Two-dimensional speckle tracking echocardiography is useful in early detection of left ventricular impairment in patients with Crohn's disease.

OBJECTIVE: Crohn's disease (CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract. Cardiac involvement is considered very rare. Pericarditis, myocarditis, endocarditis, cardiomyopathy and complete heart block are some of the cardiac extraintestinal manifestations of CD. The aim of this study was to explore the left ventricular (LV) functions with two-dimensional (2D) speckle tracking echocardiography (STE) in patients with CD with normal cardiac functions. PATIENTS AND METHODS: We enrolled 50 consecutive patients with CD and 50 age and sex matched healthy controls. All patients underwent a transthoracic echocardiogram with evaluation of LV functions with 2D STE. RESULTS: Baseline characteristics were similar between patients with CD (24 male, mean age: 41.0 ± 13.9 years) and controls (24 male, mean age: 40.1 ± 7.3 years). Although conventional echocardiographic parameters were similar between two groups, global longitudinal strain was significantly lower in patients with CD compared to controls (19.6 ± 3.3 versus 21.2 ± 2.9, p = 0.014). Correlation analysis revealed that Crohn's Disease Activity Index is inversely correlated with LV global longitudinal strain (r = -0.703, p < 0.001) in patients with CD. We also evaluated inflammatory parameters such as CRP, erythrocyte sedimentation rate, and complete blood counts in patients with CD. Correlation analysis revealed that only platelet value is weakly correlated with Crohn's Disease Activity Index (r = 0.311, p = 0.083). CONCLUSIONS: Crohn's disease is associated with impairment in LV global longitudinal myocardial function. Crohn's Disease Activity Index is also strongly correlated with LV global longitudinal strain. 2D-STE may be an useful method for early detection of LV impairment in patients with CD.

The effects of psychiatric treatment on depression, anxiety, quality of life, and sexual dysfunction in patients with inflammatory bowel disease.

OBJECTIVE: Depression and anxiety are common disorders in inflammatory bowel disease (IBD). Our aim is to prospectively determine the effect of psychiatric treatment on scores for depression, anxiety, quality of life (QoL), and sexual dysfunction in an outpatient population diagnosed with IBD and also anxiety and/or depression disorder. PATIENTS AND METHODS: Patients who scored higher than the cutoff point on the Hospital Anxiety Depression Scale were referred for further structured psychiatric evaluation and determination of the need for psychiatric drug treatment. Patients who underwent drug therapy completed Short Form-36 (SF-36) and the Arizona Sexual Experience Scale at baseline and after 6 months of follow-up. RESULTS: Major depressive disorder and generalized anxiety disorder were the most common diagnoses. After 6 months, 47 patients had completely adhered to drug treatment (group A), whereas 20 were nonadherent (group B). In group A, all domains of SF-36, Arizona Sexual Experience Scale, depression/anxiety scores, and Crohn's disease activity index were statistically improved after treatment when compared with the baseline. In group B, the three domains of SF-36, platelet count, and mean corpuscular volume were worse between baseline and at 6 months. CONCLUSION: In IBD patients having any psychiatric disorder, 6 months of antidepressant drug treatment is associated with an improvement in depression, anxiety, QoL, and sexual functioning scores, as well as an improvement in Crohn's disease activity index. On the other hand, insufficient psychiatric treatment seems to be related to a poor QoL.

Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in patients with type 2 diabetes.

