Ulcers

What Is New in the Understanding of Non Healing Wounds Epidemiology, Pathophysiology, and Therapies

Sun, 12 May 2013 11:56:40 +0000

Chronic wounds are a growing socioeconomic problem in the western world. Knowledge on recalcitrant wounds relies on in vitro studies or clinical observations, and there is emerging evidence on the clinical impact of bacterial biofilm on skin healing. Chronic wounds are locked in the inflammatory state of wound healing, and there are multiple explanations for this arrest with the theory of exaggerated proteolysis as the most commonly accepted. Previously, there has not been enough focus on the different etiologies of chronic wounds compared to acute, healing wounds. There is an urgent need to group chronic wounds by its cause when searching for possible diagnostic or therapeutic targets. Good wound management should therefore consist of recognition of basic wound etiology, irrigation, and debridement in order to reduce microbial and necrotic load, frequently changed dressings, and appropriate antimicrobial and antibiofilm strategies based on precise diagnosis. Representative sampling is required for diagnosis and antimicrobial treatment of wounds. The present review aims at describing the impact of biofilm infections on wounds in relation to diagnosing, treatment strategies, including experimentally adjuvant approaches and animal models.

Accumulation of Mast Cells in the Lesions and Effects of Antiallergic Drugs on the Patients with Inflammatory Bowel Disease

Motohiro Kurosawa and Hiroichi Nagai — Thu, 09 May 2013 14:36:01 +0000

The pathomechanism of inflammatory bowel disease (IBD) has not yet been fully demonstrated. However, it is well known that mast cells are present in the gastrointestinal tract, suggesting that mast cells may take part in it. So, we investigated the number of mast cells in IBD, such as ulcerative colitis (UC) and eosinophilic colitis, and showed that the number of mast cells was increased in the inflammatory lesions. We also presented a case of UC which was treated successfully with an antiallergic drug, tranilast. Furthermore, possible new approaches to treating the disease with immunomodulators including suplatast are introduced. However, our investigations were performed with a limited number of patients with IBD, and additional further studies are required to confirm the findings.

Chronic Leg Ulcers: Epidemiology, Aetiopathogenesis, and Management

Shubhangi Vinayak Agale — Mon, 22 Apr 2013 11:16:44 +0000

Chronic leg ulcer is defined as a defect in the skin below the level of knee persisting for more than six weeks and shows no tendency to heal after three or more months. Chronic ulceration of the lower legs is a relatively common condition amongst adults, one that causes pain and social distress. The condition affects 1% of the adult population and 3.6% of people older than 65 years. Leg ulcers are debilitating and greatly reduce patients' quality of life. The common causes are venous disease, arterial disease, and neuropathy. Less common causes are metabolic disorders, hematological disorders, and infective diseases. As many factors lead to chronic lower leg ulceration, an interdisciplinary approach to the systematic assessment of the patient is required, in order to ascertain the pathogenesis, definitive diagnosis, and optimal treatment. A correct diagnosis is essential to avoid inappropriate treatment that may cause deterioration of the wound, delay wound healing, or harm the patient. The researchers are inventing newer modalities of treatments for patients with chronic leg ulceration, so that they can have better quality life and reduction in personal financial burden.

Antioxidant Capacity, Cytoprotection, and Healing Actions of the Leaf Aqueous Extract of Ocimum suave in Rats Subjected to Chronic and Cold-Restraint Stress Ulcers

Paul V. Tan, C. Mezui, G. E. Enow-Orock, and G. Agbor — Sun, 31 Mar 2013 08:46:53 +0000

We evaluated the qualitative chemical composition and tested the antiulcer actions on cold/restraint stress ulcers, the healing effect on chronic acetic acid-induced gastric ulcers, and the in vivo and in vitro antioxidant capacity of Ocimum suave extract. Triterpenes, flavonoids, sugars, phenols, sterols, and multiple bonds were among the phytochemicals detected. The extract (250–500 mg/kg) dose-dependently inhibited the formation of gastric ulcers induced by cold/restraint stress (52.30%–83.10%). The prophylactic actions were associated with significant increases in gastric mucus production. There was significant histological healing of chronic ulcers following 14-day treatment with O. suave extract (250–500 mg/kg). We also evaluated the efficacy of O. suave extract in cold/restraint-induced oxidative stress in rat stomach tissue. O. suave (500 mg/kg) ameliorated the decreased levels of reduced glutathione from 0.85 (control group) to 2.08 nmol/g tissue. The levels of SOD and catalase were also improved in rats treated with O. suave extract. The extract had a high phenol content (899.87 mg phenol/g catechin equivalent), in vitro DPPH radical scavenging activity (89.29%), and FRAP (antioxidant capacity) (212.64 mg/g catechin equivalent). The cytoprotective and ulcer healing effects of the extract are attributed to enhanced mucus production and the antioxidant properties which may likely be associated with the high presence of flavonoids and polyphenols.

