The medical management of ulcerative colitis in children often requires aggressive pharmacological therapy or colonic resection. We hypothesized that synbiotic therapy, consisting of <i>B. longum</i> R0175 and inulin would improve symptoms and quality of life (QOL) in children diagnosed with ulcerative colitis. Consenting pediatric subjects (8-18 years; n = 9) with ulcerative colitis in remission were provided synbiotic therapy, (Probiotic: <i>Bifidobacterium longum</i> R0175 2.0 x 1010 cfu/day; Prebiotic: 15 g/day of inulin) (n = 4) or placebo (maltodextrin + ascorbic acid capsule; 15 g/day of non-resistant maltodextrin) (n = 5) for ten months in a pilot study (Phase I). After ten months, the study was unblinded and synbiotic therapy was administered to eight pediatric subjects (Phase II). In attempt to increase sample size, three adult subjects with active UC were recruited and provided the synbiotic therapy (Phase III). In all phases of the research, QOL was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). The SIBDQ was administered at baseline and every two months. Subjects kept a daily records of symptoms (stool consistency and frequency, presence of blood and mucous, presence of abdominal pain and overall feeling). Phase I QOL scores were significantly better for those receiving the synbiotic therapy versus the placebo (p = 0.014). Severe symptoms occurred in 60% of the control subjects, where as subjects receiving synbiotic therapy did not experience severe symptoms (p = 0.032). Phase II QOL scores were significantly better post-treatment with synbiotic therapy (p=0.034). One subject (steroid dependant) was able to wean off Prednisone® while receiving the synbiotic therapy; she remained in remission and was symptom free for over 26 months. In Phase III, synbiotic therapy did not induce remission in the adult subjects with active UC. No adverse effects were reported.<p>Synbiotic therapy consisting of <i>Bifidobacterium longum</i> R0175 and inulin, when provided in addition to conventional treatment, appears to be a safe and effective strategy for managing pediatric ulcerative colitis in remission.Further clinical trials are warranted to confirm these preliminary results.

The medical management of ulcerative colitis in children often requires aggressive pharmacological therapy or colonic resection. We hypothesized that synbiotic therapy, consisting of <i>B. longum</i> R0175 and inulin would improve symptoms and quality of life (QOL) in children diagnosed with ulcerative colitis. Consenting pediatric subjects (8-18 years; n = 9) with ulcerative colitis in remission were provided synbiotic therapy, (Probiotic: <i>Bifidobacterium longum</i> R0175 2.0 x 1010 cfu/day; Prebiotic: 15 g/day of inulin) (n = 4) or placebo (maltodextrin + ascorbic acid capsule; 15 g/day of non-resistant maltodextrin) (n = 5) for ten months in a pilot study (Phase I). After ten months, the study was unblinded and synbiotic therapy was administered to eight pediatric subjects (Phase II). In attempt to increase sample size, three adult subjects with active UC were recruited and provided the synbiotic therapy (Phase III). In all phases of the research, QOL was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). The SIBDQ was administered at baseline and every two months. Subjects kept a daily records of symptoms (stool consistency and frequency, presence of blood and mucous, presence of abdominal pain and overall feeling). Phase I QOL scores were significantly better for those receiving the synbiotic therapy versus the placebo (p = 0.014). Severe symptoms occurred in 60% of the control subjects, where as subjects receiving synbiotic therapy did not experience severe symptoms (p = 0.032). Phase II QOL scores were significantly better post-treatment with synbiotic therapy (p=0.034). One subject (steroid dependant) was able to wean off Prednisone® while receiving the synbiotic therapy; she remained in remission and was symptom free for over 26 months. In Phase III, synbiotic therapy did not induce remission in the adult subjects with active UC. No adverse effects were reported.<p>Synbiotic therapy consisting of <i>Bifidobacterium longum</i> R0175 and inulin, when provided in addition to conventional treatment, appears to be a safe and effective strategy for managing pediatric ulcerative colitis in remission.Further clinical trials are warranted to confirm these preliminary results.

