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 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human colonic microbiota imparts metabolic versatility on the colon, interacts at many levels in healthy intestinal and systemic metabolism, and plays protective roles in chronic disease and acute infection. Colonic bacterial metabolism is largely dependant on dietary residues from the upper gut. Carbohydrates, resistant to digestion, drive colonic bacterial fermentation and the resulting end products are considered beneficial. Many colonic species ferment proteins but the end products are not always beneficial and include toxic compounds, such as amines and phenols. Most components of a typical Western diet are heat processed. The Maillard reaction, involving food protein and sugar, is a complex network of reactions occurring during thermal processing. The resultant modified protein resists digestion in the small intestine but is available for colonic bacterial fermentation. Little is known about the fate of the modified protein but some Maillard reaction products (MRP) are biologically active by, e. g. altering bacterial population levels within the colon or, upon absorption, interacting with human disease mechanisms by induction of inflammatory responses. This review presents current understanding of the interactions between MRP and intestinal bacteria. Recent scientific advances offering the possibility of elucidating the consequences of microbe-MRP interactions within the gut are discussed.
Mol Nutr Food Res 2006 Sep
PMID:Metabolism of Maillard reaction products by the human gut microbiota--implications for health. 1667 Oct 57

Caloric restriction extends longevity and reduces the onset of chronic disease in many animal models. Recently, caloric restriction was shown in humans to be associated with lower blood pressure, decreased systemic inflammation, and improved cardiac diastolic parameters. However, the causation and mechanisms of caloric restriction were obscured by the varied diet composition of the participants. The Dahl salt-sensitive rat which develops gradual, hypertension-associated diastolic dysfunction was used in this study to assess the impact of caloric restriction upon decompensated pressure-overload hypertrophy. Male Dahl salt-sensitive rats were provided either a low-salt diet or a high-salt diet to initiate heart failure progression. A further subset of high-salt rats underwent 15% calorie restriction, with salt load held constant. Parameters measured included serial systolic blood pressure, body weight, and changes of left ventricular systolic and diastolic parameters and ventricular geometry by echocardiography. After 18 weeks, fasting glucose, blood lipids, heart weight, kidney weight, lung weight, plasma interleukin-6 and TNF-alpha, and cardiac lipid peroxidation were measured. Low-salt rats did not develop heart failure. While high-salt rats displayed features of decompensated pressure-overload hypertrophy, moderate calorie restriction remarkably reduced morbidity. Compared to the high-salt fed group, the high-salt, calorie-restricted group showed reduced blood pressure, delayed onset of cachexia, lower fasting hyperlipidemia, lower cardiac, renal and lung weight, less plasma IL-6 and TNF-alpha, less cardiac oxidative damage, and improved diastolic chamber function and cardiac index. Modest calorie restriction, independent of salt intake, reduced pathogenesis in this well described model of decompensated pressure-overload hypertrophy.
J Mol Cell Cardiol 2006 Oct
PMID:Moderate calorie restriction improves cardiac remodeling and diastolic dysfunction in the Dahl-SS rat. 1693 90

Asthma is a common disease in the worldwide and it affects over 3.5 million adults and children in the UK. Asthma is a chronic disease characterized by airway hyperresponsiveness, airway inflammation, airway remodelling and reversible airway obstruction. Inflammatory cells, cytokines, chemokines, adhesion molecules, and mediators are involved in pathogenesis of asthma. Chronic airway inflammation and remodelling are the major characters in asthma, which result in decreased pulmonary function. The precise processes are far understood at moment. Although corticosteroid therapy plus other exiting drugs (bronchodilators and oral leukotriene receptor antagonists) influences many different inflammatory and structural cell types and continues to be as the "gold standard" of therapy in asthma, many thousands have chronic, severe diseases and suffer daily symptoms which make their lives a misery. There remains a clear need for novel approaches to therapy, which will be informed by a clearer understanding of disease pathogenesis, particularly in the target organ where airway inflammation and remodelling, the hallmarks of asthma occur.
Cell Mol Immunol 2006 Oct
PMID:How much do we know about atopic asthma: where are we now? 1709 29

