IGF-I and IGFBP-3 during continuous and interval exercise.

The purpose of this research was to compare changes in circulating levels of total IGF-I and IGFBP-3 during continuous, moderate-intensity exercise (CE) and high-intensity interval exercise (IE) of equal duration. Ten healthy males completed 2 exercise sessions and a resting control session (R) in random order. The CE was 20 minutes of cycling at 60 - 65 % of V.O(2max). During IE, subjects cycled at 80 - 85 % of V.O(2max) for 1 minute followed by 40 seconds of active recovery, with the cycle repeated for a total of 20 minutes. In each session blood samples were drawn at - 10, 0, 5, 10, 20 and 30 minutes. Both IGF-I and IGFBP-3 increased during exercise (p < 0.05) and repeated measures ANOVA revealed a significant effect for session (IE, CE > R, p < 0.05). Area under the curve (AUC) analyses showed no difference in IGF-I between sessions, however, the IGFBP-3 AUC was significantly greater during IE than R (p < 0.05). These results suggest interval and continuous exercise will result in similar changes in circulating IGF-I and IGFBP-3. This could be beneficial to individuals who can exercise longer and at a higher intensity in intervals than would be possible using a continuous protocol.

Many parallel losses of infA from chloroplast DNA during angiosperm evolution with multiple independent transfers to the nucleus.

We used DNA sequencing and gel blot surveys to assess the integrity of the chloroplast gene infA, which codes for translation initiation factor 1, in >300 diverse angiosperms. Whereas most angiosperms appear to contain an intact chloroplast infA gene, the gene has repeatedly become defunct in approximately 24 separate lineages of angiosperms, including almost all rosid species. In four species in which chloroplast infA is defunct, transferred and expressed copies of the gene were found in the nucleus, complete with putative chloroplast transit peptide sequences. The transit peptide sequences of the nuclear infA genes from soybean and Arabidopsis were shown to be functional by their ability to target green fluorescent protein to chloroplasts in vivo. Phylogenetic analysis of infA sequences and assessment of transit peptide homology indicate that the four nuclear infA genes are probably derived from four independent gene transfers from chloroplast to nuclear DNA during angiosperm evolution. Considering this and the many separate losses of infA from chloroplast DNA, the gene has probably been transferred many more times, making infA by far the most mobile chloroplast gene known in plants.

Evidence for a lipid specific effect in nutrient induced human proximal gastric relaxation.

BACKGROUND/AIM: The presence of lipid in the upper gut is able to modify gastrointestinal motor performance, but its influence on the relaxation of the human stomach, which is known to modify gastric emptying, remains incompletely understood. The relaxation of the proximal stomach in response to various lipid concentrations was therefore studied in healthy volunteers. Since the observed effects could be mediated through osmolality or energy sensitive pathways, the effects of equicaloric and equiosmolar non-lipid solutions were also determined. METHODS: The tone of the proximal stomach was measured during stepwise inflation of a non-compliant bag sited in the proximal stomach, both before and after a test meal was delivered intragastrically. Iso-osmolar lipid emulsions were diluted in iso-osmolar saline at concentrations of 1.25, 2.5, 5, 10, and 20%. NaCl solutions at osmolalities of 300, 600, 1200 and 2400 mmol/kg and glucose solutions of 836 and 3344 kJ/l were also given. RESULTS: All lipid meals of 2.5% or greater concentration induced a reduction in gastric tone in a non-dose-dependent manner, responses to 5% lipid (median (range) 74 (62-92)%) being similar to those to 20% lipid (80 (55-83)%; p > 0.05). No relaxation was elicited by isocaloric glucose. NaCl only consistently caused relaxation at 2400 mmol/kg. CONCLUSION: Lipid meals reduce human proximal gastric tone by a lipid specific mechanism, independently of their energy content or osmolality.

Relations between upper abdominal symptoms and gastric distension abnormalities in dysmotility like functional dyspepsia and after vagotomy.

