Poster Session : PS 1001 ; Altered Colonic Bacterial Fermentation as a Steadfast Pathophysiological Factor in Irritable Bowel Syndrome

( Changhwan Choi ),( Tamar Ringel Kulka ),( Daniel Temas ),( Ari Kim ),( Yehuda Ringel ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Dysbiosis leading to abnormal intestinal fermentation has been suggested as a possible etiological mechanism in Irritable bowel syndrome (IBS). We aimed to investigate the location and magnitude of altered intestinal bacterial fermentation in IBS and its clinical subtypes. Methods: 114 IBS patients who satisfi ed Rome III criteria and 33 healthy controls (HC) were investigated. Intestinal fermentation was assessed using two surrogate measures: Intestinal intraluminal pH and fecal short chain fatty acids (SCFAs). Intraluminal pHs were measured at four quartiles (Q1-4) in each small and large bowel using a wireless motility capsule (SmartPill™). Fecal SCFAs including acetate, propionate, butyrate and lactate were analyzed by capillary gas chromatography. Correlations between intestinal pH, fecal SCFAs, intestinal transit time and IBS symptom scores were analyzed. Results: Intraluminal pH levels in Q1, Q4, and total colon were signifi cantly lower in IBS compared to those in HC (6.83 for IBS vs. 7.29 for HC, P = 0.042). There were no differences in total and segmental pH levels in the small bowel between IBS and HC (6.84 vs. 6.83, P = NS). The intraluminal colonic pH differences were consistent in all IBS subtypes. Total SCFAs level was signifi cantly lower in C-IBS than in D-IBS and M-IBS. The total SCFAs level in all IBS was similar with that in HC. Colonic pH levels correlated positively with colon transit time (CTT) and IBS symptom severities. Total SCFAs levels correlated negatively with CTT, and positively with stool frequency. Conclusions: Bacterial fermentation is increased in IBS across all subtypes compared with HC. The altered intestinal fermentation in IBS appeared to be in the colon but not in the small bowel. Fecal SCFAs negatively correlated with CTT and may not be a sensitive marker to estimate intraluminal bacterial fermentation.

Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome

Carroll, I.M.,Ringel-Kulka, T.,Keku, T.O.,Chang, Y.-H.,Packey, C.D.,Sartor, R.B.,Ringel, Y. AMERICAN PHYSIOLOGICAL SOCIETY 2011 American journal of physiology, Gastrointestinal a Vol.301 No.5

Effects of Copper, Zinc and Cadmium on the Recovery Pattern of Aryl Sulfotransferase IV Activity in Rats fed 2-Acetylaminofluorene Diet

Chung Keun Hee,Ringel David P.,Shin Kyung Ok The Korean Nutrition Society 2006 Nutritional Sciences Vol.9 No.1

Purified rat liver aryl sulfotransferase IV (AST IV) was found to be inhibited in vitro by zinc, copper, cadmium and terbium. Among these four elements, zinc, copper and cadmium were all strongly inhibitory to the AST IV activity at very low concentrations (2.5 $\mu$M to 0.025 $\mu$M). In rat liver cytosol, zinc, copper and cadmium at 25 $\mu$M to 0.025 $\mu$M also decreased the AST IV activity to $50\%$ of the controls. In order to assess the possible effects of these metals on the AST IV activity recovery pattern in vivo, studies on the relationship between these minerals and dietary 2-acetylaminofluorene were conducted. Total of forty rats were fed one of five diets for 6 weeks: diet 1, Control diet plus 2-acetlyaminofluorene ($0.05\%$); diet 2, zinc-deficient diet plus 2-acetlyaminofluorene; diet 3, zinc-supplement diet plus 2-acetylaminofluorene; diet 4, copper-supplement diet plus 2-acetylaminofluorene; diet 5, cadmium-supplement diet plus 2-acetylaminofluorene. Half of the rats from each diet were changed to individual diet after 3 weeks of 2-acetylaminofluorene feeding. Placement of rats on the control diet following one cycle of 2-acetylaminofluorene feeding of 3 weeks without 2-acetylaminofluorene resulted in nearly full recovery of AST IV activity within 3 or 4 weeks. However, the rats fed diets that supplemented with zinc, copper or cadmium without 2-acetylaminofluorene showed a new pattern of lowered AST IV activity as early as the first cycle. Also, lowering in cytosolic AST IV contents was appeared in the livers from the rats, following one cycle of 2-acetylaminofluorene feeding of 3 weeks, fed one of the diets that supplemented with copper, cadmium or zinc without 2-acetylaminofluorene for ensuing 3 weeks.

Influence of Dietary Zinc, Copper and Cadmium Levels on Rat Liver Aryl Sulfotransferase IV Activity

Chung Keun Hee,Ringel David P.,Shin Kyung Ok The Korean Nutrition Society 2006 Nutritional Sciences Vol.9 No.1

