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Biomedical subjects

P Thor

Publications and source records attributed to P Thor.

At least 19 recordsLinked to original sources

Influence of cyclooxygenase inhibitors on the central histaminergic stimulations of hypothalamic - pituitary - adrenal axis.

Brain histamine participates in central regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Endogenous prostaglandins modulate signal transduction of different neurotransmitters involved in activation of HPA axis. In the present experiment we investigated whether endogenous prostaglandins are involved in the stimulation of ACTH and corticosterone secretion by histaminergic systems in the rat brain. Histamine (50 microg), histamine-trifluoromethyl-toluidine derivative (HTMT, 75microg) a selective and potent H(1)-receptor agonist, and amthamine (50 microg) a H(2)-receptor agonist given intracerebroventricularly (i.c.v.) to non-anesthetized rats considerably increased ACTH and corticosterone secretion 1h after administration. A non-selective cyclooxygenase inhibitor indomethacin (2 mg/kg i.p. or 10 microg i.c.v.), piroxicam (0.02 and 0.2 microg i.c.v.) a more potent antagonist of constitutive cyclooxygenase (COX-1) and compound NS-398 (0.1 and 1.0 microg i.c.v.), a selective inhibitor of inducible cyclooxygenase (COX-2) were given 15 min before histamine and histamine receptor agonists. One hour after the last injection trunk blood from decapitated rats was collected for hormones determination. The histamine-induced ACTH and corticosterone secretion was significantly diminished by piroxicam and was not markedly altered by indomethacin and compound NS-398. The HTMT-elicited increase in ACTH and corticosterone secretion was significantly prevented by indomethacin and was not affected by piroxicam or compound NS-398. The amthamine-evoked increase in ACTH and corticosterone secretion was not markedly influenced by any cyclooxygenase blocker applied in the present experiment. These results indicate that the histamine H(1)-receptor transmitted central stimulation of the HPA axis is considerably mediated by prostaglandins generated by consititutive cyclooxygenase, whereas stimulation transmitted via H(2)-receptor does not significantly depend on endogenous prostaglandins mediation.

Adrenocorticotropic Hormone↗

The cybergut. An experimental study on permanent microchip neuromodulation for control of gut function.

UNLABELLED: Acute electrical stimulation of vagal nerve changes gut motility, secretion as well as absorption, and it may have effect on food intake and satiety regulation. The aim of the study was to evaluate the effect of permanent microchip mediated neuromodulation (McNm) of vagal afferent activity on GI function and body mass in the experimental model. MATERIAL AND METHODS: Two-steps study was performed. In the first step (evaluation of food intake) 16 rabbits were divided in two groups, 8 animals each. Group A was subjected to microchip mediated neuromodulation (McNm), and control group B was sham operated. In both groups laparotomy and vagal exploration were performed. In the second step pathomechanism of Mc action was analysed in fourteen Wistar rats divided in two groups (C and D), 7 animals each. Group C was subjected to Mc implantation and gastrostomy placement and group D (controls) to gastrostomy placement alone. RESULTS: Food intake and body mass significantly decreased in group A after Mc implantation compared with the preoperative period and control group B. No differences were found in the frequency of gastric contractions between groups C and D, however, their amplitude was significantly stronger in group C. Neuromodulation had significant effect on BAO without changes in MAO levels. CONCLUSIONS: Low frequency permanent vagal neuromodulation affects gastric function and influences food intake in the experimental model.

Afferent Pathways↗

The influence of cholecystokinin on gastric myoelectrical activity in duodenal ulcer following Helicobacter pylori eradication--an electrogastrographic study.

