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Biomedical subjects

P Bass

Publications and source records attributed to P Bass.

At least 55 records · Page 3Linked to original sources
PubMed1993

Gastrointestinal transit is not impaired by regional loss of myenteric neurons in rat jejunum.

Chronic absence of myenteric neurons from a 5-cm segment of rat jejunum causes alterations in myoelectric activity. Spike potentials characteristic of phase III activity of the migrating motor complex (MMC) are present; however, the number of propagating spike potentials through the myenterically denervated region is reduced. The objective of this study was to examine the effect of the regional loss of myenteric neurons on gastrointestinal transit of a solid marker in the fasted rat. The rate of gastric emptying was not affected by the absence of the myenteric plexus in a 5-cm segment of the jejunum. However, 15 days after either myenteric denervation or vehicle treatment of a segment of jejunum, a more cephalad distribution and decreased rate of intestinal propulsion of the solid marker was observed in the small intestine. This delay in small intestinal transit observed at 15 days was not seen at 48 and 120 days. The decrease in transit at 15 days can be attributed to the handling of the bowel during the surgical procedure. The mouth-to-cecum transit time (MCT) was also not affected by chronic absence of the myenteric plexus. Furthermore, the MCT indicated that bacterial overgrowth, a common manifestation when gut motility is disrupted, did not occur in the small intestine after the experimental destruction of the myenteric plexus. The results of this study indicate that the regional loss of the myenteric plexus does not impair gastrointestinal transit in the fasted rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Chronic denervation of rat jejunum results in cholinergic supersensitivity due to reduction of cholinesterase activity.

We examined the effects of chronic myenteric/extrinsic denervation of a segment of rat small intestine on specific acetylcholinesterase (AChE) and nonspecific cholinesterase (ChE) activities. Myenteric/extrinsic denervation of a 5-cm length of jejunum was accomplished by serosal application of the cationic surfactant benzyldimethyltetradecylammonium chloride. Fifteen days after denervation, biochemical determinations of AChE and ChE revealed that the smooth muscle layers, but not the mucosa, of denervated tissues have decreased levels of both AChE (approximately 65% decreased) and ChE (approximately 30% decreased). Histochemical staining of sections of denervated small intestine for AChE activity failed to detect any AChE activity in the region formerly occupied by the myenteric plexus. There appeared to be a qualitative decrease in ChE staining in the longitudinal muscle of denervated small intestine. Isolated muscle contraction experiments were conducted with the aim of determining changes in muscle responsiveness to acetylcholine (ACh) subsequent to denervation. Denervated circular and longitudinal muscle layers displayed increased sensitivity to ACh compared to nondenervated tissues (pEC50 values: 5.23 vs. 3.53, circular muscle; 5.33 vs. 4.08, longitudinal muscle). Incubation of tissues with 10 microM neostigmine caused a similar shift in pEC50 values of ACh concentration-response curves from denervated circular and longitudinal muscle layers (approximately 20% increase in pEC50). In contrast to the similar effects of neostigmine on both muscle layers of denervated tissues, neostigmine exerted a differential effect on the muscle layers of control intestine. Neostigmine produced a 65% increase in pEC50 value in control circular muscle and a 49% increase in pEC50 value in control longitudinal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

Effect of epidermal growth factor on experimental colitis in the rat.

The effect of epidermal growth factor on the rate of healing was examined in a rat model of colitis. Ulceration and inflammation of the distal colon were induced by a single intracolonic administration of 0.25 ml of 30% ethanol containing 30 mg of trinitrobenzenesulfonic acid. Epidermal growth factor was delivered intracolonically via the rectum or s.c. for 7 days after induction of colitis. Repeated s.c. injections of epidermal growth factor (25 and 100 micrograms/kg/12 hr) or continuous s.c. delivery with Alzet osmotic pumps (50 and 200 micrograms/kg/24 hr) significantly reduced colonic ulceration and inflammation. Epidermal growth factor significantly reduced myeloperoxidase activity in colonic tissue and there was restitution of the glandular mucosa after epidermal growth factor treatment. In contrast, daily intracolonic treatment with epidermal growth factor (25, 100 and 200 micrograms/kg/24 hr) did not significantly reduce the colonic damage. However, intracolonic delivery of 5-aminosalicylic acid (100 and 200 mg/kg/24 hr) dose-dependently reduced the colonic damage as assessed macroscopically and histologically. We conclude that systemic and not intracolonic administration of epidermal growth factor can accelerate healing of colonic ulceration and is effective in reducing inflammation in this model of colitis.

