[Diagnosis of oesophageal reflux by PH, impedance, and bilirubin measurement: recommendations of the German Society of Neurogastroenterology and of the working group for neurogastroenterology of the German Society for Digestive and Metabolic Diseases]. / Ösophageale Refluxdiagnostik - pH-Metrie, Impedanzmessung, Bilirubin-Messung: Empfehlungen der Deutschen Gesellschaft für Neurogastroenterologie und Motilität und der Arbeitsgruppe Neurogastroenterologie der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten.

The current recommendations on indications, technical performance, and interpretation of diagnostic techniques for oesophageal reflux update the German recommandations about 24 hour pH measurement of 2003. The recommendations encompass conventional pH measurement, wireless pH measurement, pH and impedance measurements, and bilirubin measurement (duodenogastro-oesophageal reflux).

Effects of Oenothera biennis L. and Hypericum perforatum L. extracts on some central nervous system myelin proteins, brain histopathology and oxidative stress in mice with experimental autoimmune encephalomyelitis.

We investigated the effects of Oenothera biennis L. and Hypericum perforatum L. extracts on brain tissue histopathology, myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) in mice with experimental autoimmune encephalomyelitis (EAE). Forty-seven C57BL/6J mice were divided into the following groups: multiple sclerosis (MS), control (healthy mice), MS + H. perforatum treated (MS + HP), MS + O. biennis treated (MS + OB). All groups except the control group were immunized by EAE methods. Two weeks after the immunization, the mice in the MS + HP group were fed normal food containing 18 - 21 g/kg H. perforatum extract, the mice in MS + OB group were fed normal food containing 18 - 21 g/kg O. biennis extract, and the mice in control and MS groups were fed normal food for six weeks. Brain tissue samples were collected from all mice for histopathological and biochemical analysis. Clinical signs of the disease were scored using functional systems scores (FSS) daily. The H. perforatum and O. biennis extracts ameliorated the increased brain tissue MOG and MBP values for animals with MS. H. perforatum and O. biennis extract decreased the TOS and OSI values for brain tissue and increased TAS levels in brain tissue of animals with MS. In addition, H. perforatum and O. biennis extracts decreased the clinical signs at the end of the experiment compared to the beginning of extract administration. We found that myelin was lost in MS group vs. control group. H. perforatum and O. biennis extract treatments decreased the amount of myelin loss in the MS + HP and MS + OB groups. We also observed amyloid deposition on vascular walls, in the cytoplasm of the neurons and in the intercellular space in the MS group. O. biennis and H. perforatum treated groups exhibited neither abnormal amyloid deposition nor obvious cell infiltration. The beneficial effects of O. biennis and H. perforatum for attenuating myelin loss and amyloid deposition suggest their therapeutic utility for treatment of MS.

CB1 and TRPV1 receptors mediate protective effects on colonic electrophysiological properties in mice.

CB1 and TRPV1 receptors modulate enteric neurotransmission and colonic inflammation. This study investigates early electrophysiological changes in distal colon of wild-type and receptor deficient mice after an inflammatory insult set by dinitrobenzene sulfonic acid (DNBS). Colitis was induced by DNBS in CB1(-/-) mice, TRPV1(-/-) mice, and their respective wild-type littermates. Electrophysiological properties consisting of membrane potentials and electrically induced inhibitory junction potentials (IJP) of circular smooth muscle cells were evaluated at different time points. Additionally a histological colitis severity score was evaluated in CB1(+/+) and CB1(-/-) mice 24 h after DNBS. Inflammation caused spontaneous atropine insensitive rhythmic action potentials in CB1(-/-) and TRPV1(-/-) mice but not in wild-type animals. This indicates that membrane stability is disturbed, which in turn indicates a lack of protective mechanisms. Focal electrical neuronal stimulation of the myenteric plexus induced IJP in the smooth muscle cells. Twenty-four hours after initiation of inflammation, the duration of the IJP is prolonged in all animals, indicating disturbances within neuromuscular interaction. In CB1(-/-) mice, it is interesting that the duration of IJP was significantly extended, as compared to CB1(+/+) mice pointing toward missing protective mechanisms in the CB1(-/-) mice. Inflammatory insults in the mouse colon induce reproducible changes in the electrophysiological properties and such changes correlate with duration of colitis. In mutants, these electrophysiological changes display different patterns, suggesting the lack of protective properties for neuromuscular interactions and membrane stability.

Cannabinoid 1 receptors modulate intestinal sensory and motor function in rat.

