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Experimental Animal Models (experimental + animal_models)
Selected AbstractsInsights into the Pathogenesis of Hydrocephalus from Transgenic and Experimental Animal ModelsBRAIN PATHOLOGY, Issue 3 2004Leslie Crews Hydrocephalus is a progressive brain disorder characterized by abnormalities in the flow of cerebrospinal fluid (CSF) and ventricular dilatation that leads to cerebral atrophy, and if left untreated, can be fatal. Genetic mutations, congenital malformations, infectious diseases, intracerebral hemorrhages and tumors are common conditions resulting in hydrocephalus. Although the causes of obstructive hydrocephalus are better understood, the mechanisms resulting in chronic, progressive communicating congenital and acquired hydrocephalus are less well understood. In this regard, recent studies in transgenic (tg) mice suggest that increased expression of cytokines such as TGF-,1 might play an important role by disrupting the vascular extracellular matrix (ECM) remodeling, promoting hemorrhages, and altering the reabsorption of CSF. In this context, the main objective of this manuscript is to provide an overview on the cellular and molecular mechanisms of hydrocephalus based on studies derived from tg and experimental animal models. [source] Advances in understanding bone cancer painJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2005M.J. Goblirsch Abstract Experimental animal models of bone cancer pain have emerged and findings have provided a unique glimpse into unraveling the mechanism that drives this debilitating condition. Key contributors to the generation and maintenance of bone cancer pain are tumor-induced osteolysis, tumor itself, and production of nociceptive mediators in the bone-tumor microenvironment. J. Cell. Biochem. © 2005 Wiley-Liss, Inc. [source] An updated view of hemostasis: mechanisms of hemostatic dysfuntion associated with sepsisJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 2 2005DACVECC, Kate Hopper BVSc Abstract Objective: To review the current understanding of mechanisms involved in normal hemostasis and to describe the changes associated with pro-inflammatory disease processes such as sepsis. Data sources: Original research articles and scientific reviews. Human data synthesis: Organ damage caused by sepsis is created in part by the interdependent relationship between hemostasis and inflammation. Markers of coagulation have been found to have prognostic value in human patients with sepsis and there are both experimental and clinical investigations of the therapeutic potential of modulating the hemostatic system in sepsis. Improvement of 28-day all-cause mortality in severe sepsis by treatment with recombinant human activated Protein C strongly supports the interdependence of hemostasis and inflammation in the pathophysiology of sepsis. Veterinary data synthesis: Publications reporting clinical evaluation of the hemostatic changes occurring in septic dogs or cats are minimal. Experimental animal models of sepsis reveal significant similarity between human and animal sepsis and may provide relevance to clinical veterinary medicine until prospective clinical evaluations are published. Conclusions: It is now apparent that inflammation and the coagulation system are intimately connected. Understanding this relationship provides some insight into the pathogenesis of the hemostatic changes associated with sepsis. This new updated view of hemostasis may lead to the development of novel therapeutic approaches to sepsis and disseminated intravascular coagulation in veterinary medicine. [source] In vivo imaging of retinal inflammation in experimental autoimmune uveoretinitisACTA OPHTHALMOLOGICA, Issue 2009Purpose Experimental animal models are essential for us to understand the pathogenesis of human diseases. Posterior uveoretinitis can be modelled in mice with IRBP immunization (i.e. experimental autoimmune uveitis, EAU), whereas a number of mouse models are also available for age-related macular degeneration (AMD). With the advancement in new technologies, it is now possible to image inflammatory retinal changes in experimental mice in vivo none invasively. The aim of the study is to clinical revisit the traditional retinal inflammation animal models with modern imaging techniques. Methods EAU was induced in C57B/6 mice with IRBP peptide 1-20. Aged CCL2 knockout mice were used as an AMD model. Retinal inflammatory changes were imaged in vivo non-invasively using topical endoscopic fundus imaging system and the scanning laser ophthalmoscopy (SLO) system. Results Inflammatory retinal changes in the early stages of EAU were characterised as retinal oedema, vascular sheathing, multiple small retinal infiltrates or large linear retinal infiltrates. "Snow-ball"-like vitreous