W.J. Snape

Colonic motility and transit in health and ulcerative colitis

Preprandial and postprandial colonic motility and transit (scintigraphy), with respect to the splenic flexure, were studied in 10 patients with ulcerative colitis and in 9 healthy subjects. The healthy subjects had a postprandial increase in intraluminal pressure that was significantly (P less than 0.03) greater in the descending colon than in other regions of the colon. In ulcerative colitis, the pressure was decreased in all regions compared with healthy subjects, with no significant pressure gradient among different regions. In normal subjects, transit was quiescent during fasting; eating stimulated both antegrade and retrograde transit. In ulcerative colitis, transit was variable before as well as after the meal. Both healthy subjects and patients with ulcerative colitis had more rapid emptying from the splenic flexure into the sigmoid than into the transverse colon. More frequent, low-amplitude, postprandial propagating contractions occurred in ulcerative colitis (P less than 0.05) than in healthy subjects. Propagating contractions were always antegrade and caused a rapid movement of the tracer into the sigmoid. In conclusion, ulcerative colitis is characterized by (a) decreased contractility, (b) increased low-amplitude propagating contractions, and (c) variable transit. These disturbances may accentuate the diarrhea in ulcerative colitis.

Association Between Postprandial Changes in Colonic Intraluminal Pressure and Transit

The aim of this study was to correlate the movement of colonic luminal contents with the changes in intraluminal pressure. Studies were performed in 9 healthy volunteers. Intraluminal pressure was measured with perfused catheter ports in the transverse, splenic flexure, descending, and sigmoid colon. Movement of the luminal contents was measured by following the movement of technetium 99m-ethylenetriamine-pentaacetic acid that was instilled as a bolus in the splenic flexure. During fasting there was very little change in pressure or in the movement of intraluminal contents. After eating a 1000-kcal meal, the tracer moved from the splenic flexure into the transverse colon and the sigmoid colon. Nonpropagating colonic motor activity increased in all colonic segments immediately after eating the meal (p less than 0.05). The increase in motility was significantly greater in the descending colon than in the transverse and sigmoid colon (p less than 0.05). In one-half of the subjects propagating contractions occurred postprandially. The movement of the intraluminal tracer occurred during both types of motility. The nonpropagating contractions were associated with a gradual movement of the luminal contents. The direction of the movement of the contents was determined by the differences in pressure in the different segments of the colon. The propagating contractions were associated with a rapid movement of intraluminal contents. These studies suggest that (a) colonic motility and transit are quiescent during fasting and (b) the transverse colon acts as a mixing and storage area, as retrograde transit into the transverse colon is the characteristic postprandial pattern.

Differences in the response of proximal and distal rabbit colonic muscle after electrical field stimulation

Electrical field stimulation (EFS) was performed on rabbit proximal and distal circular colonic smooth muscle to study the mechanisms of neural control of the colon. Electrical pulses were applied with parallel silver plate electrodes to muscle that had been stretched to Lo. The proximal muscle demonstrated an on-contraction during EFS. In distal muscle, EFS initiated an on-relaxation, followed by an on-contraction and an off-contraction. The time delay for the on-contraction of distal muscle was longer by 2.5 +/- 0.5 s than was the delay in proximal muscle (p less than 0.02). The amplitudes of the on- and off-contraction were dependent on the frequency of the EFS. The on- and off-responses were completely inhibited by 3 x 10(-6) M tetrodotoxin. Atropine inhibited the distal on-contraction at all EFS frequencies and the proximal on-response at EFS frequencies less than 16 Hz. Atropine had a partial inhibitory effect on the distal off-response (approximately 30%). Bombesin and substance P were released during prolonged EFS. Desensitization of the distal colonic muscle to bombesin did not affect the distal off-contraction. However, desensitization of the tissue to substance P and exposure to substance P antagonists inhibited the distal off-contraction. These studies suggest that (a) acetylcholine mediates the on-contraction of the distal circular colonic muscle, and a major part of the on-contraction for the proximal muscle, and (b) substance P is responsible for the off-contraction of the distal muscle.