Screening for Osteomyelitis Using Thermography in Patients with Diabetic Foot

Makoto Oe, Rie Roselyne Yotsu, Hiromi Sanada, Takashi Nagase, and Takeshi Tamaki — Sun, 31 Mar 2013 08:22:04 +0000

One of the most serious complications of diabetic foot (DF) is osteomyelitis, and early detection is important. To assess the validity of thermography to screen for osteomyelitis, we investigated thermographic findings in patients with both DF and osteomyelitis. The subjects were 18 diabetic patients with 20 occurrences of DF who visited a dermatology department at a hospital in Tokyo and underwent evaluation by magnetic resonance imaging (MRI) and thermography between June 2010 and July 2012. Osteomyelitis was identified by MRI. Thermographs were taken of the wounds and legs after bed rest of more than 15 minutes. Two wound management researchers evaluated the range of increased skin temperature. There were three types of distribution of increased skin temperature: the periwound, ankle, and knee patterns. Fisher’s exact test revealed that the ankle pattern was significantly more common in the group with osteomyelitis than in the group without osteomyelitis (). The positive predictive value was 100%, and the negative predictive value was 71.4%. Our results suggest that an area of increased skin temperature extending to the ankle can be a sign of osteomyelitis. Thermography might therefore be useful for screening for osteomyelitis in patients with DF.

Chronic Nonhealing Wounds: Could Leg Ulcers Be Hereditary?

Sun, 10 Mar 2013 14:14:20 +0000

Background. A number of well-known acquired and putative inherited etiological factors contribute to the development of venous leg ulcer (VLU). Aim. In this study we set out to perform a meta-analysis of putative genetic and acquired factors predisposing to VLU development. Methods. VLU patients () were divided into three subgroups in accordance with their acquired etiological factors. The frequencies of four genetic factors were determined: the R506Q (Leiden) mutation of the F5 gene, the G20210A mutation of the F2 (prothrombin) gene, the 2451 A/G SNP of the fibroblast growth factor receptor 2 (FGFR2) 3′ UTR, and the −308 G/A SNP of the tumor necrosis factor α (TNFA) promoter. Results. The −308 TNFA SNP exhibited a higher frequency among VLU patients without known acquired predisposing factor in their history, than among patients with thrombosis or soft tissue infection in their history (Fisher ). Conclusions. This study has demonstrated that the group of VLU patients is heterogeneous in their genetic predisposing factors. Further large-scale studies are needed to delineate the associations among genetic and acquired etiological factors with regard to VLU development and to integrate the consequences of the already known genetic factors to the management of VLU.

Chronic Ulcers in Thromboangiitis Obliterans (Buerger's Disease): Updating Epidemiology, Physiopathology, and Bosentan—A Novel Strategy of Therapy

Sun, 24 Feb 2013 10:30:07 +0000

Thromboangiitis obliterans (TAO) or Buerger's disease is associated with both distal ulcers in the extremities and the possibility of amputation. The only treatment that has been shown to be effective in TAO is complete abstention from smoking. In spite of this, the disease progresses in up to 30 percent of cases and finally results in limb amputation. Only a few pharmacological and surgical options are available to date to improve healing ulcers in TAO. The efficacy of prostaglandin analogues is controversial. This paper summarizes the current evidence for medical treatment with bosentan in chronic ulcers in TAO patients. These available data up to date allow us to conclude that the beneficial effects of bosentan on improving endothelial function, inflammatory processes, and selective vasodilatation of damaged vessels result in a clinical enhancement regarding healing and preventive digital ulcers in such patients. In any case, these promising findings have to be confirmed with larger randomised trials.

