Dose-dependent effects of kefir on colitis induced by trinitrobenzene sulfonic acid in rats.

Evidence suggests that gut microbiota dysbiosis plays a critical role in the initiation and promotion of inflammatory bowel disease (IBD). Kefir is a fermented dairy product including yeast and bacterial species. We aimed to investigate the effect of kefir on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats using two different doses. Fifty-four Wistar rats were divided into six groups. For 14 days, the normal control and colitis control groups were given tap water, kefir10 control, kefir10 colitis, and kefir30 control, and the kefir30 colitis groups were given phosphate-buffered saline containing 10% or 30% kefir, respectively, instead of tap water. Colitis was induced by intracolonically administrating TNBS in the colitis control, kefir10 colitis, and kefir30 colitis groups. On the 14th day, the rats were sacrificed. The weights and lengths of the colons were measured and macroscopically evaluated, and the distal 10 cm segments were subjected to a histopathological examination. The incidence of bloody stool and diarrhea in the kefir10 colitis group was found to be less than the colitis control and kefir30 colitis groups. The colonic weight/length ratio in the kefir10 colitis group was lower than that in the colitis control and kefir30 colitis groups. We detected that the 10% kefir treatment reduced TNBS-induced macroscopic colonic damage, while it was exacerbated by the 30% kefir treatment. No significant difference was observed between the colitis groups in terms of microscopic colonic damage scoring. These results indicate that kefir, with a careful dose selection, may be a useful agent in the treatment of IBD.

Kefir treatment ameliorates dextran sulfate sodium-induced colitis in rats.

AIM: To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium (DSS) in rats. METHODS: Twenty-four male Wistar-albino rats were randomized into four groups: normal control, kefir-control, colitis, and kefir-colitis groups. Rats in the normal and kefir-control groups were administered tap water as drinking water for 14 d. Rats in the colitis and kefir-colitis groups were administered a 3% DSS solution as drinking water for 8-14 d to induce colitis. Rats in the kefir-control and kefir-colitis groups were administered 5 mL kefir once a day for 14 d while rats in the normal control and colitis group were administered an identical volume of the placebo (skim milk) using an orogastric feeding tube. Clinical colitis was evaluated with reference to the disease activity index (DAI), based on daily weight loss, stool consistency, and presence of bleeding in feces. Rats were sacrificed on the 15(th) day, blood specimens were collected, and colon tissues were rapidly removed. Levels of myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-10, malondialdehyde, and inducible nitric oxide synthase (iNOS) were measured in colon tissue. RESULTS: The DAI was lower in the kefir-colitis group than in the colitis group (on the 3(rd) and 5(th) days of colitis induction; P < 0.01). The DAI was also significantly higher in the colitis group between days 2 and 6 of colitis induction when compared to the normal control and kefir-control groups. The DAI was statistically higher only on the 6(th) day in the kefir-colitis group when compared to that in the normal control groups. Increased colon weight and decreased colon length were observed in colitis-induced rats. Mean colon length in the colitis group was significantly shorter than that of the kefir-control group. Kefir treatment significantly decreased histologic colitis scores (P < 0.05). MPO activity in the colitis group was significantly higher than in the kefir-control group (P < 0.05). Kefir treatment significantly reduced the DSS colitis-induced TNF-α increase (P < 0.01). No statistically significant differences were observed among groups for IL-10 and MDA levels. Colon tissue iNOS levels in the colitis group were significantly higher than those in the control and kefir-colitis groups (P < 0.05). CONCLUSION: Kefir reduces the clinical DAI and histologic colitis scores in a DSS-induced colitis model, possibly via reduction of MPO, TNF-α, and iNOS levels.

A case of ulcerative colitis with digital arterial thrombosis.

Thromboembolic events are rare in the course of ulcerative colitis and related with the activity of the disease. These complications are especially seen in young patients and cause high mortality and morbidity. Arterial thrombotic complications are less frequent and are usually seen after a surgical procedure. Here, we present a 36-year-old man with active ulcerative colitis presenting via digital arterial thrombosis and digital necrosis that was not associated with a surgical procedure.