Anatomic contribution to differences in rabbit colonic muscle contraction

The aim of this study was to determine if differences in the force of contraction in different regions of the rabbit colon are associated with variations in the histology of the corresponding muscle tissues. Circular and longitudinal muscles were isolated from strips of proximal and distal colonic muscle. Muscle strips stretched to L0 were either stimulated to contract or were processed for electron microscopy. Cross-sections of the smooth muscle cells of the taenia coli had a larger perimeter (P less than 0.001) and were surrounded by increased extracellular matrix (28% of the standardized box) compared with the muscle cells from the other sites in the colon (7%-13%) (P less than 0.001). Cross-sections of the proximal circular muscle cells had a smaller perimeter and were present in a greater number than the cells from other areas of the colon. The distal circular muscle generated a larger force than the other muscles after stimulation with bethanechol or K+ (P less than 0.05). The taenia developed less force than the other muscles (P less than 0.05). Bethanechol was a less potent stimulant for the longitudinal muscles than for the circular muscles (P less than 0.05). This study suggests that (1) the decreased efficacy of bethanechol and K+ stimulation of the taenia coli is caused in part by the smaller number of cells that are available to contract and (2) the increased efficacy for the stimulation of the distal circular muscle compared with the proximal circular muscle is unrelated to the mass of muscle and seems to be related to an inherent property of the muscle.

Effect of secoverine on colonic myoelectric activity in diverticular disease of the colon

The effect of secoverine on colonic smooth muscle was measured in pationts with diverticular disease and in healthy subjects. The frequency of slow wave activity was determined using the fast Fourier transform (FFT) and peak identification analysis (SWSA). The mean slow wave frequency was similar (6 cycles/minute) in healthy subjects using both analytic methods. The slow wave frequency in patients with diverticular disease was similar to that in healthy subjects. The peak frequency measured with SWSA was uniformly higher than that measured with FFT. Secoverine, a muscarinic antagonist, did not affect the slow wave frequency. Eating a 1000-kcal meal initiates an increase in colonic spike activity (22±2 spike potential/30 min) (P<0.001) in healthy subjects during the immediate postprandial period. The gastrocolonic response in patients with diverticular disease was prolonged for 60 min. Secoverine inhibited the gastrocolonic response in patients with diverticular disease. These studies suggest (1) patients with diverticular disease have a similar slow wave frequency as healthy subjects, (2) the gastrocolonic response is prolonged in patients with diverticular disease, and (3) secoverine inhibits the colonic response.

Response of Smooth Muscle from Proximal and Distal Human Colon

Regional differences in colonic motility may be responsible for the orderly transit of intraluminal contents through the colon. The aims of this study were to compare the effect of stretch on active and passive stress development in colonic muscle from the proximal and distal colon and to compare the responses of these tissues to KC1 or bethanechol stimulation. Strips of taenia or circular smooth muscle were obtained from the disease‐free segment of the colon removed for adenocarcinoma. Passive, active, and total isometric stress were measured on full‐thickness strips of circular or longitudinal taenial muscle stimulated with bethanechol (10−4 M) as the muscles were stretched to 120% of the length of optimum tension (Lo.) The tissues then were stimulated with increasing concentrations of KCI and bethanechol while being stretched at Lo. The active stress in the proximal circular muscle was greater at all levels of stretch than in distal circular or longitudinal muscle (p <.001). The resting and passive stress were greater in distal circular and longitudinal taenial muscle than in proximal circular muscle (p < .05). There was a dose‐dependent increase in stress development to bethanechol and KCl in each type of muscle. Proximal circular muscle had the greatest response. The EDSO was shifted to the right in distal circular muscle (2.6 ± 0.1 × 10−5 M) compared to proximal circular muscle (1.1 ± 0.1 × 10−5 M) (p < .001). These studies suggest that muscle stress differs in different locations of the colon and the role of active and passive stress development must be considered in models explaining in vivo colonic motility disturbances.

Effect of 5-hydroxytryptamine and its antagonists on colonic smooth muscle of the rabbit

