Perspectives of East Asian patients and physicians on complementary and alternative medicine use for inflammatory bowel disease: results of a cross-sectional, multinational study

Background/Aims@#Complementary and alternative medicine (CAM) is prevalent in East Asia. However, information on CAM in East Asian patients with inflammatory bowel disease (IBD) is scarce. We aimed to profile the prevalence and pattern of CAM use among East Asian IBD patients and to identify factors associated with CAM use. We also compared physicians’ perspectives on CAM. @*Methods@#Patients with IBD from China, Japan, and South Korea were invited to complete questionnaires on CAM use. Patient demographic and clinical data were collected. Logistic regression analysis was applied for predictors of CAM use. Physicians from each country were asked about their opinion on CAM services or products. @*Results@#Overall, 905 patients with IBD participated in this study (China 232, Japan 255, and South Korea 418). Approximately 8.6% of patients with IBD used CAM services for their disease, while 29.7% of patients sought at least 1 kind of CAM product. Current active disease and Chinese or South Korean nationality over Japanese were independent predictors of CAM use. Chinese doctors were more likely to consider CAM helpful for patients with IBD than were Japanese and South Korean doctors. @*Conclusions@#In 8.6% and 29.7% of East Asian patients with IBD used CAM services and products, respectively, which does not differ from the prevalence in their Western counterparts. There is a significant gap regarding CAM usage among different Asian countries, not only from the patients’ perspective but also from the physicians’ point of view.

Alterations of Colonic Contractility in an Interleukin-10 Knockout Mouse Model of Inflammatory Bowel Disease

BACKGROUND/AIMS: Inflammatory bowel disease is commonly accompanied by colonic dysmotility and causes changes in intestinal smooth muscle contractility. In this study, colonic smooth muscle contractility in a chronic inflammatory condition was investigated using smooth muscle tissues prepared from interleukin-10 knockout (IL-10(-/-)) mice. METHODS: Prepared smooth muscle sections were placed in an organ bath system. Cholinergic and nitrergic neuronal responses were observed using carbachol and electrical field stimulation with L-NG-nitroarginine methyl ester (L-NAME). The expression of interstitial cells of Cajal (ICC) networks, muscarinic receptors, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) was observed via immunofluorescent staining. RESULTS: The spontaneous contractility and expression of ICC networks in the proximal and distal colon was significantly decreased in IL-10(-/-) mice compared to IL-10(+/+) mice. The contractility in response to carbachol was significantly decreased in the proximal colon of IL-10(-/-) mice compared to IL-10(+/+) mice, but no significant difference was found in the distal colon. In addition, the expression of muscarinic receptor type 2 was reduced in the proximal colon of IL-10(-/-) mice. The nictric oxide-mediated relaxation after electrical field stimulation was significantly decreased in the proximal and distal colon of IL-10(-/-) mice. In inflamed colon, the expression of nNOS decreased, whereas the expression of iNOS increased. CONCLUSIONS: These results suggest that damage to the ICC network and NOS system in the proximal and distal colon, as well as damage to the smooth muscle cholinergic receptor in the proximal colon may play an important role in the dysmotility of the inflamed colon.

Severe hyponatremia and seizures after bowel preparation with low-volume polyethylene glycol plus ascorbic acid solution / 영남의대학술지

The widely used polyethylene glycol (PEG)-based solutions have been proven effective for bowel preparation when 4 L of the solution is administered before colonoscopy. However, large volumes of the solutions are generally poorly tolerated. A new PEG-based solution consisting of 2 L of PEG and a high dose of ascorbic acid has recently become available. Electrolyte abnormalities caused by PEG-based solutions have rarely been reported. We report on a case of acute severe hyponatremia with associated generalized tonic-clonic seizures after bowel preparation with a low-volume PEG plus ascorbic acid solution in a 74-year-old woman with no history of seizures. She took a beta blocker, an angiotensin-converting enzyme inhibitor, and glimepiride for hypertension and diabetes mellitus. She showed general weakness, nausea, agitation, muscle cramping, and seizures after ingestion of the PEG plus ascorbic acid solution. Her serum sodium level was 112 mEq/L. Her symptoms improved after intravenous administration of hypertonic saline. Physicians should pay attention to screening for electrolytes and development of neurological symptoms during bowel preparation.