BACKGROUND: Cannabinoid receptors are involved in visceral pain perception and control of intestinal motility in vivo. The underlying mechanisms are not well characterized. We aimed to determine whether the cannabinoid-1 (CB(1)) receptor modulates intestinal afferent nerve discharge and the peristaltic reflex. METHODS: Rats were anesthetized and intestinal segments were removed. Afferent nerve discharge from a mesenteric nerve was investigated in vitro in the presence of the CB(1) antagonist SR 141716A or the CB(1) agonist WIN 55212-2. The myenteric peristaltic reflex was induced by electrical field stimulation and influence of SR 141716A or WIN 55212-2 was recorded. KEY RESULTS: Afferent nerve discharge to the algesic mediator bradykinin was reduced to 11 +/- 5.1 imp s(-1) following pretreatment with SR 141716A and unchanged after WIN 55212-2 compared to 63 +/- 15.4 imp s(-1) in controls. At maximum distension pressure (80 cmH(2)O) during ramp distension, 92 +/- 12.4 imp s(-1) were reached following SR 141716A compared to 260 +/- 13.2 in vehicle controls and 227 +/- 15.4 in WIN 55212-2 pretreated animals. In contrast, afferent discharge to 5-HT (500 micromol L(-1)) was increased to 75 +/- 24.6 imp s(-1) following WIN 55212-2 compared to 18 +/- 5.9 imp s(-1) in controls, whereas SR 141716A had no effect. Ascending neuronal contractions were dose-dependently attenuated in the presence of SR 141716A and latency of these contractions was reduced. WIN 55212-2 had opposite effects that were abolished by SR 141716A. CONCLUSIONS & INFERENCES: Activation of the CB(1) receptor differentially alters afferent intestinal nerve sensitivity to bradykinin, 5-HT, and noxious mechanical distension, while it strengthens ascending neuronal contractions. Further studies are needed to determine the physiological relevance of these observations.

Involvement of cannabinoid-1 and cannabinoid-2 receptors in septic ileus.

BACKGROUND Cannabinoid (CB) receptors are involved in the regulation of gastrointestinal (GI) motility under physiological and pathophysiological conditions. We aimed to characterize the possible influence of CB(1) and CB(2) receptors on motility impairment in a model of septic ileus. METHODS Lipopolysaccharide (LPS) injections were used to mimic pathophysiological features of septic ileus. Spontaneous jejunal myoelectrical activity was measured in rats in vivo, and upper GI transit was measured in vivo by gavaging of a charcoal marker into the stomach of mice, in absence or presence of LPS, and CB(1) and CB(2) receptor agonists and antagonists. Tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 levels were measured using enzyme-linked immunosorbent assay. Histology was performed with haematoxylin-eosin staining. KEY RESULTS Lipopolysaccharide treatment significantly reduced amplitude and frequency of myoelectric spiking activity and GI transit in vivo in a dose-dependent manner. TNF-alpha and IL-6 were increased in LPS-treated animals and histology showed oedema and cell infiltration. Both, the CB(1) agonist HU210 and the CB(2) agonist JWH133 reduced myoelectrical activity whereas the CB(1) antagonist AM251 caused an increase of myoelectrical activity. Pretreatment with AM251 or AM630 prevented against LPS-induced reduction of myoelectrical activity, and also against the delay of GI transit during septic ileus in vivo. CONCLUSIONS & INFERENCES The LPS model of septic ileus impairs jejunal myoelectrical activity and delays GI transit in vivo. Antagonists at the CB(1) receptor or the CB(2) receptor prevent the delay of GI transit and thus may be powerful tools in the future treatment of septic ileus.

The role of fatty acid hydrolase gene variants in inflammatory bowel disease.

BACKGROUND: Recent studies suggest a role for the endocannabinoid system, including fatty acid amide hydrolase (FAAH), in intestinal inflammation. AIM: To analyse FAAH expression and the FAAH 385 C/A (p.Pro129Thr; rs324420) single nucleotide polymorphism (SNP) in-patients with Crohn's disease (CD) and ulcerative colitis (UC). PATIENTS AND METHODS: Genomic DNA from 1008 individuals (CD: n = 435; UC: n = 167; controls: n = 406) was analysed for the FAAH 385 C/A SNP. We determined FAAH mRNA expression by quantitative PCR in CD and UC lesions as well as in intestinal epithelial cells (IECs). RESULTS: There were no significant differences regarding the frequency of this SNP in the three study groups (CD, UC, controls). However, CD patients homozygous for the FAAH p.Pro129Thr polymorphism were more likely to develop a severe disease phenotype associated with fistulas (P = 0.03, OR 3.12, 95% CI 1.08-8.98) and extra-intestinal manifestations (P = 0.005, OR 4.29, CI 1.49-12.35). In UC, homozygous carriers had an earlier disease onset than wild-type carriers (P = 0.01). FAAH mRNA expression correlated with IL-8 mRNA expression in CD lesions (r = 0.53). However, pro-inflammatory stimuli did not significantly increase FAAH mRNA expression in IECs. CONCLUSION: The FAAH p.Pro129Thr polymorphism may modulate the CD phenotype.

A novel herbal preparation desensitizes mesenteric afferents to bradykinin in the rat small intestine.