BACKGROUND/OBJECTIVE: Artificial sweeteners were thought to be metabolically inactive, but after demonstrating that the gustatory mechanism was also localized in the small intestine, suspicions about the metabolic effects of artificial sweeteners have emerged. The objective of this study was to determine the effect of artificial sweeteners (aspartame and sucralose) on blood glucose, insulin, c-peptide and glucagon-like peptide-1 (GLP-1) levels. SUBJECTS/METHODS: Eight newly diagnosed drug-naive type 2 diabetic patients (mean age 51.5±9.2 years; F/M: 4/4) and eight healthy subjects (mean age 45.0±4.1 years; F/M: 4/4) underwent 75 g oral glucose tolerance test (OGTT). During OGTT, glucose, insulin, c-peptide and GLP-1 were measured at 15- min intervals for 120 min. The OGTTs were performed at three settings on different days, where subjects were given 72 mg of aspartame and 24 mg of sucralose in 200 ml of water or 200 ml of water alone 15 min before OGTT in a single-blinded randomized order. RESULTS: In healthy subjects, the total area under the curve (AUC) of glucose was statistically significantly lower in the sucralose setting than in the water setting (P=0.002). There was no difference between the aspartame setting and the water setting (P=0.53). Total AUC of insulin and c-peptide was similar in aspartame, sucralose and water settings. Total AUC of GLP-1 was significantly higher in the sucralose setting than in the water setting (P=0.04). Total AUC values of glucose, insulin, c-peptide and GLP-1 were not statistically different in three settings in type 2 diabetic patients. CONCLUSIONS: Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in newly diagnosed type 2 diabetic patients.

Interaction of omeprazole with enteric-coated salicylate tablets.

OBJECTIVE: Enteric-coated tablets are designed to resist gastric fluids and to disrupt and dissolve in the alkaline medium of the small intestine. Main objective of the present study was to investigate whether the increase in gastric pH due to omeprazole treatment alters the release rate of a drug from enteric-coated formulation. To this end, we have compared the single dose pharmacokinetics of a single-unit enteric-coated salicylate to that of uncoated acetylsalicylic acid tablets in the presence and absence of omeprazole treatment. METHODS: Study was carried out according to 4 x 4 Latin square design. Eight healthy subjects received either uncoated acetylsalicylic acid tablets or single-unit enteric-coated sodium salicylate tablets alone or following 4 days of treatment with single-dose 20 mg omeprazole, and blood samples were collected for 24 hours. Serum salicylate levels were determined by the modified spectrophotometric method of Brodie et al. [1994]. RESULTS: Salicylate was absorbed rapidly from uncoated tablets but absorption of salicylate from enteric-coated tablets was delayed, as expected. According to our results, omeprazole treatment did not influence the bioavailability from uncoated acetylsalicylic acid tablets but the absorption rate of salicylate from enteric-coated tablets was increased significantly. CONCLUSION: Findings of the present study demonstrate that omeprazole treatment significantly increases the rate of absorption of single-unit enteric-coated medication. Enhanced rate of absorption is most probably due to an early disruption of enteric coating and the intragastric release of the drug secondary to an omeprazole-mediated increase in gastric pH. The results of the present study also corroborate previous findings which have demonstrated highly variable absorption of enteric-coated single units.

Pericardial and pulmonary involvement in rheumatoid arthritis in Turkey.

Pericardial and lung involvement in rheumatoid arthritis (RA), suspected to be less severe in a developing nation (Turkey), have been evaluated. We have studied clinical, echocardiographic and pulmonary findings (radiological and functional) in 93 consecutive Turkish patients with definite/classical RA. Findings were compared with those of a group of patients with osteoarthritis or local rheumatological conditions (n = 60) in a blind protocol. Fifty patients with systemic lupus (SLE) were studied as a high risk control group for pericardial involvement. While pericardial disease was detected in 5.5% (5/90) of RA patients, it was detected in 6.6% (4/60) of the control patients. SLE patients had a 26% (13/50) prevalence. Interstitial lung disease was found in 27.7% of RA patients but it was present in 6.6% (4/60) of the control patients. We observed that a group of patients with RA in Turkey had a low prevalence of pericardial disease. This is further evidence that RA has a mild course in developing countries.

A study comparing the efficacy of antimicrobial agents versus enzyme (P-gp) inducers in the treatment of 2,4,6 trinitrobenzenesulfonic acid-induced colitis in rats.