infiltrates were observed in the inferior part of the fundus at the peak stage of EAU. Using SLO autofluorescent (AF)-macrophages were detected at the peak stages of EAU and were located predominately around inflamed retinal venules. At the late stages of EAU, retinal scars and intraretinal neovascular membranes were observed. In the retina aged CCL2 KO mice, regional retinal atrophy and dursen-like multiple lesions were observed. Dursen-like changes were autofluorescent in SLO examination. Ex vivo confocal microscopy indicated that they were not dursen but subretinal lipofuscin-loaded microglial cells. Conclusion EAU mimics many aspects of human posterior uveoretinitis including retinal vasculitis, multifocal choroiditis. Late stage EAU could be a good model for inflammation induced retinal neovascularisation. CCL2 KO mouse is a model of dry-AMD. [source] Genetics of anxiety disorders: the complex road from DSM to DNA,DEPRESSION AND ANXIETY, Issue 11 2009Jordan W. Smoller M.D. Sc.D. Abstract Anxiety disorders are among the most common psychiatric disorders, affecting one in four individuals over a lifetime. Although our understanding of the etiology of these disorders is incomplete, familial and genetic factors are established risk factors. However, identifying the specific casual genes has been difficult. Within the past several years, advances in molecular and statistical genetic methods have made the genetic dissection of complex disorders a feasible project. Here we provide an overview of these developments, with a focus on their implications for genetic studies of anxiety disorders. Although the genetic and phenotypic complexity of the anxiety disorders present formidable challenges, advances in neuroimaging and experimental animal models of anxiety and fear offer important opportunities for discovery. Real progress in identifying the genetic basis of anxiety disorders will require integrative approaches that make use of these biologic tools as well as larger-scale genomic studies. If successful, such efforts may yield novel and more effective approaches for the prevention and treatment of these common and costly disorders. Depression and Anxiety, 2009. © 2009 Wiley-Liss, Inc. [source] Viral infections as potential triggers of type 1 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2007Nienke van der Werf Abstract During the last decades, the incidence of type 1 diabetes (T1D) has increased significantly, reaching percentages of 3% annually worldwide. This increase suggests that besides genetical factors environmental perturbations (including viral infections) are also involved in the pathogenesis of T1D. T1D has been associated with viral infections including enteroviruses, rubella, mumps, rotavirus, parvovirus and cytomegalovirus (CMV). Although correlations between clinical presentation with T1D and the occurrence of a viral infection that precedes the development of overt disease have been recognized, causalities between viruses and the diabetogenic process are still elusive and difficult to prove in humans. The use of experimental animal models is therefore indispensable, and indeed more insight in the mechanism by which viruses can modulate diabetogenesis has been provided by studies in rodent models for T1D such as the biobreeding (BB) rat, nonobese diabetic (NOD) mouse or specific transgenic mouse strains. Data from experimental animals as well as in vitro studies indicate that various viruses are clearly able to modulate the development of T1D via different mechanisms, including direct ,-cell lysis, bystander activation of autoreactive T cells, loss of regulatory T cells and molecular mimicry. Data obtained in rodents and in vitro systems have improved our insight in the possible role of viral infections in the pathogenesis of human T1D. Future studies will hopefully reveal which human viruses are causally involved in the induction of T1D and this knowledge may provide directions on how to deal with viral infections in diabetes-susceptible individuals in order to delay or even prevent the diabetogenic process. Copyright © 2007 John Wiley & Sons, Ltd. [source] What role do extracellular matrix changes contribute to the cardiovascular disease burden of diabetes mellitus?DIABETIC MEDICINE, Issue 12 2005M. H. Tayebjee Abstract Matrix metalloproteinases (MMP) and their inhibitors (TIMP) are central factors in the control of extracellular matrix turnover. They are important in normal physiology and also during a range of pathological states. In this review, we have systematically identified clinical articles relevant to cardiovascular disease in diabetes from the last 10 years. Our aim was to outline the structure, function and regulation of metalloproteinases and their key roles in cardiomyopathy and vasculopathy in diabetes. We also explore