Aminosalicylic Acids↗
PubMed1992

Reinnervation of villi of rat jejunum following severe mucosal damage.

We studied the time course of the regeneration of the jejunal mucosa of the rat after it was damaged by exposure to the surfactant, benzalkonium chloride. We placed particular emphasis on assessing the morphology of the nerve fibers within the villi during and after regeneration. The application of benzalkonium chloride resulted in virtually complete loss of villi within the treated segment; however, the crypts were only partially damaged. The mucosa began to regenerate within 6 hr of the insult. The villus lengths and crypt depths returned to pretreatment values within two to four days. The mucosal innervation was assessed through immunohistochemistry for vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), and neuron-specific enolase (NSE). At all stages of regeneration, VIP, NPY, and NSE immunopositive fibers within the lamina propria extended to the tips of the villi. The density of the immunopositive fibers in the lamina propria at four days after mucosal insult was similar to that in control tissues regardless of the neuronal marker visualized. We conclude that the nerve fibers innervating the small intestinal mucosa grow at a rate of approximately 100 microns/day and that the entire length of each villus contains nerve fibers throughout the regeneration process. The innervation of the regenerated mucosa appears identical to that of control mucosa.

Animals↗
PubMed1992

Autosomal dominant polycystic kidney disease complicated by glomerulonephritis.

Two patients with autosomal dominant polycystic kidney disease (ADPKD) and concurrent glomerulonephritis are described. Both developed nephrotic-range proteinuria and one showed a concomitant acceleration in the rate of decline of renal function. Subsequent open renal biopsy revealed membrano-proliferative type-1 and mesangio-proliferative glomerulonephritis, respectively. Nephrotic-range proteinuria in the presence of ADPKD, with or without an accompanying decline in renal function, should prompt further investigation to exclude coexisting glomerular disease.

Adult↗
PubMed1991

Sodium channel blockers alter slow-wave frequency of the rat stomach in vivo.

Treatment with sodium-channel-blocking agents is accompanied by a high incidence of gastrointestinal side effects. We therefore studied the influence of two sodium channel blockers, mexiletine and flecanaide, on gastric and jejunal myoelectrical activity of unanesthetized rats. Bipolar electrodes were implanted chronically on the serosal surface of the antrum or the jejunum of male rats (weight: 250-350 g). Electrical activity was recorded on a Polygraph starting on day 5 after the operation After 1 h of baseline recordings, either vehicle or an active drug was given randomly. Recordings were continued for 4 h after drug administration. Vehicle did not induce changes in slow-wave frequency. In contrast, gastric slow-wave activity significantly decreased after the administration of both mexiletine and flecanaide. Jejunal myoelectrical activity was only slightly affected by sodium channel blockade. The disruption of gastric myoelectrical activity may contribute to the side effects observed during chronic treatment with class I antiarrhythmic drugs.

Animals↗
PubMed1990

Altered carbachol-induced contractile responses of rat jejunal smooth muscle following local myenteric plexus ablation.

Alterations in smooth muscle responsiveness and neural pathways in adjacent tissue may occur after local myenteric denervation. The in vitro contractile responses of both longitudinal and circular muscle to the mixed muscarinic and nicotinic cholinergic agonist carbachol were determined 15, 30, and 45 days after localized myenteric plexus ablation. Denervated longitudinal muscle exhibited decreased responsiveness to carbachol at all times examined. Denervated circulated muscle was initially supersensitive, but with time became subsensitive. These changes probably reflect the loss of the nicotinic (neuronal) component of the action of carbachol. Muscle orad to the site of denervation appeared subsensitive, while muscle caudad to the lesion was supersensitive (circular) or unaffected (longitudinal). These results suggest that there are changes in ascending and descending neural pathways. Alterations in the cholinergic responsiveness of intestinal smooth muscle, both at and beyond the site of myenteric plexus ablation, may result in altered intestinal motility that could lead to functional obstruction.

Animals↗
PubMed1990

The myenteric plexus regulates cell growth in rat jejunum.