Chronic Wounds, Biofilms and Use of Medicinal Larvae

Thu, 14 Feb 2013 13:12:12 +0000

Chronic wounds are a significant health problem in the United States, with annual associated costs exceeding $20 billion annually. Traditional wound care consists of surgical debridement, manual irrigation, moisture retentive dressings, and topical and/or systemic antimicrobial therapy. However, despite progress in the science of wound healing, the prevalence and incidence of chronic wounds and their complications are escalating. The presence & complexity of bacterial biofilms in chronic wounds has recently been recognized as a key aspect of non-healing wounds. Bacterial biofilms are sessile colonies of polymicrobial organisms (bacteria, fungus, etc.) enclosed within a self-produced exopolymeric matrix that provides high levels of tolerance to host defenses, antibiotics and antiseptics. Thus, there is a need for alternative therapies to reduce biofilms in chronic wounds. In this report, we present initial findings from in vitro experiments which show that larval debridement therapy with disinfected blow fly larvae (Phaenicia sericata) reduced total CFUs (6-logs) of planktonic and mature biofilms of Pseudomonas aeruginosa or Staphylococcus aureus grown on dermal pig skin explants by 5-logs after 24 hours of exposure, and eliminated biofilms (no measurable CFUs) after 48 hours of exposure.

Compression Stockings for Treating Venous Leg Ulcers

J. P. Benigni, A. L. Deman, and J. F. Uhl — Sun, 03 Feb 2013 08:46:51 +0000

Background. In order to treat venous leg ulcers, it is recommended to use high pressure compression (30–40 mmHg at the ankle). Compression stockings which are not operator dependant could be the best option because of their pressure control. However 30–40 mmHg compression stockings are often hard to put on. Putting two lower pressure compression stockings over each other could be a good therapeutic alternative. Objectives. To compare the in vitro pressures given by the manufacturers of 2 antiulcer kits with the in vivo interface pressures measured in healthy subjects and to evaluate the stiffness and friction indices from those kits based on the interface pressure in order to assess their clinical properties. Material and Methods. Using a Kikuhime pressure device, interface pressure was measured in 12 healthy subjects at the reference point B1. One stiffness index (Static Stiffness Index (SSI)) and a friction index have been calculated. Results. Mediven Ulcer kit gets the recommended pressures whereas Jobst’s Ulcer Care kit does not for treating a venous leg ulcer. Jobst’s Ulcer Care transmits entirely the pressure in relation to a friction index close to 1. Conclusion. This antiulcer kit study underlines that in vivo and in vitro pressures can be different (Jobst’s Ulcer Care kit and Mediven Ulcer kit). In order not to lose pressure, it is important to take into account the friction index when superimposing two stockings.

The Acute Management of Nonvariceal Upper Gastrointestinal Bleeding

Hisham AL Dhahab and Alan Barkun — Tue, 27 Nov 2012 11:14:07 +0000

Background. The mortality from nonvariceal upper gastrointestinal bleeding is still around 5%, despite the increased use of proton-pump inhibitors and the advancement of endoscopic therapeutic modalities. Aim. To review the state-of-the-art management of acute non variceal upper gastrointestinal bleeding from the presentation to the emergency department, risk stratification, endoscopic hemostasis, and postendoscopic consolidation management to reduce the risk of recurrent bleeding from peptic ulcers. Methods. A PubMed search was performed using the following key words acute management, non variceal upper gastrointestinal bleeding, and bleeding peptic ulcers. Results. Risk stratifying patients with acute non variceal upper gastrointestinal bleeding allows the categorization into low risk versus high risk of rebleeding, subsequently safely discharging low risk patients early from the emergency department, while achieving adequate hemostasis in high-risk lesions followed by continuous proton-pump inhibitors for 72 hours. Dual endoscopic therapy still remains the recommended choice in controlling bleeding from peptic ulcers despite the emergence of new endoscopic modalities such as the hemostatic powder. Conclusion. The management of nonvariceal upper gastrointestinal bleeding involves adequate resuscitation, preendoscopic risk assessment, endoscopic hemostasis, and post endoscopic pharmacological and nonpharmacological treatment.

