A new oral formulation for the release of sodium butyrate in the ileo-cecal region and colon

AIM: To develop a new formulation with hydroxy propyl methyl cellulose and Shellac coating for extended and selective delivery of butyrate in the ileo-caecal region and colon. METHODS: One-gram sodium butyrate coated tablets containing 13C-butyrate were orally administered to 12 healthy subjects and 12 Crohn's disease patients and the rate of 13C-butyrate absorption was evaluated by 13CO2 breath test analysis for eight hours. Tauroursodeoxycholic acid (500 mg) was co-administered as a biomarker of oro-ileal transit time to determine also the site of release and absorption of butyrate by the time of its serum maximum concentration. RESULTS: The coated formulation delayed the 13C-butyrate release by 2-3 h with respect to the uncoated tablets. Sodium butyrate was delivered in the intestine of all subjects and a more variable transit time was found in Crohn's disease patients than in healthy subjects. The variability of the peak 13CO2 in the kinetic release of butyrate was explained by the inter-subject variability in transit time. However, the coating chosen ensured an efficient release of the active compound even in patients with a short transit time. CONCLUSION: Simultaneous evaluation of breath 13CO2 and tauroursodeoxycholic acid concentration- time curves has shown that the new oral formulation consistently releases sodium butyrate in the ileo-cecal region and colon both in healthy subjects and Crohn's disease patients with variable intestinal transit time. This formulation may be of therapeutic value in inflammatory bowel disease patients due to the appropriate release of the active compound.

Beneficial effect of sulphate-bicarbonate-calcium water on gallstone risk and weight control

AIM:To investigate the effect of drinking sulphate-bicarbonate-calcium thermal water (TW) on risk factors for atherosclerosis and cholesterol gallstone disease.METHODS:Postmenopausal women with functional dy-spepsia and/or constipation underwent a 12 d cycle of thermal (n=20) or tap (n=20) water controlled drinking.Gallbladder fasting volume at ultrasound,blood vitamin E,oxysterols (7-β-hydroxycholesterol and 7-ketocholesterol),bile acid (BA),triglycerides,total/low density lipoprotein and high density lipoprotein cholesterol were measured at baseline and at the end of the study.Food consumption,stool frequency and body weight were recorded daily.RESULTS:Blood lipids,oxysterols and vitamin E were not affected by either thermal or tap water consumption.Fasting gallbladder volume was significantly (P<0.005) smaller at the end of the study than at baseline in the TW (15.7±1.1 mL vs 20.1±1.7 mL) but not in the tap water group (19.0±1.4 mL vs 19.4±1.5 mL).Total serum BA concentration was significantly (P<0.05) higher at the end of the study than at baseline in the TW (5.83±1.24μmol vs 4.25±1.00μmol) but not in the tap water group (3.41±0.46μmol vs 2.91±0.56μmol).The increased BA concentration after TW consumption was mainly accounted for by glycochenodeoxycholic acid.The number of pasta (P<0.001),meat (P<0.001) and vegetable (P<0.005) portions consumed during the study and of bowel movements per day (P<0.05) were significantly higher in the TW than in the tap water group.Body weight did not change at the end of the study as compared to baseline in both groups.CONCLUSION:Sulphate-bicarbonate-calcium water consumption has a positive effect on lithogenic risk and intestinal transit and allows maintenance of a stable body weight despite a high food intake.

A new iron free treatment with oral fish cartilage polysaccharide for iron deficiency chronic anemia in inflammatory bowel diseases:A pilot study

AIM:To investigate the effect of a new oral preparation,highly concentrated in fish cartilage,in a group of inflammatory bowel diseases(IBD)patients with chronic iron deficient anemia.METHODS:In an open label pilot study,we supple-mented a group of 25 patients(11 with Crohn's disease and 14 with ulcerative colitis)in stable clinical conditions and chronic anemia with a food supplement which does not contain iron but contains a standardized fraction of fish cartilage glycosaminoglycans and a mixture of antioxidants(Captafer Medestea,Turin,Italy).Patients received 500 mg,twice a day during meals,for at least 4 mo.Patients were suggested to maintain their alimentary habit.At time 0 and after 2 and 4 mo,emocrome,sideremia and ferritin were examined.Paired data were analyzed with Student's t test.RESULTS:Three patients relapsed during the study(2 in the 3rd mo,1 in the 4th mo),two patients were lost to follow up and two patients dropped out(1 for orticaria,1 for gastric burning).Of the remaining 18 patients,levels of serum iron started to rapidly increase within the 2nd mo of treatment,P < 0.05),whereas serum ferritin and hemoglobin needed a longer period to significantly improve their serum levels(mo 4)P < 0.05.The product was safe,easy to administer and well tolerated by patients.CONCLUSION:These data suggest a potential new treatment for IBD patients with iron deficiency chronic anemia and warrant further larger controlled studies.