The intestinal microflora is an important cofactor in the pathogenesis of intestinal inflammation; and the epithelial cell barrier function is critical in providing protection against the stimulation of mucosal immune system by the microflora. In the present study, therapeutic role of the antibacterial drugs rifampicin and ciprofloxacine were investigated in comparison to spironolactone, an enzyme inducer, in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis of the rats. Drugs were administered for 14 days following induction of colitis. All drug treatments ameliorated the clinical hallmarks of colitis as determined by body weight loss and assessment of diarrhea, colon length, and histology. Oxidative damage and neutrophil infiltration as well as nuclear factor κB (NF-κB) and tumor necrosis factor α (TNF-α) expressions that were increased during colitis, were decreased significantly. Rifampicin and ciprofloxacin were probably effective due to their antibacterial and immunomodulating properties. The multidrug resistence gene (MDR1) and its product p-glycoprotein (P-gp) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). In the present study, findings of the P-gp expression were inconclusive but regarding previous studies, it can be suggested that the beneficial effects of rifampicin and spironolactone may be partly due to their action as a P-gp ligand. Spironolactone has been reported to supress the transcription of proinflamatory cytokines that are considered to be of importance in immunoinflammatory diseases. It is also a powerful pregnane X receptor (PXR) inducer; thus, inhibition of the expression of NF-κB and TNF-α, and amelioration of inflammation by spironolactone suggest that this may have been through the activation of PXR. However, our findings regarding PXR expression were inconclusive. Activation of PXR by spironolactone probably also contributed to the induction of P-gp, resulting in extrusion of noxious substances from the tissue.

Association between the presence of brown adipose tissue and non-alcoholic fatty liver disease in adult humans.

BACKGROUND: The presence of active brown adipose tissue (BAT) has been associated with a reduced risk of obesity in adult humans. AIM: To examine whether the presence and activity of BAT in patients undergoing PET-CT examinations is related to the presence of fatty liver. METHOD: We retrospectively analysed 3666 consecutive PET-CT whole-body scans performed on a total of 1832 patients who were referred for suspected malignancies. BAT-positive subjects (BAT+) were defined as subjects who showed substantial amounts of brown adipose tissue on PET-CT scans. In areas where uptake of [(18)F]FDG was identified by CT for BAT, the maximal standardised uptake values (SUVmax), defined as the maximum activity per millilitre within the region of interest divided by the injected dose in megabecquerels per gram of body weight, were determined. A ratio of mean liver attenuation to spleen attenuation <0.8 on CT scans was considered to indicate NAFLD. RESULTS: Thirty patients of the 1832 screened individuals (2%) demonstrated brown fat uptake (BAT+ subjects). Ninety matched individuals without evidence of BAT on PET scans (BAT- subjects) were enrolled for comparison purposes. After adjustment for potential confounders, the odds ratio for having NAFLD was significantly higher for BAT- subjects (3.12, 95% confidence interval = 1.03-9.88, P < 0.05). The SUVmax for brown fat tissue was significantly correlated with the ratio of mean liver attenuation to spleen attenuation (P < 0.05). CONCLUSION: The presence of brown adipose tissue in adulthood is independently associated with a lower likelihood of NAFLD diagnosed by CT findings.

Mechanisms of basolateral Na+ transport in rabbit esophageal epithelial cells.

We examined the mechanisms of cellular Na+ transport, both Cl- dependent and Cl- independent, in the mammalian esophageal epithelium. Rabbit esophageal epithelium was dissected from its muscular layers and mounted in a modified Ussing chamber for impalement with ion-selective microelectrodes. In bicarbonate Ringer, transepithelial potential difference was -14.9 +/- 0.9 mV, the transepithelial resistance (RTE) was 1,879 +/- 142 Omega. cm2, the basolateral membrane potential difference (VmBL) was -53 +/- 1.5 mV, and the intracellular activity of Na+ (aNai) was 24.6 +/- 2.1 mM. Removal of Na+ and Cl- from the serosal and luminal baths decreased aNai to 6.6 +/- 0.6 mM. Readdition of Na+ to the serosal bath in the absence of Cl- increased aNai by 21.8 +/- 3.0 mM, whereas VmBL and RTE remained unchanged. When serosal Na+ was readded in the presence of amiloride the increase in aNai and the rate of Na+ entry were decreased by approximately 50%. 5-(N-ethyl-N-isopropyl)amiloride mimicked the effect of amiloride, whereas phenamil did not. Subsequent readdition of Cl- to the serosal bath further increased aNai by 4.4 +/- 1.9 mM. When the cells were acid loaded by pretreatment with NH+4 in nominally HCO-3-free Ringer, intracellular pH measurements showed a pHi recovery that is dependent on the presence of Na+ in the serosal bath and that can be blocked by amiloride. These data indicate that esophageal epithelial cells possess a Na+-dependent, amiloride-sensitive electroneutral mechanism for Na+ entry consistent with the presence of a basolateral Na+/H+ exchanger. The ability of Cl- to further enhance Na+ entry supports the existence of at least one additional Cl--dependent component of basolateral Na+ entry.

Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms.

Exogenous administration of glucagon-like peptide-1-(7-36) amide (GLP-1), an insulinotropic hormone, inhibits gastric emptying and acid secretion in humans. The role of GLP-1 as a regulator of gastric function is elusive. In gastric fistula rats, vagal afferent denervation and peripheral administration of the GLP-1 receptor antagonist exendin-(9-39) amide enhanced emptying of a glucose meal, whereas intracerebroventricular exendin was ineffective. The rate of saline emptying was attenuated by peripheral as well as by central administration of GLP-1, and pretreatment with exendin by the respective routes reversed the inhibition by GLP-1. Vagal afferent denervation abolished the central and peripheral action of GLP-1 on gastric emptying. Neither peripheral cholinergic nor adrenergic blockade altered the delay of methyl cellulose meal emptying by intracisternal GLP-1 injection. Acid secretion in conscious pylorus-ligated rats was inhibited by intracisternal GLP-1 administration, whereas systemic GLP-1 was ineffective. These results support the notion that GLP-1 receptors participate in the central and peripheral regulation of gastric function. Furthermore, vagal afferent nerves mediate the inhibitory action of GLP-1 on gastric motor function. GLP-1 may be a candidate brain-gut peptide that acts as a physiological modulator of gastric function.

Corticosteroid therapy augments gastroduodenal permeability to sucrose.

OBJECTIVE: The aim of the present study was to investigate whether corticosteroid therapy alters gastroduodenal mucosal permeability and whether permeability alteration is associated with macroscopic mucosal damage. METHODS: Eight patients taking oral corticosteroid therapy (total prednisone-equivalent dose, 1.5+/-0.1 g; duration, approximately 30 days), nine patients with multiple sclerosis taking high-dose intravenous methyl-prednisolone therapy (total dose, 11.7+/-0.5 g; duration, approximately 9 days), and 20 age- and gender-matched controls were studied. Gastroduodenal permeability was determined using sucrose as a site-specific permeability probe. Five-hour urine was collected after ingesting 100 g of sucrose and its urinary excretion rate was measured using high-pressure liquid chromatography. Gastroduodenal endoscopy was performed before steroid therapy to exclude subjects with evidence of macroscopic mucosal lesions. The sucrose test and endoscopy were repeated after completion of corticosteroid therapy. RESULTS: The urinary sucrose excretion rates were similar in the control group and in patient groups before corticosteroid therapy. The median excretion rate of sucrose increased four (one to 28)- and eight (two to 35)-fold, respectively, as compared with pretreatment values in patients taking oral steroid and high-dose intravenous methyl-prednisolone therapy (p < 0.01). Considering all patients together, subjects who received a mean prednisone-equivalent dose of 8.4+/-1.5 g exhibited mucosal lesions, whereas patients who received 3.3+/-1.8 g did not (p = 0.06). The post-therapy increments in sucrose excretion rates were associated with neither the presence of macroscopic lesions nor with the total steroid dose received. CONCLUSIONS: Corticosteroid therapy augments gastroduodenal permeability and high doses are associated with macroscopic mucosal lesions. Steroid-induced permeability increase does not appear to be associated with the presence of macroscopic mucosal lesions.

