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Biomedical subjects

P Bass

Publications and source records attributed to P Bass.

At least 37 records · Page 2Linked to original sources
PubMed1998

Jejuno-ileal bypass, enteric hyperoxaluria, and oxalate nephrosis: a role for polarised light in the renal biopsy.

Enteric hyperoxaluria, a complication of jejuno-ileal bypass, is associated with renal failure owing to oxalate nephrosis or tubulo-interstitial nephritis. A 54 year old woman developed renal failure 17 months after jejuno-ileal bypass for morbid obesity. Renal biopsy showed widespread acute on chronic damage to the tubulo-interstitial compartment with extensive deposition of oxalate crystals. The extent of oxalate deposition was only evident on polarisation of the biopsy.

Acute Kidney Injury↗
PubMed1998

Hymenolepis diminuta fractions but not previous tapeworm infection stimulate intestinal myoelectric alterations in vivo in the rat.

Infection of rats with the enteric, lumen-dwelling tapeworm Hymenolepis diminuta causes electric changes in host intestinal smooth muscle and decreased luminal transit. The mechanisms that stimulate host intestinal alterations during this nontissue invasive infection may include the tapeworm's biomass, its diurnal migratory behavior, a host immune-mediated response, or direct parasite stimulation of host motor activity. In vivo intestinal myoelectric activity was monitored to evaluate the following: (1) that reinfection with H. diminuta is influenced by host immune regulation and (2) that administration of tapeworm fractions to never-before-infected rats initiates an alteration of enteric smooth muscle activity. To address the first hypothesis, we determined that altered intestinal myoelectric activity patterns were no different and did not occur earlier in a second infection with H. diminuta than in a primary infection. The lack of either a change in myoelectric pattern or an earlier onset of intestinal myoelectric changes indicates that tapeworm-induced myoelectric activity is not anamnestically stimulated by host immunomodulatory mechanisms. Consistent with the second hypothesis, administration of either H. diminuta carcass homogenate or tegument-enriched fractions directly into the intestinal lumen of tapeworm-naive rats initiated myoelectric patterns previously characteristic of chronic H. diminuta infection. Additionally, the appearance of characteristic nonmigrating myoelectric patterns in uninfected rats administered tapeworm fractions indicates that a substance from H. diminuta acts as the triggering signal molecule for intestinal myoelectric alterations. These findings also indicate that neither the tapeworm's biomass nor its diurnal movement is required for initiation of H. diminuta-altered myoelectric patterns. We have shown that H. diminuta possess a signal molecule(s) that alters host enteric electric activity, and we suggest that these alterations may play an important role in the symbiotic rat-tapeworm interrelationship.

Action Potentials↗
PubMed1997

Tapeworm infection decreases intestinal transit and enteric aerobic bacterial populations.

Intestinal myoelectric patterns in rats are altered after chronic luminal infection with the tapeworm Hymenolepis diminuta. This study evaluates whether these altered patterns were associated with changes in intestinal fluid transit and endogenous enteric microbe levels. Luminal transit, measured throughout the small intestine during the interdigestive state, was significantly decreased during tapeworm infection. Reduced transit was regional, occurring in the same location as that of the tapeworm and maximal myoelectric alterations. In other experimental systems, aerobic and anaerobic bacterial overgrowth is associated with decreased transit; however, reduced transit during tapeworm infection was unexpectedly associated with decreased numbers of aerobic bacteria, whereas anaerobic bacterial populations remained unchanged. The lack of overgrowing endogenous microflora suggests that overgrowth is not responsible for tapeworm-stimulated alterations in host myoelectric patterns. We speculate that a tapeworm secretion could be responsible for both transit and motility changes while delayed intestinal transit could prevent tapeworm expulsion, aid the tapeworms' migration, and contribute to the digestion and absorption of nutrients by hosts and/or parasites.

Animals↗
PubMed1996

Evaluation of early events in the creation of amyenteric opossum model of achalasia.

