Future expectations in digestive endoscopy: competition with other novel imaging techniques

Digestive endoscopy has been evolving from primary diagnostic to extensive therapeutic modalities in the management of gastrointestinal diseases. The present endoscopic imaging includes (A) standard endoscopy alone and /or with adjunct technologies such as point enhancement, e.g. confocal endomicroscopy and field enhancement technologies such as chromoendoscopy, NBI and FICE and (B) endoscopic ultrasound. Other novel imaging technologies including virtual colonoscopy or CT/MR colonography, CT or MRI enterography and capsule endoscopy have also been developed. This article reviews the diagnostic and therapeutic role of digestive endoscopy and future directions of digestive endoscopy are discussed. Digestive endoscopy is also compared with emerging novel imaging techniques in gastrointestinal diseases such as capsule endoscopy and CT colonography. The fact that digestive endoscopy has become a multidisciplinary specialty combining advances in all fields (radiology, bioengineering, surgery and gastroenterology) is highlighted.     

Gut microbiota mediated molecular events and therapy in liver diseases

Gut microbiota is a community of microorganisms that reside in the gastrointestinal tract. An increasing number of studies has demonstrated that the gut-liver axis plays a critical role in liver homeostasis. Dysbiosis of gut microbiota can cause liver diseases, including nonalcoholic fatty liver disease and alcoholic liver disease. Preclinical and clinical investigations have substantiated that the metabolites and other molecules derived from gut microbiota and diet interaction function as mediators to cause liver fibrosis, cirrhosis, and final cancer. This effect has been demonstrated to be associated with dysregulation of intrahepatic immunity and liver metabolism. Targeting these findings have led to the development of novel preventive and therapeutic strategies. Here, we review the cellular and molecular mechanisms underlying gut microbiota-mediated impact on liver disease. We also summarize the advancement of gut microbiota-based therapeutic strategies in the control of liver diseases.     

Applications of molecular genetics to gastrointestinal and liver diseases. I. Technical approaches

Recent developments in recombinant DNA techniques have allowed an understanding of the molecular genetics of many diseases, some affecting the gastrointestinal tract and liver. DNA probes which detect sequences within or near disease genes can be selected by direct approaches, if the gene product or primary gene function is known, or by indirect methods when the chromosomal location is known. Such probes have resulted in extensive family studies which can now define risks to family members of developing a genetic disease. The development of the polymerase chain reaction will also be of considerable use in clinical genetics and in the diagnosis of some infectious diseases. The techniques are summarized and examples of their use are given. A glossary of terms is also provided.     

Autoimmunity in hepatitis C and D virus infection

SUMMARY. A large number of viruses are capable of inducing acute or chronic hepatitis. The syndrome of chronic hepatitis encompasses not only viral but also autoimmune liver diseases. The hepatitis C virus, and recently also the hepatitis D virus have been found to be associated with an array of autoimmune syndromes, diseases and markers of autoimmunity. The relationship of hepatotropic virus infection and the immune system leading to virus-associated autoimmunity, and its distinction from genuine autoimmune disease represents a fascinating field of research. Clinically, the differentiation between autoimmune liver diseases, virus infection and virus-associated autoimmunity is difficult and epidemiological evaluations have not come up with universally applicable and valid classification criteria. However, both autoimmune liver diseases and viral hepatitis can readily be diagnosed and distinguished through precise and molecularly determined immunological testing systems. The overlap of both, virus-associated autoimmunity, is still at the centre of research activities aimed at establishing diagnostic and risk-assessment criteria. Studies of molecular autoantigens and autoepitopes have begun to define the differences of the B-cell response in autoimmune disease and virus-associated autoimmunity. This provides data that may contribute to the safe application of therapeutic strategies as different as immunosuppression and interferon-α (IFN-α). The present review focuses on the clinical, epidemilogical and molecular aspects of these disease entities.     

Role of endoscopic ultrasound in the field of hepatology: Recent advances and future trends

The role of endoscopic ultrasound (EUS) as a diagnostic and therapeutic modality for the management of various gastrointestinal diseases has been expanding. The imaging or intervention for various liver diseases has primarily been the domain of radiologists. With the advances in EUS, the domain of endosonologists is rapidly expanding in the field of hepatology. The ability to combine endoscopy and sonography in one hybrid device is a unique property of EUS, together with the ability to bring its probe/transducer near the liver, the area of interest. Its excellent spatial resolution and ability to provide real-time images coupled with several enhancement techniques, such as contrast-enhanced (CE) EUS, have facilitated the growth of EUS. The concept of “Endo-hepatology” encompasses the wide range of diagnostic and therapeutic procedures that are now gradually becoming feasible for managing various liver diseases. Diagnostic advancements can enable a wide array of techniques from elastography and liver biopsy for liver parenchymal diseases, to CE-EUS for focal liver lesions to portal pressure measurements for managing various liver conditions. Similarly, therapeutic advancements range from EUS-guided eradication of varices, drainage of bilomas and abscesses to various EUS-guided modalities of liver tumor management. We provide a comprehensive review of all the different diagnostic and therapeutic EUS modalities available for the management of various liver diseases. A synopsis of all the technical details involving each procedure and the available data has been tabulated, and the future trends in this area have been highlighted.     