The effect of 5-hydroxytryptamine (5HT) was studied in circular and longitudinal muscle from the proximal and distal colon of New Zealand white rabbits. 5HT stimulated a dose-dependent isometric contraction of distal and proximal circular muscle that was greater than in distal longitudinal muscle (P<0.01). 5HT did not stimulate taenia coli longitudinal muscle. The EC50 for 5HT stimulation of distal circular muscle (−7.0±0.1), distal longitudinal muscle, and proximal circular muscle was similar. Methysergide dose-dependently inhibited the 5HT stimulation of both proximal and distal circular muscle. The IC50 for methysergide inhibition of 5HT (5×10−7 M) stimulation was −5.5±0.2. Ketanserine and ICS 205-930 did not inhibit 5HT stimulation of colonic muscle. Tetrodotoxin (TTX) decreased the potency, but not the efficacy of 5HT stimulation of proximal and distal circular muscle. Atropine decreased the potency (EC50=−6.6±0.1) (P<0.05) and the efficacy by 40%. Electrical field stimulation (EFS) caused an on-contraction and off-contraction of distal circular muscle and an on-contraction of proximal circular muscle. 5HT decreased the off-contraction of the distal circular muscle but did not affect the on-contraction of the other muscle strips. 5HT receptor antagonists did not affect EFS of the tissue. The studies suggest: (1) 5HT stimulates circular colonic muscle with greater efficacy than longitudinal muscle, (2) 5HT stimulates circular muscle through a 5HT1 receptor, (3) there is atropine-sensitive and atropine-insensitive 5HT stimulation of circular colonic muscle, (4) 5HT inhibits neurons responsible for the off-contraction in distal circular muscle without affecting the on-contraction. Thus, 5HT affects colonic contraction by a direct effect on muscle and indirectly through the enteric nerves.

Calcium dependence of neurotensin stimulation of circular colonic muscle of the rabbit.

The effect of neurotensin on smooth muscle contraction was compared in strips from rabbit proximal and distal circular colonic muscle. The effective dose for neurotensin stimulation that caused a 50% response in both tissues was similar (1.3 X 10(-10) M). The maximal isometric stress, however, was greater in the distal colon than in the proximal colon (p less than 0.01). Neurotensin stimulation of both proximal and distal colon was unaffected by tetrodotoxin, phentolamine, propranolol, naloxone, or atropine. Neurotensin-stimulated contraction was inhibited by Ca2+-free (pCa = 5.1) or La3+ buffer. Verapamil (10(-6) M) or nitroprusside (10(-4) M) decreased neurotensin stimulation of proximal and distal colon by approximately 40% (p less than 0.05). Removal of Ca2+ from the buffer inhibited stimulation of muscle contraction by high extracellular potassium [( K+]o) more than bethanechol stimulation (p less than 0.01). La3+ (1 mM) inhibited the contraction stimulated by bethanechol or increased [K+]o. Although verapamil inhibited contraction by bethanechol and increased [K+]o by approximately 50%, nitroprusside had no effect on the contraction mediated by these stimulants. 8-Bromo-guanosine 3,5-cyclic monophosphate (cGMP) inhibited neurotensin, but not [K+]o or bethanechol-stimulated contraction. These data suggest (a) neurotensin stimulated colonic contractions at a concentration that is potentially physiologic, (b) neurotensin stimulated colonic smooth muscle directly without neural mediation, (c) neurotensin stimulation of colonic muscle is controlled by [Ca2+]o and [cGMP]i.

Cryptosporidium in acquired immunodeficiency syndrome

Une observation de cette protozoose chez un malade de 31 ans, homosexuel, atteint de SIDA. Diagnostic par etude de biopsies en microscopie electronique

Mechanism of neurotensin depolarization of rabbit colonic smooth muscle

The aims of this study were (1) to measure the effect of neurotensin on the membrane potential of circular muscle of the distal colon of the rabbit and (2) to determine the mechanism by which neurotensin affects the membrane potential of this tissue. The membrane potential was measured with microelectrodes placed intracellularly and the double sucrose gap. Neurotensin (10(-11) M to 10(-7) M) dose-dependently decreased the membrane potential. The maximum decrease in membrane potential occurred with 10(-9) M neurotensin. The ED50 of neurotensin depolarization of the membrane potential was 0.87 +/- 0.33 X 10(-10) M. The frequency of the slow waves was unchanged after neurotensin. The voltage response to a constant current pulse decreased as the concentration of neurotensin increased. The amplitude of the voltage response after a 0.6 microA current pulse decreased by 6 +/- 0.5 mV after neurotensin (10(-7) M) compared to the Krebs control (P less than 0.05). Decreasing the [Na+]o to 0-23 mM did not affect the decrease in membrane potential after neurotensin. However, perfusion with a test solution containing no added Ca2+ or verapamil (10(-5) M) inhibited neurotensin depolarization of the tissue. Evidence was found that neurotensin depolarizes colonic circular smooth muscle, and the decrease in membrane potential is associated with an increase in conductance which is dependent on influx of Ca2+.