Cholecystokinin (CCK) plays an important role in the regulation of postprandial gastric motor activity which was found to be abnormal in duodenal ulcer patients. This study was designed to compare the influence of CCK on gastric myoelectrical function in duodenal ulcer patients and healthy controls. Fifteen patients with active duodenal ulcer and Helicobacterpylori (H. pylori) infection and 15 healthy controls were included into this study. Electrogastrography (EGG) was performed before and 4 weeks after the eradication of H. pylori in ulcer patients and in healthy controls. We compared EGG parameters in the fasting and postprandial period and during intravenous infusion of caerulein, an analog of CCK with or without addition of loxiglumide, a specific CCK-1 receptor antagonist. The amplitude of fasting EGG in duodenal ulcer patients was similar to that in control subjects and was not affected by H. pylori eradication. In contrast, the amplitude of postprandial EGG was markedly increased in duodenal ulcer patients when compared to that in healthy controls and it was significantly reduced following the eradication of H. pylori. The blockade of CCK-1 receptors with loxiglumide in healthy controls or H. pylori eradicated ulcer patients significantly enhanced postprandial EGG amplitude almost to the level observed in the infected duodenal ulcer patients, but failed to affect this amplitude in ulcer patients. Exogenous caerulein, an analog of CCK, failed to affect EGG amplitude in duodenal ulcer patients with H. pylori infection, but it reduced significantly EGG amplitude in these patients after H. pylori eradication and in control subjects. This inhibitory effect of caerulein in H. pylori negative ulcer patients and healthy controls was abolished by the addition of loxiglumide. Ulcer patients showed significant dysrhythmia with tachygastria up to 20% of the recording time both under basal conditions and postprandially and H. pylori eradication was followed by a significant decrease in tachygastria to about 5%, the value being similar to that in healthy controls. We conclude that the amplitude and frequency of gastric myoelectrical activity are enhanced in duodenal ulcer patients and impaired in response to CCK but these changes can be normalized by successful H. pylori eradication.

Adult↗

Effect of different cycling frequencies during incremental exercise on the venous plasma potassium concentration in humans.

The effect of different muscle shortening velocity was studied during cycling at a pedalling rate of 60 and 120 rev.min(-1) on the [K+]v in humans. Twenty-one healthy young men aged 22.5+/-2.2 years, body mass 72.7+/-6.4 kg, VO2 max 3.720+/-0.426 l. min(-1), performed an incremental exercise test until exhaustion. The power output increased by 30 W every 3 min, using an electrically controlled ergometer Ergoline 800 S (see Zoladz et al. J. Physiol. 488: 211-217, 1995). The test was performed twice: once at a cycling frequency of 60 rev.min(-1) (test A) and a few days later at a frequency of 120 rev. min(-1) (test B). At rest and at the end of each step (i.e. the last 15 s) antecubital venous blood samples for [K+]p were taken. Gas exchange variables were measured continuously (breath-by-breath) using Oxycon Champion Jaeger. The pre-exercise [K+]v in both tests was not significantly different amounting to 4.24+/-0.36 mmol.l(-1) in test A, and 4.37+/-0.45 mmol.l(-1) in test B. However, the [K+]p during cycling at 120 rev. min(-1) was significantly higher (p<0.001, ANOVA for repeated measurements) at each power output when compared to cycling at 60 rev.min(-1). The maximal power output reached 293+/-31 W in test A which was significantly higher (p<0.001) than in test B, which amounted to 223+/-40 W. The VO2max values in both tests reached 3.720+/-0.426 l. min(-1) vs 3.777+/-0.514 l. min(-1). These values were not significantly different. When the [K+]v was measured during incremental cycling exercise, a linear increase in [K+]v was observed in both tests. However, a significant (p<0.05) upward shift in the [K+]v and a % VO2max relationship was detected during cycling at 120 rev.min(-1). The [K+]v measured at the VO2max level in tests A and B amounted to 6.00+/-0.47 mmol.l-1 vs 6.04+/-0.41 mmol.l-1, respectively. This difference was not significant. It may thus be concluded that: a) generation of the same external mechanical power output during cycling at a pedalling rate of 120 rev.min(-1) causes significantly higher [K+]v changes than when cycling at 60 rev.min(-1), b) the increase of venous plasma potassium concentration during dynamic incremental exercise is linearly related to the metabolic cost of work expressed by the percentage of VO2max (increase as reported previously by Vollestad et al. J. Physiol. 475: 359-368, 1994), c) there is a tendency towards upward up shift in the [K+]v and % VO2max relation during cycling at 120 rev.min(-1) when compared to cycling at 60 rev.min(-1).

Adult↗

Reversible autonomic dysfunction in hyperthyroid patients affects gastric myoelectrical activity and emptying.