Arterial hypertension is the most frequent chronic disease and it is an important cause of morbidity and mortality in the developed world. Arterial hypertension is associated with such adverse effects as accelerated arteriosclerosis and pathological left ventricular hypertrophy, among others. The molecular mechanisms affecting left ventricular hypertrophy remain mostly unknown. The advent of proteome profiling has facilitated the elucidation of disease-associated proteins, paving the way for molecular diagnostics and the identification of novel therapeutic targets. We explored the proteomic profile of pathological left ventricular hypertrophy in comparison with normal heart in a model of rats and investigated the proteomic changes in response to different antihypertensive regimens in order to elucidate their cardioprotective effects. Here we describe in depth the protocol for this type of study.
Methods Mol Biol 2007
PMID:Analysis of antihypertensive drugs in the heart of animal models: a proteomic approach. 1717 77

Immunological studies of aging and of patients with chronic immune-mediated diseases document overlap of immune phenotypes. Here, the term "immune remodeling" refers to these phenotypes that are indicative of biological processes of deterioration and repair. This concept is explored through lessons from studies about the changes in the T-cell repertoire and the functional diversity of otherwise oligoclonal, senescent T cells. Immune remodeling suggests a gradual process that occurs throughout life. However, similar but more drastic remodeling occurs disproportionately among young patients with chronic disease. In this article, I propose that immune remodeling is a beneficial adaptation of aging to promote healthy survival beyond reproductive performance, but acute remodeling poses risk of premature exhaustion of the immune repertoire and, thus, is detrimental in young individuals.
Trends Mol Med 2007 Mar
PMID:Immune remodeling: lessons from repertoire alterations during chronological aging and in immune-mediated disease. 1726 87

Natural vitamin E consists of four different tocopherol and four different tocotrienol homologues (alpha,beta, gamma, delta) that all have antioxidant activity. However, recent data indicate that the different vitamin E homologues also have biological activity unrelated to their antioxidant activity. In this review, we discuss the anti-inflammatory properties of the two major forms of vitamin E, alpha-tocopherol (alphaT) and gamma-tocopherol (gammaT), and discuss the potential molecular mechanisms involved in these effects. While both tocopherols exhibit anti-inflammatory activity in vitro and in vivo, supplementation with mixed (gammaT-enriched) tocopherols seems to be more potent than supplementation with alphaT alone. This may explain the mostly negative outcomes of the recent large-scale interventional chronic disease prevention trials with alphaT only and thus warrants further investigation.
Mol Aspects Med
PMID:Anti-inflammatory properties of alpha- and gamma-tocopherol. 1731 80

One of the great demands and challenges for vaccination is to successfully target the pathogens responsible for much of mankind's chronic disease burden including: AIDS, infectious hepatitis, tuberculosis and malaria. Another is realizing the potential of therapeutic immunization to cure diseases such as cancer, allergy and inflammatory autoimmunity. To achieve these objectives, the fundamental insights gained from immunology, genomics, molecular-cellular biology and vaccinology must be implemented in order to develop more effective, better defined and safer vaccines. As an illustrative example of this we examine the key features of viruses that are known to be responsible for eliciting superb host immune responses. These insights have formed a basis for understanding the effectiveness of existing vaccines and provide a framework for designing and developing new vaccines better able to meet pressing unmet medical needs. The key immunogenic properties of viruses that are understood to date and are currently being applied include: their particulate nature, their highly repetitive and ordered structures, their ability to induce innate immunity with consequent conditioning of adaptive responses and the kinetics and distribution of viral antigens during infection. Vaccines and vaccine-formulations recently registered for use in humans already incorporate some of these elements. Of great anticipation is the progress of the next-generation vaccines now advancing through the various stages of research and development. Vaccines which, by way of rational design, incorporate viral properties to induce tailored responses and thus have the potential to provide safer and more effective prophylaxis and therapies.
Curr Mol Med 2007 Mar
PMID:Designing recombinant vaccines with viral properties: a rational approach to more effective vaccines. 1734 67