[The effect of kefir consumption on human immune system: a cytokine study]. / Kefir tüketiminin insan bagisiklik sistemi üzerine etkileri: Bir sitokin çalismasi

The systemic effects of bioactive peptides which are produced by the fermentation of milk via the microorganisms found in kefir have been the subject of interest in recent years. Bioactive peptides activate innate immunity by stimulating macrophages, increasing phagocytosis, augmenting NO and cytokine production and boosting the lumen levels of IgG and IgA+ B-lymphocytes. The aim of the present study was to determine the serum cytokine profiles of healthy volunteers after kefir consumption to evaluate helper T (TH) cell polarization and to bring out the effects on native and allergic immune responses. The study was designed as a prospective and self-controlled study. A total of 18 healthy volunteers (age range: 20-40 yrs, mean age: 35.5 ± 7.38 yrs) from a university hospital staff were recruited to the study, with the approval of ethical board and informed consent. The body mass indices of all participants were between normal range (20.10-25.70 kg/m2). After two weeks of a diet free from fermented products, the participants consumed 200 mL kefir daily, for six weeks. Kefir product was prepared by using kefir starter culture (Danisco Biolacta Sp - 05223B 10001, Poland) which contains Lactobacillus spp., Leuconostoc spp., Lactococcus lactis ssp. lactis and Streptococcus termophilus, an overnight incubation at 26°C, and consumed freshly. Fasting blood samples of subjects were collected just before kefir use (0th week), at the end of the 3rd and 6th weeks of kefir consumption, and three weeks after cessation of kefir usage (9th week). Serum TNF-a, IL-1, IL-5, IL-8 and TGF-ß levels were measured by using commercial ELISA kits (BioSource, Belgium and Invitrogen, USA). Hemoglobin, serum creatinine and ALT levels of all subjects were also determined for follow-up. All volunteers completed the study period without any problem and declared no complaint. Hemoglobin, creatinine and ALT levels did not change with kefir consumption. Serum IL-8 levels were decreased at 3rd and 6th weeks (p< 0.001) and were at low levels at 9th week (p= 0.005) when compared with baseline levels (0th week). Serum IL-5 levels were increased at 3rd week (0th-3rd weeks; p= 0.01) and decreased by a rebound effect at 9th week (6th-9th week p= 0.003). TNF-α levels were increased with kefir consumption (p= 0.046) but the increase was insignificant in paired comparisons and the level was borderline between 0th and 6th weeks (p= 0.013). IL-5 and TNF-α levels returned to their original levels (0th week) at 9th week. Levels of the other cytokines (IL-1 and TGF-ß) did not change significantly with kefir usage. These results indicated that kefir use increased polarization of the immune response towards TH1 type and decreased TH2 type response and accordingly allergic response. The decrease in IL-8 level due to kefir use, might control the inflammatory response by suppressing neutrophil chemotaxis and activation. On the other hand it was also concluded that increased IL-5 might stimulate secretory IgA at gastrointestinal mucosa leading to a more efficient immune response in the intestinal lumen.

Effects of probiotics on methionine choline deficient diet-induced steatohepatitis in rats.