Ulcerative Lesions in Behcet's Disease

Ümit Türsen and Belma Türsen — Mon, 12 Nov 2012 14:49:14 +0000

Ulcerative lesions in Behcet’s disease (BD) are regarded as important manifestation for diagnosis. Various kinds of ulcerative lesions appear in patients with BD. They present as orogenital ulcers, necrotizing vasculitis and pyoderma gengrenosum. Gastrointestinal system involvement (Gis) in Behçet’s disease affects all areas from the esophagus to the anus. Most authors believe that the Gis manifestations of Behçet’s disease should be confined to aphthous ulcers, which can occur throughout the Gis tract. All patients with oro-genital and Gis ulcerations should be fully investigated to establish a definitive diagnosis and eliminate the possibility of an underlying BD.

Update on Peptic Ulcers in the Pediatric Age

Graziella Guariso and Marco Gasparetto — Mon, 05 Nov 2012 17:03:14 +0000

Background. Peptic ulcer disease (PUD) in children is reported worldwide, although it is relatively rare as compared with adults. Helicobacter pylori (HP) infection is a common cause of PUD in the pediatric age. Other risk factors include the use of nonsteroidal anti-inflammatory agents (NSAIDs), steroids, immunosuppressive drugs, and stressful events. Aim. To critically review the evidence on epidemiology, diagnostic management, and available treatments for PUD in the pediatric age. Methods. A MEDLINE search was performed indicating keywords as “Peptic Ulcer Disease,” “Epidemiology,” “Pediatric,” “Helicobacter pylori,” “Gastric ulcer,” “Bulbar Ulcer,” and “Upper Gastrointestinal Bleeding.” A selection of clinical trials, systematic reviews, and meta-analyses within the time period 2002–2012 was performed. Results. PUD in children is reported worldwide with an estimated frequency of 8.1% in Europe and of 17.4% in the US. When the underlying cause of PUD is addressed, the prognosis is excellent. Standard triple therapy, bismuth-based quadruple therapy, and the sequential therapy represent the current recommended treatments for HP related ulcers. NSAIDs related ulcers are treated by stopping the causative medications and by administration of proton-pump inhibitors or antisecretory drugs. Conclusions. PUD still represents a major concern in the paediatric age. A careful differential diagnosis and an adequate treatment constitute an excellent prognosis.

Stratification of Highest-Risk Patients with Chronic Skin Ulcers in a Stanford Retrospective Cohort Includes Diabetes, Need for Systemic Antibiotics, and Albumin Levels

Omar Amir, Andy Liu, and Anne Lynn S. Chang — Tue, 09 Oct 2012 16:35:52 +0000

Chronic nonsurgical skin wounds such as venous stasis and diabetic ulcers have been associated with a number of comorbid conditions; however, the strength of these associations has not been compared. We utilized the Stanford Translational Research Integrated Database Environment (STRIDE) system to identify a cohort of 637 patients with chronic skin ulcers. Preliminary analysis () showed that 49.7% of the patients had a poor prognosis such as amputation or a nonhealing ulcer for at least a year. Factors significantly associated () with these outcomes included diabetes mellitus, chronic kidney disease, peripheral neuropathy, peripheral arterial disease, and need for systemic antibiotics. Patients with poor outcomes also tended to have lower hemoglobin levels (), higher WBC levels (), and lower albumin levels (). On multivariate analysis, however, only diabetes mellitus (OR 5.87, 1.36–25.3), need for systemic antibiotics (OR 3.88, 1.06–14.2), and albumin levels (0.20 per unit, 0.07–0.60) remained significant independent predictors of poor wound-healing outcomes. These data identify patients at the highest risk for poor wound-healing and who may benefit the most from more aggressive wound care and treatment.

In-Hospital Nonvariceal Upper Gastrointestinal Bleeding following Cardiac Surgery: Patient Characteristics, Endoscopic Lesions and Prognosis

Tue, 28 Aug 2012 14:22:10 +0000

Background. Nonvariceal upper gastrointestinal bleeding (NVUGIB) can occur following cardiac surgery, with sparse contemporary data on patient characteristics and predictors of outcome in this setting. Aim. To describe the clinical and endoscopic characteristics of patients with NVUGIB following cardiac surgery and characterize predictors of outcome. Methods. Retrospective review of 131 consecutive patients with NVUGIB following cardiac surgery from 2002 to 2005. Demographic characteristics, therapeutic management, and predictors of outcomes were determined. Results. 69.5% were male, mean age: 68.8 ± 10.2 yrs, mean Parsonnet score: 24.6 ± 14.2. Commonest symptoms included melena (59.4%) or coffee ground emesis (25.8%). In-hospital medications included ASA (88.5%), heparin (95.4%, low molecular weight 6.9%), coumadin (48.1%), clopidogrel (22.9%), and NSAIDS (42%). Initial hemodynamic instability was noted in 47.1%. Associated laboratory results included hematocrit 26 ± 6, platelets 243 ± 133 109/L, INR 1.7 ± 1.6, and PTT 53.3 ± 35.6 s. Endoscopic evaluation (122 patients) yielded ulcers (85.5%) with high-risk lesions in 45.5%. Ulcers were located principally in the stomach (22.5%) or duodenum (45.9%). Many patients had more than one lesion, including esophagitis (28.7%) or erosions (26.8%). 48.8% received endoscopic therapy. Mean lengths of intensive care unit and overall stays were 10.4 ± 18.4 and 39.4 ± 46.9 days, respectively. Overall mortality was 19.1%. Only mechanical ventilation under 48 hours predicted mortality (O.R = 0.11; 95% CI = 0.04−0.34). Conclusions. This contemporary cohort of consecutive patients with NVUGIB following cardiac surgery bled most often from ulcers or esophagitis; many had multiple lesions. ICU and total hospital stays as well as mortality were significant. Mechanical ventilation for under 48 hours was associated with improved survival.

Gastroprotective Efficacy of Coenzyme Q10 in Indomethacin-Induced Gastropathy: Other Potential Mechanisms

Asmaa M. Malash, Dalaal M. Abdallah, Azza M. Agha, and Sanna A. Kenawy — Mon, 06 Feb 2012 14:36:27 +0000

Though recently the mitochondrial bioenergetic coenzyme (Co)Q10 has been shown to protect against indomethacin-induced gastric ulceration, yet the full mechanistic cassettes have not been investigated. Therefore, the current investigation assessed further gastroprotective mechanisms of CoQ10 using the indomethacin-induced gastropathy model. While CoQ10 was administered at 3 dose levels to male Wistar rats, the proton pump inhibitor, pantoprazole, was given at 4 dose levels ahead of pyloric ligation and indomethacin administration. Indomethacin evoked gastric ulcerations that were associated by decreased gastric mucosal nitric oxide and glutathione levels. The NSAID reduced gastric volume and mucin content, but increased titratable acidity, acid output, and peptic activity. CoQ10, especially at the higher dose levels, as well as pantoprazole pretreatments reverted almost all diversions induced by the NSAID to different extends. Moreover, preadministration with the nonselective nitric oxide synthase inhibitor, L-NAME, boosted ulcer formation that was associated by suppression of gastric mucosal nitric oxide in CoQ10 and pantoprazole-treated groups. The current investigation shows that CoQ10 guards against gastric ulceration via its partial inhibition of titratable acidity and peptic activity, as well as enhancement of mucin secretion due to both gastric mucosal nitric oxide and glutathione replenishment, especially at the higher dose levels.

Cytoprotective Effect of Morinda tinctoria Roxb. against Surgical and Chemical Factor Induced Gastric and Duodenal Ulcers in Rats

D. Sivaraman and P. Muralidharan — Sun, 25 Dec 2011 10:01:29 +0000

The present paper relates to the pharmacological validation of the antiulcer efficacy of ethanol leaf extract of Morinda tinctoria Roxb. (EEMT) against aspirin pyloric ligation-induced gastric ulcer model and cysteamine-induced duodenal ulcer in Wistar rats. Oral administration of EEMT at a dose of 200 and 400 mg/kg significantly prevented the occurrence of aspirin pyloric ligation and cysteamine-induced gastric and duodenal ulceration. The volume and acidity of gastric juice in pyloric ligated rats were significantly (𝑃<0.01) reduced by EEMT. There was a significant decrease in the number of ulcers, and its severity in both the models proved the ulcer protective activity of EEMT. Administration of extract at both dose levels has shown a significant increase in potassium and sodium ion concentration in the gastric juice of pylorus ligation group. On the basis of these observations, we concluded that EEMT possessing antiulcer activity may be due to the modulation of defensive factors by improvement in gastric cytoprotection.

