Search PubMed⌕ Search

Biomedical subjects

T Frieling

Publications and source records attributed to T Frieling.

At least 73 records · Page 4Linked to original sources

[Neuroimmune interactions in the gastrointestinal tract].

The enteric nervous system and immune system are integrated systems that play an important role in the regulation of gastrointestinal functions. Recent studies suggest a bidirectional interaction between both systems. The relationship is based on the synthesis and release of neuropeptides from immune cells and the receptor-mediated alteration of nervous and immune functions by neurotransmitters and inflammatory mediators. The activity of the enteric nervous and immune system can be modulated by the central nervous system. These psycho-neuro-immuno-interactions are involved in gut inflammation, in functional bowel diseases and in the physiological control of gastrointestinal functions.

Animals↗

Anatomy of the anal sphincters. Comparison of anal endosonography to magnetic resonance imaging.

PURPOSE: A recent application of endosonography in the evaluation of anal sphincter morphology has led to controversy about the possibility of precisely assessing the diameter of external and internal anal sphincter muscles. On the other hand, magnetic resonance imaging (MRI) has been proposed to allow a more detailed view of the anatomy of the pelvic floor. However, both techniques have not yet been compared directly. METHODS: Eight healthy volunteers (age range, 25-40 years; 5:3, male:female) participated. Anal ultrasound was performed using a 7.5-MHz rectal transducer which produced a transversal panorama display of 360 degrees, allowing an image perpendicular to the anal canal. Imaging of the diameter of the internal and external anal sphincter muscles was performed with the transducer placed in the midanal canal, and measurement was always performed by the same investigator in dorsal projection. MRI was performed using a 1.5 Tesla Magnetom (Siemens, Erlangen, Germany) to obtain sagittal and angled axial (perpendicular to the anal canal) planes for consecutive 3-mm slices which were evaluated by four independent raters. RESULTS: Muscle thickness of the sphincter muscles in dorsal projection was 1.96 +/- 0.61 mm for the internal sphincter and 6.35 +/- 1.07 mm for the external sphincter using ultrasound. It was 1.72 +/- 0.13 mm and 3.99 +/- 0.99 mm, respectively, using MRI. When both measures were compared, only the internal sphincter data correlated significantly (r = 0.818, P = 0.0023) between both measures. Sagittal resonance imaging of the anal canal did not allow for differentiation of both muscles at all. Differentiation among mucosa, submucosa, and internal anal sphincter is not possible with MRI but may well be performed with high-resolution ultrasound. CONCLUSION: Anal ultrasound carries the potential of becoming a routine clinical procedure for evaluation of the anal anatomy and morphology in defecation disorders, but current MRI assessment of the anal anatomy is elaborate, costly, and does not provide any further insights.

Adult↗

Neuroimmune communication in the submucous plexus of guinea pig colon after infection with Trichinella spiralis.

BACKGROUND/AIMS: Enteric neuroimmune communication in gastrointestinal hypersensitivity responses includes antigen detection by mast cells and release of chemical messages to the enteric nervous system. The aim of this study was to analyze the electrical and synaptic behavior of neurons in the colonic submucous plexus during exposure to Trichinella spiralis antigen in animals infected earlier with the parasite. METHODS: Microelectrodes were used to record in submucous neurons of guinea pig distal colon during application of Trichinella antigen. RESULTS: Neurons in sensitized animals were more excitable than in controls. Hyperexcitability was seen as a greater probability of spontaneous action potential discharge and repetitive firing to depolarizing current or exposure to acetylcholine. Application of histaminergic antagonists reversed the augmented excitability, suggesting endogenously released histamine as a responsible factor. Antigenic exposure increased neuronal excitability and suppressed nicotinic transmission at fast cholinergic synapses only in sensitized animals. Effects on excitability, but not presynaptic inhibitory effects, were blocked by cimetidine. CONCLUSIONS: Signaling between mucosal mast cells and the enteric nervous system is involved in colonic anaphylactic responses to sensitizing antigens. Histamine is a paracrine signal in the communication pathway.