Role of spleen tyrosine kinase in liver diseases

Spleen tyrosine kinase (SYK),a non-receptor tyrosine kinase,is expressed in most hematopoietic cells and non-hematopoietic cells and play a crucial role in both immune and non-immune biological responses.SYK mediate diverse cellular responses via an immune-receptor tyrosine-based activation motifs (ITAMs)-dependent signalling pathways,ITAMs-independent and ITAMs-semidependent signalling pathways.In liver,SYK expression has been observed in parenchymal (hepatocytes) and non-parenchymal cells (hepatic stellate cells and Kupffer cells) and found to be positively correlated with the disease severity.The implication of SYK pathway has been reported in different liver diseases including liver fibrosis,viral hepatitis,alcoholic liver disease,non-alcoholic steatohepatitis and hepatocellular carcinoma.Antagonism of SYK pathway using kinase inhibitors have shown to attenuate the progression of liver diseases thereby suggesting SYK as a highly promising therapeutic target.This review summarizes the current understanding of SYK and its therapeutic implication in liver diseases.     

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??Abstract??Viral infections are common complications after hematopoietic stem cell transplantation (HSCT).Recently??polymerase chain reaction (PCR)-based molecular diagnostic methods are rapidly replacing or supplementing the traditional viral diagnostic methods such as viral culture and antigen detection.Nowadays??diagnosis of viral infections relies on polymerase chain reaction (PCR)-based methods.Viral infections after allogeneic HSCT result in a spectrum of diseases including fever??end-organ diseases to malignancies.Reactivation of latent viruses??e.g.herpesviruses??is common in the immunosuppressive recipients.Some viruses such as the respiratory and gastrointestinal viruses are mainly acquired from community.Prophylaxis including preemptive therapy has successfully reduced incidences of some viral diseases.Early diagnosis and timely treatment may significantly improve outcome of viral infections.     

Antivirale Therapie bei viraler Herzerkrankung

Several investigations showed that in addition to genetic factors also virological and chronic inflammatory aspects are relevant pathogenic mechanisms for the development of dilated cardiomyopathy (DCM). Based on the etiopathogenic importance of viral persistence and chronic myocardial inflammation for disease progression, novel rational therapeutic strategies have been developed. The diagnosis of chronic myocardial inflammation and viral persistence has been a controversial issue for a long time due to diagnostic pitfalls. Detection of persistence of viral genomes with adequate sensitivity and specificity succeeded only by the establishment of sensitive molecular biological techniques such as in situ hybridization and nested polymerase chain reaction (nPCR). By the use of these molecular biological methods, further viruses have been detected in DCM patients in addition to the classic cardiotropic viruses (entero- and adenoviruses), particularly parvovirus B19, human herpes virus type 6 (HHV-6), and Epstein-Barr virus. Considering these different cardiotropic viruses, viral persistence can be proven in > 50% of the DCM patients, consistent with the diagnosis of viral heart disease.This differentiated diagnosis enables, in addition to symptomatic therapy of heart failure, novel rational therapeutic regimens (e. g., beta-interferon) in the setting of randomized trials such as the BICC Study (Betaferon In Patients with Chronic Viral Cardiomyopathy).     

Molecular mimicry and autoimmune liver disease: virtuous intentions, malign consequences.

The pathogenesis of autoimmune liver disease and autoimmunity associated with chronic viral hepatitis remains poorly understood. One of the major hurdles to a deeper understanding of these pathological processes is the absence of clearly defined inductive mechanisms, which, if identified and characterised, could guide clinical strategies for their prevention or allow therapeutic intervention. Molecular mimicry leading to crossreactive autoimmune responses has gained strong experimental support in the past decade. A fundamental premise of this hypothesis is the involvement of a mimicking environmental trigger. In view of the numerous viral and bacterial agents epidemiologically linked to autoimmune liver diseases, we and others have proposed molecular mimicry to be an important mechanism in these diseases. We also propose similar crossreactive mechanisms to operate in the generation of autoimmunity in viral hepatitis. This review focuses on molecular mimicry at the level of the B-cell, as few data on T-cell crossreactivity in liver disease are thus far available.     