The distribution of HLA-DRB alleles in ulcerative colitis patients in Turkey.

Recently described distinct associations of HLA class II genes with ulcerative colitis (UC) suggest a genetic heterogeneity for disease susceptibility. In this study, HLA-DRB alleles of UC patients (n = 59) from Turkey were investigated and compared with healthy controls (n = 244). Using molecular genotyping by polymerase chain reaction (PCR) and sequence-specific oligonucleotide hybridization, we have shown a positive association of UC patients with the HLA-DRB1*1502 allele (10/59 vs. 16/244; P = 0.02; OR: 2.9) and a negative association with the DRB1*13 allele (7/59 vs. 64/244; P = 0.03; OR: 0.38) compared to controls. HLA-DRB1*0701 was significantly increased in perinuclear antineutrophil cytoplasmic antibody (pANCA)-positive UC patients compared to pANCA-negative patients (8/32 vs. 0/27; P = 0.005), whereas DRB1*1502 was observed more frequently in pANCA-negative patients (8/27 vs. 2/32; P = 0.03). These results extended the reported positive association of DRB1*1502 with UC to another population and supported the genetic susceptibility associated with HLA genes for disease development.

Gender influence on jejunal migrating motor complex.

The role of gender and the menstrual cycle in small bowel motility has not been clearly elucidated. Jejunal motility was recorded with a nasojejunal catheter incorporating five solid-state pressure transducers in ambulatory menstruating women and men of comparable age over 24 h. All women were studied twice, in the early follicular (early-F) and midluteal (mid-L) phases of the menstrual cycle, verified by determining serum levels of gonadal steroids and gonadotropins. The propagation velocity of phase III was slow and the contraction amplitude was high in both menstrual cycle phases compared with men, and these parameters were correlated with serum estrogen levels in the mid-L phase. In the early-F phase, migrating motor complex (MMC) cycle duration during sleep was long compared with other groups and positively correlated with estrogen concentrations, whereas in the mid-L phase MMC cycle duration during sleep was negatively correlated with serum progesterone levels. In all groups, the frequency of phase III contractions was low and the intercontractile interval measured from pressure peak to peak was long during sleep compared with the awake state. Postprandial motility did not display gender difference in any parameter examined. The results demonstrate that the majority of patterns of motility are similar in menstruating women and men, whereas certain aspects of the MMC, most conspicuously propagation velocity and phase III contraction amplitude, differ. We have also documented circadian variation of phase III contraction frequency in both women and men.

Inhibition of gastric emptying by acarbose is correlated with GLP-1 response and accompanied by CCK release.

We investigated the effect of acarbose, an alpha-glucosidase and pancreatic alpha-amylase inhibitor, on gastric emptying of solid meals of varying nutrient composition and plasma responses of gut hormones. Gastric emptying was determined with scintigraphy in healthy subjects, and all studies were performed with and without 100 mg of acarbose, in random order, at least 1 wk apart. Acarbose did not alter the emptying of a carbohydrate-free meal, but it delayed emptying of a mixed meal and a carbohydrate-free meal given 2 h after sucrose ingestion. In meal groups with carbohydrates, acarbose attenuated responses of plasma insulin and glucose-dependent insulinotropic polypeptide (GIP) while augmenting responses of CCK, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). With mixed meal + acarbose, area under the curve (AUC) of gastric emptying was positively correlated with integrated plasma response of GLP-1 (r = 0.68, P < 0.02). With the carbohydrate-free meal after sucrose and acarbose ingestion, AUC of gastric emptying was negatively correlated with integrated plasma response of GIP, implying that prior alteration of carbohydrate absorption modifies gastric emptying of a meal. The results demonstrate that acarbose delays gastric emptying of solid meals and augments release of CCK, GLP-1, and PYY mainly by retarding/inhibiting carbohydrate absorption. Augmented GLP-1 release by acarbose appears to play a major role in the inhibition of gastric emptying of a mixed meal, whereas CCK and PYY may have contributory roles.