Benzyldimethyltetradecylammonium chloride (BAC) has previously been used to create amyenteric rat jejunal models. Fifteen opossums (D. virginiana) were injected with 10-15 mL 4 mM BAC or saline in the distal oesophagus and along with controls underwent oesophagoscopy, manometry and barium oesophagrams. Atropine and sodium nitroprusside were studied in six of the BAC-treated and five controls using oesophageal manometry. Histologically several neuronal markers, B-NADPH-diaphorase and acetylcholine esterase histochemical staining were used. NADPH-diaphorase activity was assayed at the lower oesophageal sphincter (LOS) and 3 and 5 cm above LOS in both groups. Oesophagoscopy of the treated animals showed no mucosal inflammation, or strictures. Manometrically, LOS pressures were significantly higher in the BAC-treated group (25.7 +/- 8.6 mmHg) when compared to controls (8.7 +/- 1.8 mmHg). The oesophageal contraction amplitudes were similar in both groups. While sodium nitroprusside (SNP) significantly reduced the LOS pressure, atropine did not alter the resting LOS pressure in the BAC-treated animals. Histologically at the LOS the treated group showed: (i) absence of myenteric neurons, in contrast to prominent NADPH-diaphorase and other neuron and peptide markers in the control and (ii) increase in the number of nerve bundles that were not positive for AchE. No differences were seen in the oesophageal body between the groups. The NADPH-diaphorase assay showed a significant decrease of activity in the BAC-treated LOS, but no differences in the oesophageal body compared to controls. Several of these radiologic, manometric and histological observations resemble features of achalasia and the mechanism of the tonic pressure increase at this early time point appears to be due to a non-cholinergic mechanism.

Animals↗
PubMed1995

Myenteric denervation of rat jejunum alters calcium responsiveness of intestinal smooth muscle.

BACKGROUND/AIMS: Long-term myenteric and extrinsic denervation of a segment of rat jejunum results in increased stress generation by the longitudinal muscle layer of the denervated segment 15 days after denervation. This study examined whether alterations in the properties of either cell membrane calcium channels and/or sarcoplasmic reticular Ca(2+)-adenosine triphosphatase (ATPase) contribute to the increased stress development. METHODS: The effects of the calcium channel blocker nifedipine and the sarcoplasmic reticular Ca(2+)-ATPase inhibitor cyclopiazonic acid on the contractile activity of denervated and control smooth muscle were determined. RESULTS: The ability of nifedipine to inhibit KCl-induced contractions was significantly increased in denervated tissues; however, there was no difference in the potency of nifedipine when tissues were stimulated with carbachol. Calcium concentration-response curves obtained in the presence of either KCl or carbachol were determined in tissues previously depleted of calcium. Long-term denervated tissues showed an increased sensitivity to calcium and a decreased maximum contractile response after stimulation with carbachol. Cyclopiazonic acid inhibited repletion of intracellular calcium stores of control muscle but had no effect in denervated tissue. CONCLUSIONS: Long-term denervation of a segment of rat small intestine results in profound alterations in calcium metabolism at the cell membrane and, to a lesser extent, at the sarcoplasmic reticulum of smooth muscle cells of the longitudinal muscle layer.

Animals↗
PubMed1995

Electrophysiological and pharmacological responses of chronically denervated lower esophageal sphincter of the opossum.

BACKGROUND & AIMS: Achalasia is characterized by loss of myenteric neurons and incomplete relaxation of the lower esophageal sphincter (LES). The aim of this study was to develop an achalasia model in the opossum using the surfactant benzyldimethyltetradecylammonium chloride (BAC). This study further characterizes the achalasia model. METHODS: BAC or saline was injected circumferentially into the LES of 14 adult opossums. Eight months after injection, manometry, isolated muscle bath studies, electrical field stimulation, and histochemical analysis were performed. RESULTS: Manometrically, the LES of BAC-treated opossums showed higher pressures (38.7 +/- 12 mm Hg vs. 17 +/- 3.0 mm Hg) and reduced esophageal body contraction amplitudes (4.2 +/- 3 mm Hg vs. 27.4 +/- 12 mm Hg). Isolated muscle strips challenged with carbachol and sodium nitroprusside contracted and relaxed similarly to controls. Electrical field stimulation failed to induce relaxation in BAC-treated tissue but did induce contraction. Contractile responses were markedly reduced by tetrodotoxin and atropine in BAC-treated animals and controls. An altered nitric oxide system was shown by the lack of response to L-arginine and N omega-nitro-L-arginine. Histology showed loss of myenteric neurons and increased cholinergic nerve bundles. CONCLUSIONS: Loss of NO inhibitory myenteric neurons markedly reduces the relaxation of the LES, and histology and pharmacological responses suggest a proliferation of cholinergic nerves into the LES contributing to the static elevated pressures of the amyenteric LES.

Analysis of Variance↗
PubMed1995

Praziquantel treatment normalizes intestinal myoelectric alterations associated with Hymenolepis diminuta-infected rats.

