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J Tack

Publications and source records attributed to J Tack.

At least 109 records · Page 6Linked to original sources
PubMed2000

Analysis of ambulatory duodenogastroesophageal reflux monitoring.

Some methodological in vitro observations concerning bile reflux monitoring (Bilitec) suggested that Bilitec monitoring is underestimating reflux in an acid environment. Moreover, other studies showed that the area above the cutoff level of bilirubin absorbance would provide an adequate quantitative marker for reflux of duodenal contents. Our aim was to study whether correction for intraesophageal acidity and the area above cutoff during Bilitec monitoring affects the results and the correlation with pH measurement and esophageal lesions. In 84 patients (46 men; mean age 46 +/- 2.7 years) evaluated for suspected gastroesophageal reflux disease, we performed ambulatory 24-hr esophageal pH and Bilitec monitoring after an upper gastrointestinal endoscopy. We obtained total area, percent total time, and correction by computer software. The correction factor for bilirubin absorbance was based on literature data for acidified bile (0.06 for pH < 3.6; 0.21 for pH < 2.6). Endoscopy revealed esophagitis grade 1-2 (E1-2) and 3-4 (E3-4) in 23 and 16 patients, respectively. A progressive increase of mixed (acid + bile) reflux occurred with increasing severity of endoscopic lesions (E3-4 vs no esophagitis, P < 0.05). A pathologic Bilitec monitoring result was present in the same 35 patients before and after correction and the correlation between the pH measurement and percent time of bile reflux was not improved by correction for intraesophageal pH (r = 0.386 and r = 0.391; P < 0.05). The total area of bilirubin absorbance above 0.14 (abs x min) was 7.8 +/- 2.2 in patients without esophagitis, and 11.7 +/- 4.4 and 17.0 +/- 4.2 in the E1-2 and E3-4 groups, respectively (E3-4 vs no esophagitis, P < 0.05). The correlation between the Bilitec monitoring and pH measurement regarding percent (r = 0.427, P < 0.01) or area of time below 4 (r = 0.280, P < 0.05) was not improved by considering the area of bilirubin absorbance above the cutoff level. Correction for intraesophageal pH has only a minor effect on the results of ambulatory Bilitec monitoring. Taking into account the surface rather than the percent of time above the cutoff level for bilirubin absorbance does not improve the correlation of Bilitec with acid reflux and with esophageal lesions.

Adolescent↗
PubMed2000

Synaptic transmission induces transient Ca2+ concentration changes in cultured myenteric neurones.

The enteric nervous system controls most of the gastrointestinal functions. We applied confocal microscopy and the Ca2+ indicator Fluo-3 as an optical approach to study synaptic activation in cultures of myenteric neurones. The optical recording of [Ca2+]i (the intracellular Ca2+ concentration) was used to monitor activation, since [Ca2+]i is crucial in the coupling between neuronal excitation and the activation of several intracellular events. Extracellular fibre tract stimulation (2 s, 30 Hz) caused a transient [Ca2+]i rise in a subset of neurones (50%). These transients lasted for 5.2 s (n=36), with an average amplitude of 3.4 +/- 1.3 times the basal concentration. The removal of extracellular Ca2+ (n=15) or the application of 10-6 M tetrodotoxin (n=16) blocked this response. The N-type Ca2+-channel blocker omega-conotoxin (5 x 10 -7M) abolished the [Ca2+]i increase, while blockade of L-type and P/Q type Ca2+ channels had no effect. Single stimuli evoked a [Ca2+]i rise in the processes. omega-conotoxin-sensitive postsynaptic events required repetitive stimulation. Cholinergic blockade did not inhibit the [Ca2+]i rise in all neurones, suggesting that, besides acetylcholine, other neurotransmitters are involved. Optical imaging of [Ca2+]i can be used to study synaptic spread of activation in enteric neuronal circuits expressed in culture.