the effects of drug intervention on both human subjects with diabetes and experimental animal models. The modulation of MMP and TIMP activity using drugs that affect the expression and function of these proteins may provide us with new ways to treat this serious and disabling disease, and we explore potential mechanisms and treatments. [source] Neuroprotective Strategies to Avert Seizure-Induced Neurodegeneration in EpilepsyEPILEPSIA, Issue 2007Janice R. Naegele Summary:, Neurodegeneration in limbic circuits is a hallmark feature of chronic temporal lobe epilepsy (TLE). Studies in experimental animal models and human patients indicate that seizure-induced neuronal injury involves some active, as well as passive cell death processes. Experimental approaches that inhibit active steps in cell death programs have been shown to reduce neuronal cell death and sclerosis, but not to prevent epileptogenesis in animal models of TLE. These findings suggest that we need additional research using both animal models and brain slices from human patients to understand the pathological mechanisms underlying seizure generation. Such comparative studies will also aid in evaluating the potential therapeutic value of inhibiting cell death in seizure disorders. [source] Signaling defects in anti-tumor T cellsIMMUNOLOGICAL REVIEWS, Issue 1 2008Alan B. Frey Summary: The immune response to cancer has been long recognized, including both innate and adaptive responses, showing that the immune system can recognize protein products of genetic and epigenetic changes in transformed cells. The accumulation of antigen-specific T cells within the tumor, the draining lymph node, and the circulation, either in newly diagnosed patients or resultant from experimental immunotherapy, proves that tumors produce antigens and that priming occurs. Unfortunately, just as obviously, tumors grow, implying that anti-tumor immune responses are either not sufficiently vigorous to eliminate the cancer or that anti-tumor immunity is suppressed. Both possibilities are supported by current data. In experimental animal models of cancer and also in patients, systemic immunity is usually not dramatically suppressed, because tumor-bearing animals and patients develop T-cell-dependent immune responses to microbes and to either model antigens or experimental cancer vaccines. However, inhibition of specific anti-tumor immunity is common, and several possible explanations of tolerance to tumor antigens or tumor-induced immunesuppression have been proposed. Inhibition of effective anti-tumor immunity results from the tumor or the host response to tumor growth, inhibiting the activation, differentiation, or function of anti-tumor immune cells. As a consequence, anti-tumor T cells cannot respond productively to developmental, targeting, or activation cues. While able to enhance the number and phenotype of anti-tumor T cells, the modest success of immunotherapy has shown the necessity to attempt to reverse tolerance in anti-tumor T cells, and the vanguard of experimental therapy now focuses on vaccination in combination with blockade of immunosuppressive mechanisms. This review discusses several potential mechanisms by which anti-tumor T cells may be inhibited in function. [source] Probiotics and inflammatory bowel disease: Is there a scientific rationale?INFLAMMATORY BOWEL DISEASES, Issue 2 2000Dr. Fergus Shanahan Abstract Most conventional forms of drug therapy suppress or modify the host immunoinflammatory response and neglect the other contributor to disease pathogenesis,the environmental microflora. Probiotics are live microbial food ingredients that alter the enteric microflora and have a beneficial effect on health. The rationale for using probiotics in IBD is mainly based on evidence from human studies and experimental animal models implicating intestinal bacteria in the pathogenesis of these disorders. The relationship between bacteria and intestinal inflammation is complex and does not appear to reflect a simple cause and effect. Similarly, the field of probiotics is complex and in need of rigorous research. Until the indigenous flora are better characterized and mechanisms of probiotic action defined, the promise of probiotics in IBD is unlikely to be fulfilled. Because of strain-specific variability and clinical and therapeutic heterogeneity within Crohn's disease and ulcerative colitis, it cannot be assumed that a given probiotic is equally suitable for all individuals. Although preliminary results of probiotic therapy in animal models and humans with ulcerative colitis and pouchitis have been encouraging, their efficacy in treatment or maintenance of remission of Crohn's disease remains to be clarified. However, the circumstantial evidence for some form of biotherapeutic modification of the enteric flora in Crohn's disease seems compelling. In the future, probiotics may offer a simple adjunct to conventional therapy with the emphasis on diet shifting from one of nutritional replenishment alone to a more functional role. [source] Matrix-induced autologous chondrocyte implantation in sheep: objective assessments including confocal arthroscopyJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2008C. W. Jones Abstract The assessment of cartilage repair has largely been limited to macroscopic observation, magnetic resonance imaging (MRI), or destructive biopsy. The aims of this study were to establish an ovine model of articular cartilage injury repair and to examine the efficacy of nondestructive techniques for assessing cartilage regeneration by matrix-induced autologous chondrocyte implantation (MACI). The development of nondestructive assessment techniques facilitates the monitoring of repair treatments in both experimental animal models and human clinical subjects. Defects (Ø 6 mm) were created on the trochlea and medial femoral condyle of 21 sheep randomized into untreated controls or one of two treatment arms: MACI or collagen-only membrane. Each group was divided into 8-, 10-, and 12-week time points. Repair outcomes were examined using laser scanning confocal arthroscopy (LSCA), MRI, histology, macroscopic ICRS grading, and biomechanical compression analysis. Interobserver analysis of the randomized blinded scoring of LSCA images validated our scoring protocol. Pearson correlation analysis demonstrated the correlation between LSCA, MRI, and ICRS grading. Testing of overall treatment effect independent of time point revealed significant differences between MACI and control groups for all sites and assessment modalities (Asym Sig,<,0.05), except condyle histology. Biomechanical analysis suggests that while MACI tissue may resemble native tissue histologically in the early stages of remodeling, the biomechanical properties remain inferior at least in the short term. This study demonstrates the potential of a multisite sheep model of articular cartilage defect repair and its assessment via nondestructive methods. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:292,303, 2008 [source] Phytochemical analysis and anti-allergic study of Agave intermixta Trel. and Cissus sicyoides L.JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2004A. M. Quílez Agave intermixta Trel. (Maguey) and Cissus sicyoides L. (Bejuco caro) are Caribbean plant species from the Dominican Republic used locally in traditional popular medicine that have shown an anti-inflammatory effect in experimental animal models. A phytochemical analysis on these species allowed us the isolation and identification of the steroidal sapogenins hecogenin and diosgenin from Maguey and the hydroxystilbene resveratrol from Bejuco caro. The effects of these plant extracts and their isolated constituents on compound-48/80-induced histamine release from peritoneal mast cells were investigated. Significant inhibition was produced by 0.5 mg mL,1 of a methanolic extract of Bejuco (41.1%) and by its constituent resveratrol (82.4%) at a dose of 250 ,M. However, none of the steroidal sapogenins from A. intermixta showed a significant inhibitory effect on histamine release from mast cells. From these results, it can be deduced that the in-vitro anti-allergic activity towards the release of histamine from mast cells shown by the methanolic extract of C. sicyoides may be mediated by its constituent resveratrol and might contribute to the anti-inflammatory activity shown by this species. [source] Controversies related to red blood cell transfusion in critically ill patientsJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 2 2010DACVECC, DACVIM, Jennifer E. Prittie DVM Abstract Objective , To review the evolution of and controversies associated with allogenic blood transfusion in critically ill patients. Data sources , Veterinary and human literature review. Human Data Synthesis , RBC transfusion practices for ICU patients have come under scrutiny in the last 2 decades. Human trials have demonstrated relative tolerance to severe, euvolemic anemia and a significant outcome advantage following implementation of more restricted transfusion therapy. Investigators question the ability of RBCs stored longer than 2 weeks to improve tissue oxygenation, and theorize that both age and proinflammatory or immunomodulating effects of transfused cells may limit efficacy and contribute to increased patient morbidity and mortality. Also controversial is the ability of pre- and post-storage leukoreduction of RBCs to mitigate adverse transfusion-related events. Veterinary Data Synthesis , While there are several studies evaluating the transfusion trigger, the RBC storage lesion and transfusion-related immunomodulation