Cell therapy for cardiovascular disease: what cells, what diseases and for whom?

Experimental and human data suggesting progenitor cells possess the capacity to regenerate tissue and augment repair in injured organs has generated widespread interest in the basic research and clinical communities. Nowhere have these findings been more tantalizing than in human cardiovascular disease, in which vasculogenesis and myocardial regeneration logically and understandably remain as attractive therapeutic targets. Burgeoning experimental evidence attests to the proangiogenic, vasculogenic and tissue reparative capabilities of a broad range of progenitor cells derived from the bone marrow, circulation and a number of other tissues in vivo. Studies demonstrating the most apparent therapeutic success are those implicated in revascularization and repair of acute or chronically ischemic tissues in the heart and the peripheral vascular system. Numerous small clinical trials have yielded promising preliminary results without clear evidence of a superiority for a specific cell type or clinical disease entity as the most suitable target for cell therapy. This review will evaluate the scientific rationale for use of a specific cell or cells, the cardiovascular disease states most appropriate for targeted cell therapy, and the patient-specific barriers to therapeutic success, including emerging hurdles such as cardiovascular risk factors and comorbidities in eligible subjects.     

Antibiotics,gut microbiota,and irritable bowel syndrome: What are the relations?

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder in which recurrent abdominal pain is associated with defecation or a change in bowel habits (constipation, diarrhea, or both), and it is often accompanied by symptoms of abdominal bloating and distension. IBS is an important health care issue because it negatively affects the quality of life of patients and places a considerable financial burden on health care systems. Despite extensive research, the etiology and underlying pathophysiology of IBS remain incompletely understood. Proposed mechanisms involved in its pathogenesis include increased intestinal permeability, changes in the immune system, visceral hypersensitivity, impaired gut motility, and emotional disorders. Recently, accumulating evidence has highlighted the important role of the gut microbiota in the development of IBS. Microbial dysbiosis within the gut is thought to contribute to all aspects of its multifactorial pathogenesis. The last few decades have also seen an increasing interest in the impact of antibiotics on the gut microbiota. Moreover, antibiotics have been suggested to play a role in the development of IBS. Extensive research has established that antibacterial therapy induces remarkable shifts in the bacterial community composition that are quite similar to those observed in IBS. This suggestion is further supported by data from cohort and case-control studies, indicating that antibiotic treatment is associated with an increased risk of IBS. This paper summarizes the main findings on this issue and contributes to a deeper understanding of the link between antibiotic use and the development of IBS.     

A role for inflammation in irritable bowel syndrome?

Attention has been directed to the putative role of low grade mucosal inflammation in irritable bowel syndrome (IBS) on the basis of evidence showing that some patients with IBS have an increased number of inflammatory cells in the colonic and ileal mucosa. Previous episodes of infectious enteritis, genetic factors, undiagnosed food allergies, and changes in bacterial microflora may all play a role in promoting and perpetuating this low grade inflammatory process. Human and animal studies support the concept that inflammation may perturb gastrointestinal reflexes and activate the visceral sensory system even when the inflammatory response is minimal and confined to the mucosa. Thus abnormal neuroimmune interactions may contribute to the altered gastrointestinal physiology and hypersensitivity that underlies IBS. A brief review of the human and animal studies that have focused on the putative role of intestinal inflammation and infections in the pathogenesis of IBS is given.     

How does cognitive behavior therapy for irritable bowel syndrome work? A mediational analysis of a randomized clinical trial

BACKGROUND AND AIMS: Although multiple clinical trials support the efficacy of psychological treatments for reducing irritable bowel syndrome (IBS) symptoms, the mechanisms responsible for symptomatic improvement are unknown. One hypothesis is that psychological treatments work by alleviating comorbid psychological distress implicated in the worsening of bowel symptoms and quality of life. An alternative hypothesis assumes that changes in distress are not strictly a cause but a consequence of IBS that will decrease with symptomatic improvement. METHODS: We evaluated these 2 hypotheses by applying structural equation modeling (SEM) to the data set of a large number (n = 147) of Rome II diagnosed participants randomized to CBT, psychoeducation, or wait list. Per Rome guidelines, the primary end point was global improvement of gastrointestinal (GI) symptoms measured 2 weeks after a 10-week regimen. Secondary end points were distress and quality of life (QOL). RESULTS: SEM analyses lend support to a model in which CBT is associated with improvements in IBS symptoms, but that therapeutic gains do not depend on changes in patients' overall level of psychological distress. Symptom severity, but not clinical status (pain catastrophizing, predominant bowel habits, symptom duration, abuse, diagnosable psychiatric disorder) or relevant sociodemographic variables (eg, gender, age), moderated treatment outcome. CONCLUSION: CBT has a direct effect on global IBS symptom improvement independent of its effects on distress. Improvement in IBS symptoms is associated with improvements in the QOL, which may lower distress. Symptom improvements are not moderated by variables reflecting the mental well-being of IBS patients.     