The roles of the myenteric and extrinsic nerves in the control of proliferation and cell growth in the rat jejunum were studied. The myenteric plexus and/or the extrinsic nerves in a segment of rat jejunum were ablated by serosal application of the surfactant benzyldimethyltetradecylammonium chloride or by crushing the nerves passing through the mesentery, respectively. Ablation of both myenteric and extrinsic nerves, but not the extrinsic nerves alone, resulted in a significant increase in the mitotic rate of the crypt-epithelial cells and in the size of VIP-immunoreactive neurons in the submucosal plexus. The increased mitotic rate was correlated with an increase in the weight of the mucosa per unit length of gut and in the villus length and crypt depth. Neither extrinsic denervation alone nor serosal application of saline had any effect on these parameters. Our results suggest that the myenteric plexus is able to influence the rate of cell proliferation and cell growth in the rat jejunum.

Animals↗
PubMed1990

Submucosal plexus alone integrates motor activity and epithelial transport in rat jejunum.

It has been well established in several mammalian species, including humans, that contractions of jejunal smooth muscle correlate temporally with increases in mucosal ion transport. Furthermore, this correlation is abolished through local application of neurotoxins, suggesting interaction of enteric neurons. The purpose of this study was to determine whether the myenteric plexus is involved in this correlation. In the rat jejunum in vivo, we simultaneously measured phasic changes in intraluminal pressure and transmural potential difference (PD) as indicators of smooth muscle motor activity and epithelial ion transport, respectively. We compared the temporal association of these parameters in control animals with animals in which either the extrinsic nerves only or the extrinsic nerves and the myenteric plexus of a 5-cm jejunal segment had been ablated 30 days previously. A one-to-one coupling between muscle contractions and transmural PD fluctuations was observed in all animals; ablation of the extrinsic and/or myenteric neurons did not eliminate this correlation. We conclude that, in the rat jejunum, the submucosal plexus alone can integrate the reflex that couples ion secretion to muscle contraction.

Animals↗
PubMed1990

Pharmacologic characterization of the changes in cholinergic sensitivity of rat jejunal circular muscle after myenteric plexus ablation.

Neurons located in the myenteric plexus are generally believed responsible for motor control of intestinal circular muscle. The in vitro isometric responses of naive and myenterically denervated (MD) rat jejunal circular muscle to bethanechol and carbachol, alone and in the presence and absence of neuronal antagonists (hexamethonium bromide, tetrodotoxin and Botulinum toxin A) 15 and 30 days after myenteric plexus ablation, were determined. The responses to bethanechol indicated no differences in muscarinic sensitivity between naive and MD tissue. The relative potency of carbachol, which acts at both muscarinic and nicotinic receptors, in MD tissue 15 days after denervation was significantly higher than that in naive tissue. However, 30 days after denervation, the relative potencies of carbachol in naive and MD circular muscle were comparable. The presence of neuronal antagonists had no effect on the relative potency of carbachol 15 days after myenteric denervation, but altered significantly the responses 30 days after denervation. The effects produced by the neuronal antagonists 30 days after myenteric denervation were qualitatively and quantitatively different than those produced in naive tissue, suggesting that the nature of the innervation in these tissues was different. These results demonstrate that circular muscle was denervated initially after myenteric plexus ablation but reinnervation occurred within 30 days. The reinnervation observed is likely due to neurons located in the submucosal plexus.

Animals↗
PubMed1989

Enteric neuronal ablation: structure-activity relationship in a series of alkyldimethylbenzylammonium chlorides.

Serosal application of a commercial solution of benzalkonium chloride (BAC) has been shown to selectively ablate myenteric neurons in the rat jejunum. This experimental model has proven useful in the study of the role of the myenteric plexus in intestinal function. The commercial BAC is a mixture of at least three homologous N-alkyldimethylbenzylammonium chlorides (ADBAC). The purpose of this study was to determine neuronal ablative activity in a series of ADBAC homologs when applied on the serosa of rat jejunum. Homologs not commercially available were synthesized and purified. Seven ADBAC homologs with alkyl chain lengths ranging from C6 to C18 were tested. A solution of each homolog (2 mM in saline) was applied directly on the serosa of an exteriorized portion of jejunum from anesthetized rats. Fifteen days after treatment, animals were sacrificed and treated tissues were processed for neuronal cell counts and muscle thickness determinations. All ADBAC homologs, except C18, ablated neurons of the myenteric plexus and produced thickening of intestinal smooth muscle. The number of submucosal neurons was not affected by any of the homologs. The structure-activity relationship observed in this study paralleled that of the reported antimicrobial activity of the ADBAC homologs, and is related to the aqueous solubility and relative surface activities of the homologs. The C14 homolog was found to be the most effective ablative agent, and reduced the number of myenteric neurons in a concentration-dependent manner. Thus, the C14 homolog can be used to produce a selectively denervated jejunal model for use in acute or chronic in vitro or in vivo studies of intestinal function.