Postprandial bloating and fullness are commonly found both in dysmotility like functional dyspepsia, and after vagotomy but the relation between gastric accommodation and symptom production has not been investigated. Intragastric pressure levels and symptoms developed during controlled distension of the gastric fundus were recorded in nine patients with functional dyspepsia, in seven patients after truncal vagotomy, and in 11 healthy volunteers. The procedure was repeated after ingestion of a liquid nutrient meal (250 ml; 250 kcal). Gastric tone, expressed as the average value of pressure over the distension period was lower in controls (median: 11.3 mm Hg) than in either the dyspeptic patients (median: 16.48 mm Hg) or postvagotomy patients (median: 19.12 mm Hg) (p < 0.05). Meal ingestion reduced gastric tone in controls, but no significant change occurred in either the dyspepsia or the postvagotomy patients. Volumes at which discomfort was elicited by distension during fasting were lower both in dyspeptic patients (median: 210 ml) and in postvagotomy patients (median: 180 ml) than in healthy volunteers (median: 660 ml) (p < 0.05). Discomfort thresholds were unaffected by meal ingestion. These results suggest that a disturbance of gastric relaxation may be related to symptom development in dysmotility like functional dyspepsia, while similarities between dyspeptic patients and postvagotomy patients suggest that the impaired gastric accommodation in functional dyspepsia may be due to an underlying vagal defect.

Beta adrenergic modulation of human upper intestinal propulsive forces.

beta Adrenoceptor blockade is known to accelerate transit through the small intestine without changing either the number or pattern of intestinal contractions. This study therefore tested the hypothesis that an increase in intraluminal aboral propulsive force may contribute to this transit acceleration. Twenty paired studies were performed, in 10 healthy volunteers, after oral administration of either 100 mg atenolol (a selective beta 1 antagonist) or matched dummy tablets according to a double blind, randomised protocol. The frequency of occurrence of, and the propulsive force exerted by, traction events related to intestinal contractions were measured, using a combined traction force detector and manometry assembly. After atenolol, a consistent increase in the force generated per traction event was noted, both for propagating contractions mean (SEM) (12.0 (1.8) g v control 5.9 (0.07) g; p < 0.05) and for stationary (11.6 (1.4) g v control 7.0 (0.7) g; p < 0.05). In contrast no change in the number of traction events was noted (control v atenolol = 1.6 (0.3) v 1.64 (0.4) per min for propagating and 0.7 (0.1) v 0.85 (0.16) per min for stationary contraction; p > 0.05). beta Adrenoceptor blockade thus increases the propulsive force generated by intestinal contractions, possibly by removing a sympathetic neural inhibition of intestinal tone.

Human small intestinal contractions and aboral traction forces during fasting and after feeding.

Small intestinal intraluminal pressure activity and aboral traction forces were explored in 19 healthy volunteers using a combined manometry and traction force detecting assembly sited in the upper small intestine. Each aboral traction event was classified as being associated with either a propagating or a stationary contraction and its force measured. During phase I no contractions or traction events were seen. During phase II, traction events related to propagating contractions mean (SEM) (2.2 (0.2)/min) and to stationary contractions (0.3 (0.1)/min) generated similar force/event (7.5(0.9 g v 8.7 (1.4) g, p > 0.05). During phase III, all traction events were related to propagating contractions and generated 9.3 (2.4) g force/event (p > 0.05 v phase II). After feeding, traction events related to propagating contractions generated similar force/event to those related to stationary contractions (5.9 (1.0) g v 9.3 (2.7) g, p > 0.05 v each other and v fasting). No consistent pattern was seen in the temporal distribution of the traction events or in the pattern of the amplitude of the force of successive traction events.

Diminished oesophageal traction forces with swallowing in gastro-oesophageal reflux disease and in functional dysphagia.

Relations between primary oesophageal peristaltic amplitude and traction force were studied in 30 normal volunteers, 12 patients with functional dysphagia, and 48 patients with gastro-oesophageal reflux disease, using a new intraluminal strain gauge device. Forces generated by swallowing in the normal oesophagus were 42 (35-60) g (median and interquartile range), a close positive correlation existing between traction force and contractile amplitude for each subject (r = 0.5 (0.38-0.6). Traction force increased with increasing balloon volume from 62 (50-73) g at 2 ml to 86 (70-105) g at 4 ml (p < 0.05), indicating distension related modulation of peristaltic force. Patients with oesophagitis generated lower traction forces on swallowing 30 (20-40) g compared with the normal subjects (p < 0.01), the degree of impairment being greatest in those patients with the most severe mucosal damage. Patients with gastro-oesophageal reflux without endoscopic oesophagitis also showed abnormal forces (32 22-38) g p < 0.01 v controls), which were similar to those patients with mild oesophagitis but were greater than those with severe oesophagitis (p < 0.05). In patients with functional dysphagia, forces were also impaired (28 (10-60) g p < 0.05 v controls) despite normal standard manometry. Our results show that measurement of the traction force generated by primary peristalsis provides information about oesophageal neuromuscular function that is not demonstrable by manometry alone and can be abnormal in patients with oesophageal symptoms in whom standard techniques are normal.