The autonomic nervous system (ANS) function in hyperthyroidism has been so far investigated mainly from the cardiovascular point of view. The aim of this study is to show that the ANS dysfunction in hyperthyroidism is also expressed in gastric myoelectrical activity disturbances and gastric emptying disorders and to search for a correlation between the severity of clinical manifestation and free thyroid hormone levels and the degree of the ANS dysfunction. The analyzed group included 50 recently diagnosed patients with hyperthyroidism who were examined twice: before and after 3 months of thyrostatic treatment. Results were compared with those of a sex-, age- and BMI-matched control group of 50 healthy volunteers. The study included: heart rate variability analysis in time and frequency domain, at rest and during a deep-breathing test, surface electrogastrography in preprandial and postprandial periods measured simultaneously with the ultrasound assessment of gastric emptying time by Bolondi method. In patients with hyperthyroidism in comparison with the control group, the following significant differences were observed: a sharp reduction of the high-frequency component and a decrease of heart rate variability, a high incidence of dysrhythmia with dominant bradyarrhythmia, and a delay of gastric emptying. The degree of disorders related to the degree of clinical manifestation of hyperthyroidism's symptoms and free triiodothyronine serum concentration both. All the disorders were functional and disappeared in a stable euthyroidism. To conclude, the ANS dysfunction in hyperthyroidism results not only in withdrawal of vagal inhibitory effect on sinoatrial node, but in impaired mutual neuro-hormonal regulation (decrease of vagal influence) of gastric myoelectrical activity followed by delay of gastric emptying.

Adult↗

Relationship between specific dynamic action and protein deposition in calanoid copepods.

The link between specific dynamic action (SDA) and protein deposition was investigated in copepodites stage V of two calanoid copepod species, the neritic Acartia tonsa and the oceanic Calanus finmarchicus. This was done by measuring respiration before, during, and after a specific feeding period and measuring the incorporation of carbon into proteins. These were also measured on individuals incubated with cycloheximide, an antibiotic that inhibits protein synthesis. The cycloheximide treatment significantly diminished the magnitude of SDA in both A. tonsa and C. finmarchicus, and inhibited carbon incorporation into protein in both species. This provides evidence that the rate at which protein deposition takes place greatly affects the magnitude of SDA. The specific respiration rates of both starving and feeding copepods were generally higher in A. tonsa than in C. finmarchicus. This influenced SDA, the magnitude of SDA normalised to an 8 h feeding period being threefold higher in A. tonsa (78.7+/-25.7 nlO(2) µgC(-1)) than in C. finmarchicus (27.5+/-11.6 nlO(2) µgC(-1)). This difference may arise due to differences in energy allocation in the organisms of the copepodite V stage of the two species. In this stage C. finmarchicus deposits large quantities of storage lipids, predominately wax esters, whereas A. tonsa deposits proteins during somatic growth.

Journal Article↗

[Circadian rhythm of autonomic heart activity in patients with primary essential hypertension treated with angiotensin converting enzyme inhibitor].

UNLABELLED: Although the immediate effects of angiotensin converting enzyme inhibitors (ACEI) on cardiac autonomic innervation have been extensively studied, little is known about circadian rhythm of heart rate variability (HRV) in these patients. The purpose of the present study was to investigate circadian changes of the autonomic activity in patients with essential hypertension treated with ACEI, which may play some role in the pathogenesis of hypertension. We studied 10 middle age patients with essential hypertension (treated with ACEI--enarenal at least 1 yr.) and 10 age, gender matched control subjects. Heart rate variability (HRV) was calculated from the 24-hr ambulatory electrocardiograms by the Fourier transformation. Power spectra were quantified at 0.003-0.04 Hz--very low frequency power (VLF), 0.04-0.15 Hz--low frequency power (LF) and 0.15-0.40 Hz--high frequency power (HF). The HF component and the ratio LF to HF were used as indices of the parasympathetic activity and balance between sympathetic and parasympathetic activities. RESULTS: The circadian rhythms of the LF, HF and LF/HF ratio differed significantly. In control group, LF, HF increased but LF/HF decreased (p < 0.05) at night, in hypertensive patients LF, HF increase was attenuated at night but LF/HF increased (p < 0.05). In control subjects when compared to hypertensive patients power spectrum HF was doubled at night. CONCLUSION: These findings suggest that in hypertension primary cardiac autonomic dysfunction might contribute to altered circadian rhythm leading to the development of cardiovascular diseases despite long term normalisation of high blood pressure.

