equina syndrome is an uncommon complication of ankylosing spondylitis (AS) characterized by the slow and insidious development of severe neurologic impairment. Imaging studies usually show a wide lumbar canal with dural ectasia. No medical or surgical treatment has been proven effective. We managed the care of a 66-year-old man who had longstanding AS and clinical features of cauda equina syndrome, including anal incontinence and buttock hypoesthesia. Magnetic resonance imaging demonstrated no cause for these symptoms other than AS. The patient was treated with infliximab, a monoclonal antibody to tumor necrosis factor , that is used for the treatment of active AS. After 3 infliximab infusions, sphincter control and sensation were normal. The treatment was continued, and he was still doing well 1 year later. This is the first report of an effective treatment for cauda equina syndrome complicating AS. Our case report strongly supports an inflammatory mechanism to this condition. [source]

The Blood,Brain Barrier and Epilepsy

EPILEPSIA, Issue 11 2006
Emily Oby
Summary:, During the past several years, there has been increasing interest in the role of the blood,brain barrier (BBB) in epilepsy. Advances in neuroradiology have enhanced our ability to image and study the human cerebrovasculature, and further developments in the research of metabolic deficiencies linked to seizure disorders (e.g., GLUT1 deficiency), neuroinflammation, and multiple drug resistance to antiepileptic drugs (AEDs) have amplified the significance of the BBB's relationship to epilepsy. Prior to 1986, BBB research in epilepsy focused on three main areas: ultrastructural studies, brain glucose availability and transport, and clinical uses of AEDs. However, contrast-based imaging techniques and medical procedures such as BBB disruption provided a framework that demonstrated that the BBB could be reversibly disrupted by pathologic or iatrogenic manipulations, with important implications in terms of CNS drug delivery to "multiple drug resistant" brain. This concept of BBB breakdown for therapeutic purposes has also unveiled a previously unrecognized role for BBB failure as a possible etiologic mechanism in epileptogenesis. Finally, a growing body of evidence has shown that inflammatory mechanisms may participate in the pathological changes observed in epileptic brain, with increasing awareness that blood-borne cells or signals may participate in epileptogenesis by virtue of a leaky BBB. In this article we will review the relationships between BBB function and epilepsy. In particular, we will illustrate consensus and divergence between clinical reality and animal studies. [source]

Cytokines and Cognition,The Case for A Head-to-Toe Inflammatory Paradigm

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 12 2002
Craig J. Wilson MBBS
The brain is not only immunologically active of its own accord, but also has complex peripheral immune interactions. Given the central role of cytokines in neuroimmmunoendocrine processes, it is hypothesized that these molecules influence cognition via diverse mechanisms. Peripheral cytokines penetrate the blood-brain barrier directly via active transport mechanisms or indirectly via vagal nerve stimulation. Peripheral administration of certain cytokines as biological response modifiers produces adverse cognitive effects in animals and humans. There is abundant evidence that inflammatory mechanisms within the central nervous system (CNS) contribute to cognitive impairment via cytokine-mediated interactions between neurons and glial cells. Cytokines mediate cellular mechanisms subserving cognition (e.g., cholinergic and dopaminergic pathways) and can modulate neuronal and glial cell function to facilitate neuronal regeneration or neurodegeneration. As such, there is a growing appreciation of the role of cytokine-mediated inflammatory processes in neurodegenerative diseases such as Alzheimer's disease and vascular dementia. Consistent with their involvement as mediators of bidirectional communication between the CNS and the peripheral immune system, cytokines play a key role in the hypothalamic-pituitary-adrenal axis activation seen in stress and depression. In addition, complex cognitive systems such as those that underlie religious beliefs, can modulate the effects of stress on the immune system. Indirect means by which peripheral or central cytokine dysregulation could affect cognition include impaired sleep regulation, micronutrient deficiency induced by appetite suppression, and an array of endocrine interactions. Given the multiple levels at which cytokines are capable of influencing cognition it is plausible that peripheral cytokine dysregulation with advancing age interacts with cognitive aging. [source]