Esophageal clearance function following treatment of esophagitis.

BACKGROUND/AIMS: To investigate whether healing of the esophagitis was associated with an improvement in esophageal clearance function, 15 patients with endoscopic and histologically confirmed erosive esophagitis were studied both before and after 1-month treatment with 40 mg/day of omeprazole. METHODS: All patients were studied before and after treatment by perfusion manometry to measure esophageal pressures, and a traction measuring device was used to record aboral forces generated by graded intraluminal distension. RESULTS: Before treatment, standard manometry showed reduced lower esophageal sphincter pressures (4 mm Hg [range, 2-9] vs. a control of 12 mm Hg [range, 5-25]; P < 0.01) and distal peristaltic amplitudes (29 mm Hg [range, 5-57] vs. a control of 55 mg Hg [range, 32-90]; P < 0.01). Responses to distension were also abnormal with a higher threshold for induction of contractile activity (12 mL [range, 8.5-14] vs. control values of 5 mL [range, 3-10]; P < 0.01) and weaker clearance forces (5 g [range, 0-80] vs. control values of 20 g [range, 8-90]; P < 0.01). After treatment, all patients showed endoscopic and histological evidence of healing, but not consistent improvement in either lower esophageal sphincter pressure (5 mm Hg [range, 3-7]; P > 0.05 vs. pretreatment) or peristaltic amplitude (35 mm Hg [range, 10-55]) was found. However, responses to distension did improve, with a decrease in distension threshold to 10 mL (range, 7-14; P = 0.04) and enhancement of traction force to 14 g (range, 0-95; P < 0.01). Patients with the worst pretreatment distension responses showed the least improvement with therapy. CONCLUSIONS: Improvement in esophageal clearance can be achieved by the healing of esophagitis, although the capacity for functional benefit appears to be related to the degree of dysfunction present before therapy.

Responses of the human esophagus to experimental intraluminal distension.

Contractile and propulsive forces generated in response to intraluminal distension of the human esophagus were measured in 30 volunteers with the use of a novel intraluminal catheter assembly. Distension was achieved by graded inflation of a balloon for periods of 30 s using volumes of air varying between 0 and 12 ml. In the lower esophagus, distension above a threshold volume of 5 (3-10) ml (median and interquartile range) induced a traction force together with contractile activity proximal to the balloon and quiescence distally. Proximal contractile activity and aboral traction force increased with increasing inflation volume, the magnitude of the response being additionally dependent on the site and the length of esophageal wall stimulated. Although the threshold for induction of motor responses was similar at different distension sites, the magnitude of both contractile and traction responses was higher in the distal than in the midesophagus. In the upper esophagus, the contractions induced proximal to the distension propagated aborally, whereas in the lower esophagus nonpropagating proximal contractions were induced. With the use of a dual balloon technique, it was possible to demonstrate that the distal quiescence represented a true descending inhibitory response since inflation of a proximal balloon suppressed the contractile response induced by a distal balloon. These results thus provide a description of the human esophageal response to distension against which responses in disease states can be compared.

Identification of an abnormal esophageal clearance response to intraluminal distention in patients with esophagitis.

Esophageal clearance responses were studied by a new technique comprising a miniature electronic strain gauge attached to an inflatable balloon in 30 normal volunteers and 48 patients with gastroesophageal reflux disease. The pressure changes around the balloon and traction forces acting on the balloon were measured during graded balloon distention (0-12 mL of air for 30 seconds each inflation) in the lower and midesophagus. All normal volunteers responded to distention with development of swallow independent contractions above the balloon [65 mm Hg/30 s (range, 45-100 mm Hg/30 s)] together with generation of an aboral traction force [15 g (range, 9-20 g)]. Patients with reflux esophagitis showed a higher distention threshold for initiation of these responses, induced fewer proximal contractions [24 mm Hg/30 s (range, 0-38 mm Hg/30 s); P less than 0.01 vs. normal], and generated weaker traction forces [4 g (range, 0-6 g) at 10 mL P less than 0.01 vs. normal]. Patients with the most severe esophagitis showed greatest impairment of the clearance response (correlation = 0.7, P less than 0.01) and the greatest esophageal residence of refluxed acid (correlation = 0.5, P less than 0.01). These abnormalities appear to be of relevance to the pathophysiology of esophageal reflux disease although it remains to be determined whether they are the cause, or the result, of the esophagitis.