Hymenolepis diminuta-associated alterations in rat intestinal myoelectric patterns are abolished following therapeutic administration of the anthelmintic praziquantel (PZQ). Host intestinal smooth muscle myoelectric patterns, reflecting smooth muscle contractility and intestinal phasic motility, were recorded using in vivo serosal electrodes, surgically implanted on the duodenum, jejunum, and ileum. Repeated electromyographic recording from unrestrained and unanesthetized rats began 5 days after electrode implantation surgery. Three initial control recordings from each rat confirmed the appearance of normal intestinal myoelectric patterns, characterized by the interdigestive migrating myoelectric complex (MMC). All animals were subsequently infected with H. diminuta and myoelectric recordings beginning after day 8 postinfection confirmed the appearance of diminished frequency of the MMC and 2 nonmigrating myoelectric patterns, i.e., repetitive bursts of action potentials and sustained spike potentials. PZQ was used to remove the tapeworms from rats 12 days after Hymenolepis diminuta infection, as intestinal myoelectric changes become maximal at this time in tapeworm-infected rats. PZQ administered to uninfected rats at either of 2 dose levels did not affect host interdigestive myoelectric activity. After removal of the parasite with PZQ, electromyographic recordings indicated a return to normal uninfected electrical patterns within 24 hr of drug treatment. We have demonstrated that the presence of Hymenolepis diminuta is necessary to induce and maintain abnormal intestinal myoelectric patterns. The altered motor properties of tapeworm-infected rat intestine and the rapid reconversion to preinfection myoelectric patterns provides a new and unique model to examine the regulatory mechanisms of intestinal motility and its control by luminal parasites.

Animals↗
PubMed1994

Intestinal myoelectric alterations in rats chronically infected with the tapeworm Hymenolepis diminuta.

This study determined that intestinal myoelectric activity was profoundly altered during a strictly luminal, chronic, tapeworm infection. Chronically implanted bipolar electrodes were attached to five sites on the serosal surface of the rat small intestine. One was placed on the duodenum, three on the jejunum, and the fifth on the ileum. Electromyographic recording in nonfasted unanesthetized animals was begun at day 5 postsurgery. All electromyographic recordings were analyzed for slow wave (SW) frequency, phase III frequency, duration of phase III, and percentage of SW with spike potentials. Three initial control recordings prior to infection confirmed the presence of normal interdigestive motility characterized by the three phases (I, II, III) of the migrating myoelectric complex (MMC). Two nonpropulsive myoelectric alterations were observed in infected animals: the repetitive bursts of action potentials (RBAP) and periods of sustained spike potentials (SSP). Myoelectric activity from infected animals indicated decreased cycling of the interdigestive MMC. RBAP and SSP were more prevalent in the distal small intestine corresponding to tapeworm location. The percent of spike potential activity indicated that there was a reversal in the spike potential gradient on the small intestine. The number of spike potentials was maximal in caudal and minimal in oral intestine. We propose that overall localized increases in myoelectric spike potential activity represent increased contractility and decreased propulsion triggered by the presence of the tapeworm. These motility changes were surprising, since the tapeworm Hymenolepis diminuta does not penetrate the intestinal mucosa. This interaction between parasite and host may prevent expulsion of the tapeworm from the small intestine.

Action Potentials↗
PubMed1994

Inhibition of ornithine decarboxylase does not prevent intestinal smooth muscle hyperplasia in the rat.

The objective of this research is to examine the relationship between intestinal smooth muscle cell proliferation and polyamine metabolism. Proliferation of muscle is induced by serosal application of benzyldimethyltetradecylammonium chloride (BAC) to a segment of rat jejunum. This treatment destroys all of the longitudinal muscle, one-half of the circular muscle, and the myenteric and extrinsic nerves. The remaining muscle cells undergo mitosis and, by 15 days, the number of muscle cells is increased in both the longitudinal and circular muscle layers. Within 12 h after BAC treatment, there is an increase in the activity of ornithine decarboxylase (ODC) that returns to preinjury levels by 4 days. The smooth muscle content of the three polyamines putrescine, spermidine, and spermine is increased 6 h after injury, returning to preinjury levels within 1 day. DL-alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, prevents the transient increases in both ODC activity and the three polyamines in the smooth muscle. In addition to preventing the transient increases in the three polyamines, DMFO has different effects on smooth muscle content of putrescine, spermidine, and spermine. Putrescine content is permanently depleted by DFMO. Spermidine and spermine content is initially decreased within 24 h by DFMO administration. In contrast to the persistent depletion of putrescine by DFMO, spermidine and spermine return to preinjury levels by 2 days. The maximal peak in DNA synthesis occurs 2 days after injury. In DFMO-administered animals, the maximal DNA synthesis occurs 5 days after injury. The increases in smooth muscle wet weight and DNA content 15 days after injury are not affected by DFMO.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Increased active stress generation of denervated rat intestinal smooth muscle: functional analysis of muscarinic receptor population.