Action Potentials↗

Effects of the inflammatory mediator prostaglandin D2 on submucosal neurons and secretion in guinea pig colon.

Conventional flux chamber and intracellular recording methods were used to investigate the mode of action of prostaglandin D2 (PGD2) on ion transport in muscle-stripped segments of guinea pig colon and on colonic submucosal ganglion cells. Application of PGD2 resulted in a dose-dependent increase in short-circuit current that was reduced by serosal addition of bumetanide, tetrodotoxin, atropine, or piroxicam, but not hexamethonium. Application of PGD2 to submucosal neurons evoked a depolarization of the membrane potential that was associated with an enhanced spike discharge. In AH/type 2 neurons, postspike afterhyperpolarizations were reduced in amplitude and duration. The depolarizing responses to PGD2 were not affected by tetrodotoxin, indicative of a direct effect of PGD2 on the impaled neurons. Whereas fast excitatory postsynaptic potentials (EPSPs) were not affected by PGD2, slow EPSPs were reduced by a presynaptic effect, indicating presynaptic suppression of noncholinergic neurotransmitter release. The study demonstrates that PGD2 acts as a neuromodulator to evoke nerve-mediated chloride secretion, predominantly through activation of cholinergic submucosal neurons. The results further indicate that PGD2 released from lamina propria immune cells during antigenic stimulation may influence mucosal function by altering electrical behavior of submucosal neurons.

Animals↗

Neuroimmune communication in the submucous plexus of guinea pig colon after sensitization to milk antigen.

We investigated electrical and synaptic behavior of neurons in the colonic submucous plexus during exposure to beta-lactoglobulin in guinea pigs sensitized by ingestion of milk. Microelectrodes were used to record electrical and synaptic behavior in neurons from milk-sensitized and nonsensitized age-matched animals during exposure to beta-lactoglobulin. Neurons in sensitized animals were hyperexcitable. Application of the histamine H2 antagonist cimetidine reversed the hyperexcitability, suggesting endogenously released histamine as one of the responsible factors. Antigenic exposure suppressed stimulus-evoked nicotinic cholinergic fast excitatory postsynaptic potentials (EPSPs). This was blocked by the selective histamine H3 antagonist burimamide. Suppression of the EPSPs resulted from presynaptic inhibition of acetylcholine release. Increased neuronal excitability and suppression of synaptic transmission was only found in milk-sensitized intestine, not in the intestine from age-matched nonsensitized animals. We concluded that signaling from mucosal mast cells to the enteric nervous system is important in colonic defense against antigenic threats. Histamine is a paracrine messenger in the communication network.

Acetylcholine↗

Endosonography of the anal sphincters: incontinent and continent patients and healthy controls.

It has previously been shown that in healthy subjects anal sphincter functions as assessed by anorectal manometry and anal sphincter anatomy as measured by endoluminal ultrasound are poorly correlated. It remains to be shown, however, whether this is true for a larger series of patients with anorectal dysfunctions such as incontinence, and what is the clinical relevance of anal sonography. Anal sonography was performed in 42 consecutive patients with fecal incontinence, in 19 patients with constipation and/or anal pain, and in 15 healthy volunteers to determine anal sphincter integrity and the dorsal diameter of the internal and external anal sphincter muscles. Conventional multilumen anorectal manometry was performed in all subjects and patients to determine, among others, external and internal sphincter (EAS, IAS) performance at rest and during squeezing. It was shown that healthy subjects exhibit significantly higher muscle diameters of the IAS than both patient groups, but the EAS was similar in all groups. In 11/42 cases of incontinent patients, in 3/19 constipated patients, but in none of the controls a muscle defect of the EAS was found with sonography. Thirteen of these 14 patients were women with previous birth traumas. EAS but not IAS muscle thickness and muscle performance (squeezing and resting, respectively) were significantly correlated. Across all groups, women had smaller EAS muscle diameters than men. It is concluded, that in incontinent patients anal sonography may reveal additional information of clinical relevance in a substantial fraction of patients, and, thus, both anal manometry and anal ultrasound are of clinical value.