Influence of Cord Blood Fraction (below 5 kDa) on Reparative Processes during Subchronic Ulcerative Gastropathy

Mon, 05 Sep 2011 13:19:36 +0000

The low molecular fraction (below 5 kDa) was extracted from cord blood by ultrafiltration. It has been shown that the cord blood fraction possesses antiulcer activity on the model subchronic stomach ulcer. The cord blood fraction injections caused a significant reduction in the area of ulcer lesions and promoted recovery of microcirculation, thickness, and structure of gland layer, which was accompanied by a decrease in leucocytes infiltration and an increase in glycosaminoglycans synthesis. That resulted in a faster recovery of mucus membrane of stomach as compared with Actovegin. Application of the cord blood fraction in animals with stomach ulcer normalized the alkaline phosphatase activity and thiobarbituric acid-active product content. Gel-penetrating chromatography showed that the patterns of the low molecular substances from cord blood and Actovegin differed both qualitatively and quantitatively.

The Human Gastric Pathogen Helicobacter pylori and Its Association with Gastric Cancer and Ulcer Disease

Bianca Bauer and Thomas F. Meyer — Mon, 18 Jul 2011 18:22:59 +0000

With the momentous discovery in the 1980's that a bacterium, Helicobacter pylori, can cause peptic ulcer disease and gastric cancer, antibiotic therapies and prophylactic measures have been successful, only in part, in reducing the global burden of these diseases. To date, ~700,000 deaths worldwide are still attributable annually to gastric cancer alone. Here, we review H. pylori's contribution to the epidemiology and histopathology of both gastric cancer and peptic ulcer disease. Furthermore, we examine the host-pathogen relationship and H. pylori biology in context of these diseases, focusing on strain differences, virulence factors (CagA and VacA), immune activation and the challenges posed by resistance to existing therapies. We consider also the important role of host-genetic variants, for example, in inflammatory response genes, in determining infection outcome and the role of H. pylori in other pathologies—some accepted, for example, MALT lymphoma, and others more controversial, for example, idiopathic thrombocytic purpura. More recently, intriguing suggestions that H. pylori has protective effects in GERD and autoimmune diseases, such as asthma, have gained momentum. Therefore, we consider the basis for these suggestions and discuss the potential impact for future therapeutic rationales.

Novel Techniques in Endoscopy Are Useful in Evaluating Patients with Ulcerative Colitis

Wed, 22 Jun 2011 15:02:07 +0000

Ulcerative colitis (UC), one of the most common forms of chronic inflammatory bowel disease, is characterized by exacerbations and remissions. Even when conventional colonoscopy suggests remission and a normal mucosal finding, microscopic or histological abnormalities may persist, and relapse may be imminent. Confocal microendoscopy allows histological diagnosis during the endoscopic examination. High-resolution video-magnifying colonoscopy with chromoscopy enables the observation of colorectal mucosal pit patterns and prediction of the probability of subsequent disease relapse in patients in remission. Endoscopic ultrasonography provides an immediate and accurate evaluation of the health status of the colonic wall without the need to wait for histological results and provides an indication of the efficacy of treatment. These novel endoscopic techniques are useful for the evaluation of disease activity and the efficacy of treatment in patients with UC and the prediction of relapse.

Use of Lozenges Containing Lactobacillus brevis CD2 in Recurrent Aphthous Stomatitis: A Double-Blind Placebo-Controlled Trial

Vito Trinchieri, Stefano Di Carlo, Maurizio Bossu', and Antonella Polimeni — Tue, 24 May 2011 13:46:09 +0000

Recurrent aphthous stomatitis is a common disorder of the oral cavity, affecting mainly young people. It is characterized by small ulcers which can be very painful and generally heal spontaneously within 7–14 days. There is currently no therapy that can provide rapid healing. This study evaluated the efficacy and rapidity of response of a lozenge containing Lactobacillus brevis CD2. 30 patients were randomized to take 4 lozenges a day of active product or placebo for 7 days. Signs and symptoms as well as laboratory parameters in the saliva were assessed at the start of the study and after 7 days of treatment. The study demonstrated the efficacy and the rapidity of response of the Lactobacillus brevis CD2 lozenges in resolving the clinical signs and symptoms of aphthous stomatitis, with a significantly rapid improvement of pain. This is the first study confirming the efficacy of a probiotic product in this pathology.