HIV-Tat protein induces oxidative and inflammatory pathways in brain endothelium

JOURNAL OF NEUROCHEMISTRY, Issue 1 2003
Michal Toborek
Abstract Impaired function of the brain vasculature might contribute to the development of HIV-associated dementia. For example, injury or dysfunction of brain microvascular endothelial cells (BMEC) can lead to the breakdown of the blood,brain barrier (BBB) and thus allow accelerated entry of the HIV-1 virus into the CNS. Mechanisms of injury to BMEC during HIV-1 infection are not fully understood, but the viral gene product Tat may be, at least in part, responsible for this effect. Tat can be released from infected perivascular macrophages in the CNS of patients with AIDS, and thus BMEC can be directly exposed to high concentrations of this protein. To study oxidative and inflammatory mechanisms associated with Tat-induced toxicity, BMEC were exposed to increasing doses of Tat1,72, and markers of oxidative stress, as well as redox-responsive transcription factors such as nuclear factor-,B (NF-,B) and activator protein-1 (AP-1), were measured. Tat1,72 treatment markedly increased cellular oxidative stress, decreased levels of intracellular glutathione and activated DNA binding activity and transactivation of NF-,B and AP-1. To determine if Tat1,72 can stimulate inflammatory responses in brain endothelium in vivo, expression of monocyte chemoattractant protein-1 (MCP-1), an NF-,B and AP-1-dependent chemokine, was studied in brain tissue in mice injected with Tat1,72 into the right hippocampus. Tat1,72 markedly elevated the MCP-1 mRNA levels in brain tissue. In addition, a double immunohistochemistry study revealed that MCP-1 protein was markedly overexpressed on brain vascular endothelium. These data indicate that Tat1,72 can induce redox-related inflammatory responses both in in vitro and in vivo environments. These changes can directly lead to disruption of the BBB. Thus, Tat can play an important role in the development of detrimental vascular changes in the brains of HIV-infected patients. [source]

Important research questions in allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis , a GA2LEN study

ALLERGY, Issue 4 2009
C. Bachert
Chronic rhinosinusitis is one of the most common health care challenges, with significant direct medical costs and severe impact on lower airway disease and general health outcomes. The diagnosis of chronic rhinosinusitis (CRS) currently is based on clinical signs, nasal endoscopy and CT scanning, and therapeutic recommendations are focussing on 2 classes of drugs, corticosteroids and antibiotics. A better understanding of the pathogenesis and the factors amplifying mucosal inflammation therefore seems to be crucial for the development of new diagnostic and therapeutic tools. In an effort to extend knowledge in this area, the WP 2.7.2 of the GA2LEN network of excellence currently collects data and samples of 1000 CRS patients and 250 control subjects. The main objective of this project is to characterize patients with upper airway disease on the basis of clinical parameters, infectious agents, inflammatory mechanisms and remodeling processes. This collaborative research will result in better knowledge on patient phenotypes, pathomechanisms, and subtypes in chronic rhinosinusitis. This review summarizes the state of the art on chronic rhinosinusitis and nasal polyposis in different aspects of the disease. It defines potential gaps in the current research, and points to future research perspectives and targets. [source]

Eosinophil cationic protein in infants with respiratory syncytial virus bronchiolitis: Predictive value for subsequent development of persistent wheezing

PEDIATRIC PULMONOLOGY, Issue 6 2001
Massimo Pifferi MD
Abstract Infants with acute bronchiolitis during the first months of life are at increased risk of developing persistent wheezing and bronchial asthma later in life. The study of eosinophil cationic protein (ECP) suggests that eosinophil-related inflammatory mechanisms may play a role in respiratory syncytial virus (RSV) bronchiolitis. The aim of our study was to verify whether serum ECP (s-ECP) measurements are useful in predicting the development of persistent wheezing in children affected by RSV bronchiolitis during a 5 years follow-up period. Forty-eight infants were enrolled prospectively (mean age: 153.5 days). All had a clinical and radiological diagnosis of acute bronchiolitis and confirmed RSV infection. Peripheral eosinophil counts, levels of s-ECP, and serum IgE concentrations were measured during bronchiolitis. Five years later the children were re-evaluated in regard to their respiratory symptoms (standardized questionnaires) and atopic status (specific IgE levels). We observed significantly higher s-ECP levels (P <,0.001) at enrollment in subjects who developed persistent wheezing compared to subjects who did not show late wheezing. Initial s-ECP values allowed significant and correct prediction of persistent wheezing (P <,0.001). The risk to develop respiratory symptoms was 9.73 higher for infants with s-ECP levels ,,8,,g/L than for those with s-ECP levels <8,,g/L (P <,0.0001). In conclusion, our study suggests that s-ECP levels in infants with bronchiolitis are useful in predicting the risk to develop wheezing in the subsequent 5 years. Pediatr Pulmonol. 2001; 31:419,424. © 2001 Wiley-Liss, Inc. [source]