Action Potentials↗
PubMed2000

IL-1beta and IL-6 excite neurones and suppress cholinergic neurotransmission in the myenteric plexus of the guinea pig.

The effects of the inflammatory mediators interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) on myenteric neurones were investigated by intracellular recordings in a conventional myenteric plexus preparation of guinea pig ileum. Micropressure ejection of IL-1beta and IL-6 (10-7 mol L-1) both caused an excitatory effect in, respectively, 19% (13/70) and 7% (5/70) of the myenteric neurones. The IL-1beta-induced depolarizations were inhibited by superfusion of the IL-1beta receptor antagonist. The responses seen were tetrodotoxin-resistant, indicating a direct neuronal effect. Responses to both cytokines were seen in nitric oxide synthase-immunoreactive as well as choline acetyltransferase-immunoreactive neurones. In addition, both IL-1beta and IL-6 reversibly caused a presynaptic inhibition of acetylcholine release from cholinergic nerve terminals. Both cytokines had no effect on the slow excitatory postsynaptic potentials. Therefore, we can conclude that the inflammatory mediators IL-1beta and IL-6 can act as excitatory neuromodulators of gastrointestinal motility through direct excitatory actions on a subset of myenteric neurones and through the presynaptic inhibition of acetylcholine release.

Animals↗
PubMed2000

Influence of sumatriptan on gastric fundus tone and on the perception of gastric distension in man.

BACKGROUND: In animals, activation of 5-HT(1) like receptors causes a relaxation of the gastric fundus through the activation of intrinsic inhibitory neurones. AIMS: To investigate the effect of sumatriptan, an agonist at enteric neuronal 5-HT(1) receptors, on fasting fundus tone and sensitivity to gastric distension in man. METHODS: A gastric barostat was used to study the effect of placebo and sumatriptan, 6 mg subcutaneously, on basal fundic tone in healthy subjects. In addition, stepwise isobaric and isovolumetric gastric distensions were performed and perception was measured before and after the administration of placebo and sumatriptan. RESULTS: Placebo had no significant effects on gastric tone and on perception. Sumatriptan induced an immediate relaxation of the gastric fundus, reflected by an intragastric volume increase of 209 (39) ml (p<0.0005). After sumatriptan, intragastric pressures at the thresholds for perception or discomfort were not significantly altered. However, the intragastric volumes and the corresponding calculated wall tensions at perception and discomfort thresholds were significantly increased. CONCLUSIONS: Administration of the 5-HT(1) receptor agonist sumatriptan induces a relaxation of the gastric fundus in man, allowing larger intragastric volumes before thresholds for perception or discomfort are reached. The effects of sumatriptan on the gastric fundus may have therapeutic potential in the treatment of patients with functional dyspepsia.

Adult↗
PubMed2000

Receptor-induced Ca(2+) signaling in cultured myenteric neurons.

We studied the effect of excitatory neurotransmitters (10(-5) M) on the intracellular Ca(2+) concentration ([Ca(2+)](i)) of cultured myenteric neurons. ACh evoked a response in 48.6% of the neurons. This response consisted of a fast and a slow component, respectively mediated by nicotinic and muscarinic receptors, as revealed by specific agonists and antagonists. Substance P evoked a [Ca(2+)](i) rise in 68.2% of the neurons, which was highly dependent on Ca(2+) release from intracellular stores, since after thapsigargin (5 microM) pretreatment only 8% responded. The responses to serotonin, present in 90.7%, were completely blocked by ondansetron (10(-5) M), a 5-HT(3) receptor antagonist. Specific agonists of other serotonin receptors were not able to induce a [Ca(2+)](i) rise. Removing extracellular Ca(2+) abolished all serotonin and fast ACh responses, whereas substance P and slow ACh responses were more persistent. We conclude that ACh-induced signaling involves both nicotinic and muscarinic receptors responsible for a fast and a more delayed component, respectively. Substance P-induced signaling requires functional intracellular Ca(2+) stores, and the 5-HT(3) receptor mediates the serotonin-induced Ca(2+) signaling in cultured myenteric neurons.