BACKGROUND/AIMS: Intestinal bacteria induce endogenous signals that play a pathogenic role in hepatic insulin resistance and non-alcoholic fatty liver disease. Probiotics could modulate the gut flora and could influence the gut-liver axis. We aimed to investigate the preventive effect of two probiotic mixtures on the methionine choline-deficient diet-induced non-alcoholic steatohepatitis model in rats. METHODS: Two studies, short-term (2 weeks) and long-term (6 weeks), were carried out using 60 male Wistar rats. The 2-week study included six groups. Rats were fed with methionine choline-deficient diet or pair-fed control diet and were given a placebo or one of two probiotic mixtures (Pro-1 and Pro-2) by orogastric gavage. In the 6-week study, rats were allocated into four groups and were fed with methionine choline-deficient diet or pair-fed control diet and given a placebo or Pro-2. At the end of the 2- and 6-week periods, blood samples were obtained, the animals were sacrificed, and liver tissues were removed. Serum alanine aminotransferase activity was determined; histologic and immunohistochemical analysis was performed for steatosis, inflammation, protein expression of tumor necrosis factor-α, and apoptosis markers. RESULTS: In both studies, methionine choline-deficient diet caused an elevation of serum alanine aminotransferase activity, which was slightly reduced by Pro-1 and Pro-2. In the 2- and 6-week studies, feeding with methionine choline-deficient diet resulted in steatosis and inflammation, but not fibrosis, in all rats. In the 2-week study, in rats fed with methionine choline-deficient diet and given Pro-1, steatosis and inflammation were present in 2 of 6 rats. In rats fed with methionine choline-deficient diet and given Pro-2, steatosis was detected in 3 of 6 rats, while inflammation was present in 2 of 6 rats. In the 6-week study, in rats fed with methionine choline-deficient diet and given Pro-2, steatosis and inflammation were present in 3 of 6 rat livers. In both the 2- and 6-week studies, methionine choline-deficient diet resulted in tumor necrosis factor-α, proapoptotic Bax, caspase 3, caspase 8, and anti-apoptotic Bcl-2 expression in all rat livers. Pro-1 and Pro-2 treatment influenced protein expression involved in apoptosis and tumor necrosis factor-α in varying degrees. CONCLUSIONS: Pro-1 and Pro-2 decrease methionine choline-deficient diet-induced steatohepatitis in rats. The preventive effect of probiotics may be due, in part, to modulation of apoptosis and their anti-inflammatory activity.

From suspicion of liver metastases to the diagnosis of Wilson disease in a patient with seminoma.

Wilson disease is an autosomal recessive disorder characterized by copper accumulation in the liver, brain, kidneys, and cornea due to inadequate biliary copper excretion. It should be considered especially in young patients who have findings of liver disease with unexplained etiology. Clinical presentation of the disease can be variable, and different types of parenchymal changes of the liver can be seen on imaging modalities. Multiple nodular lesions mimicking metastases can be detected. This condition can obligate physicians to screen for a malignant disease. Moreover, it may cause misdiagnosis as advanced stage of disease when coexistent with a malignancy. The coexistence of Wilson disease with some malignant diseases has been reported; however, coexistence with seminoma was not reported before. Approximately 40% of testicular cancers are pure seminoma. Liver metastases are rare in seminoma. In this article, a case of Wilson cirrhosis is reported. The patient was first followed with diagnosis of seminoma with suspicion of liver metastases.

Effect of probiotics on aspirin-induced gastric mucosal lesions.

BACKGROUND/AIMS: We aimed to investigate the role of a probiotic mixture, including 13 different bacteria, in the prevention of aspirin-induced gastric mucosal injury. METHODS: Forty rats were allocated into 4 groups: normal control, aspirin, probiotic control, and probiotic plus aspirin. Normal control and aspirin groups received 0.2 ml of skim milk by daily gavage for 14 days. Probiotic control and probiotic plus aspirin groups were administered 0.2 ml/day of probiotic mixture (1.3 x 10(10) cfu/ml) suspended in skim milk by daily gavage for 14 days. On day 15, gastric lesions were induced by administration of aspirin (200 mg/kg) in the aspirin and probiotic plus aspirin groups. Normal control and probiotic control groups were given saline. RESULTS: Pretreatment with probiotic mixture reduced aspirin-induced gastric damage scores (4.50 ± 0.43 and 2.60 ± 0.40, p<0.01) and exerted tendency of downregulation of proinflammatory cytokines elicited by aspirin (p>0.05). We also found that the probiotic mixture increased sIgA production approximately 7.5-fold in the stomach, and significantly reduced the malondialdehyde (MDA) increase in the gastric mucosa elicited by aspirin (p<0.001). Additionally, pretreatment with the probiotic mixture alleviated aspirin-induced reduction of mast cell count in the gastric mucosa. CONCLUSIONS: Probiotic mixture pretreatment attenuates the aspirin-induced gastric lesions by reducing the lipid peroxidation, enhancing mucosal sIgA production, and stabilizing mucosal mast cell degranulation into the gastric mucosa.