The ,Indirect' Effects of Cytomegalovirus Infection

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009
R. B. Freeman
Cytomegalovirus (CMV) remains the most important infection in the immunocompromized host even in the era of effective therapy. CMV is usually acquired early in life and can be transmitted by contact with infected body fluids. In the immunocompetent population, primary infection is almost always of little clinical consequence. However, CMV infection in immunocompromized patients, especially those naive to CMV exposure, can cause tissue invasive disease, severe symptoms and/or death. However, beyond these direct effects, increasing in vitro evidence is accumulating that suggests CMV has many other effects on the host's immune response which may explain some of the detrimental consequences for the immunosuppressed patient, and may also be partially responsible for a variety of conditions in immunocompetent individuals. In its latent state, CMV employs several mechanisms to evade detection by the host's immune system. The virus also employs other methods to take advantage of activation of the immune system and replicate in sites of inflammation. This review focuses on the immunosuppressive and inflammatory mechanisms that have been attributed to CMV and will relate them to some of the clinical sequellae that have been associated with the indirect effects of CMV infection. [source]

Donor Fas Is Not Necessary for T-Cell-Mediated Rejection of Mouse Kidney Allografts

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2008
D. Kayser
It is important to resolve whether T-cell-mediated rejection (TCMR) is mediated by contact-dependent cytotoxicity or by contact-independent inflammatory mechanisms. We recently showed that the cytotoxic molecules perforin and granzymes A and B are not required for TCMR of mouse kidney transplants. Nevertheless, TCMR could still be mediated by cytotoxicity via Fas on donor cells engaging Fas ligand on host T cells. We examined whether the diagnostic TCMR lesions would be abrogated if donor Fas was absent, particularly in hosts deficient in perforin or granzymes A and B. Kidneys from Fas-deficient donors transplanted into major histocompatibility complex (MHC)- mismatched hosts developed tubulitis and diffuse interstitial infiltration indistinguishable from wild-type (WT) allografts, even in hosts deficient in perforin and granzymes A and B. Gene expression analysis revealed similar molecular disturbances in Fas-deficient and WT allografts at day 21 transplanted into WT, perforin and granzyme A/B-deficient hosts, indicating epithelial injury and dedifferentiation. Thus, donor Fas is not necessary for TCMR diagnostic lesions or molecular changes, even in the absence of perforin,granzyme mechanisms. We propose that in TCMR, interstitial effector T cells mediate parenchymal injury by inflammatory mechanisms that require neither the perforin,granzyme nor the Fas,Fas ligand cytotoxic mechanisms. [source]

S100A12 is a novel molecular marker differentiating systemic-onset juvenile idiopathic arthritis from other causes of fever of unknown origin

ARTHRITIS & RHEUMATISM, Issue 12 2008
Helmut Wittkowski
Objective Fever of unknown origin (FUO) in children presents a diagnostic challenge. The differential diagnosis includes systemic-onset juvenile idiopathic arthritis (JIA), an autoinflammatory syndrome associated with activation of phagocytic cells that, at presentation, is difficult to differentiate from severe systemic infections. The aim of this study was to investigate whether serum concentrations of the phagocytic proinflammatory protein S100A12 may help in deciding whether to treat patients with FUO with antibiotics or immunosuppressive agents. Methods Serum samples were obtained from 45 healthy control subjects and from 240 patients (60 with systemic-onset JIA, 17 with familial Mediterranean fever [FMF], 18 with neonatal-onset multisystem inflammatory disease [NOMID], 17 with Muckle-Wells syndrome [MWS], 40 with acute lymphoblastic leukemia [ALL], 5 with acute myeloblastic leukemia [AML], and 83 with systemic infections). All samples were collected at the time of presentation, before the initiation of any treatment, and concentrations of S100A12 were determined by enzyme-linked immunosorbent assay. Results The mean ± 95% confidence interval serum levels of S100A12 were as follows: in patients with JIA, 7,190 ± 2,690 ng/ml; in patients with FMF, 6,720 ± 4,960 ng/ml; in patients with NOMID, 720 ± 450 ng/ml; in patients with MWS, 150 ± 60 ng/ml; in patients with infections, 470 ± 160 ng/ml; in patients with ALL, 130 ± 80 ng/ml; in patients with AML, 45 ± 60 ng/ml; in healthy control subjects, 50 ± 10 ng/ml. The sensitivity and specificity of S100A12 to distinguish between systemic-onset JIA and infections were 66% and 94%, respectively. Conclusion S100A12, a marker of granulocyte activation, is highly overexpressed in patients with systemic-onset JIA or FMF, which may point to as-yet unknown common inflammatory mechanisms in these diseases. The measurement of S100A12 serum levels may provide a valuable diagnostic tool in the evaluation of FUO. [source]

Immunological and inflammatory mechanisms in ocular allergy with special reference to vernal keratoconjunctivitis.

ACTA OPHTHALMOLOGICA, Issue 2 2001
Clinical, experimental studies
No abstract is available for this article. [source]