Acetylcholine↗
PubMed2000

Differential Ca(2+) signaling characteristics of inhibitory and excitatory myenteric motor neurons in culture.

Physiological studies on functionally identified myenteric neurons are scarce because of technical limitations. We combined retrograde labeling, cell culturing, and fluorescent intracellular Ca(2+) concentration ([Ca(2+)](i)) signaling to study excitatory neurotransmitter responsiveness of myenteric motor neurons. 1, 1-Didodecyl-3,3,3',3'-tetramethyl indocarbocyanine (DiI) was used to label circular muscle motor neurons of the guinea pig ileum. DiI-labeled neurons were easily detectable in cultures prepared from these segments. The excitatory neurotransmitters (10(-5) M) acetylcholine, substance P, and serotonin induced a transient rise in [Ca(2+)](i) in subsets of DiI-labeled neurons (66.7, 56.5, and 84. 3%, respectively). DiI-labeled motor neurons were either inhibitory (23.8%) or excitatory (76.2%) as assessed by staining for nitric oxide synthase or choline acetyltransferase. Compared with excitatory motor neurons, significantly fewer inhibitory neurons in culture responded to acetylcholine (0 vs. 69%) and substance P (12.5 vs. 69.2%). We conclude that combining retrograde labeling and Ca(2+) imaging allows identification of differential receptor expression in functionally identified neurons in culture.

Acetylcholine↗
PubMed2000

The physiology and the pathophysiology of the gastric accommodation reflex in man.

Summarizing the previous sections, we have demonstrated that the gastric accommodation reflex in man involves the release of serotonin and the activation of a nitrergic motor neuron. We observed that almost half of the patients with functional dyspepsia have an impaired accommodation reflex, and this is associated with early satiety and weight loss. Drug-induced inhibition of the accommodation reflex is able to induce early satiety in healthy subjects. Administration of the anti-migraine drug sumatriptan, an agonist at 5-HT1P receptors on gastric myenteric neurons, causes a relaxation of the proximal stomach in man through a nitrergic pathway. Pretreatment with sumatriptan is able to restore impaired accommodation and to improve early satiety in patients with functional dyspepsia. We conclude from these data that fundus-relaxing drugs may have a therapeutic potential in functional dyspepsia, and we hypothesize that fundus-contracting drugs may have therapeutic potential in the treatment of obesity.

Adaptation, Physiological↗
PubMed1999

Neurochemical coding of myenteric neurons in the guinea-pig antrum.

Electrophysiological studies of myenteric neurons in the guinea-pig antrum suggest that different neuroactive compounds are involved in synaptic transmission. It is not known what neurotransmitters and neuropeptides are present and to what extent they colocalize. Immunohistochemical stainings were performed on whole-mount preparations of the guinea-pig antrum. Immunoreactivity for neuron-specific enolase was used as a general marker and was set at 100%. There was no overlap between cholinergic and nitrergic neurons, resulting in two separate subpopulations. The presence of choline acetyltransferase immunoreactivity was used to identify the cholinergic subset, which accounted for 56% of the cells. Immunoreactivity for nitric oxide synthase, on the other hand, was displayed in 40.7% of the neurons. Substance-P immunoreactivity was present in 37.4% of the cells and vasoactive intestinal peptide and neuropeptide Y in 21.7% and 28.6%, respectively. Small subsets of neurons had immunoreactivity for serotonin (3.9%), calretinin (6.8%) and calbindin (0.5%). Colocalization studies revealed several subgroups of neurons, containing one or more of the screened markers. Though some similarity is found in the chemical coding of the antrum compared to that of the small intestine and the corpus, remarkable differences can be seen in the occurrence of some subpopulations. Cholinergic neurons are not as predominant as in other parts of the gut, serotonin presence is doubled and some vasointestinal-peptide-positive neurons express substance P. These differences might reflect the highly specialized function of the antrum; however, the exact role of these classes remains to be established.