in experimental animal models, there is little research pertaining to clinical veterinary patients. Conclusions , RBC transfusion is unequivocally indicated for treatment of anemic hypoxia. However, critical hemoglobin or Hct below which all critically ill patients require transfusion has not been established and there are inherent risks associated with allogenic blood transfusion. Clinical trials designed to evaluate the effects of RBC age and leukoreduction on veterinary patient outcome are warranted. Implementation of evidence-based transfusion guidelines and consideration of alternatives to allogenic blood transfusion are advisable. [source] Insights into Serotonin Signaling Mechanisms Associated with Canine Degenerative Mitral Valve DiseaseJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2010M.A. Oyama Little is known about the molecular abnormalities associated with canine degenerative mitral valve disease (DMVD). The pathology of DMVD involves the differentiation and activation of the normally quiescent mitral valvular interstitial cell (VIC) into a more active myofibroblast phenotype, which mediates many of the histological and molecular changes in affected the valve tissue. In both humans and experimental animal models, increased serotonin (5-hydroxytryptamine, 5HT) signaling can induce VIC differentiation and myxomatous valve damage. In canine DMVD, numerous lines of evidence suggest that 5HT and related molecules such as transforming growth factor-, play a critical role in the pathogenesis of this disease. A variety of investigative techniques, including gene expression, immunohistochemistry, protein blotting, and cell culture, shed light on the potential role of 5HT in the differentiation of VIC, elaboration of myxomatous extracellular matrix components, and activation of mitogen-activated protein kinase pathways. These studies help support a hypothesis that 5HT and its related pathways serve as an important stimulus in canine DMVD. This review describes the pathological characteristics of canine DMVD, the organization and role of the 5HT pathway in valve tissue, involvement of 5HT in human and experimental models of valve disease, avenues of evidence that suggest a role for 5HT in naturally occurring DMVD, and finally, a overarching hypothesis describing a potential role for 5HT in canine DMVD. [source] Validation of connective tissue growth factor (CTGF/CCN2) and its gene polymorphisms as noninvasive biomarkers for the assessment of liver fibrosisJOURNAL OF VIRAL HEPATITIS, Issue 9 2009E. Kovalenko Summary., Clinical and experimental studies have demonstrated that connective-tissue growth factor (CTGF) expression is increased in fibrotic human liver and experimental animal models of liver fibrogenesis. CTGF has been linked to transforming growth factor-beta (TGF-,) pathways in fibroproliferative diseases and specific polymorphisms within the CTGF gene may predispose for fibrosis in systemic sclerosis. As CTGF is detectable in various human fluids (serum, plasma and urine), it may provide information about fibrotic remodelling processes and reflect hepatic TGF-, bioactivity. We established a novel ELISA for the measurement of serum CTGF and tested its clinical value in patients with chronic hepatitis C virus (HCV) infection and chronic liver disease (CLD). HCV infected patients (n = 138) had significantly higher serum CTGF levels than healthy controls. CTGF was linked to the histological degree of liver fibrosis. To expand the results to other aetiologies, a separate cohort of CLD patients (n = 129) was evaluated, showing higher serum CTGF than healthy controls and again an association with advanced stages of liver cirrhosis (Child B and C). Although independent of the underlying aetiology, serum CTGF was most powerful in indicating fibrosis/advanced disease states in HCV-related disorders. The genotyping of six polymorphisms (rs6917644, rs9399005, rs6918698, rs9493150, rs2151532 and rs11966728) covering the CTGF locus in 365 patients suffering from chronic hepatitis C revealed that none of these polymorphisms showed a genotypic or allelic association with the severity of hepatic fibrosis. Taken together, serum CTGF is suitable for determination of hepatic fibrosis and most powerful in patients with chronic HCV infection. [source] Identification of operationally tolerant liver transplant recipients,LIVER TRANSPLANTATION, Issue S2 2010Alberto Sánchez-Fueyo KEY POINTS: (1) Liver allografts exhibit intrinsic tolerogenic properties that result in their spontaneous acceptance in many experimental animal models. (2) In clinical transplantation, liver allografts require milder immunosuppression (IS) regimens than other organs, are remarkably resistant to antibody-mediated rejection, and only very rarely are lost because of immunological insults. (3) A