Adult↗

Hereditary hemorrhagic telangiectasia associated with multiple pulmonary arteriovenous malformations and juvenile polyposis.

A case with multiple telangiectases of the gastrointestinal tract that caused recurrent bleeding is reported. The hemorrhagic telangiectases were associated with multiple pulmonary arteriovenous malformations leading to significant right-to-left shunting and in combination with an atrial septal defect to progressive right heart failure and finally to the death of the patient. Juvenile polyps and tubulovillous adenomas of the colon were removed. Hemicolectomy had to be performed because of carcinomatous infiltration originating from adenomatous epithelium developing in a juvenile polyp. The pathogenesis of hemorrhagic telangiectases is unknown. It is an important source of intestinal hemorrhage and may be complicated by the additional finding of arteriovenous fistulas and the occurrence of recurrent juvenile, adenomatous epithelium containing colonic polyps eventually leading to carcinoma. The present case suggests an inherited association of hemorrhagic telangiectases and juvenile polyposis. It also highlights that rapidly progressive right-to-left shunting rather than hemorrhagic anemia my be the major determinant of the course of the disease.

Adenomatous Polyposis Coli↗

The effect of trospium chloride on oesophageal motility.

Trospium chloride is a muscarinergic antagonist acting on oesophageal smooth muscle and on ganglionic and/or myenteric neurons. The effect of this drug on oesophageal motility was tested in 16 healthy male subjects in a double-blind randomized cross-over examination of trospium chloride or placebo following phentolamine or placebo application. Each subject underwent two separate investigations at least one week apart. Trospium chloride was effective in the oesophagus to reduce contractile activity (amplitude and duration of peristalsis) in all parts of the oesophageal body, and this effect was not blocked by phentolamine. Its potent action and its minor side-effects appear to be promising for clinical use in patients with motility disorders such as the hypercontractile oesophagus.

Adult↗

Histamine receptors on submucous neurons in guinea pig colon.

Intracellular microelectrodes were used to investigate the actions of histamine in the submucous plexus of the distal colon of the guinea pig. Three effects resulted from application of histamine to submucous neurons. The first was membrane depolarization associated with increased input resistance and augmented excitability. The second was presynaptic suppression of acetylcholine release at nicotinic synapses. The third occurred during long-term application and consisted of recurrent trains of action potentials associated with periodic depolarization of membrane potential. Pharmacological analysis, with selective agonists and antagonists, suggested mediation of the first and third response by postsynaptic histamine H2 receptors. The second response was mediated by presynaptic histamine H3 receptors. These actions of histamine represent a mechanism for neuroimmune signaling between mucosal mast cells and submucous neurons in gastrointestinal type 1 hypersensitivity reactions to allergens.

Animals↗

Rhein stimulates electrogenic chloride secretion by activation of submucosal neurons in guinea pig colon.

Conventional flux chamber methods were applied to investigate the mode of action of rhein, an active metabolite derived from colonic microbial fermentation of the naturally occurring sennoside laxatives, in muscle-stripped segments of guinea pig colon. Mucosal or serosal application of rhein (10 nmol/1 to 0.5 mmol/l) resulted in a dose-dependent increase in short-circuit current (Isc) that was superimposed by irregular fluctuations in Isc. The response to electrical field stimulation was increased. The rhein-evoked increase in Isc was reduced by serosal addition of 50 mumol/l bumetanide, 1 mumol/l tetrodotoxin, 1 mumol/l atropine and 10 mumol/l piroxicam but not 100 mumol/l hexamethonium, 1 mumol/l ICS 205 930 or 10 mumol/l cimetidine. The study suggests that rhein activates chloride secretion by excitation of submucosal neurons and release of acetylcholine and endogenous prostaglandins, but not by release of histamine or serotonin.

