Medicine JournalFeeds

Antioxidants and Chronic Pancreatitis: Theory of Oxidative Stress and Trials of Antioxidant Therapy.

Dig Dis Sci. 2012 Feb 3;

Authors: Grigsby B, Rodriguez-Rilo H, Khan K

Abstract

Chronic pancreatitis (CP) is an inflammatory disease characterized by the progressive destruction of pancreatic tissue and resulting in pancreatic exocrine and endocrine insufficiency. Increased oxidative stress has been implicated as a potential mechanism in its etiology and pathology. A number of studies have demonstrated that CP patients have a compromised antioxidant status, which may be a contributing factor to the enhanced oxidative state associated with the disease. Nutrition is an essential consideration in the treatment of CP, especially since diet is a source of several antioxidants and cofactors required for the production of cellular antioxidant enzymes. Many CP patients have an inadequate intake of macro and micronutrients because of abdominal pain and discomfort, which often increase postprandially and discourage eating. Exocrine insufficiency leads to further complications by preventing adequate digestion and absorption of ingested food, thus causing even greater deficiencies and impairment of antioxidant status. The aims of this article are to review the oxidative stress model of CP and to examine the evidence for nutrition, and, particularly, antioxidants, in the treatment of CP.

PMID: 22302241 [PubMed - as supplied by publisher]

Myosin Light Chain Kinase Is Involved in the Mechanism of Gastrointestinal Dysfunction in Diabetic Rats.

Dig Dis Sci. 2012 Feb 3;

Authors: Hu W, Feng P

Abstract

BACKGROUND: It is well established that smooth muscle contractility is regulated by an elevation of cytosolic Ca(2+) via myosin light chain phosphorylation, which is activated by myosin light chain kinase (MLCK). Recently, MLCK has been demonstrated to play an important role in smooth muscle contraction and normal gastrointestinal motility. AIMS: The aim of our study is to investigate whether MLCK is involved in the mechanism of gastrointestinal dysfunction and the ameliorating effects of insulin on gastrointestinal dysfunction in diabetic rats. METHODS: A diabetic rat model was established by an intravenous injection with streptozotocin. Rats were randomized into three groups: control group, diabetic group, and insulin-treated group. The gastrointestinal functions were assessed in terms of gastric emptying and intestinal transit. The expression of MLCK in the pylorus and ileum of the three groups was determined by real-time polymerase chain reaction (PCR) and Western blot methods. RESULTS: The diabetic group exhibited a significant delay in gastric emptying and intestinal transit than the control group. Insulin treatment significantly ameliorated the gastric emptying and intestinal transit in diabetic rats. The expression levels of MLCK in the pylorus and ileum of the diabetic group were both significantly decreased compared with the control group, and the changes of MLCK expression in these tissues of diabetic rats were partially reversed after treatment with insulin. CONCLUSIONS: Decreased expression of MLCK in gastrointestinal tissues could be a possible cause for gastrointestinal dysfunction. Insulin may partly ameliorate gastrointestinal dysfunction by restoring the expression of MLCK.

PMID: 22302242 [PubMed - as supplied by publisher]

Liver Stiffness Measurement Using Acoustic Radiation Force Impulse (ARFI) Elastography and Effect of Necroinflammation.

Dig Dis Sci. 2012 Feb 3;

Authors: Yoon KT, Lim SM, Park JY, Kim DY, Ahn SH, Han KH, Chon CY, Cho M, Lee JW, Kim SU