Nutritional factors and nutritional therapy for irritable bowel syndrome--what is worthwhile?

The prevalence of irritable bowel syndrome (IBS) has increased over the last 50 years in countries where a Western-style diet has been prominent or introduced and 20 - 65 % of patients with irritable bowel syndrome (IBS) attribute their symptoms to something in food that activates an abnormal response. However, data from dietary elimination and re-challenge studies are inconclusive. Although investigations have shown that bran may be helpful in some patients, a complete review of the literature does not reveal conclusive evidence that a high fibre diet therapy is effective in IBS. From the limited reports on probiotics, there appears to be a trend to decreasing symptoms. Despite numerous reviews on this subject, it is very difficult to give general dietary advice to IBS patients, but dietary experts may have a positive role in managing such patients. It is clear that much more prospective research is needed to study both dietary factors and probiotics in these areas.     

When is irritable bowel syndrome not irritable bowel syndrome? Diagnosis and treatment of chronic functional abdominal pain

Functional abdominal pain syndrome (FAPS) is a distinct chronic gastrointestinal (GI) pain disorder characterized by the presence of constant or frequently recurring abdominal pain that is not associated with eating, change in bowel habits, or menstrual periods. The pain experience in FAPS is predominantly centrally driven as compared to other chronic painful GI conditions such as inflammatory bowel disease and chronic pancreatitis where peripherally acting factors play a major role in driving the pain. Psychosocial factors are often integrally associated with the disorder and can pose significant challenges to evaluation and treatment. Patients suffer from considerable loss of function, which can drive health care utilization. Treatment options are limited at best with most therapeutic regimens extrapolated from pain management of other functional GI disorders and chronic pain conditions. A comprehensive approach to management using a biopsychosocial construct and collaboration with pain specialists and psychiatry is most beneficial to the management of this disorder.     

Acupuncture-moxibustion in treating irritable bowel syndrome: How does it work?

Irritable bowel syndrome (IBS) is a functional intestinal disease characterized by abdominal pain or discomfort and altered bowel habits. It has drawn great attention because of its high prevalence, reoccurring symptoms, and severe influence on patients’ lives. Many clinical studies have demonstrated the efficacy of acupuncture-moxibustion in treating IBS. Increasing attention has been paid to research regarding the action mechanisms of acupuncture-moxibustion for IBS, and the adoption of modern techniques has achieved some progress. This article reviews the latest advances among action mechanism studies from the perspectives of gastrointestinal motility, visceral hypersensitivity, the brain-gut axis, the neuroendocrine system, and the immune system. It is shown that acupuncture-moxibustion can effectively regulate the above items, and thus, this treatment should have a high efficacy in the treatment of IBS. This article also identifies existing problems in current mechanism research and raises several ideas for future studies. Further revelations regarding these action mechanisms will promote the application of acupuncture-moxibustion in treating IBS.     

Optimum therapeutic approaches for lupus nephritis: what therapy and for whom?

The optimum therapy for patients with lupus nephritis is a hotly debated topic. Prospective randomized studies in patients with proliferative lupus nephritis have established the superiority of cyclophosphamide to azathioprine, both of which are used in combination with corticosteroids. Although high-dose, intermittent administration of cyclophosphamide (pulse therapy) has significantly reduced the toxicity associated with this drug, premature ovarian failure and infections remain considerable problems. Short-term to intermediate-term, randomized controlled trials have shown that mycophenolate mofetil is a good option for the induction and maintenance of remission in lupus nephritis patients. Additional longer-term trials involving more patients and stricter outcomes based on renal function are needed, however, before claims that mycophenolate mofetil is superior to cyclophosphamide can be substantiated. Until such data are available, physicians caring for patients with lupus nephritis can use mycophenolate mofetil as induction or maintenance therapy for selected patients under close observation. Small noncontrolled trials with short-term follow-up suggest that up to 50% of patients who are refractory to cyclophosphamide might have a clinically significant response to rituximab, a monoclonal antibody directed against B cells.     