Animals↗
PubMed1999

Duodenogastroesophageal reflux and esophageal mucosal injury in mechanically ventilated patients.

BACKGROUND & AIMS: Esophagitis has been reported to be the most frequent cause of upper gastrointestinal bleeding in intensive care patients. The mechanisms causing esophagitis are unclear. The aim of this study was to measure esophageal acid and bile reflux and to examine the relationship between reflux and mucosal injury in mechanically ventilated patients. METHODS: Twenty-five critically ill, mechanically ventilated patients with nasogastric tubes were prospectively included for 24-hour esophageal pH and duodenogastroesophageal bile reflux studies (Bilitec 2000 system). All patients received acid-suppressive therapy for stress ulcer prophylaxis with ranitidine. On the day before the study, patients underwent esophageal endoscopy to determine the presence or absence of esophagitis. RESULTS: After approximately 5 days of mechanical ventilation, 12 patients (48%) had erosive esophagitis, 2 patients had pathological acid reflux, and 12 patients had pathological bile reflux. The presence of esophagitis was significantly associated with pathological bile reflux (P = 0.017, Fisher exact test). The severity of esophagitis was significantly correlated with the volume of gastric residual volume and with increasing times of bile reflux. The latter was significantly correlated with the number of organ failures. CONCLUSIONS: Despite acid-suppressive therapy, esophagitis is a frequent finding in critically ill patients after less than a week of mechanical ventilation. In these patients, besides mechanical irritation by the nasogastric tube, chemical injury caused by duodenogastroesophageal reflux seems to have a major role in the pathogenesis of esophageal mucosal lesions.

Acids↗
PubMed1999

Effect of sumatriptan, a 5HT1 agonist, on the frequency of transient lower esophageal sphincter relaxations and gastroesophageal reflux in healthy subjects.

OBJECTIVE: Meals increase the rate of transient lower esophageal sphincter (LES) relaxations, in part by gastric distension. The 5HT1 agonist sumatriptan reduces fasting fundic tone, prolongs the meal-induced fundic relaxation, and delays gastric emptying. We therefore hypothesized that sumatriptan might have a significant effect on the rate of postprandial transient LES relaxations and gastroesophageal reflux. We aimed to study the effect of sumatriptan on postprandial transient LES relaxations and reflux in healthy subjects. METHODS: Esophageal manometry and pH monitoring were performed in 13 healthy volunteers for 30 min before and 90 min after a semiliquid meal (790 kcal). Sumatriptan 6 mg subcutaneous (s.c.) or s.c. placebo were administered on separate days 30 min after the meal. RESULTS: Sumatriptan significantly increased postprandial LES pressure from 11.0 +/- 1.2 mm Hg to 17.6 +/- 1.2 mm Hg (p < 0.05). However, reflux events were not diminished. In the contrary, reflux was more frequent after sumatriptan than after placebo (3 [1.5-4.5]/30 min vs 2 [0-3]/30 min, p < 0.05). Transient LES relaxations were more frequent after sumatriptan, particularly in the second 30-min period after drug administration (3 [2.5-5]/30 min vs 2 [1.5-2]/30 min, p < 0.05). CONCLUSIONS: Sumatriptan prevents the natural decay in rate of transient LES relaxations that occurs after a meal and favors the occurrence of gastroesophageal reflux despite increasing LES pressure. The sustained postprandial high rate of transient LES relaxations after sumatriptan may be a consequence of a prolonged fundus relaxation and retention of meal in the proximal stomach.

Adolescent↗
PubMed1999

Role of nitric oxide in fasting gastric fundus tone and in 5-HT1 receptor-mediated relaxation of gastric fundus.