Abstract

BACKGROUND: Acoustic radiation force impulse (ARFI) elastography can be used to assess the degree of liver fibrosis. AIM: We evaluated the performance of ARFI elastography in assessment of liver fibrosis and compared it with the performance of aspartate aminotransferase-to-platelet ratio index (APRI) and transient elastography with Fibroscan (FS). METHODS: We prospectively analyzed 250 consecutive patients who underwent liver biopsy and ARFI from June 2010 to May 2011. Reliable FS values were obtained for 97 (38.8%) patients. RESULTS: The mean age of patients (147 male and 103 female) was 46.6 years. Liver stiffness values obtained by use of ARFI elastography significantly correlated with histological fibrosis stage (R = 0.575, P < 0.001). Area under the receiver operating characteristics curves (AUROCs) of ARFI elastography for predicting significant fibrosis (≥F2) and cirrhosis (F4) was 0.74 (95% confidence interval [CI], 0.64-0.86, P = 0.001) and 0.79 (95% CI, 0.67-0.91, P = 0.001), respectively, and those for APRI were 0.69 (95% CI, 0.58-0.79, P = 0.001) and 0.76 (95% CI, 0.64-0.85, P < 0.001), respectively. The optimum cutoff values for ARFI elastography were 1.13 m/s for ≥F2 and 1.98 m/s for F4; these decreased to 1.09 m/s for ≥F2 and 1.81 m/s for F4 when 131 patients with normal alanine aminotransferase (ALT) were selected. In the sub-group of 97 patients with reliable FS values, the performance in predicting ≥F2 or F4 was equivalent between ARFI elastography and FS. CONCLUSIONS: ARFI elastography is a reliable surrogate marker of liver fibrosis, if its relationship with biochemical markers, for example ALT level, is taken into account.

PMID: 22302243 [PubMed - as supplied by publisher]

Diabetes Mellitus Is an Independent Risk Factor for Colorectal Cancer.

Dig Dis Sci. 2012 Feb 1;

Authors: Sun L, Yu S

Abstract

BACKGROUND: Epidemiological studies have suggested positive associations between diabetes and colorectal cancer. However, the findings were inconsistent, especially regarding specific sex or cancer subsite. AIMS: To conduct a systematic review with meta-analysis to examine the association of diabetes mellitus with risk of colorectal cancer and to investigate whether the association is dependent on sex, cancer subsite, race/ethnicity, or duration of diabetes. METHODS: Relevant studies were identified by searching Pubmed to May 12, 2011. The reference lists of identified articles were also reviewed. Two authors independently selected the studies and extracted relevant data. The study quality was assessed. RESULTS: Thirty-nine studies (28 cohort studies and 11 case-control studies) were included in the final analysis. Compared with non-diabetic subjects, the pooled risk estimate of colorectal cancer for diabetic subjects was 1.29 (95% CI = 1.23-1.35). The subgroup analyses revealed that the risk was significantly increased for both genders, for every cancer subsite, and for both short duration and long duration of diabetes. Exposure to diabetes increased the risk of colorectal cancer for White and Asian, whereas there was no evidence of such an association either among Black or native Hawaiians. CONCLUSIONS: Our results confirmed that subjects with diabetes are at modestly increased risk of developing colorectal cancer.

PMID: 22302244 [PubMed - as supplied by publisher]

Letter in Response to the Recently Published Study: Prophylactic Pancreatic Stents: Does Size Matter? A Comparison of 4-Fr and 5-Fr Stents in Reference to Post-ERCP Pancreatitis and Migration Rate.

Dig Dis Sci. 2012 Feb 3;

Authors: Chahal P, Baron TH

PMID: 22302245 [PubMed - as supplied by publisher]

Impairment of Gastric Nitrergic and NRF2 System in Apolipoprotein E Knockout Mice.

Dig Dis Sci. 2012 Feb 3;

Authors: Ravella K, Yang H, Gangula PR

Abstract

BACKGROUND AND AIM: Gastric motility dysfunction is most commonly seen in diabetic and idiopathic gastroparesis patients. Recently we reported that impaired nitrergic relaxation and a reduced NO (nitric oxide) bioavailability were responsible for gastric motility dysfunction in diabetic female rats. One of the main factors involved in the inactivation of the nitrergic system is oxidative stress commonly seen in diabetic patients. Hyperlipidemia may also be one of the detrimental causes for impaired gastric motility associated with diabetes. In the current study, we investigated whether apolipoprotein E knockout mice (ApoE-KO), an oxidative stress animal model with a hyperlipidemia burden, also displays an impaired nitrergic system. To test this, nitrergic relaxation (AUC/mg tissue) was measured at 2 Hz through electric field stimulation using gastric pyloric strips prepared from C57BL WT or ApoE-KO female mice. Protein expression was determined by Western blots. RESULTS: Nitrergic relaxation was reduced in gastric strips from ApoE-KO versus WT mice. Protein levels of nNOS (neuronal nitric oxide synthase), GCH-1 (GTP cyclohydrolase 1), Nrf2 (nuclear factor E-2 related factor 2) and GCSc (glutamate-cysteine ligase catalytic) were also reduced in ApoE-KO compared to controls, with no significant change in GCSm (glutamate-cysteine ligase modifier) and HO-1 (heme oxygenase 1). The activities of DHFR (dihydrofolate reductase) and antioxidant enzymes were also reduced in ApoE-KO mice. CONCLUSIONS: This novel study is the first to reveal that a deficiency in ApoE impairs gastric motility functions, and that hyperlipidemia and the suppression of selective antioxidants may be an underlying mechanism for this pathological change.