Chronic Inflammation and Malignancy in Ulcerative Colitis

Sai Sunkara, Garth Swanson, Christopher B. Forsyth, and Ali Keshavarzian — Wed, 20 Apr 2011 10:50:33 +0000

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) associated with multiple colonic and extraintestinal complications, the most severe being the development of colorectal cancer (CRC). Compared to the general population, there is an increased risk of CRC associated with UC. Although the pathogenesis of CRC in UC is unknown, most studies have linked it to long-standing inflammation as well as other risk factors such as duration of disease, extent of inflammation, family history of CRC, and coexisting conditions such as primary sclerosing cholangitis (PSC). UC is a life-long disease for which patients enter a vigilant screening program which includes surveillance colonoscopy to promote early detection of CRC yet some controversies exist regarding the cost effectiveness of surveillance colonoscopy and improving survival. Newer modalities such as chromoendoscopy, narrow band imaging, high definition colonoscopy, and confocal microscopy have aided in developing a more targeted approach for early detection of dysplasia in surveillance colonoscopy. This review focuses on the role of chronic colonic inflammation and dysplasia in development of UC-associated CRC and current methods of screening, detection, chemoprevention, and treatment of UC-associated CRC.

Cytokine Networks in Ulcerative Colitis

Giulia Roda, Margherita Marocchi, Alessandro Sartini, and Enrico Roda — Mon, 10 Jan 2011 16:05:58 +0000

Ulcerative colitis (UC) is a relapsing inflammatory bowel disease whose pathogenesis has yet to be defined completely. A genetic predisposition is needed to develop the colitis, but environmental factors are necessary to trigger an exaggerated and aberrant immune response, which stands at the basis of the mucosal healing. Cytokines, small cell-signaling protein molecules secreted by various types of cells including immune and glia cells, are the main mediators of the mucosal healing in IBD; ulcerative colitis is characterized by a Th2 atypical immune response, since, beside the classical proinflammatory cytokines, such as IL-1, IL-6, and TNF-α, in the pathogenesis of UC, we find a complex network in which the Th2 cytokines, IL-10 and IL-13, play a key role, but little IL-4 was found. Our aim was to review the literature to point out the state of the art in terms of cytokines because the knowledge of cytokine network in UC could lead to the discovery of new therapeutical targets.

Short-and Long-Term Clinical Outcomes of Infliximab in Fulminant Ulcerative Colitis

Mon, 03 Jan 2011 13:46:13 +0000

The aim was to characterize short- and long-term clinical outcomes of infliximab in fulminant ulcerative colitis. Patients with severe ulcerative colitis meeting the criteria of fulminant colitis after 3 days of glucocorticosteroid treatment were randomized to control or additional induction therapy of infliximab followed by an on demand/maintenance therapy of infliximab. Twenty six patients with fulminant colitis were equally randomized. At Day 7, ten patients in the control group and none in the infliximab group were in the need of colectomy (𝑃<.001). Due to superior effect of infliximab, patients in the control group were of ethical reasons transformed to infliximab treatment instead of performing colectomy. The probability to avoid colectomy was 0.66 with a median observation time of 52 months and a maximal of 91 months. The addition of azathioprine reduced the risk of late colectomy. We conclude that infliximab is effective in preventing early and late colectomy in fulminant colitis.

Cytomegalovirus Reactivation in Ulcerative Colitis Patients

Minh Nguyen, Kara Bradford, Xiaolan Zhang, and David Q. Shih — Sun, 02 Jan 2011 14:29:59 +0000

Ulcerative colitis (UC) patients are believed to have an increased risk for the colonic reactivation of cytomegalovirus (CMV) infection due to both inherent and iatrogenic factors. Numerous studies and case reports have described CMV infection as complicating the disease course of ulcerative colitis patients; the existing evidence suggests an association between the presence of CMV infection and increased colectomy and mortality rates in UC patients. Whether CMV is nonpathogenic with a tropism towards areas of dysplasia and inflammation in the colon of UC or plays an active role in pathogenesis is still debated. In this paper, we examine the existing evidence for the diagnosis and management of CMV infection in UC patients.