Non-invasive panel tests for gastrointestinal motility monitoring within the MARS-500 Project

AIM:To develop an integrated approach for monitoring gastrointestinal motility and inflammation state suitable for application in long-term spaceflights.METHODS:Breath tests based on the oral administration of 13 C-labeled or hydrogen-producing substrates followed by the detection of their metabolites(13 CO 2 or H 2) in breath were used to measure gastrointestinal motility parameters during the 520-d spaceflight ground simulation within the MARS-500 Project.In particular,the gastric emptying rates of solid and liquid contents were evaluated by 13 C-octanoic acid and 13 Cacetate breath tests,respectively,whereas the orocecal transit time was assessed by an inulin H 2-breath test,which was performed simultaneously with the 13 C-octanoic acid breath test.A ready-to-eat,standardized pre-packaged muffin containing 100 mg of 13 C-octanoic acid was used in the 13 C-octanoic acid breath test to avoid the extemporaneous preparation of solid meals.In addition,a cassette-type lateral flow immunoassay was employed to detect fecal calprotectin,a biomarker of intestinal inflammation.Because no items could be introduced into the simulator during the experiment,all materials and instrumentation required for test performance during the entire mission simulation had to be provided at the beginning of the experiment.RESULTS:The experiments planned during the simulation of a manned flight to Mars could be successfully performed by the crewmembers without any external assistance.No evident alterations(i.e.,increasing or decreasing trends) in the gastric emptying rates were detected using the 13 C-breath tests during the mission simulation,as the gastric emptying half-times were in the range of those reported for healthy subjects.In contrast to the 13 C-breath tests,the results of the inulin H 2-breath test were difficult to interpret because of the high variability of the H 2 concentration in the breath samples,even within the same subject.This variability suggested that the H 2-breath test was strongly affected by external factors,which may have been related to the diet of the crewmembers or to environmental conditions(e.g.,the accumulation of hydrogen in the simulator microenvironment).At least in closed microenvironments such as the MARS-500 simulator,13 C-breath tests should therefore be preferred to H 2-breath tests.Finally,the fecal calprotectin test showed significant alterations during the mission simulation:all of the crewmembers were negative for the test at the beginning of the simulation but showed various degrees of positivity in at least one of the subsequent tests,thus indicating the onset of an intestinal inflammation.CONCLUSION:Breath tests,especially those 13 Cbased,proved suitable for monitoring gastrointestinal motility in the 520-d isolation experiment withinMARS-500 project and can be applied in long-term spaceflights.

Production of reactive oxygen species and expression of inducible nitric oxide synthase in rat isolated Kupffer cells stimulated by Leptospira interrogans and Borrelia burgdorfen

瞄准：为了评估反应的氧种类(ROS ) 和可诱导的氮的氧化物的表示的生产，在老鼠的 synthase (i NOS ) 孤立肾脏钩端螺旋体和包柔氏螺旋体属 burgdorferi 刺激的 Kupffer 房间(KC ) 。方法：老鼠 Kupffer 房间被肝的灌注用 0.05% 胶原酶分开，并且由 Percoll 坡度净化了。净化的 Kupffer 房间是有活着的 L 的测试在试管内。interogans 和 B。burgdorferi 准备。ROS 的生产被化合光决定，而 i NOS 蛋白质表达式被西方的污点试金用 anti-iNOS 抗体计算。结果：B。burgdorferi 并且到一更少的程度 L。interrogans 与一座山峰导致了 ROS 生产在感染以后的 35 min。化合光信号日益增多地减少了并且由孵化的 180 min 是无法发现的。Leptospirae 和 borreliae 在在 6 个小时达到顶点并且仍然是明显的 Kupffer 房间导致了增加的 i NOS 表情在感染以后的 22 h。结论：螺旋菌的两个类在老鼠 Kupffer 细胞导致了 ROS 和 i NOS 生产。自从在 leptospiral 以及在 borrelial 感染的肝损坏的原因，仍然是未知的，我们建议那螺旋体和肝的包柔氏螺旋体属损坏能被氧激进分子开始调停，并且然后被氮的氧化物部分地至少维持。