PMID: 22302246 [PubMed - as supplied by publisher]

Down-Regulation of Claudin-3 Is Associated with Proliferative Potential in Early Gastric Cancers.

Dig Dis Sci. 2012 Jan 31;

Authors: Okugawa T, Oshima T, Chen X, Hori K, Tomita T, Fukui H, Watari J, Matsumoto T, Miwa H

Abstract

BACKGROUND: Claudins are tight junction (TJ) proteins, and the relationship between the level of expression and localization of TJ protein, and tumor aggressiveness in early gastric cancer (GC) is still far from clear. AIMS: To investigate the expression of claudins and Ki-67 in early GC cells and surrounding normal gastric mucosa. METHODS: A total of 53 early GC lesions removed via endoscopic mucosal resection or endoscopic submucosal resection were evaluated. All of the GCs were characterized as well to moderately differentiated adenocarcinoma. The labeling index (LI) of Ki-67 was calculated for each sample. To assess the prevalence of epithelial TJs, immunofluorescent staining for claudin-3, claudin-4, and claudin-7 was performed. The immunoreactivity was graded according to the percentage of stained cells. RESULTS: Claudin-3, claudin-4, and claudin-7 expression at TJs in GC and intestinal metaplasia were significantly higher than that in gastric mucosa with no intestinal metaplasia. The Ki-67 LI of GC specimens was inversely correlated with claudin-3 expression, but not with claudin-4 or claudin-7 expression. Claudin-3 expression was significantly lower at the submucosal invasive front of GCs. CONCLUSIONS: The down-regulation of claudin-3 was associated with the proliferative potential of GC cells, indicating that claudins may have a pivotal role in the progression of GC.

PMID: 22290341 [PubMed - as supplied by publisher]

Comprehensive Self-Management Reduces the Negative Impact of Irritable Bowel Syndrome Symptoms on Sexual Functioning.

Dig Dis Sci. 2012 Jan 31;

Authors: Eugenio MD, Jun SE, Cain KC, Jarrett ME, Heitkemper MM

Abstract

BACKGROUND: Women with irritable bowel syndrome (IBS) report sexual dysfunction. Comprehensive self-management (CSM) intervention has been shown to reduce gastrointestinal, psychological, and somatic symptoms in IBS women. Whether this intervention also reduces sexual dysfunction is not known. AIMS: We sought to compare demographic and clinical factors in IBS women with and without sexual dysfunction as defined by the Arizona sexual experiences scale (ASEX) and to test the effects of CSM treatment on sexual dysfunction scores and on the sexual relations subscale of an IBS quality of life (IBSQOL) scale which measures the effect of IBS on sexual QOL. METHODS: IBS (Rome II) women enrolled in a randomized clinical trial of CSM treatment were characterized as having sexual dysfunction (N = 89) or not (N = 86) at baseline based on ASEX criteria. Baseline characteristics and symptoms were compared between the two groups. Post-intervention changes were compared between the CSM and the usual care arms of the randomized trial. RESULTS: Women meeting ASEX criteria for sexual dysfunction were older, had higher lifetime depression and antidepressant use, more primary care/MD visits, fewer mental healthcare visits, and greater sleep disturbance than those without sexual dysfunction. No significant group differences in gastrointestinal or somatic symptoms were observed. Compared with usual care treatment, CSM increased sexual QOL scores and had a weaker effect on ASEX scores. CONCLUSIONS: Severity of IBS symptoms at baseline did not differ between IBS women with or without sexual dysfunction. The CSM intervention can reduce the effect of IBS on sexual QOL.