Changing Paradigm in the Management of Inflammatory Bowel Disease / 대한소화기학회지

Inflammatory bowel disease (IBD) is a chronic progressive idiopathic inflammatory disorder that involves the digestive tract from the mouth to the anus. Over the past decades, many therapeutic strategies have been developed to manage IBD, but therapeutic strategies based only on relief of clinical symptoms have not changed the natural history of this disease entity. This underlines the importance of understanding the natural history of IBD itself. When we look at the natural history of Crohn's disease (CD), it first begins with inflammation of the intestinal mucosa and this inflammatory reaction proceeds to stenosing or penetrating reaction if not adequately controlled. However, it takes a considerable amount of time before mucosal inflammation proceeds to stenosis of the intestinal lumen or penetration into the adjacent bowel. Therefore, it can be expected that if proper care is given during that period, progression of CD to such a complicated disease could be prevented. Even though the concept of mucosal healing was introduced in the early 1990s, no correlation could be observed between healing of mucosal lesions and relief of clinical symptoms. However, the introduction of biologic agents targeting tumor necrosis factor has changed the way to treat IBD that is refractory to standard medications and has allowed us to aim for a new therapeutic goal, 'deep remission'. Further advances in biologic agents have provided highly effective treatments for IBD, making deep remission a realistic goal. Whether IBD patients may benefit by experiencing a 'deep' remission beyond the control of clinical symptoms need to be evaluated in further investigation. Nevertheless, it can be anticipated that attaining deep remission might ultimately have an impact on important outcomes such as the need for surgery and the quality of life.

Targeted Therapy in Inflammatory Bowel Disease; Current Status and Future Perspectives / 한양의대학술지

Novel biologic agents that selectively target specific molecules and pathways have been developed recently for the management of inflammatory bowel disease (IBD). Anti-TNF-alpha, an antibody to TNF-alpha is one of the first newly developed drugs to dramatically improve the symptoms of patients with IBD. Therapy with anti-TNF-alpha demonstrates a new paradigm for management of IBD and early treatment with these drugs has demonstrated increased benefit. However, more than one-third of the patients have lost response to the drug. Also, there is the problem of antibody formation. Therefore, enormous efforts to develop novel drugs as an alternatives to anti-TNF-alpha are underway. Anti CD4+ T cell cytokine including IL-12/23 and IL-17 blockers, selective anti-adhesion molecules known as natalizumab, vedolizumab and alicaforsen, T-cell proliferation inhibitors, anti-inflammatory cytokines, immune stimulators, growth factors and mitogen activated protein kinase (MAPK) inhibitors are among the novel therapeutic agents that are currently being investigated for efficacy and safety in the management of IBD. The aim of this paper is to review current knowledge concerning the mechanism of action, the short and long term efficacy, and the safety of these novel biologic therapies, as well as that of anti-TNF-alpha, in IBD.

Clinical Characteristics of Gastroesophageal Reflux Disease with Esophageal Injury in Korean: Focusing on Risk Factors / 대한소화기학회지

BACKGROUND/AIMS: Recent studies suggest that the prevalence of gastroesophageal reflux disease (GERD) is increasing in Korea. However, studies on risk factors for GERD have yielded inconsistent results. The aims of this study were to compare clinical features between symptomatic syndromes without esophageal injury (=non-erosive disease [NED]) and syndromes with esophageal injury (=erosive disease [ED]), and to determine risk factors associated ED. METHODS: A total of 450 subjects who visited gastroenterology clinics of six training hospitals in Daegu from March 2008 to April 2010 were consecutively enrolled. The subjects were asked to complete a questionnaire which inquired about gastroesophageal reflux symptoms. The questionnaire also included questions about smoking, alcohol drinking, consumption of coffee, use of drugs, exercise, and other medical history. The subjects were subdivided into NED and ED groups. RESULTS: The proportion of subjects in each NED and ED group was 172 (38.2%) and 278 (61.8%). Male gender, smoking, alcohol drinking, consumption of coffee, large waist circumference, infrequent medication of antacids, aspirin and NSAIDs, infrequent and mild GERD symptoms were all significantly associated with ED on univariate analysis. Age, hiatal hernia, diabetes mellitus, body mass index, change in weight during 1 year, and number of typical GERD symptoms were not independent risk factors for ED. However, the association between ED and alcohol drinking, infrequent medication of antacids, mild typical GERD symptoms remained as strong risk factors after adjustments on multivariate logistic analysis. CONCLUSIONS: Independent risk factors associated with ED were alcohol drinking, infrequent medication of antacids and mild typical GERD symptoms.