Herbal preparations are evolving as promising agents for the treatment of functional gastrointestinal disorders which are considered to be secondary to visceral hypersensitivity. We aimed to determine whether a new combination of six herbal extracts reduces the sensitivity of intestinal afferents in rat. Male Wistar rats (250-350 g, n = 6 per group) were gavaged with either vehicle or 2.5, 5 or 10 mL kg(-1) of STW 5-II, a herbal preparation which contains six extracts. Two hours later, animals were anaesthetized and extracellular multi-unit mesenteric afferent nerve recordings were obtained in the proximal jejunum in vivo. Afferent discharge to 5-hydroxy-tryptamine (5-HT) (5, 10, 20 and 40 microg kg(-1), i.v.), luminal distension (0-60 mmHg) and bradykinin (BK) (15, 30 and 60 microg kg(-1), i.v.) was recorded. At baseline, spontaneous afferent discharge was not different following pretreatment with the various doses of STW 5-II compared with vehicle. The pressure-dependent increase in afferent discharge to intraluminal ramp distension and the dose-dependent increase in afferent firing following 5-HT were also uninfluenced by STW 5-II pretreatment. In contrast, the afferent nerve responses to 15, 30 and 60 microg kg(-1) of BK were reduced following 10 mL kg(-1) STW 5-II with peaks at 106 +/- 19, 153 +/- 22 and 156 +/- 25 imp s(-1) compared with 160 +/- 15, 228 +/- 14 and 220 +/- 16 imp s(-1) following vehicle pretreatment (mean +/- SEM, P < 0.05). Intestinal afferent sensitivity to BK which plays a prime role in nociception was reduced following STW 5-II. Thus, STW 5-II may be of therapeutic use for conditions that involve neuronal hypersensitivity and the release of BK in the intestine.

The role of the endocannabinoid system in the pathophysiology and treatment of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a spectrum of disorders characterized by abdominal discomfort and pain, associated with altered bowel habits. Though gut motility, secretion and sensation may be altered in patients with IBS, the pathophysiology of this condition remains to be fully understood. The endocannabinoid system is involved in the regulation of numerous gastrointestinal functions including motility, sensation and secretion under both physiological and pathophysiological conditions. Activation of cannabinoid (CB)(1) and CB(2) receptors under various circumstances reduces motility, limits secretion and decreases hypersensitivity in the gut. Drugs that alter the levels of endocannabinoids in the gut also reduce motility and attenuate inflammation. In this review, we discuss the role of the endocannabinoid system in gastrointestinal physiology. We go on to consider the involvement of the endocannabinoid system in the context of symptoms associated with IBS and a possible role of this system in the pathophysiology and treatment of IBS.

[Perspectives of cannabinoids in gastroenterology]. / Perspektiven von Cannabinoiden in der Gastroenterologie.

In early cultures, extracts of the plant Cannabis sativa were medically used for the treatment of gastrointestinal symptoms like nausea, vomiting, diarrhoea and abdominal pain. In the United States cannabis extracts were frequently used as drugs, e. g., for the treatment of diarrhoea, until around 1920. The possibility of cannabis abuse resulted in a worldwide prohibition and thus the temporary ending of the medical use of cannabinoids. The characterisation of an endogenous cannabinoid system consisting of receptors, endogenous agonists, antagonists and degrading enzymes opens the door for a comeback of cannabinoids in medicine. The clinically proven effects in the treatment of pain, cachexia in conjunction with HIV, or malignant disease and treatment of nausea and vomiting in conjunction with chemotherapy now result in the prescription of cannabinoids as valuable medication. This review will discuss the value of cannabinoids in the treatment of nausea and vomiting, i. e., the indications for which cannabinoids are presently used in gastroenterology. Additionally, this review will discuss potential indications within gastroenterology, where results from basic research or individual observations suggest that a future use of cannabinoids in gastroenterology seems possible.

Hepatitis induced by Noni juice from Morinda citrifolia: a rare cause of hepatotoxicity or the tip of the iceberg?

A 24-year-old female patient presented to her community hospital with mild elevations of serum transaminase and bilirubin levels. Because of multiple sclerosis, she was treated with interferon beta-1a for 6 weeks. After exclusion of viral hepatitis due to hepatitis A-E, interferon beta-1a was withdrawn under the suspicion of drug-induced hepatitis. One week later, she was admitted again to her community hospital with severe icterus. The transaminase and bilirubin levels were highly elevated, and a beginning impairment of the liver synthesis was expressed by a reduced prothrombin time. The confinement to our department occurred with a fulminant hepatitis and the suspicion of beginning acute liver failure. There was no evidence for hepatitis due to potentially hepatotoxic viruses, alcoholic hepatitis, Budd-Chiari syndrome, hemochromatosis, and Wilson's disease. In her serum there were high titers of liver-kidney microsomal type 1 autoantibody; the serum gamma globulin levels were in the normal range. Fine-needle aspiration biopsy of the liver ruled out an autoimmune hepatitis but showed signs of drug-induced toxicity. During the interview, she admitted that for 'general immune system stimulation' she had been drinking Noni juice, a Polynesian herbal remedy made from a tropical fruit (Morinda citrifolia), during the past 4 weeks. After cessation of the Noni juice ingestion, her transaminase levels normalized quickly and were in the normal range within 1 month.