Aryl sulfotransferase (AST) IV is a liver enzyme involved in detoxication and has been shown to be susceptible to down regulation by a number of hepatotoxic xenobiotics. Studies presented here to investigate the ability of biological and non-biological divalent metal cations on AST IV activity showed that AST IV was strongly inhibited following in vitro or in vivo exposure to. Zn ( II ), Co ( II ) or Cd ( II ). It was found that $0.025\sim$2.5 uM of these metal ions were sufficient to cause $50\%$ of inhibition in vitro in purified AST IV and $0.25\sim$25 uM of these metal ions in liver cytosolic fractions. For the in vivo study, 1,000 mg Cu ( II )/kg, 2,000 mg Zn ( II )/kg or 250 mg Cd( II )/kg was added to individual diets and administered to three (3) group; of mts over a 7 week period The Co ( II )-supplemented diet produced no apparent change in rat growth rate and resulted in 30-fold increase in liver cytotolic Cu ( II ) levels, suggesting that elevated levels of Cu ( II ) ion in the liver were responsible for the loss of AST IV activity. In contrast, the Zn ( II )-supplemented diet caused a decrease in rat growth rates and resulted in zero increase in liver Zn ( II ) levels, which suggested an indirect inhibition mechanism was caused by Zn ( II ) in the liver. Rats were fed the Cd-supplemented diet also displayed a decrease in growth rate with little or no change in liver Cu ( II ) or Zn ( II ) levels. When the liver cytosols of mts from the metal ion diets were immunochemically analyzed for the AST IV and albumin contents, no significant changes were observed in albumin levels. However, AST IV contents in the cytosols of mts fed the Zn ( II )-supplemented diets showed a slight decrease in amount These results showed that AST IV activity in vitro and in vivo can be inhibited by Co ( II ), Zn ( II ), and Cd ( II ) by apparently different mechanisms. The immediate response to a Zn injection showed a decrease in AST IV activity but not in the AST IV content in liver cytosol. These mechanisms appeared to involve direct actions of the metal ion on AST IV activity and indirect actions affecting AST IV amount.

Closed-Loop Transmit Diversity Techniques for Small Wireless Terminals and Their Performance Assessment in a Flat Fading Channel

Raqibul Mostafa,Ramesh C. Pallat,Uwe Ringel,Ashok A. Tikku,Jeffrey H. Reed 한국전자통신연구원 2012 ETRI Journal Vol.34 No.3

Closed-loop transmit diversity is considered an important technique for improving the link budget in the third generation and future wireless communication standards. This paper proposes several transmit diversity algorithms suitable for small wireless terminals and presents performance assessment in terms of average signal-to-noise ratio (SNR) and outage improvement,convergence, and complexity of operations. The algorithms presented herein are verified using data from measured indoor channels with variable antenna spacing and the results explained using measured radiation patterns for a two-element array. It is shown that for a two-element array, the best among the proposed techniques provides SNR improvement of about 3 dB in a tightly spaced array (inter-element spacing of 0.1wavelength at 2 GHz) typical of small wireless devices. Additionally, these techniques are shown to perform significantly better than a single antenna device in an indoor channel considering realistic values of latency and propagation errors. Closed-loop transmit diversity is considered an important technique for improving the link budget in the third generation and future wireless communication standards. This paper proposes several transmit diversity algorithms suitable for small wireless terminals and presents performance assessment in terms of average signal-to-noise ratio (SNR) and outage improvement,convergence, and complexity of operations. The algorithms presented herein are verified using data from measured indoor channels with variable antenna spacing and the results explained using measured radiation patterns for a two-element array. It is shown that for a two-element array, the best among the proposed techniques provides SNR improvement of about 3 dB in a tightly spaced array (inter-element spacing of 0.1wavelength at 2 GHz) typical of small wireless devices. Additionally, these techniques are shown to perform significantly better than a single antenna device in an indoor channel considering realistic values of latency and propagation errors.

Anti-Enteric Neuronal Antibodies and the Irritable Bowel Syndrome

( Jackie D Wood ),( Su Mei Liu ),( Douglas A Drossman ),( Yehuda Ringel ),( William E Whitehead ) 대한소화기기능성질환·운동학회 (구 대한소화관운동학회) 2012 Journal of Neurogastroenterology and Motility (JNM Vol.18 No.1

Background/Aims Functional gastrointestinal disorders are those in which no abnormal metabolic or physical processes, which can account for the symptoms, can be identified. The irritable bowel syndrome (IBS) is a significant functional disorder, which affects 10-20 percent of the population worldwide. Predominant symptoms of IBS are abnormal defecation associated with abdominal pain, both of which may be exacerbated by psychogenic stress. Our study was designed to test a hypothesis that symptoms in a subset of patients with a diagnosis of IBS are associated with an autoimmune degenerative neuropathy in the enteric nervous system. Methods Serum was collected from Rome II-IBS patients and controls at the University of North Carolina Functional Gastrointestinal Diseases Center. Assay procedures were immunohistochemical localization of antibody binding to enteric neurons and human protein microarray assay for antigens recognized by antibodies in the sera. Results Eighty-seven percent of IBS sera and 59% of control sera contained anti-enteric neuronal antibodies. Antibody immunostaining was seen in the nucleus and cytoplasm of neurons in the enteric nervous system. Protein microarray analysis detected antibody reactivity for autoantigens in serum with anti-enteric neuronal antibodies and no reactivity for the same autoantigens in samples not containing anti-enteric neuronal antibodies in our immunostaining assay. Antibodies in sera from IBS patients recognized only 3 antigens out of an 8,000 immunoprotein array. The 3 antigens were: (1) a nondescript ribonucleoprotein (RNP-complex); (2) small nuclear ribonuclear polypeptide A; and (3) Ro-5,200 kDa. Conclusions Results of the present study suggest that symptoms in a subset of IBS patients might be a reflection of enteric neuronal dam - age or loss, caused by circulating anti-enteric autoimmune antibodies. (J Neurogastroenterol Motil 2012;18:78-85)