Efficacy of Rifaximin Compared with Ciprofloxacin for the Treatment of Acute Infectious Diarrhea: A Randomized Controlled Multicenter Study

BACKGROUND/AIMS: Ciprofloxacin has been widely prescribed for acute infectious diarrhea. However, the resistance to this drug is increasing. Rifaximin is a novel but poorly absorbed rifamycin derivative. This study evaluated and compared the efficacies of rifaximin and ciprofloxacin for the treatment of acute infectious diarrhea. METHODS: We performed a randomized controlled multicenter study in Korea. Patients with acute diarrhea were enrolled and randomized to receive rifaximin or ciprofloxacin for 3 days. The primary efficacy endpoint was the time to last unformed stool (TLUS). Secondary endpoints were enteric wellness (reduction of at least 50% in the number of unformed stools during 24-hour postenrollment intervals), general wellness (subjective feeling of improvement), and proportion of patients with treatment failure. RESULTS: Intent-to-treat analysis (n=143) showed no significant difference between the rifaximin and ciprofloxacin groups in the mean TLUS (36.1 hours vs 43.6 hours, p=0.163), enteric wellness (49% vs 57%, p=0.428), general wellness (67% vs 78%, p=0.189), or treatment failure rate (9% vs 12%, p=0.841). The adverse events did not differ significantly between the two groups. CONCLUSIONS: These results suggest that rifaximin is as safe and effective as ciprofloxacin in the treatment of acute infectious diarrhea.

Ulcerative Colitis Mimicking Acute Hemorrhagic Colitis / 영남의대학술지

Ulcerative colitis (UC) is a chronic inflammatory disorder of the gastrointestinal tract that affects the large bowel. Its etiology remains controversial. However, an infectious or immunologic origin is considered the primary cause. The onset of UC is typically slow and insidious, but some patients may present acutely with symptoms mimicking infectious colitis. We report a case of ulcerative colitis mimicking acute hemorrhagic colitis at initial presentation. A 60-year-old man was referred to Yeungnam University Hospital for bloody diarrhea and abdominal pain. Sigmoidoscopy revealed mildly edematous mucosa in the rectum and hyperemic mucosa with petechiae in the sigmoid colon. The patient was treated with antibiotics for several days, and his symptoms improved. However, after one month, his bloody diarrhea relapsed. Follow-up sigmoidoscopy revealed mucosal friability in the rectum and sigmoid colon. He was diagnosed with ulcerative colitis, and his symptoms were improved with mesalazine and a steroid enema.

Effect of the Flavonoid Luteolin for Dextran Sodium Sulfate-induced Colitis in NF-kappa BEGFP Transgenic Mice / 영남의대학술지

BACKGROUND: Luteolin, a flavone found in various Chinese herbal medicines is known to possess anti-inflammatory properties through its ability to inhibit various proinflammatory signaling pathways including NF-kappa B and p38 MAPK. In this study, we investigated the potential therapeutic effect of luteolin on dextran sodium sulfate (DSS)-induced colitis. MATERILAS AND METHODS: We used a transgenic mouse model expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-kappa B cis-elements. C57BL/6 NF-kappa BEGFP mice received 2.5% DSS in their drinking water for six days in combination with daily luteolin administration (1mg/kg body weight, 0.1ml vol, intragastric) or vehicle. NF-kappa B activity was assessed macroscopically with a Charge-Coupled Device (CCD) camera and microscopically by confocal analysis. RESULTS: A significant increase in the Disease Activity Index (DAI), histological score (p<0.05), IL-12 p40 secretion in colonic stripe culture (p<0.05) and EGFP expression was observed in luteolin and/or DSS-treated mice compared to water-treated mice. Interestingly, a trend toward a worse colitis (DAI, IL-12p40) was observed in luteolin-treated mice compared to non-treated DSS-exposed mice. In addition, EGFP expression (NF-kappa B activity) strongly increased in the luteolin-treated mice compared to control mice. Confocal microscopy showed that EGFP positive cells were primarily lamina propria immune cells. CONCLUSIONS: These results suggest that luteolin is not a therapeutic alternative for intestinal inflammatory disorders derived for primary defects in barrier function. Thus, therapeutic intervention targeting these signaling pathways should be viewed with caution.