Preventive effect of probiotics and α-tocopherol on ethanol-induced gastric mucosal injury in rats.

The protective effect of a probiotic mixture of 13 different bacteria and α-tocopherol on 98% ethanol-induced gastric mucosal injury was evaluated. Levels of gastric mucosal pro- and anti-inflammatory cytokines, malondialdehyde, and secretory immunglobulin A were measured. Rats were allocated into four groups: control, ethanol, probiotic, and α-tocopherol. The control and ethanol groups received skim milk for 14 days. Probiotic and α-tocopherol groups were administered probiotic mixture suspended in skim milk and 100 mg/kg α-tocopherol, respectively, by daily gavage for 14 days. On Day 15, gastric lesions were induced by administration of ethanol 98% (1 mL) to all rats except those in the control group. Probiotic, but not α-tocopherol, seemed to inhibit ethanol-induced gastric mucosal tumor necrosis factor-α, interferon-γ, and interleukin-2 production (P > .05). Ethanol caused the elevation of mucosal interleukin-4 level (compared to the control, P < .05). Probiotic pretreatment significantly suppressed the ethanol-induced increase of gastric mucosal interleukin-4 levels. Pretreatment with either probiotic or α-tocopherol inhibited the ethanol-induced increase of mucosal malondialdehyde concentration (P < .01 and P < .05, respectively). Probiotic pretreatment enhanced the gastric mucosal secretory immunoglobulin A concentration (P < .001). In conclusion, probiotic mixture and α-tocopherol reduced ethanol-induced gastric mucosal lipid peroxidation, suggesting that they may be beneficial for gastric lesions induced by lower ethanol concentration.

Comparison of FibroTest-ActiTest with histopathology in demonstrating fibrosis and necroinflammatory activity in chronic hepatitis B and C.

AIMS: FibroTest and ActiTest are noninvasive tests used in determining the level of fibrosis and the degree of necroinflammatory activity in the liver. In our study, we aimed to investigate whether these tests could be alternative to liver biopsy. MATERIALS AND METHODS: Fifty patients were included in the study. Serum samples were obtained and liver needle biopsy was performed on the same day. Levels of fibrosis in FibroTest and levels of activity in ActiTest, both determined via serum biochemical markers, were compared with levels of fibrosis and activity in histopathological examination. For statistical analyses, Mc Nemar chi square test and Spearman's correlation tests were used. RESULTS: There was a significant positive correlation between fibrosis in biopsy and the level of fibrosis in FibroTest in patients with hepatitis B virus (HBV) (rho: 0.67, P < 0.0001). However, no significant correlation was determined between the activity in biopsy and the degree of activity in ActiTest (rho: 0.29, P < 0.05). No significant correlation was determined between both fibrosis and activity established in biopsy and the results of FibroTest and ActiTest in the group of patients with hepatitis C virus (HCV) (rho: 0.22, P < 0.05 and rho: 0.15, P < 0.05, respectively). CONCLUSION: Our results suggest that novel and safer noninvasive biochemical tests are needed as an alternative to histopathology in patients infected with HBV and HCV. Consequently, we believe that liver biopsy maintains its place as a gold standard in determining the histopathological condition of the liver.

A sewing needle in the liver: 6 years later.

A 27-year-old male patient was admitted for renal colic. In the radiographic findings of his kidney-ureter-bladder, a 6-cm-long sewing needle was detected in the right upper abdominal region. The needle displayed a direction toward the diaphragm, and the center of the needle had a radiolucent discontinuity. He refused to be operated. No complication was observed during the 6-year follow-up. Foreign bodies in the liver are generally recommended to be removed. This case is the first one in the literature with a needle in the liver remaining for 6 years without a change of location or causing a complication.

Hepatobiliary fascioliasis: a case with unusual radiological features.