Animals↗
PubMed1988

Hyperplasia of jejunal smooth muscle in the myenterically denervated rat.

Application of a cationic surfactant, benzalkonium chloride, to the serosa of rat jejunum results in an increase in thickness of both longitudinal and circular smooth muscle layers. The increase in thickness is due primarily to an increase in the number of smooth muscle cells (hyperplasia). Little cellular hypertrophy was observed. The time sequence of surfactant-induced effects on the muscle layers was determined. Within 24 h, total destruction of the longitudinal muscle and partial destruction of the circular muscle was evident. The myenteric plexus was also necrotic; however, the submucosal plexus remained intact. By 48 h after surfactant treatment, the smooth muscle cells remaining in the circular muscle layer had begun to divide, as indicated by the presence of mitotic figures and incorporation of 3H-thymidine. A repopulation of the longitudinal muscle layer began at this time, apparently the result of migration of cells arising in the circular muscle layer. By 5 days post-treatment, both muscle layers had regenerated to their original states. The myenteric plexus was totally absent. The denervated smooth muscle cells proceeded to divide until approximately day 15, resulting in hyperplasia of both muscle layers. Between 15 and 105 days, the number of muscle cells in the circular layer progressively declined, eventually returned to the value seen in control tissue. In contrast, the number of smooth muscle cells in the longitudinal layer remained elevated through the period of study (165 days). We hypothesize that the smooth muscle hyperplasia observed after serosal benzalkonium chloride application results from loss of the myenteric nerves.

Animals↗
PubMed1988

Clinical evaluation of methylcellulose as a bulk laxative.

We studied a bulk laxative containing methylcellulose in a group of normal subjects as well as in a group of chronically constipated individuals. The initial study in normal subjects was performed to show that the compound could increase fecal weight without significant side effects. Fifty healthy subjects were studied. Methylcellulose in daily doses of 4 g demonstrated a statistically significant increase in fecal frequency, fecal water, and fecal solids. In the second phase, we studied a group of 59 chronically constipated individuals treated with daily doses of the laxative containing either 1, 2, or 4 g of methylcellulose or 3.4 g psyllium. All of these doses resulted in statistically significant increases in stool frequency, water content, and fecal solids. There was no increase in individual stool weight from any of the laxative doses. Methylcellulose, in a daily dose as low as 1 g, is an effective laxative.

Adolescent↗
PubMed1988

Improved intestinal cannula for drug delivery studies in the dog.

A modified light-weight intestinal cannula, based on the modified Thomas type (Thomas, 1941; Jones et al., 1971) was fabricated and tested. The design extends the useful life of the cannula and expands the versatility of the canine gastrointestinal (GI) system for pharmaceutical and physiological research. The cannula permits easy administration of pharmaceutical dosage forms directly into or access to ingested substances anywhere along the small intestine.

Animals↗
PubMed1988

Human electrogastrograms: comparison of techniques of recording.

There are different methods for recording physiologic electrical signals cutaneously. Monopolar recording has been used, by us and by others, to record the basic electrical rhythm of the stomach. In an effort to improve our ability to routinely obtain a recording of the basic electrical rhythm of the stomach, using cutaneous electrodes (electrogastrography), we have investigated different electrode recording techniques, and compared them with monopolar recording. We studied 10 healthy asymptomatic volunteers who were fasting, using each of the techniques while simultaneously monitoring a monopolar electrogastrogram. Three different recording techniques were studied: a Wilson central terminal, comparing alternative placements of the reference electrodes; a Wilson central terminal with a single placement of the reference electrodes, but alternative placements of the active exploratory electrode; and, last, a differential recording technique. We found all of the studied techniques to be superior to monopolar recording in the amount of time a recognizable three/min basic electrical rhythm could be recorded. However, the differential recording arrangement yielded an improvement in percent of recording time so significant that the electrogastrographic signal could be visually discerned to greater than 80%, compared with 37%, of the monopolar recording. Thus, the differential recording technique is far superior for recording the electrogastrogram.

Electrodes↗