Adult↗

Involvement of nitric oxide in central histaminergic stimulation of the hypothalamic-pituitary-adrenal axis.

Brain histamine participates in central regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Endogenous nitric oxide (NO) modulates signal transduction of some neurotransmitters involved in activation of the HPA axis. In the present study we investigated whether endogenous NO and histaminergic systems in the rat brain interact in their regulation of ACTH and corticosterone secretion. Histamine (50 microg), histamine-trifluoromethyl-toluidide derivative (HTMT, 75 microg) a selective and potent H1-receptor agonist, and amthamine (75 microg) a H2-receptor agonist given intracerebroventricularly (i.c.v.) considerably increased ACTH and corticosterone secretion 1 h after administration. A potent and competitive inhibitor of rat brain neuronal NO synthase, (NOS), 7-nitroindazole (7-NI), given i.p. 15 min before histamine moderately increased the histamine-induced ACTH secretion and did not substantially alter the histamine-induced corticosterone secretion. Pretreatment with 7-NI totally abolished the HTMT-induced increase in ACTH and corticosterone secretion. The amthamine-evoked rise in ACTH secretion was moderately diminished and the amthamine-induced corticosterone secretion was not substantially altered by preatreatment with 7-NI. These results suggest that the histamine H -receptor transmited central stimulation of the HPA axis is considerably mediated by endogenous NO, whereas stimulation by histamine and via H2-receptor does not significantly depend on endogenous NO mediation.

Adrenocorticotropic Hormone↗

Myoelectric bowel activity in ischemia/reperfusion damage. Role of sensory neurons.

The present knowledge indicates that afferent sensory neurons (C-fibres) play an important role in the relationship between intestinal myoelectric activity (IMA) and blood flow (LDBF). The aim of this study was to evaluate the role of C-fibers in myoelectric activity of small intestine during its ischemia and reperfusion. A neurotoxin-capsaicin (CAP) was used to induce functional ablation of afferent sensory neurons. Experiments were performed on 6 groups of anesthetized rats. In the I, II, III group of rats IMA and LDBF were recorded during 100% ischemia induced by AMA 15, 30 and 60 min total occlusion and during 60 min reperfusion period. In group V and VI, IMA and LDBF were registered after intrajejunal placement of 1% CAP. In group IV we measured effects of intraluminal instillation of CAP alone. Intraluminal placement of CAP induced an early increase in slow wave amplitude SWA and slow wave frequency SWF by 35+/-11% and 19+/-10% (p<0.05) with the subsequent decrease in both by 25+/-6 and 24+/-8% (p<0.05) respectively. Short 15 min lasting ischemia induced by 100% occlusion of AMA evoked only a slight increase of SWA. During reperfusion period SWA and SWF returned to the baseline values after 15 min. Total 30 min occlusion decreased SWA and SWF by 25+/-9 and 24+/-6% (p<0.05) respectively. During reperfusion period recovery of IMA parameters to preocclusion values were slower. Intestinal hyperemia was smaller than in previous group. After 60 min lasting intestinal ischemia SWA and SWF were decreased by 58+/-7 and 40+/-6% (p<0.01) respectively. There was no return of IMA parameters to control values. These data demonstrated that intestinal ischemia induces typical changes in the bowel myoelectric activity. These changes possess their own electrical characteristics which can be used in clinical practice for evaluation of the degree ischemically-induced intestinal injury. Capsaicin pretreatment significantly decreased SWA and SWF and LDBF in comparison with those observed in group II and III during 30 and 60 min occlusion and reperfusion period. We conclude that afferent neurons C activated during mesenteric ischemia/reperfusion play an important role in protecting ischemic bowel viability.

Animals↗

[Mechanism of action of neurotensin on microcirculation, metabolism and motility of the small intestine].