fraction of stable liver transplant recipients can withdraw from all IS therapy and then maintain normal graft function and not experience rejection. This phenomenon is known as spontaneous operational tolerance. (4) The intentional discontinuation of IS in stable liver transplant recipients has led to successful weaning in almost 20% of recipients, but the true prevalence of spontaneous operational tolerance in unselected recipients is still unknown. (5) The prevalence could be higher in pediatric recipients undergoing transplantation before 1 year of age and in adult recipients with more than 10 years of posttransplant follow-up. (6) Rejection occurring during medically supervised IS weaning trials tends to be mild and, in the overwhelming majority of cases, can be easily resolved without the administration of high-dose IS. (7) Tolerant liver recipients exhibit specific transcriptional patterns in peripheral blood and in liver tissue that may constitute future diagnostic markers of tolerance. (8) There is still no formal proof that the discontinuation of low-dose IS in long-term surviving liver recipients improves the morbidity and mortality rates associated with IS therapy. Liver Transpl 16:S82-S86, 2010. © 2010 AASLD. [source] Mesangial cell proliferation inhibitors for the treatment of proliferative glomerular diseaseMEDICINAL RESEARCH REVIEWS, Issue 1 2003Yasuhisa Kurogi Abstract Mesangial cells (MC) serve a number of functions in the renal glomerular capillary including structural support of the capillary tuft, modulation of glomerular hemodynamics, and a phagocytic function allowing removal of macromolecules and immune complexes. The proliferation of MC is a prominent feature of glomerular disease including IgA nephropathy, membranoproliferative glomerulonephritis, lupus nephritis, and diabetic nephropathy. In experimental animal models of nephritis, MC proliferation frequently precedes and is linked to the increase of extracellular matrix in the mesangium and glomerulosclerosis. Reduction of MC proliferation in glomerular disease models by treatment with heparin, low-protein diet, or antibodies to platelet-derived growth factor (PDGF), have been shown to reduce extracellular matrix expansion and glomerulosclerotic changes. Therefore, MC proliferation inhibitors may offer therapeutic opportunities for the treatment of proliferative glomerular disease. It is also known that the MC proliferation is inhibited by many kinds of pharmacological drugs, for example, angiotensin converting enzyme (ACE) inhibitors, leukotriene D4 (LTD4) antagonists, PDGF inhibitors, matrix metalloproteinases (MMP) inhibitors, 3-hydroxy-3 methyl glutaryl-coenzymeA (HMG-CoA) inhibitors, cyclin-dependent kinases (CDK) inhibitors, and others. This review summarizes the recently reported MC proliferation inhibitors with their pharmacological properties on the basis of their chemical structures. © 2002 Wiley Periodicals, Inc. Med Res Rev, 23, No. 1, 15,31, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10028 [source] T cell-mediated immunoregulation in the gastrointestinal tractALLERGY, Issue 4 2009L. Saurer In the intestinal tract, only a single layer of epithelial cells separates innate and adaptive immune effector cells from a vast amount of antigens. Here, the immune system faces a considerable challenge in tolerating commensal flora and dietary antigens while preventing the dissemination of potential pathogens. Failure to tightly control immune reactions may result in detrimental inflammation. In this respect, ,conventional' regulatory CD4+ T cells, including naturally occurring and adaptive CD4+ CD25+ Foxp3+ T cells, Th3 and Tr1 cells, have recently been the focus of considerable attention. However, regulatory mechanisms in the intestinal mucosa are highly complex, including adaptations of nonhaematopoietic cells and innate immune cells as well as the presence of unconventional T cells with regulatory properties such as resident TCR,, or TCR,, CD8+ intraepithelial lymphocytes. This review aims to summarize the currently available knowledge on conventional and unconventional regulatory T cell subsets (Tregs), with special emphasis on clinical data and the potential role or malfunctioning of Tregs in four major human gastrointestinal diseases, i.e. inflammatory bowel diseases, coeliac disease, food allergy and colorectal cancer. We conclude that the clinical data confirms some but not all of the findings derived from experimental animal models. [source] Dietary fiber, low-molecular-weight food constituents and colo-rectal inflammation in animal models , A reviewMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 10 2009Dieter Schrenk Abstract This review provides an overview over studies in experimental animals aimed at elucidating the influence of dietary