Molecular mimicry and autoimmune liver disease: virtuous intentions,malign consequences

Abstract: The pathogenesis of autoimmune liver disease and autoimmunity associated with chronic viral hepatitis remains poorly understood. One of the major hurdles to a deeper understanding of these pathological processes is the absence of clearly defined inductive mechanisms, which, if identified and characterised, could guide clinical strategies for their prevention or allow therapeutic intervention. Molecular mimicry leading to crossreactive autoimmune responses has gained strong experimental support in the past decade. A fundamental premise of this hypothesis is the involvement of a mimicking environmental trigger. In view of the numerous viral and bacterial agents epidemiologically linked to autoimmune liver diseases, we and others have proposed molecular mimicry to be an important mechanism in these diseases. We also propose similar crossreactive mechanisms to operate in the generation of autoimmunity in viral hepatitis. This review focuses on molecular mimicry at the level of the B‐cell, as few data on T‐cell crossreactivity in liver disease are thus far available.     

Balloon-distension studies in the gastrointestinal tract: current role

Balloon distension is a commonly used technique in visceral organs. Research studies take advantage of this technique for studying organ physiology, e.g. for studying the force-deformation relationship and mechanosensitive receptors in the gastrointestinal wall. Balloon distension is also used for diagnostic purposes, e.g. in the diagnostics of non-cardiac chest pain and for treatment of diseases such as bleeding esophageal varices caused by liver disease and lower esophageal sphincter occlusion caused by achalasia. Balloon distension can be carried out with concomitant measurements of pressure, volume and cross-sectional area alone or in combination. Furthermore, balloon-distension techniques can be combined with various imaging techniques such as B-mode ultrasonography and MRI to obtain three-dimensional geometric data about the three-dimensional surface with subsequent calculation of the tension or stress in the gastrointestinal organs. This article describes balloon-distension techniques, in particular new developments of the impedance planimetric technique including methods for studying gastrointestinal muscle function.     

Monoclonal antibody and intravenous immunoglobulin therapy for rheumatic diseases: rationale and mechanisms of action

Advances in our understanding of the pathogenesis of rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus have led to the emergence of immunoglobulin-based therapy as a major therapeutic force. Numerous monoclonal antibodies that target proinflammatory cytokines or their receptors (e.g. infliximab, adalimumab, tocilizumab, belimumab, HuMax-IL-15), and cell-surface or co-stimulatory molecules (e.g. rituximab) are either in clinical development or have been approved for clinical use. These antibodies are safe and effective in the long-term therapy of many rheumatic diseases. In addition, polyclonal immunoglobulins (intravenous immunoglobulin) obtained from pooled plasma from healthy blood donors are an effective therapeutic approach in certain rheumatic diseases. The mechanisms of action of monoclonal antibodies and intravenous immunoglobulin include cytolysis of target cells through complement or antibody-dependent cell-mediated cytotoxicity, induction of apoptosis of target cells, blockade of co-stimulatory molecules, and neutralization of pathogenic antibodies and soluble factors such as cytokines and their receptors, which ultimately lead to amelioration of the inflammatory process. The success of currently available therapeutic immunoglobulins has led to considerable interest in the identification of novel molecular therapeutic targets in rheumatic diseases.     

Functional relevance of soluble TNF-alpha,transmembrane TNF-alpha and TNF-signal transduction in gastrointestinal diseases with special reference to inflammatory bowel diseases

As a result of extensive clinical and basic research, the pivotal role of tumour necrosis factor (TNF) in the pathogenesis of chronic inflammatory diseases such as inflammatory bowel disease (IBD) has now generally been acknowledged. This has led to promising clinically effective anti-TNF-strategies. Of note, there is more and more evidence that TNF seems to play a key role in other gastrointestinal diseases including Helicobacter pylori infection, pancreatitis, viral hepatitis and toxic liver damage, too. The action of TNF at the cellular level is mediated by two cell surface receptors, TNF-R1 (p60) and TNF-R2 (p80). The function of these receptors and the downstream intracellular signal transduction pathway have been extensively studied in vitro and it can be expected, that there are critically important steps in TNF-signal transduction that might be dysregulated in these disease states. Their elucidation could lead to a better understanding of the pathogenesis of these diseases, in particular IBD and potentially reveal new, more specific therapeutic targets. Objective of this review is to give an overview about the current knowledge on TNF signal transduction in relationship to selected examples of important gastrointestinal disorders with special focus on IBD. Finally, the implications for future research efforts will be discussed.     