The aim of this study was to investigate the influence of neurotensin on total microcirculatory blood flow, oxygen consumption, myoelectric activity and motility of the small bowel. The attempts were made to evaluate the role of L-Arginine, NO-system in the mechanism of action of this peptide on microcirculation, metabolism and motor-activity of the intestine. The experiments were performed in two experimental models--dogs and rats. In Vetbutal anesthetised animals the systemic arterial pressure, superior mesenteric artery blood flow, microcirculatory blood flow and myoelectric activity of the small bowel were continuously monitored. In experiments with dogs effective capillary index, arterio-venous oxygen difference and oxygen consumption were analysed. Neurotensin administered intraarterially caused a dose depended increase in total and microcirculatory blood flow in the small bowel in both groups of animals. The experiment with dogs showed the rise of effective capillary index and intestinal oxygen consumption. Administration of neurotensin changed the profile of myoelectric activity of the small bowel similar to that of postprandial hyperaemia. Inhibition of NO-synthase by the intravenous administration of L-NNA reduced significantly the amplitude of neurotensin hyperaemia. Pretreatment with L-Arginine, the substrate of NO-synthase reversed the hemodynamic, but not motility effects of neurotensin. The results presented proved the role of the L-Arginine-NO in circulatory mechanism, but not motility effects of neurotensin.

Animals↗

[Evaluation of autonomic nervous system function with heart rate variability analysis in patients with hyperthyroidism and during euthyroidism after pharmacologic and surgical treatment].

The aim of the present study was both to estimate autonomic nervous system (ANS) function in patients with hyperthyroidism by the heart rate variability (HRV) analysis and to evaluate the impact of pharmacological and surgical treatment on the ANS function. Analysis of the HRV underwent 10 female patients in course of thyreotoxicosis and after reaching full clinical and biochemical euthyroidism, after pharmacological therapy and in month after surgical treatment. The 10 minutes records at rest, in horizontal position were evaluated. The HRV parameters like mean of the heart rate, mean of RR intervals, standard deviation of all normal RR intervals (SDNN), range of the heart rate variability, low frequency (LF), high frequency (HF) components of the heart rate power spectral density and LF/HF ratio were assessed. The results were compared to those obtained from 10 age-, sex-, and body mass index-matched control subjects. The statistical significance (p < 0.05) was found in reduction of range of RR intervals, in increase of LF/HF ratio and in decrease of SDNN in hyperthyroidism in comparison to the control group (151.6/346.8 ms; 2.4/0.74; 24.4/57.2 ms2). In course of pharmacological euthyroidism there were statistically significant (p < 0.05) increase of range of RR intervals, reduction of LF/HF ratio and increase of SDNN in comparison to hyperthyroidism (270/151.6 ms; 0.995/2.4; 39/24.4 ms2). In euthyroidism after surgical treatment all the above parameters kept the similar levels as in pharmacological euthyroidism (no statistical significance for p < 0.05). On the base of the outcomes it was considered that in hyperthyroid patients there is advantage of sympathetic part of ANS over parasympathetic one which is due to sharp reduction of parasympathetic system activity. Pharmacological therapy with thyreostatics normalises balance of ANS to the level of the control group and after surgical treatment the balance keeps the same. Moreover, in the estimation of ANS as important as LF/HF ratio is the mean range of RR intervals.

Adult↗

[Autonomic nervous system dysfunction in Parkinson's disease evaluated by the heart rhythm variability test].

It is well recognized that autonomic dysfunction are common in Parkinson's disease (PD). Fourteen patients with early PD and 8 patients with advanced PD aged from 38-71 were investigated. Heart rate variability at rest differ significantly between patients with advanced PD and age-matched controls. Cardiovascular autonomic dysfunction in PD mainly affects parasympathetic but also sympathetic system, and occurs only in advanced cases. Heart rate variability is a useful non-invasive test to assess autonomic dysfunction in PD.

Adult↗

Endogenous nitric oxide in the control of esophageal motility in humans.