Fasting gastric fundus tone is maintained by continuous cholinergic input. 5-Hydroxytryptamine-1 (5-HT1) receptor activation decreases gastric fundus tone in humans. Whether this fundus-relaxing effect is mediated via inhibition of cholinergic input or via activation of a nitrergic pathway is unknown. The aim of the present study was to determine the effect of nitrergic inhibition on feline gastric fundus tone and on 5-HT1 receptor-mediated relaxation of the fundus. Administration of Nomega-nitro-L-arginine methyl ester (L-NAME) alone caused a significant decrease of the mean baseline volume (P < 0.005), which was restored completely by addition of L-arginine. Sumatriptan caused a dose-dependent relaxation of the gastric fundus (P < 0.0005). This relaxation was inhibited by L-NAME (P < 0.02) and was restored by prior administration of L-arginine. Buspirone did not cause any change in mean baseline volume, whereas the sumatriptan-induced relaxation was not affected by prior administration of NAN-190. Our data indicate that fasting fundus tone relies not only on continuous cholinergic input but also on continuous nitrergic input, implying that fasting fundus tone is maintained by the balance of a cholinergic and nitrergic drive. Furthermore, fundus relaxation via 5-HT1 receptor activation is mediated through activation of a nitrergic pathway.

Animals↗
PubMed1999

Microdomain arrangement of the SERCA-type Ca2+ pump (Ca2+-ATPase) in subplasmalemmal calcium stores of paramecium cells.

We localized SERCA pumps to the inner region of alveolar sac membranes, facing the cell interior, by combining ultrastructural and biochemical methods. Immunogold labeling largely predominated in the inner alveolar sac region which displayed aggregates of intramembrane particles (IMPs). On image analysis, these represented oligomeric arrangements of approximately 8-nm large IMP subunits, suggesting formation of SERCA aggregates (as known from sarcoplasmic reticulum). We found not only monomers of typical molecular size ( approximately 106 kD) but also oligomeric forms on Western blots (using anti-SERCA antibodies, also against endogenous SERCA from alveolar sacs) and on electrophoresis gelautoradiographs of 32P-labeled phosphoenzyme intermediates. Selective enrichment of SERCA-pump molecules in the inner alveolar sac membrane region may eliminate Ca2+ after centripetal spread observed during exocytosis activation, while the plasmalemmal Ca2+ pump may maintain or reestablish [Ca2+] in the narrow subplasmalemmal space between the outer alveolar sac membrane region and the cell membrane. We show for the first time the microzonal arrangement of SERCA molecules in a Ca2+ store of a secretory system, an intensely discussed issue in stimulus-secretion coupling research.

Animals↗
PubMed1998

Role of impaired gastric accommodation to a meal in functional dyspepsia.

BACKGROUND & AIMS: Impaired accommodation of the proximal stomach to a meal has been reported in functional dyspepsia, but its relevance to symptoms is unclear. The aim of this study was to test the hypothesis that impaired gastric accommodation causes early satiety. METHODS: A gastric barostat was used to study postprandial fundus relaxation in 35 healthy subjects and 40 patients with functional dyspepsia. Gastric emptying, Helicobacter pylori status, sensitivity to gastric distention, and a dyspepsia symptom score were obtained from all patients. In addition, the effect of sumatriptan, a fundus-relaxing 5-hydroxytryptamine1 agonist, on gastric accommodation and on early satiety in dyspeptic patients was studied. RESULTS: Impaired gastric accommodation to a meal was found in 40% of the patients. In univariate analysis, this was associated with early satiety and weight loss but not with hypersensitivity to gastric distention, presence of H. pylori, or delayed gastric emptying. In a multivariate analysis, only early satiety was associated with impaired gastric accommodation. Sumatriptan restored gastric accommodation, thereby significantly improving meal-induced satiety. CONCLUSIONS: Impaired relaxation of the proximal stomach to a meal is present in a high proportion of patients with functional dyspepsia. It is associated with symptoms of early satiety. Restoring gastric accommodation with a fundus-relaxing drug improves early satiety.

Adult↗