Adaptation of bacteria to the intestinal niche: probiotics and gut disorder

The gastrointestinal tract is a complex ecosystem host to a diverse and highly evolved microbial community composed of hundreds of different microbial species. The interactions that occur between this complex microbial community and the human host have become the focus of scientific research due to increases in the incidence of illnesses associated with deficient or compromised microflora (e.g., gastrointestinal tract infections, inflammatory bowel disease (Crohn's disease and ulcerative colitis), irritable bowel syndrome, antibiotic-induced diarrhea, constipation, food allergies, cardiovascular disease, and certain cancers). Effective multidisciplinary research programs now complement conventional microbiology with molecular ecology techniques to provide culture-independent analysis of the gastrointestinal ecosystem. Furthermore, as we acquire an understanding of gut microflora composition and processes such as intestinal adherence, colonization, translocation, and immunomodulation, we are also elucidating mechanisms by which these can be influenced. This knowledge not only allows scientists to define the activities and interactions of "functional food"-borne beneficial bacteria in the gut, but will also provide the scientific basis for the development of innovative biotechnology-based products tailored to prevent specific diseases and promote overall human gastrointestinal health.     

Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects

A multitude of physiological effects and putative pathophysiological roles have been proposed for the endogenous cannabinoid system in the gastrointestinal tract, liver and pancreas. These range from effects on epithelial growth and regeneration, immune function, motor function, appetite control, fibrogenesis and secretion. Cannabinoids have the potential for therapeutic application in gut and liver diseases. Two exciting therapeutic applications in the area of reversing hepatic fibrosis as well as antineoplastic effects may have a significant impact in these diseases. This review critically appraises the experimental and clinical evidence supporting the clinical application of cannabinoid receptor-based drugs in gastrointestinal, liver and pancreatic diseases. Application of modern pharmacological principles will most probably expand the selective modulation of the cannabinoid system peripherally in humans. We anticipate that, in addition to the approval in several countries of the CB(1) antagonist, rimonabant, for the treatment of obesity and associated metabolic dysfunctions, other cannabinoid modulators are likely to have an impact on human disease in the future, including hepatic fibrosis and neoplasia.     

The classification of pericardial disease in the age of modern medicine

The spectrum of pericardial diseases comprises pericarditis, pericardial neoplasms, cysts, and congenital defects. Due to the insufficient diagnostic value of standard, noninvasive diagnostic techniques, many cases remained etiologically unclear, and were therefore classified as idiopathic. A major improvement in the classification of pericardial disease is its clear distinction between the two most frequent forms of idiopathic pericarditis: viral infection and autoreactive pericarditis. This classification has major therapeutic consequences. In autoreactive forms, systemic and intrapericardial corticosteroid treatment has a favorable effect; its application in viral forms is contraindicated. The new classification of pericardial diseases synthesizes the achievements of modern imaging with molecular biology and immunology. Systematic implementation of new techniques of pericardial fluid analyses, pericardioscopy and pericardial biopsy, and the application of molecular biology and immunology techniques have opened new windows to the pericardial diseases, permitting early specific diagnosis, and creating foundations for etiologic treatment in many cases.     

MicroRNAs in hepatic pathophysiology

MicroRNAs (miRNAs) are a group of small non‐coding RNAs that range in length from 20 to 25 nucleotides. MicroRNAs are specific for multiple cellular functions, including cell generation, differentiation, multiplication, carcinogenesis, and apoptosis. Many researchers have recently reported that the aberrant expression of miRNAs in hepatic tissue was related to the pathogenesis of liver disease, including viral hepatitis, hepatocellular carcinoma, and fatty liver disease. Multiple studies have proposed that an analysis of circulating miRNAs may be useful for diagnosing etiologies or staging the progression of liver disease, as well as for therapeutic purposes, for example, nucleic acid therapy. This review summarizes and discusses recent advances in the knowledge of miRNAs for chronic liver diseases, with special interest in viral hepatitis, liver fibrosis, and biomarkers.     

Interventional endoscopic ultrasonography in patients with surgically altered anatomy: Techniques and literature review

There are various reconstruction techniques that are used after upper gastrointestinal surgery. In recent years, opportunities for endoscopic diagnosis and treatment have been increasing in patients undergoing gastrointestinal surgery. With the advent of interventional endoscopic ultrasound (IV-EUS), various procedures have been developed mainly for patients in whom endoscopic retrograde cholangiopancreatography is difficult to carry out. Indications for such procedures are expanding. IV-EUS for surgically altered anatomy (SAA) includes EUS-guided fine-needle aspiration, biliary interventions (e.g. biliary drainage, treatment of bile duct stricture, removal of bile duct stones, and the rendezvous technique), and pancreatic interventions (e.g. rendezvous technique after Whipple surgery). In addition, there have been reports of various EUS-related procedures using a forward-viewing curved linear-array echoendoscope that are carried out for postoperative intestinal tract reconstruction. Although interventional EUS is a useful therapeutic procedure for SAA, there are still no dedicated devices, and standardization of the procedure is warranted.