Diabetes mellitus (DM) is a chronic disease which is associated with numerous serious health complications such as diabetic retinopathy, and is the leading cause of new cases of blindness in adults at the age of 20-74 years old. The aim of the study was to establish and optimize a two-dimensional polyacrylamide gel electrophoresis (2-DE) technique for retina proteomics to improve the resolution and reproducibility, and to observe the proteomic changes of retinal tissues in diabetic and normal rats. Proteins were extracted from retinal tissues of normal and 8 weeks diabetic SD rats and used in two-dimensional electrophoresis. Various conditions of retina proteomic 2-DE were adjusted, optimized and protein spots of differential expression were obtained through analysis of 2-DE images with PDQuest software. By choosing appropriate sample amount, using pre-cast IPG dry strips (pH 5-8) and casting 12% equal gel, satisfactory 2-DE images of retina were obtained and a steady 2-DE technique was established. In this way, we found 36 spots in 2-DE gel of diabetic retinas that exhibited statistically significant variations, including up-regulation of 5 proteins in diabetic rat retinas, down-regulation of 23, and disappearance of 8, in comparison with normal tissues. The differences of protein expression were observed in retinas between diabetic and normal rats. Our established 2-DE technique of retina proteins could be effectively applied in proteomics of retina diseases.
Cell Mol Immunol 2007 Feb
PMID:Application of two-dimensional electrophoresis in the research of retinal proteins of diabetic rat. 1734 13

The treatment of cardiovascular disease has benefited from advances in pharmacologic and intravascular intervention reducing the morbidity and mortality associated with this disease. To address the need in managing clinically complex vascular disease with limited therapeutic options studies have focused on cellular therapy as a means to augment compensatory mechanisms and to potentially prevent escalation and advancement of disease. Umbilical cord blood (UCB) is a rich source of hematopoietic stem cells (HSC) and thus may be a potential source of cells for this type of therapy. UCB can be collected at no risk to the donor, is immediately available, has a wider availability of HLA phenotypes with a possible lower immune reactivity and does not provoke ethically charged debates. Moreover, stem cells isolated from patients with chronic disease have impairment of their reparative abilities thus limiting their therapeutic impact. The potential of UCB HSC in augmenting this process has been studied extensively both in vitro and in vivo and has shown a benefit in acute and chronic vascular ischemia. Although studies suggest efficacy with no obvious safety concerns the mechanism for this therapeutic effect is unknown.
J Mol Cell Cardiol 2007 May
PMID:Umbilical cord blood stem cells: implications for cardiovascular regenerative medicine. 1736 66

Multiple sclerosis is a demyelinating disease of the central nervous system with a presumed autoimmune etiology. Previous microarray analyses identified conserved gene expression signatures in peripheral blood mononuclear cells of patients with autoimmune diseases. We used quantitative real-time polymerase chain reaction analysis to identify a minimum number of genes of which transcript levels discriminated multiple sclerosis patients from patients with other chronic diseases and from controls. We used a computer program to search quantitative transcript levels to identify optimum ratios that distinguished among the different categories. A combination of a 4-ratio equation using expression levels of five genes segregated the multiple sclerosis cohort (n=55) from the control cohort (n=49) with a sensitivity of 91% and specificity of 98%. When autoimmune and other chronic disease groups were included (n=78), this discriminator still performed with a sensitivity of 79% and a specificity of 87%. This approach may have diagnostic utility not only for multiple sclerosis but also for other clinically complex autoimmune diseases.
J Mol Diagn 2007 Apr
PMID:Identification of molecular biomarkers for multiple sclerosis. 1738 11


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