What does irritable bowel syndrome share with non-alcoholic fatty liver disease?

Non-alcoholic fatty liver disease(NAFLD)and irritable bowel syndrome(IBS)are two very common diseases in the general population.To date,there are no studies that highlight a direct link between NAFLD and IBS,but some recent reports have found an interesting correlation between obesity and IBS.A systematic PubMed database search was conducted highlighting that common mechanisms are involved in many of the local and systemic manifestations of NAFLD,leading to an increased cardiovascular risk,and IBS,leading to microbial dysbiosis,impaired intestinal barrier and altered intestinal motility.It is not known when considering local and systemic inflammation/immune system activation,which one has greater importance in NAFLD and IBS pathogenesis.Also,the nervous system is implicated.In fact,inflammation participates in the development of mood disorders,such as anxiety and depression,characteristics of obesity and consequently of NAFLD and,on the other hand,in intestinal hypersensitivity and dysmotility.     

Is irritable bowel syndrome an infectious disease?

Irritable bowel syndrome (IBS) is the most common of all gastroenterological diseases. While many mechanisms have been postulated to explain its etiology, no single mechanism entirely explains the heterogeneity of symptoms seen with the various phenotypes of the disease. Recent data from both basic and clinical sciences suggest that underlying infectious disease may provide a unifying hypothesis that better explains the overall symptomatology. The presence of small intestinal bowel overgrowth (SIBO) has been documented in patients with IBS and reductions in SIBO as determined by breath testing correlate with IBS symptom improvement in clinical trials. The incidence of new onset IBS symptoms following acute infectious gastroenteritis also suggests an infectious cause. Alterations in microbiota-host interactions may compromise epithelial barrier integrity, immune function, and the development and function of both central and enteric nervous systems explaining alterations in the brain-gut axis. Clinical evidence from treatment trials with both probiotics and antibiotics also support this etiology. Probiotics appear to restore the imbalance in the microflora and improve IBS-specific quality of life. Antibiotic trials with both neomycin and rifaximin show improvement in global IBS symptoms that correlates with breath test normalization in diarrhea-predominant patients. The treatment response to two weeks of rifaximin is sustained for up to ten weeks and comparable results are seen in symptom reduction with retreatment in patients who develop recurrent symptoms.     

Is irritable bowel syndrome an organic disorder?

Irritable bowel syndrome(IBS)is a common gastrointestinal disorder that is generally considered to be functional because there appears to be no associated anatomical defect.Stress and psychological factors are thought to play an important role in IBS.The gut neuroendocrine system(NES),which regulates all functions of the gastrointestinal tract,consists of endocrine cells that are scattered among the epithelial cells of the mucosa,and the enteric nervous system.Although it is capable of operating independently from the centra nervous system(CNS),the gut NES is connected to and modulated by the CNS.This review presents evidence for the presence of an anatomical defect in IBS patients,namely in the gastrointestinal endocrine cells.These cells have specialized microvilli that project into the lumen and function as sensors for the luminal content and respond to luminal stimuli by releasing hormones into the lamina propria,which starts a chain reaction that progresses throughout the entire NES.The changes in the gastrointestinal endocrine cells observed in IBS patients are highly consistent with the other abnormalities reported in IBS patients,such as visceral hypersensitivity,dysmotility,and abnormal secretion.     

Is irritable bowel syndrome an inflammatory disorder?

Histopathologic data demonstrate low-grade mucosal inflammation in a subset of patients with irritable bowel syndrome (IBS). This inflammatory infiltrate is mainly represented by increased numbers of T lymphocytes and mast cells lying in the lamina propria. The close apposition of immunocytes to gut nerves supplying the mucosa provides a basis for neuroimmune cross-talk, which may explain gut sensorimotor dysfunction and related symptoms in patients with IBS. A previous gastroenteritis (due to Campylobacter jejuni, Salmonella, Shigella, Escherichia coli, and, likely, viruses) is now an established etiologic factor for IBS (hence, postinfectious IBS). Other putative causes, such as undiagnosed food allergies, genetic abnormalities, stress, or bile acid malabsorption, may also promote and maintain a low-grade mucosal inflammation in IBS. The identification of mucosal inflammation in IBS has pathophysiologic implications and paves the way for novel therapeutic options.