constituents on colo-rectal inflammation. Human studies as well as in vitro investigations will not be covered. In experimental animals, a variety of chemical treatments and genetic modifications, lead to various types of gut inflammation. In a number of these models, there is good evidence for an anti-inflammatory action of dietary tocopherols, certain polyphenols, and curcumin at relatively high oral doses. It has also been established, that oral application of fats and oils rich in n-3 PUFAs and/or conjugated linoleic acid (CLA) can attenuate certain types of colitis in experimental animal models. While the effect of dietary calcium on experimental colitis is less clear, there are hints indicating that certain high-fiber diets or diets rich in digestion-resistant carbohydrates ("fiber") can attenuate experimental colitis in animals, although contradictory results have been reported. In summary, the anti-inflammatory potency of dietary constituents on colon inflammation in experimental animals seems to be rather limited. The reasons for this lack of activity seem to be manifold including pharmacokinetic limitations and intestinal degradation of the compounds, in particular insufficient local, i. e., intra- or sub-mucosal levels of the effective compounds, and general limitations of animal models. [source] Potential of resveratrol in anticancer and anti-inflammatory therapyNUTRITION REVIEWS, Issue 8 2008Chibuike C Udenigwe Phytochemicals present in food have shown significant prospects in the treatment and management of a vast array of human diseases. Resveratrol is a stilbene-type aromatic phytoalexin predominantly found in grapes, peanuts, berries, turmeric, and other food products. Resveratrol has been reported to exhibit several physiological activities including anticancer and anti-inflammatory activities in vitro and in experimental animal models, as well as in humans. Anticancer activity of this compound is mainly due to induction of apoptosis via several pathways, as well as alteration of gene expressions, all leading to a decrease in tumor initiation, promotion, and progression. Resveratrol exhibits anti-inflammatory activity through modulation of enzymes and pathways that produce mediators of inflammation and also induction of programmed cell death in activated immune cells. Resveratrol has been shown to produce no adverse effects, even when consumed at high concentrations. Hence, resveratrol possesses good potential to be used as an adjunctive or alternative therapy for cancer and inflammatory diseases. [source] Probiotics: Immunomodulation and Evaluation of Safety and EfficacyNUTRITION REVIEWS, Issue 1 2006Janine Ezendam PhD The intake of probiotics has been associated with beneficial effects on the immune system, such as improved disease resistance and diminished risk of allergies. This review gives an overview of the immunomodulatory effects of probiotics investigated with in vitro assays, experimental animal models, and clinical trials, and explores possible mechanisms underlying the immunomodulatory effects. Immunomodulation, however, is not always beneficial and might induce detrimental effects; therefore, a scheme is proposed for benefit-risk assessment of immunomodulation by probiotics. Within this scheme, expert judgment based on data derived from a panel of in vitro assays, animal models, and clinical trials should lead to conclusions on efficacy and safety aspects of probiotics. [source] Insights into the Pathogenesis of Hydrocephalus from Transgenic and Experimental Animal ModelsBRAIN PATHOLOGY, Issue 3 2004Leslie Crews Hydrocephalus is a progressive brain disorder characterized by abnormalities in the flow of cerebrospinal fluid (CSF) and ventricular dilatation that leads to cerebral atrophy, and if left untreated, can be fatal. Genetic mutations, congenital malformations, infectious diseases, intracerebral hemorrhages and tumors are common conditions resulting in hydrocephalus. Although the causes of obstructive hydrocephalus are better understood, the mechanisms resulting in chronic, progressive communicating congenital and acquired hydrocephalus are less well understood. In this regard, recent studies in transgenic (tg) mice suggest that increased expression of cytokines such as TGF-,1 might play an important role by disrupting the vascular extracellular matrix (ECM) remodeling, promoting hemorrhages, and altering the reabsorption of CSF. In this context, the main objective of this manuscript is to provide an overview on the cellular and molecular mechanisms of hydrocephalus based on studies derived from tg and experimental animal models. [source] Perspectives on cancer immuno-epidemiologyCANCER SCIENCE, Issue 12 2004Kei Nakachi Estimating human cancer risk based on host-environment interaction is one task of epidemiology, and it