Acetylcholine↗

[Therapy of fecal incontinence from the internal medicine viewpoint].

Despite a general belief is fecal incontinence a symptom rather than a diagnosis, usually occurring as a consequence of an underlying disease. Treatment of fecal incontinence, thus, is primarily treatment of this underlying disorder. If this causal treatment is not possible or effective, symptomatic treatment may become the goal. Furthermore, conservative management has to utilize all its possibilities before surgery may become a therapeutic option. This, however, is restricted by the limited number of conservative options available: Only a very few drugs act directly on the anal sphincter mechanism to increase the tone, all other medication may be contra-indicated. Laxatives are no treatment option at all in fecal incontinence, and the efficacy of electric stimulation of pelvic floor muscles has not been proven so far. Therefore, pelvic floor exercises have become treatment of choice, most effective with biofeedback support. This is supported by a variety of studies published in the past years.

Biofeedback, Psychology↗

[Effect of body position and food composition on esophageal motility in healthy probands].

In this study we investigated the influence of body position and bolus consistency on esophageal motility. Esophageal motility was investigated during randomized swallowing (10 women, 10 men) of liquid (5 ml water) and solid boluses (piece of apple). Esophageal motility was altered by body position and bolus consistency: Contraction amplitude, duration, percentage of multipeaked and repetitive contraction and the resting pressure of the lower sphincter were significantly reduced and the relaxation duration of the lower sphincter was significantly prolonged in sitting as compared to supine position. With a food bolus compared to swallows of water we found significantly higher values for the contraction amplitude and the percentage of repetitive contractions, for the duration and for the percentage of multipeaked contractions at some orifices and for the relaxation duration of the lower esophageal sphincter. Propagation velocity and the resting pressure of the lower esophageal sphincter were significantly reduced with the food as compared to the water bolus. The alterations of esophageal motility by body position and bolus consistency has to be taken into account in clinical manometry.

Adolescent↗

Submucosal reflexes: distension-evoked ion transport in the guinea pig distal colon.

Muscle-stripped segments of distal colon from guinea pigs were mounted in modified flux chambers to determine the effect of distension on mucosal secretion. Ion secretion was monitored as changes in short-circuit current (Isc). Distending forces were pressure gradients established by controlled reduction in liquid volume of the submucosal compartment of the chamber. Volume removal for 10 s or 5 min evoked a monophasic or biphasic increase in Isc, which returned to baseline within 5-20 min. The amplitude of the response correlated with the volume removed and was reduced by bumetanide and Cl-free solutions but not by tetraethylammonium or amiloride. Tetrodotoxin and atropine also suppressed the response. Neither the nicotinic receptor antagonist mecamylamine, the 5-hydroxytryptamine3 (5-HT3) receptor antagonist ICS 205-930, or the prostaglandin synthesis inhibitor piroxicam altered the response. Addition of prostaglandin D2 to the submucosal bath significantly enhanced the response. The results suggest that distension of the colon evokes anion secretion by activation of reflex circuits with cholinergic neurons and muscarinic synapses. Prostaglandins and 5-hydroxytryptamine acting at 5-HT3 receptors appear not to be signal substances in the reflex pathway, which evokes the secretory response to distension.

Animals↗

Electrophysiological properties of neurons in submucosal ganglia of guinea pig distal colon.

Intracellular recording methods were used in vitro to study the electrophysiological behavior of neurons in ganglia of the submucosal plexus in the distal colon of the guinea pig. The results revealed subpopulations of submucosal ganglion cells that corresponded to the AH/type 2, S/type 1, type 3, and type 4 subpopulations found elsewhere in the intestine. Electrical behavior of colonic submucosal neurons differed from the myenteric plexus of the colon, rectum, and stomach and the small intestinal submucosal plexus mainly in the relative proportions of the different subpopulations. Regional differences in this respect may be a reflection of functional specialization in the diverse regions of the alimentary canal.

Action Potentials↗