Potential Application of Probiotics in the Prevention and Treatment of Inflammatory Bowel Diseases

Mon, 27 Dec 2010 15:58:05 +0000

Lactic acid bacteria (LAB) represent a heterogeneous group of microorganisms that are naturally present in many foods and possess a wide range of therapeutic properties. The aim of this paper is to present an overview of the current expanding knowledge of the mechanisms by which LAB and other probiotic microorganisms participate in the prevention and treatment of inflammatory bowel diseases. These include changes in the gut microbiota, stimulation of the host immune responses, and reduction of the oxidative stress due to their antioxidant properties. A brief overview of the uses of genetically engineered LAB that produce either antioxidant enzymes (such as catalase and superoxide dismutase) or anti-inflammatory cytokines (such as IL-10) will also be discussed. This paper will show that probiotics should be considered in treatment protocols of IBD since they provide many beneficial effects and can enhance the effectiveness of traditional used medicines.

Fat Restriction Is Associated with Impaired Quality of Life in Patients with Ulcerative Colitis and Crohn's Disease

A. Kuwabara, H. Nakase, H. Tsuji, K. Shide, T. Chiba, N. Inagaki, and K. Tanaka — Tue, 30 Nov 2010 11:16:47 +0000

Inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease, is reported to be associated with impaired health-related quality of life (QOL). Although decreased QOL in these subjects has been reported to be associated with various factors, the effect of nutritional therapy, especially nutrients intake on QOL has received less attention. In this study, we evaluated the various factors including nutrients intake on QOL using SF-8 in 64 patients with IBD. Patients with IBD seem to have decreased QOL especially in the mental aspects. The percentage energy intake from fat of total energy fat intake (% energy) of the whole subjects, was lower than those of the annual National Nutrition Survey in Japan. Multiple regression analyses revealed that fat intake (% energy) was a significant predictor for mental component summary. In conclusion, fat restriction contributes to impaired QOL especially in the mental aspects in IBD patients.

Involvement of Cell Proliferation Induced by Dual Intracellular Signaling of HB-EGF in the Development of Colitis-Associated Cancer during Ulcerative Colitis

Tue, 26 Oct 2010 12:05:31 +0000

In ulcerative colitis (UC), the duration and severity of inflammation are responsible for the development of colorectal cancer. Reactive oxygen species (ROS), reactive nitric metabolites (RNMs) and interleukin (IL)-8, released by epithelial and immune cells, are involved in the pathogenesis of colitis-associated cancer. Nitric oxide and peroxynitrite activate epidermal growth factor receptor (EGFR), and therapeutic agents targeted towards EGFR are currently used to treat advanced colorectal cancer. IL-8 (a G-protein coupled receptor (GPCR) agonist), which is involved in neutrophil recruitment and activation in persistent active colitis, also promotes cleavage of the proheparin-binding epidermal growth factor-like growth factor (proHB-EGF) through a disintegrin and metalloproteinase (ADAM). The cleaved HB-EGF and C-terminal fragments (intracellular CTF) regulate proliferation via EGFR activation and nuclear export of promyelocytic leukemia zinc finger, transcription repressor, respectively. Here, we focus on the mechanisms by which RNM- and IL-8-induced EGF signaling regulate cell proliferation during the development of colitis-associated cancer.

Possible Association between Th1 Immune Polarization and Epithelial Permeability with Toll-Like Receptors 2 Dysfunction in the Pathogenesis of the Recurrent Aphthous Ulceration

Tue, 27 Apr 2010 08:36:49 +0000

Recurrent Aphthous Ulceration (RAU) is a chronic oral inflammatory disease that affects approximately 25% of the general population. The etiology of the disease is unknown; however, factors that favor the onset of RAU have been correlated with a Th1 immune polarization, while factors that reduce RAU episodes have been associated with down regulation of immune reaction or stimulation of the peripheral tolerance. In this context, the integrity of the epithelial barrier is also fundamental for the prevention of the disease and conditions that augment its permeability or produce disruption are considered potential triggers. The key factor responsible for increased susceptibility is unclear, though a deficiency of Toll-like receptor (TLR) activity seems to be a good candidate. TLRs are a group of membrane proteins that recognize conserved molecules derived from bacterial, virus, fungal, or host tissues. Particularly, the TLR2 is involved in both immune regulation and control of epithelial barrier integrity. Thus, based on literature review, we showed evidences that correlate the TLR2 dysfunction and the diverse predisposing factors with the elements considered critical for disease pathogenesis: the Th1 immune reaction and the increased epithelial permeability.