Recent animal studies have suggested that nitric oxide (NO) plays an important role in the regulation of esophageal motility, being partly responsible for latency period and latency gradient between the onset of a swallow and contractions of esophageal circular smooth muscles. The aim of this study was to evaluate whether endogenous NO is responsible for physiological timing of forthcoming contractions in the human esophageal body after swallowing. Eight male volunteers (age 21-25 years, weight 67-82 kg) were involved in this placebo controlled study on the effects of increasing doses of the NO synthase blocker, NG-monomethyl-L-arginine (L-NMMA 1.0-4.0 mumol/min i.v.), and/or L-arginine (L-arg) (30 mumol/kg-min i.v.) on the peristalsis of esophageal body in response to wet swallows (5 ml of water) and lower esophageal sphincter (LES) resting pressure. The esophageal motor activity was determined manometrically using 3-channel electronic catheter. Additionally, during all examinations arterial blood pressure (BP) was measured every 5 min. L-NMMA resulted in a significant and dose-dependent reduction in the latency period between swallows and the onset of contractions which was most pronounced in the distal esophagus (control: 7.07 +/- 0.74 s vs. L-NMMA 4.0 mumol/min: 5.87 +/- 0.57 s), and this effect was partially reversed after addition of L-arg to the L-NMMA infusion (6.91 +/- 0.62 s). L-NMMA infusion significantly reduced the duration of contractions and increased the velocity of onset propagation but did not change the amplitude of contractions and again, these effects were reversed during simultaneous infusion of L-arg. The resting tone of LES increased significantly during infusion of L-NMMA and these effects were reversed by addition of L-arg. The mean BP significantly increased during infusion of L-NMMA (control 97.0 +/- 5.7 vs. L-NMMA 4.0 mumol/min: 116.4 +/- 3.1 mm Hg) and this was also reversed by L-arg. We conclude that in humans endogenous NO is involved, at least in part, in the physiological regulation of motility patterns of the distal esophageal body and LES.

Adult↗

[Electromyographic and histologic evaluation of intestinal viability].

Myoelectrical small bowel activity was measured intraoperatively with two serosal electrodes in two groups of patients. 16 patients operated electively for other indications than bowel ischaemia and 10 with small bowel ileus with symptoms of ischaemia. In later cases necrotic bowel was resected. Resected ischaemic bowel was submitted to histological examination and changes in intramural neurones were assessed. Areas of mild, moderate and severe ischaemia were compared to unchanged bowel. Both amplitude and frequency of slow waves in ischaemic bowel was markedly diminished corresponding well with changes in bowel histology. Intraoperative measurements of intestine myoelectrical activity might help a surgeon to estimate a bowel viability.

Aged↗

Dysfunction in gastric myoelectric and motor activity in Helicobacter pylori positive gastritis patients with non-ulcer dyspesia.

Helicobacter pylori (Hp) infection has been shown to affect gastric acid secretion and the somatostatin-gastrin ratio but its effects on gastric motility have not been evaluated. This study was carried out in 12 patients (10 males and 2 females, mean age 33 +/- 6 yrs) who underwent endoscopy and Campylobacter-like Organism (CLO)-test. All patients were found initially to be Hp positive according to CLO-test. Gastric emptying was evaluated by measuring antral diameter with ultrasonography (Hitachi EUB 240) in fasted and fed patients. Electrogastrography (EGG) with antral manometry were done 5 h before and 4 h after a meal before the therapy and one month after the eradication with triple therapy (lanzoprazole 30 mg daily- 2 x 250 mg clarithromycin 500 mg t.i.d.-3 x 500 mg and metronidazole 500 mg b.i.d.-2 x 500 mg). In Hp positive patients before the triple therapy the mean fasted antral diameter was 4.3 cm2, initial EGG showed significant dysrhythmia of electrical control activity (ECA) with tachygastria up to 25% of recording time in 9 of 12 Hp positive patients without normal increase of the power of signal in any of tested subjects. In 7 Hp positive fasted antral manometry failed to exhibit gastric phases III of the migrating motor complex (MMC). Hp eradication was accomplished in 10 of 12 examined patients and this was followed by a decrease in tachygastria to 3 cpm rhythm with an increase of the ECA power after meal. Phase III of MMC was observed again in 7 Hp negative patients with a decrease of fasted antral diameter (p < 0.05). Fasted and fed antral motility pattern increased after eradication. Two patients remained Hp positive after standard therapy. We conclude that most symptomatic non ulcer dyspeptic Hp positive patients show changes in ECA and antral hypomotility that are associated with Hp infections.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Effects of nitric oxide on antral motility and gastric emptying in humans.