We report a case of hepatobiliary fascioliasis presenting with unusual radiological findings that have not been reported previously. Imaging studies revealed hepatic cystic pouches communicating with intrahepatic bile ducts. Snail-like, oval shaped and conglomerated echogenic particles with no acoustic shadowing, suggesting F. hepatica, were detected in these cystic pouches. In addition, secondary sclerosing cholangitis developed after fascioliasis.

Biliary fascioliasis: sonographic appearance patterns.

PURPOSE: To describe the sonographic findings of biliary fascioliasis. METHOD: The study included 27 patients with fascioliasis and abdominal sonographic findings in biliary system. All diagnoses were confirmed via serologic enzyme-linked immunosorbent assay, and 5 patients underwent cholecystectomy. Sonographic findings in the biliary system were defined as primary and secondary. RESULTS: Primary findings included spontaneously moving echogenic structures, linear echoes, curvilinear echoes, oval-shaped echogenic structure, matted echogenic particle, echogenic particle adherent to the gallbladder wall, motionless freely floating round echogenic foci, and leaf-like echogenic structures. Secondary findings were dilatation or wall thickening of the biliary system. In the liver, multiple confluent subcapsular nodules were also noted on sonography and CT in 14 of 27 patients. CONCLUSION: Sonography can detect biliary system lesions in fascioliasis and can aid diagnosis of the disease. However, the radiologist should be familiar with the different sonographic appearances of biliary fascioliasis.

Quantitative correlation of Helicobacter pylori stool antigen (HpSA) test with the severity of H. pylori-related gastritis.

The Helicobacter pylori (H. pylori) load in both stomach and stool and the resulting severity of gastritis are important criteria in validating the status of H. pylori infection. We aimed to assess the reliability of the H. pylori stool antigen (HpSA) test for the primary diagnosis of H. pylori infection by calculating the best cut-off value to obtain the highest sensitivity and specificity in dyspeptic patients. We also investigated the correlation of HpSA test with the severity of gastritis and H. pylori load. The H. pylori statuses of 95 patients were evaluated by the positivity of both rapid urease test and microscopic detection of H. pylori in biopsy specimens, 88 subjects of whom were H. pylori positive. The sensitivity and specificity of the HpSA test were 51.1% (45/88) and 100% (7/7), respectively, according to the manufacturer's recommended cut-off value of 0.16. However, with the best cut-off value of 0.048, calculated by receiver operator characteristics analysis, the sensitivity of the test increased to 92.0% (81/88) with the same specificity. High values of the HpSA test were correlated with high scores of corpus H. pylori load and the severity of antrum and corpus inflammation (p < 0.05). With the best cut-off value of the HpSA test, the primary diagnosis of H. pylori infection can be made with higher sensitivity and specificity. The HpSA test is a helpful tool that evaluates the severity of H. pylori infection and the degree of gastric inflammatory activity and gastric H. pylori load.

Clomiphene-induced acute pancreatitis without hypertriglyceridemia.

Acute pancreatitis may be caused by drugs. In the literature, there are more than 260 different drugs that have been blamed for causing pancreatitis. Among these drugs, only 1 case has been reported as clomiphene-induced acute pancreatitis. However, in this single case, there was concomitant hypertriglyceridemia. We report the case of a woman who developed 2 attacks of acute pancreatitis without hypertriglyceridemia while receiving treatment with clomiphene.

Does Fasciola hepatica infection modify the response of acute hepatitis C virus infection to IFN-alpha treatment?

Immunologic response to acute hepatitis C is mainly a Th1 response, whereas fasciolopsiasis is associated with a diverse T-cell response. Interferon-alpha has immunomodulatory effects and enhances Th1 immune response. Fasciola infection could theoretically interfere with the Th1 immune response, even when acquired after an initial response to interferon-alpha treatment for acute hepatitis C virus (HCV) infection. We report here the case of a male patient who acquired Fasciola hepatica infection after an initial response to IFN-alpha therapy with a favorable outcome.