has provided indispensable knowledge for prevention of cancer. The recent development of gene-engineered mice has also provided solid evidence about the relationship between cancer development and immunity. The aim of this review is to discuss the possible contribution of epidemiology to understanding the role of immunity in host defense against cancer, and also to assess the involvement of inflammation in the occurrence of selected cancers. Here we look at the concepts of cancer immunosurveillance and infection-inflammation-cancer, and include a brief introduction to recent studies in humans and experimental animal models. It has been postulated for many years that the immune system has the ability to recognize and eliminate nascent transformed cells in the body (so-called cancer immunosurveillance hypothesis), and this idea has recently obtained strong support from animal experiments. In humans, follow-up studies among immunosuppressed transplant recipients revealed a remarkably increased risk of not only selected malignancies, but also cancers with no known viral etiology. On the other hand, a prospective cohort study among the general population revealed that individuals with low natural cytotoxic activity of peripheral blood lymphocytes had an increased risk of cancer development. More studies are warranted to allow the construction of a model for the interaction between host immunity, aging, and the environment. The host immune system is also involved in inflammatory responses to pathogen infection: insufficient immune function of the host, or repeated infection, may result in persistent inflammation, where growth/ survival factors continuously act on initiated cells. The combined use of biomarkers will be necessary to define low-grade persistent inflammation in future cohort studies; and, in addition to these phenotype marker-based cohort studies, one plausible future direction will be a genomic approach that can be undertaken within cohort studies, looking at the genetic background underlying individual variations in phenotype markers. [source] METHODS FOR STUDYING THE PHYSIOLOGY OF KIDNEY OXYGENATIONCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2008Roger G Evans SUMMARY 1An improved understanding of the regulation of kidney oxygenation has the potential to advance preventative, diagnostic and therapeutic strategies for kidney disease. Here, we review the strengths and limitations of available and emerging methods for studying kidney oxygen status. 2To fully characterize kidney oxygen handling, we must quantify multiple parameters, including renal oxygen delivery (DO2) and consumption (VO2), as well as oxygen tension (Po2). Ideally, these parameters should be quantified both at the whole-organ level and within specific vascular, tubular and interstitial compartments. 3Much of our current knowledge of kidney oxygen physiology comes from established techniques that allow measurement of global kidney DO2 and VO2, or local tissue Po2. When used in tandem, these techniques can help us understand oxygen mass balance in the kidney. Po2 can be resolved to specific tissue compartments in the superficial cortex, but not deep below the kidney surface. We have limited ability to measure local kidney tissue DO2 and VO2. 4Mathematical modelling has the potential to provide new insights into the physiology of kidney oxygenation, but is limited by the quality of the information such models are based on. 5Various imaging techniques and other emerging technologies have the potential to allow Po2 mapping throughout the kidney and/or spatial resolution of Po2 in specific renal tissues, even in humans. All currently available methods have serious limitations, but with further refinement should provide a pathway through which data obtained from experimental animal models can be related to humans in the clinical setting. [source] Effects of calcitriol on the immune system: new possibilities in the treatment of glomerulonephritisCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2003Vincenzo Panichi Summary 1.,1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the hormonal form of vitamin D, is widely appreciated to play a central role in calcium and phosphate homeostasis. However, it is becoming increasingly clear that the sterol also play an important role in the regulation of cellular growth, haematopoietic tissues and the immune system, as well as in the modulation of hormone secretion by several endocrine glands. 2.,In the present review, some of the mechanisms by which 1,25(OH)2D3 regulates immune function are highlighted. Moreover, a number of studies on the effects of calcitriol in several experimental animal models of renal disease are reported, suggesting new possibilities in the therapy of glomerulonephritis. [source] | ||||||||||||||||||||||||||||