OBJECTIVE: It has been suggested that nitric oxide is a nonadrenergic-noncholinergic (NANC) inhibitory neurotransmitter released by the nerves in the gastrointestinal tract. We studied the influence of nitric oxide on gastric emptying and antral motility using glyceryl trinitrate (GTN), a donor of nitric oxide and L-arginine as the substrate of nitric oxide synthase. DESIGN: Six male volunteers (aged 21-24 years) participated in this placebo-controlled, double-blind study. METHODS: We investigated the effects of 0.8 mg sublingual GTN, 300 mg/kg/h intravenous L-arginine or placebo on meal-stimulated antral motility and gastric emptying on four separate occasions. After an overnight fast, a 500 ml standard liquid meal was ingested and the gastric emptying rate assessed by ultrasound. The changes in antral cross-sectional areas were measured by ultrasonography and the antral motor activity was determined simultaneously using a multilumen perfused catheter. Blood samples were taken from fasted and fed patients before and after the administration of GTN, L-arginine or placebo to determine plasma glucagon and somatostatin levels. RESULTS: GTN at a sublingual dose of 0.8 mg and 300 mg/kg/h intravenous L-arginine significantly (P < 0.01) prolonged gastric emptying half-time, averaging 56 +/- 12 and 38 +/- 8 min, respectively, compared with the placebo control value (28 +/- 7 min). The antral motor activity, calculated as the motility index (number of contractions x mmHg/min) significantly decreased in both test series, i.e., after GTN from 375.5 +/- 185.1 (control) to 104.4 +/- 55.7 (P < 0.01) and after L-arginine from 401 +/- 76 (control) to 285 +/- 57 (P < 0.05). L-arginine given intravenously at a dose of 300 mg/kg/h significantly increased plasma glucagon and somatostatin in fasted patients and increased postprandially released glucagon without affecting postprandial plasma somatostatin levels. GTN did not affect plasma hormone levels. CONCLUSIONS: Our results indicate that (1) exogenous nitric oxide inhibits gastric emptying and antral motor activity, which could be useful in the treatment of patients with functional disturbances of gastric motility and emptying; and (2) the reduction in gastric emptying and antral motility observed after the administration of L-arginine results from changes in plasma enterohormone release rather than from the enhanced formation of endogenous nitric oxide.

Adult↗

Role of cholecystokinin in the control of gastric emptying and secretory response to a fatty meal in normal subjects and duodenal ulcer patients.

BACKGROUND: Exogenous cholecystokinin (CCK) is known to affect gastric motor and secretory activities, but its physiologic role in the control of gastric functions is unknown. METHODS: In this study involving 10 young healthy subjects and 10 duodenal ulcer (DU) patients, 500 ml of a standard meal without or with addition of 15% soybean oil was given, and the gastric emptying rate and the pH profile and plasma levels of gastrin, CCK, pancreatic polypeptide (PP), and somatostatin were determined in separate tests with placebo or with antagonism of type-A CCK receptors (loxiglumide, 1200 mg orally). RESULTS: In healthy controls and DU patients the emptying half-time was 44 and 34 min, respectively, and the addition of oil prolonged the emptying by about 50%. Pretreatment with loxiglumide significantly reduced fat-induced retardation of gastric emptying in both healthy controls and DU patients. A standard meal in healthy subjects resulted in an immediate rise in median gastric pH to about 6.0, and this was followed by gradual decrease within about 3 h to premeal values of about 2.0. After the meal, plasma gastrin rose by 57%, CCK by 177%, PP by 100%, and somatostatin by 39%. Addition of fat significantly attenuated and prolonged the pH decrease after the meal while reducing the increment in plasma gastrin and enhancing plasma CCK and PP levels. Loxiglumide significantly reduced the median postprandial pH (from control 4.8 to 2.5) and reversed the changes in the pH profile caused by the addition of fat. The increments in plasma gastrin and CCK were markedly augmented, whereas those of somatostatin and PP were significantly attenuated. DU patients showed lower postprandial pH (3.0) in tests with or without fat and higher increments in plasma gastrin. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin in DU patients. CONCLUSIONS: These results indicate that endogenous CCK released by a fatty meal delays gastric emptying and inhibits gastric acid and plasma gastrin responses in healthy subjects, but in DU patients the inhibitory effect of CCK is less pronounced, suggesting a defect in the action of this hormone on gastrin release and gastric acid secretion.

Adult↗