Ketamine is a short-acting dissociative anesthetic and its hallucinogenic side effects have led to increased illicit use among night clubs and party goers. Clinically, ketamine abuse is associated with severe lower urinary tract dysfunction and reduced bladder capacity and hemorrhagic cystitis with irreversible pathological changes which may develop in some cases of long-term drug abuse. Up to now, the mechanisms causing these severe side-effects are still not clear. Herein, a novel ketamine addiction rat model was used to examine the pathological changes and explore the mechanisms of urinary bladders destruction. Rats were divided into groups of control, ketamine injection 14 days and 28 days. Ketamine injection (25 mg/kg/day) was given intraperitoneally while normal saline was given for control group. In vivo isovolumetric cystometrography studies were performed, bladder stiffness parameters were measured, and the bladder tissues were collected for protein analysis and immunohistochemical staining. Ketamine treatment significantly increased micturition pressure but decreased bladder capacity in rats. Ketamine treatment also significantly decreased bladder compliance and increased bladder non-voiding contraction during storage phase. Immunofluorescence studies showing significantly decreased neurofilament staining after ketamine injection 28 days confirmed the neurotoxicity of ketamine. TUNEL staining also showed multiple degenerating cells diffusely distributed in urothelium, suburothelium, and smooth muscle layers in ketamine injected rats. Western blotting demonstrated ketamine injection increased bladder iNOS, eNOS and COX-2 expression. It is concluded that chronic exposure to low, subanesthetic concentrations of ketamine could affect cell survival and impair neuronal morphology which subsequently led to dysfunction of neural networks and altered bladder micturation reflex.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 133-160).

Diss. Linköping : Linköpings universitet, 2007.

Thesis (M. Med. Sc.)--University of Hong Kong, 2006.

Recent advances have increased the understanding that dysbiosis of the gut microbiome may be a significant contributor to the pathophysiology of ulcerative colitis. Because of this, the use of fecal microbiota transplants (FMT) has become more popular as a potential supplemental treatment option for patients suffering from this disease. Research has shown a possible benefit of FMT in conjunction with varying conventional therapies for patients with mild to moderate disease severity. However, there are scarce publications that have investigated the benefit of FMT in conjunction with a single conventional therapy for patients with moderate to severe disease, specifically. The proposed study is a multicenter, double blind, randomized controlled study of FMT, mercaptopurine (6-MP), and prednisone vs 6-MP and prednisone alone in patients with moderate to severe ulcerative colitis. The study subjects will have a baseline evaluation and the treatment trial will last 8 weeks with follow up throughout the study. Investigators will analyze the primary outcome of clinical remission and secondary outcomes of improvement of fecal calprotectin levels, Inflammatory Bowel Disease Questionnaire (IBDQ) score, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in the treatment vs control groups. The data from this study will help to identify if FMT would be an additional safe, efficacious treatment modality to the current medical management of ulcerative colitis.

Background: Reliable biomarkers are needed to evade the risk of injury, invasiveness and discomfort of endoscopies, which are required for inflammatory bowel disease (IBD) diagnosis and extent of disease assessment in ulcerative colitis (UC) patients. The need for biomarkers is accentuated in children, wherein the most frequently used IBD biomarker yields low specificity. Proteomics of clinical samples or their enriched components is a means to evaluate and identify alterations in proteins reflective of disease, with the potential for use as biomarkers and for providing insight on disease pathogenesis. Methods: Proteins were isolated from the intestinal mucosal-luminal interface (MLI), collected from the ascending and descending colon of pediatric treatment-naive patients. The intestinal MLI proteomes of 42 IBD and 18 control patients were analyzed by high resolution mass spectrometry (HRMS). Multivariate analysis and receiver operating characteristics curves were performed to develop protein biomarker panels to discriminate IBD from control, and for UC extent of disease. ELISAs were used to assess a subset of biomarker candidates in stool samples from an independent pediatric cohort (n=24). Extracellular vesicles (EVs) were isolated by ultracentrifugation from the intestinal MLI of 11 IBD and seven control patients, and analyzed by electron microscopy, nanoparticle tracking analysis and HRMS. Results: A biomarker panel of four proteins classified patients as either controls or active IBD with 97.5% accuracy. A second biomarker panel correctly classified 100% of UC patients as presenting with pancolitis or non-pancolitis. The differential protein expression of two biomarker candidates (catalase and leukotriene A-4 hydrolase) identified from the intestinal MLI was comparable in stool samples. Comparison of EV proteomes isolated from IBD patients and controls identified differential expression of processes related to host defense and immunity. Conclusions: Proteomic analysis of clinical samples identified differentially expressed proteins that can classify IBD patients from non-IBD controls and distinguish UC patients with pancolitis from those without pancolitis; proteins identified in intestinal aspirates displayed consistent differential expression in stool. Furthermore enrichment of EVs from the intestinal MLI indicates that these may contribute to the dysregulated host response against the intestinal microbiota which is observed in IBD.

No description available.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第17816号 / 医博第3814号 / 新制||医||999(附属図書館) / 30631 / 京都大学大学院医学研究科医学専攻 / (主査)教授 小柳 義夫, 教授 一山 智, 教授 武藤 学 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM