Levels of soluble CD40 ligand and P-Selectin in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is linked to an increased risk of cardiovascular disease. We aimed to research whether the levels of soluble P-selectin (sP-selectin) and soluble CD40 ligand (sCD40L), markers of endothelial function, are altered in subjects with NAFLD having no confounding factors for atherosclerosis. sCD40L, sP-selectin, and high-sensitivity C-reactive protein (hsCRP) levels, and homeostasis model assessment of insulin resistance (HOMA-IR) indexes were measured in 50 NAFLD subjects and 30 healthy controls. sCD40L, sP-selectin, and hsCRP levels were not significantly different between two groups (P = 0.48, 0.51, and 0.34, respectively). Body mass index, waist circumference, and insulin levels and HOMA indexes were significantly higher in subjects with NAFLD (all P < 0.001). The present data show that sCD40L and sP-selectin may not contribute to the accelerated atherogenesis associated with this clinically relevant condition.

Performance of acidified 14C-urea capsule breath test during pantoprazole and ranitidine treatment.

BACKGROUND AND AIM: Urea breath test (UBT) results could be false negative in patients taking antisecretory drugs. This effect would be prevented by citric acid administration during UBT. We prospectively investigated whether acidified 14C-urea capsule prevents false negative UBT results in patients taking antisecretory drugs and show interference with the duration of medications. METHODS: Sixty Helicobacter pylori positive patients were included. Pantoprazole (40 mg/day) was given to 27 patients for 28 days and ranitidine (300 mg. o.d.) to 33 patients for 60 days. Urea breath tests were repeated on days 14 and 28 in both groups and on day 60 in the ranitidine group. RESULTS: The baseline mean breath counts of two groups did not show any significant difference. Pantoprazole led to a significant decrease in mean breath counts on day 14 (P < 0.005). Six of 27 and 3 of 25 patients taking pantoprazole developed negative or equivocal UBT results on days 14 and 28, respectively. Two of 32, 2 of 32 and 3 of 21 patients taking ranitidine developed negative or equivocal UBT results on days 14, 28 and 60, respectively. CONCLUSIONS: The use of acidified 14C-urea capsule did not prevent false negative UBT results in patients taking pantoprazole and ranitidine, and the duration of medication does not affect the test results.

The effect of iNOS inhibitors and hyperbaric oxygen treatment in a rat model of experimental colitis.

AIM: Our aim was to investigate the effectiveness of aminoguanidine (AMG), an inducible nitric oxide synthase inhibitor, and hyperbaric oxygen (HBO) treatment in an experimental colitis model. METHODS: We induced colitis in rats. In the control group, we applied 2 ml serum physiologic intraperitoneally for 7 days. In the HBO group, 100% oxygen at 2.4 atm pressure was applied for 7 days. In the AMG group, 100 mg/kg AMG was applied intraperitoneally for 7 days. In the HBO + AMG group, HBO and AMG were applied, respectively. At the end of 7 days, rats were sacrificed and the distal 10 cm part of colon was examined macro- and microscopically. RESULTS: Severity of colitis and NO activities were reduced by AMG, HBO, and HBO + AMG application. There was histologically significant improvement, especially in the HBO + AMG group. CONCLUSIONS: Both HBO and AMG were significantly effective in preventing weight loss, reducing NO activities, and severity of colitis, when comparing HBO and AMG separately.

Comparison of sequential and standard triple-drug regimen for Helicobacter pylori eradication: a 14-day, open-label, randomized, prospective, parallel-arm study in adult patients with nonulcer dyspepsia.

BACKGROUND: The eradication rates of Helicobacter pylori with standard treatments are decreasing worldwide. OBJECTIVES: The primary aim of this study was to compare the eradication success of a 14-day sequential regimen with proton pump inhibitor (PPI)-based triple treatment. The secondary objectives of the study were to evaluate the effect of gastritis score and smoking on eradication rates as well as evaluation of compliance and tolerability of both regimens. METHODS: Consecutive H pylori-positive patients with nonulcer dyspepsia were randomized into 1 of 2 groups in this 14-day, open-label, randomized, prospective, parallel-arm study. An upper endoscopy with biopsy and (14)C-urea breath test ((14)C-UBT) were performed before enrollment. The first group was administered a sequential regimen consisting of pantoprazole 40 mg and amoxicillin 1 g for 7 days, followed by pantoprazole 40 mg, tetracycline 500 mg, and metronidazole 500 mg for the next 7 days. The second group was administered pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg (PAC group) for 14 days. All drugs were administered BID, with the exception of tetracycline, which was administered QID. Eradication was confirmed by (14)C-UBT 6 weeks after the end of the treatment. Histologic examination and (14)C-UBT were conducted by investigators blinded to the protocols. Patients were asked to report any adverse events (AEs) during the treatment period. RESULTS: Three hundred white patients were enrolled in the study and evenly randomized into the sequential treatment group (98 males and 52 females; mean age, 40.2 years) and the PAC group (86 males and 64 females; mean age, 41.2 years). A total of 274 patients completed the study per protocol (PP). Twenty-six patients discontinued: lost to follow-up (16), withdrawn due to AEs (9); and noncompliance (1). The intent-to-treat (ITT) and PP H pylori eradication rates were 72.6% and 80.1% in the sequential group, and 58% and 63% in the PAC group, respectively. The eradication rate was significantly higher in the sequential group compared with the PAC group in both the ITT and PP populations (P=0.01 and P=0.002, respectively). The eradication rates were higher in nonsmoking patients compared with smoking patients both in the sequential group (85.8% vs 70.5%) and the PAC group (67.7% vs 53.3%), but the results were not statistically significant when the groups were analyzed separately. Overall, 32 patients (10.7%) reported an AE. Treatment was discontinued in 9 patients because of serious AEs (sequential group--abdominal pain [2 patients], diarrhea [1], chest pain [1], and vaginal pruritus [1]; PAC group--nausea/vomiting [2], chest pain [1], and numbness [1]). There were no significant between-group differences in regard to compliance or AEs. Univariate analyses found no significant effect of sex, age, alcohol consumption, antacid usage, or gastritis score on the eradication rates. CONCLUSIONS: A 14-day sequential treatment regimen achieved a significantly higher eradication rate of H pylori compared with standard PPI-based triple regimen in this small selected population. Large, double-blind, controlled studies are needed to confirm these results.

Do the changes in the serum levels of IL-2, IL-4, TNFalpha, and IL-6 reflect the inflammatory activity in the patients with post-ERCP pancreatitis?

BACKGROUND: Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP) procedure and there are some reports showing cytokine changes in ERCP-induced pancreatits. GOALS: To investigate the association between early changes (within 24 hours) in the serum interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)alpha, and IL-6 levels and the development of post-ERCP pancreatitis. STUDY: Forty five consecutive patients who underwent therapeutic ERCP and 10 patients with acute pancreatitis without ERCP were enrolled to the study. Serum concentrations of IL-2, IL-4, TNFalpha, and IL-6 were determined immediately before, 12 hours and 24 hours after ERCP. RESULTS: Seven of the 45 patients (15.5%) developed post-ERCP pancreatitis. The levels of IL-4 at 24 hours after ERCP were significantly lower in the patients with post-ERCP pancreatitis than in those without pancreatitis, while TNFalpha levels at 12 hours after ERCP were higher in the complicated group than those of the uncomplicated group. The ratios of TNFalpha/IL-4 at 12 and 24 hours after ERCP were found significantly higher in the patients with post-ERCP pancreatitis than in those without pancreatitis. IL-6 in the complicated patients was found significantly increased at 24 hours after ERCP. CONCLUSIONS: The enhancement of serum TNFalpha and IL-6 levels in the patients with ERCP-induced pancreatitis reflects the inflammatory activity. Additionally, these cytokines together with IL-4 can be used in clinical laboratory monitoring of ERCP.

Comparison of three different second-line quadruple therapies including bismuth subcitrate in Turkish patients with non-ulcer dyspepsia who failed to eradicate Helicobacter pylori with a 14-day standard first-line therapy.

BACKGROUND AND AIM: Many studies have reported poor results with standard first-line treatment for Helicobacter pylori. Second-line regimens that may overcome bacterial resistance can minimize side-effects and optimize compliance. The aim of this study was to evaluate the efficacy of proton pump inhibitor (PPI) and bismuth subcitrate-based quadruple therapy, after failure of a PPI plus clarithromycin and amoxicillin as first-line therapy. METHODS: Patients who failed to eradicate the infection after initial therapy were randomly separated into three groups. The first group received lansoprazole, bismuth subcitrate, metronidazole and amoxicillin (LBMA); in the second group metronidazole was replaced by tetracycline (LBTA); and the third group was given metronidazole and tetracycline in addition to same doses of lansoprazole and bismuth subcitrate (LBMT). RESULTS: In the LBMA group, the eradication rate was 74.7% and was significantly related to sex, with no relationship to age. In the LBTA group the eradication rate was 81.5% with similar rates in males and females. No relation to sex or age was observed. In the LBMT group the eradication rate was 82.1% with no difference between women and men and it was not related to age, either. Eradication rates in study groups were similar (P > 0.05). CONCLUSION: A-14-day regimen of lansoprazole, bismuth subcitrate and antibiotic pairs, tetracycline-amoxicillin and tetracycline-metronidazole, is an effective quadruple therapy after one failed course of standard triple therapy. The evaluation of tolerability of and compliance with quadruple therapy needs further studies.

Decreased oxidation susceptibility of plasma low density lipoproteins in patients with Gilbert's syndrome.

BACKGROUND AND AIM: The association of hyperbilirubinemia in Gilbert's syndrome (GS) with a decrease in prevalence of coronary artery disease is a well-known phenomenon. In this study, the state of low-density lipoprotein (LDL) oxidation which has been postulated to be a significant determinant at the etiopathogenesis of atherosclerotic disorders was investigated among individuals with GS. METHODS: For this purpose, serum cholesterol, LDL cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, apolipoprotein A and B, bilirubins, thiobarbituric acid-reactive substances, and the sensitivity of LDL oxidation levels, as well as serum alanine aminotransferase, aspartate aminotranserfase, gamma glutamyl transferase, and alkaline phosphatase activities, were determined in 17 patients with Gilbert's syndrome and 15 healthy adults. RESULTS: There was no significant difference between the groups except the indirect bilirubin parameter (P < 0.001). In comparison with the healthy individuals, LDL oxidation levels between 75 and 120 min were significantly lower (P < 0.005) along with prolonged lag-phase in GS patients, indicating a delay in oxidation susceptibility. CONCLUSION: It is suggested that the chronic hyperbilirubinemia leading to a lag-phase prolongation in LDL oxidation and a decrease in LDL oxidation may be reason for the low percentage of coronary artery disease.

Pro- and anti-inflammatory cytokine balance in major depression: effect of sertraline therapy.

The specific associations between antidepressant treatment and alterations in the levels of cytokines remain to be elucidated. In this study, we aimed to explore the role of IL-2, IL-4, IL-12, TNF-alpha, TGF-beta1, and MCP-1 in major depression and to investigate the effects of sertraline therapy. Cytokine and chemokine levels were measured at the time of admission and 8 weeks after sertraline treatment. Our results suggest that the proinflammatory cytokines (IL-2, IL-12, and TNF-alpha) and MCP-1 were significantly higher, whereas anti-inflammatory cytokines IL-4 and TGF-beta1 were significantly lower in patients with major depression than those of healthy controls. It seems likely that the sertraline therapy might have exerted immunomodulatory effects through a decrease in the proinflammatory cytokine IL-12 and an increase in the anti-inflammatory cytokines IL-4 and TGF-beta1. In conclusion, our results indicate that Th1-, Th2-, and Th3-type cytokines are altered in the depressed patients and some of them might have been corrected by sertraline treatment.

Poor efficacy of ranitidine bismuth citrate-based triple therapies for Helicobacter pylori eradication.

BACKGROUND: Helicobacter pylori eradication rates have tended to decrease recently possibly related with increasing antibiotic resistance. The present study investigated the efficacy of three different ranitidine bismuth citrate (RBC) based triple regimens in a population with high prevalence of H. pylori. METHODS: 300 consecutive H. pylori positive patients with non-ulcer dyspepsia were randomized into three regimens: (1) RBC 400 mg, amoxicillin 1000 mg and tetracycline 500 mg [RBC-AT], (2) RBC 400 mg, amoxicillin 1000 mg and clarithromycin 500 mg [RBC-AC], (3) RBC 400 mg, metronidazole 500 mg and tetracycline 500 mg [RBC-MT]. Tetracycline was given q.i.d, all other drugs were given b.i.d. for 14 days. Gastroscopy and (14)C-Urea breath test (UBT) were performed before enrollment and UBT only was repeated 6 weeks after the end of treatment. RESULTS: 274 patients completed the protocols. The overall 'intention to treat' and 'per protocol' H. pylori eradication rates in all subjects were 57.6% (95% CI: 52-63) and 63.1% (95% CI: 57-68), respectively. The eradication rates achieved in the groups (RBC-AT, RBC-AC and RBC-MT) were 64.4% (95% CI: 54-74), 66.2% (95% CI: 56-76), and 58.9% (95% CI: 49-68) on 'per protocol' analyses, respectively. There was no difference in eradication rates, compliance and major side effects between the groups. CONCLUSION: The current RBC-based H. pylori eradication therapy is not adequately effective.

Levels of serologic markers of celiac disease in patients with reflux esophagitis.

AIM: To investigate the prevalence of celiac disease serologic markers (antigliadin IgA, IgG, and anti-endomysial IgA) in patients with reflux esophagitis and to detect the relationship between reflux esophagitis and celiac disease (CD). METHODS: This study was performed prospectively between January 2003 and January 2004. Sixty-eight adult reflux esophagitis patients and 40 people as control group for symptoms related with gastrointestinal system were enrolled in this study. The diagnostic work-up included an accurate medical history with gastrointestinal symptoms, routine laboratory measurements, the detection of antibodies against gliadin (IgA and IgG) and endomysium (IgA), and an upper endoscopy with postbulbar biopsy. RESULTS: IgA-AGA and IgG-AGA were positive at 8.8% and 10.3% in patients with reflux esophagitis. In control group, it was found that 10% people had positive IgA-AGA, and 7.5% people had positive IgG-AGA. There was no significant relationship between patients and control group regarding positive IgA-AGA and IgG-AGA. The patients and persons in control group had no positive IgA-EMA. On postbulbar biopsies, no finding was detected concerning celiac disease. There were no symptoms and signs for gluten enteropathy in patients and control group. CONCLUSION: This review supports that an association does not exist between celiac disease and reflux esophagitis. We think these diseases exist independently from each other.

Motor axonal polyneuropathy in the course of ulcerative colitis: a case report.

We describe an axonal motor polyneuropathy in a patient with ulcerative colitis. Symptoms of neuropathy occurred during active colitis. Electrophysiological study showed motor axonal degeneration. After treatment with steroid added to mesalazine, the patient had a gastrointestinal recovery and neurological symptoms were improved. Axonal motor polyneuropathy is an unusual extraintestinal manifestation of ulcerative colitis, and is probably associated with an autoimmune process.

Elevated plasma concentration of asymmetric dimethylarginine that is reduced by single dose testosterone administration in idiopathic hypogonadotropic hypogonadism patients.

Our aim was to investigate whether plasma l-arginine and asymmetric dimethylarginine (ADMA) concentrations and nitric oxide (NO) production are altered in male idiopathic hypogonadotropic hypogonadism (IHH) patients in the hypogonadal state and after single dose testosterone administration compared with those in control subjects. Eighteen newly diagnosed male patients with IHH and 20 healthy volunteer controls matched by age and body mass index were enrolled in the study. Single dose testosterone was administrated im. Initially, pretreatment blood samples were collected after overnight fasting. Posttreatment blood samples were drawn 10 d after the injection. ADMA, l-arginine, and NO were measured in pre- and posttreatment blood samples. The pretreatment ADMA and l-arginine levels were significantly higher, and plasma nitrite plus nitrate (NOx) levels were lower than those in the control group. After 10 d of treatment, ADMA and l-arginine levels were significantly reduced, and NOx levels were significantly increased. There was a significant positive correlation (P < 0.01) between ADMA and l-arginine and a negative correlation between ADMA and NOx levels in patients and controls. In conclusion, the patients with IHH showed elevated plasma ADMA levels associated with a reduction in NO production. Single dose parenteral T administration lowered ADMA concentrations and increased NO production to the control group values.

Elevated urine neopterin levels in nonalcoholic steatohepatitis.

OBJECTIVES: The aim of this study was to relate urine levels of neopterin, a marker of activation of the cellular immune system, with grading and staging of NASH. DESIGN AND METHODS: Urine concentrations of neopterin, routine tests, insulin and C-peptide levels were assessed in 50 patients with NASH, 25 patients with chronic viral hepatitis (CVH), and in 26 healthy controls. RESULTS: Urine neopterin levels were found elevated in the NASH and CVH groups compared with controls. There was no significant correlation between urine neopterin levels and inflammation grade in the liver. CONCLUSIONS: Urine neopterin levels are a marker of cellular immunity and are higher in patients with NASH. However, neopterin levels were not significantly associated with histopathological grade and stage of disease.

Lipid profile and anticardiolipin antibodies in Behcet's disease.

BACKGROUND: Behcet's disease (BD) is a multisystem disorder characterized by a relapsing inflammatory process of unknown etiology. It is well known that atherothrombosis in systemic inflammatory disorders is closely related to coagulation and lipid metabolism abnormalities. The purpose of this study was to investigate some parameters of lipid metabolism, lipoprotein (a) [Lp(a)] and anticardiolipin antibody (ACA) levels and the relationship of these parameters with the clinical activity of BD. METHODS: Thirty three patients with BD (15 active, 18 inactive cases) and 20 healthy controls participated in the study. After performing a detailed physical exam, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), apoprotein A and B (apo-A, apo-B), Lp(a), and ACA levels (ACA-IgG and IgM) were measured in all participants. RESULTS: Patients with active BD had higher ESR, CRP and Lp(a) levels, and lower apo-A and HDL-C levels compared with the patients with inactive BD and healthy controls. ACA-IgG and IgM levels were higher in patients with active BD than healthy controls but not higher than patients with inactive BD. On the other hand, ACA-IgG level was higher in active and inactive cases with vascular involvement than in those of active and inactive cases without vascular involvement. In the analyses of correlation, in active BD patients we found a positive correlation between CRP and Lp(a) levels. CONCLUSIONS: Our findings suggest that Lp(a) behaves as an acute phase reactant and ACA levels are increased in patients with active BD. Data from patients with active BD may be compatible with the serum profile, which is accepted as a risk for the development of atherothrombosis.

Efficacy and safety of endoscopic retrograde cholangiopancreatography in patients with Billroth II anastomosis.

BACKGROUND/AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) procedure is quite difficult to perform in patients with Billroth II anastomosis because of anatomical alterations. The aim of this study is to evaluate retrospectively the results of ERCP applications done in patients with Billroth II operation. METHODOLOGY: Out of the 1632 patients who underwent ERCP between 1992 and 2002, 27 (1.65%) had Billroth II operation. The records of these 27 patients were reviewed. Details noted included indications for ERCP, therapeutic interventions, causes of failure and complications. RESULTS: Out of the patients, 3 were female and 24 male (mean age 62+/-11). 26 patients had extrahepatic biliary obstruction. 1 patient had an external bile drain. The procedure was carried out 1-5 times (mean 1.5+/-1.1). Cannulation was achieved in 17 patients (62.96%). Out of the patients cannulated, 10 had choledocholithiasis, 4 malign choledochal stricture, 1 chronic pancreatitis, 1 bile leak and 1 periampullary tumor. Success rate of endoscopic treatment was 82.35% (14/17). Proximal migration of the stent and hemorrhage in gastric cardia were the complications observed in the distinct patients. CONCLUSIONS: ERCP procedure is quite an effective and safe method for diagnosis and treatment in patients with Billroth II anastomosis and extrahepatic cholestasis in spite of all difficulties.

Oxidative stress and antioxidant capacity in patients with inflammatory bowel disease.

OBJECTIVES: In this study we aimed to determine the levels of Glutathione peroxidase (GSH-Px) and Malondialdehyde (MDA) in patients with inflammatory bowel disease (IBD) to investigate their contribution to tissue injury in inflammatory bowel disease. DESIGN AND METHODS: Forty-seven GSH-Px patients (35 with ulcerative colitis and 12 with Crohn's disease) and 30 healthy controls were included in the study. Their plasma and MDA levels were compared using nonparametric statistical methods. RESULTS: Plasma GSH-Px levels of the patients group were significantly higher than the control group (p < 0.001). There was no significant difference between patients and controls in view of plasma levels of MDA. CONCLUSIONS: High levels of GSH-Px, which is response against oxidative stress, indicates the increase of free radicals in IBD, while normal plasma MDA levels suggest the clearance of free radicals without leading to lipid peroxidation. Our result reveals that there is an existing antioxidant capacity despite oxidative stress in patients with IBD.

Effect of supraphysiologic doses of testosterone on fasting plasma total homocysteine concentrations in men with Klinefelter's syndrome.

OBJECTIVE: To examine the effect of supraphysiologic doses of testosterone (T) on plasma total homocysteine (tHcy) concentrations in patients with Klinefelter's syndrome (KS). DESIGN: Prospective clinical study. SETTING: University hospital. PATIENT(S): Thirty-two newly diagnosed male patients with KS, and 20 healthy, volunteer controls matched by age and body mass index. INTERVENTION(S): Testosterone was administered IM every 2 weeks for 6 months. Initially, pretreatment fasting blood samples were collected after overnight fasting. Posttreatment blood samples were drawn 7 days after the last injection. MAIN OUTCOME MEASURE(S): Plasma total homocysteine. RESULT(S): The KS patients had lower tHcy levels than the controls. However, plasma fasting tHcy concentrations increased in a statistically significant manner after 6 months of treatment. As compared with the levels among controls, pretreatment levels of the serum creatinine, hemoglobin, and hematocrit were significantly lower, and increased in a statistically significant way following treatment. Posttreatment levels of total cholesterol were statistically significantly higher than the baseline. The pretreatment folate and cobalamin levels also were statistically significantly higher in patients when compared with controls, and decreased significantly after treatment. The linear regression analysis showed that only creatinine, cobalamin, and folate were independently associated with plasma tHcy levels in patients before and after treatment. CONCLUSION(S): The patients with KS showed lower tHcy concentrations than healthy, age-matched male controls. Testosterone treatment increased plasma tHcy levels.

Acute myocardial infarction and left subclavian artery occlusion in Behçet's disease: a case report.

A 42-year-old woman with Behcet's disease and pericardial effusion for 14 years presented with acute myocardial infarction and received thrombolytic therapy. Coronary angiography showed total occlusion of the left anterior descending artery. Subsequently, the left internal mammary artery was grafted to the left anterior descending artery. Approximately one year after bypass surgery, digital subtraction angiography of the left subclavian artery, performed because of chest and left arm pain, showed total occlusion of the left subclavian artery. Retrograde flow from the left vertebral artery filled the distal portion of the left subclavian artery. In conclusion, patients with Behcet's disease should be investigated closely for involvement of other arteries when one vessel's involvement has been detected. We also recommend that free arterial grafts be used for any coronary surgical intervention, because of the risk of occlusion associated with the vasculitis of Behcet's disease.

McArdle's disease: case report and review of the literature.

McArdle's disease, or myophosphorylase deficiency, is one of the most common muscle glycogenoses and typically presents in childhood or adolescence with exercise intolerance, myalgia, myoglobinuria, and cramps in the exercising muscle. We report the case of a 21-year-old male patient with liver enzyme elevation who had a history of weakness, exercise intolerance, and muscle cramps since childhood. His sister (a three-year- old) suffered from similar symptoms. Laboratory results showed that serum creatinine phosphokinase levels were elevated serum lactate did not rise on ischemic exercise testing, while muscle biopsy showed subsarcolemmal and intermyofibrillar periodic acid schiff-positive vacuoles filled with glycogen. This case report underlines the importance of taking into account rare metabolic diseases such as muscle glycogenoses in the evaluation of patients with elevated liver enzymes.