PMID: 22290342 [PubMed - as supplied by publisher]

Clinical Characteristics and the Expression Profiles of Inflammatory Cytokines/Cytokine Regulatory Factors in Asymptomatic Patients with Nodular Gastritis.

Dig Dis Sci. 2012 Jan 31;

Authors: Hong SN, Jo S, Jang JH, Choi J, Kim S, Ahn SY, Kim JH, Choe WH, Lee SY, Sung IK, Park HS, Shim CS

Abstract

BACKGROUND: Nodular gastritis (NG) has been reported in adult dyspeptic patients, whereas information on NG in asymptomatic patients is limited. AIMS: To evaluate the prevalence, clinico-epidemiological characteristics, and expression profiles of inflammatory cytokines or cytokine regulatory factors of NG in asymptomatic adults. METHODS: A cross-sectional study was conducted prospectively using 2,579 consecutive asymptomatic subjects who underwent screening esophagogastroduodenoscopy. The expression of inflammatory cytokines or cytokine regulatory factors in the gastric mucosa of NG patients was evaluated using immunofluorescence staining. RESULTS: NG was diagnosed in 52 patients (2.0%) and showed a predilection for females (M:F = 1:1.89) and young adults (median age: 34 years; range: 25-51 years). All NG patients were positive for Helicobacter pylori infection. Based on multivariate analysis, the risk of NG was increased in patients younger than 40 years (OR, 7.57; 95% CI, 3.76-15.24) and of the female gender (OR, 2.12; 95% CI; 1.05-4.28). Immunofluorescent staining for interleukin (IL)-1β, IL-10, IL-18, IL-18 binding protein, IL-32, IL-33, and neutrophil proteinase 3 (PR3) was performed on cryosections of gastric mucosa. Interestingly, the expression of PR3 was highly increased in the gastric biopsies from asymptomatic NG patients but was expressed infrequently in the controls. CONCLUSIONS: Asymptomatic NG is associated with H. pylori infection, and a predilection for this condition exists in young females. The PR3 expression of gastric mucosa might play an important role in the pathogenesis of NG.

PMID: 22290343 [PubMed - as supplied by publisher]

Synesthesia, Pseudo-Synesthesia, and Irritable Bowel Syndrome.

Dig Dis Sci. 2012 Jan 31;

Authors: Carruthers HR, Miller V, Tarrier N, Whorwell PJ

Abstract

BACKGROUND AND AIMS: Synesthesia is a sensory disorder where the stimulation of one sensory modality can lead to a reaction in another which would not usually be expected to respond; for instance, someone might see a color on hearing a word such as a day of the week. Disordered perception of sensory information also appears to contribute to the pathophysiology of irritable bowel syndrome (IBS). The purpose of this exploratory study was to ascertain whether these two conditions might be linked in any way. METHODS: Two hundred consecutive IBS outpatients were screened for synesthesia and compared with 200 matched healthy volunteers (controls). Positive responders were tested for two types of synesthesia (grapheme-color and music-color/shape) using a questionnaire which was repeated after 3 months to test for reproducibility. RESULTS: Of the 200 IBS outpatients screened, 26 (13%) patients and six (3%) controls claimed to be synesthetic (P < 0.001). Reproducibility was more variable in IBS patients than controls but despite this variability, 15 (7.5%) patients compared with 5 (2.5%) controls had greater than 75% consistency (P = 0.036), and 19 (9.5%) patients and 6 (3%) controls had greater than 50% consistency (P = 0.012). A reproducibility of less than 50% was observed in seven (3.5%) patients and no controls (0%) (P = 0.015), and these individuals were classified as having pseudo-synesthesia. CONCLUSION: IBS patients clearly differ from controls in terms of claiming to have synesthetic experiences. These results justify additional studies on the relationship between IBS and synesthesia to further understand the neural mechanisms underpinning these two conditions and to establish whether they may be linked.

PMID: 22290344 [PubMed - as supplied by publisher]