The effects of denervation on the active stress production by the longitudinal muscle (LM) layer of rat jejunum were examined. Extrinsic and myenteric denervation of a segment of rat jejunum was accomplished by the serosal application of the cationic surfactant benzyldimethyltetradecylammonium chloride (BAC). Isolated muscle contraction experiments revealed that the LM of the jejunum taken from rats treated with BAC 15 days before developed significantly increased active stress in response to bethanechol and carbachol, but not in response to potassium chloride. No change in -log EC50 values of any of the agonists was observed in the denervated LM layer, although a significant increase in the slope of the carbachol and bethanechol concentration-response curves was observed in the denervated LM. Schild analysis of several muscarinic antagonists revealed a 3-fold increase in the apparent dissociation constant of the M2 antagonist methoctramine in BAC-treated LM. These results suggest that the increased responsiveness of the denervated LM may originate in the muscarinic receptor population of the myocytes.

Animals↗
PubMed1993

Nutrient-induced changes in the permeability of the rat jejunal mucosa.

We examined the site of action of nutrients that enhance mucosal permeability by use of D-glucose as an archetype of nutrients of this class. We tested the hypothesis that D-glucose enhances mucosal permeability by either acting outside the intestinal lumen after absorption or acting inside the intestinal lumen to cause mediator release from either endocrine or nerve tissue. The rate of absorption of L-[14C]glucose, a passively absorbed molecule, from the lumen was used as an index of the permeability of the mucosa of a perfused segment. L-Glucose was absorbed more rapidly in the presence of D-glucose than in the presence of an equimolar concentration of mannitol. However, the permeability of the jejunal mucosa was unaffected by elevated blood glucose levels during intravenous infusion of D-glucose. The mucosal permeability was also unaffected by exposure of an adjacent segment to D-glucose, a result suggesting that D-glucose does not alter mucosal permeability by inducing the release of a blood-borne mediator from enteroendocrine cells. Finally, the effect of D-glucose on mucosal permeability could not be blocked by hexamethonium or tetrodotoxin, a result suggesting that the intestinal nerves do not mediate this phenomenon. Lidocaine significantly increased the rate of L-glucose absorption when D-glucose was present in the lumen but had no effect on L-glucose absorption under basal conditions. Our findings indicate that D-glucose must be in contact with the apical membranes of enterocytes to alter mucosal permeability. This suggestion is consistent with the hypothesis that the modulation of mucosal permeability results from the activation of sodium-dependent cotransport systems.

Animal Nutritional Physiological Phenomena↗
PubMed1993

Gastrointestinal parameters that influence oral medications.

The successful functioning of oral medication depends primarily on how the gastrointestinal (Gl) tract processes drugs and drug delivery systems. Parameters such as regional pH, motility (and hence residence time), and brush border and colonic microflora enzymatic activity play an important role in the performance of orally administered dosage forms. In addition, medications are required to treat disease states that alter normal functions of the body. This review (which summarizes the symposium of the same title undertaken in the 2nd Jerusalem Conference on Pharmaceutical Sciences and Clinical Pharmacology, Jerusalem, Israel, May 1992) focuses on two aspects: (1) how some physiological parameters of the intestine can be manipulated to achieve control over drug absorption (P. Bass: alteration of the paracellular space of enterocytes with glucose to modulate the passive movement of drugs; E. Ziv: intestinal absorption of insulin) and spatial placement of drugs (D.R. Friend: use of colonic beta-glucosidases to target glycoside prodrugs of steroids to the large bowel; A. Rubinstein: specific degradation of polysaccharide matrices by colonic bacteria); and (2) how abnormalities of the Gl tract affect drug performance (J.B. Dressman: physiological and pathophysiological changes in upper Gl tract pH may lead to alterations in drug bioavailability; W. A. Ritschel: influence of diseases on the pharmacokinetics of drugs).

Administration, Oral↗
PubMed1993

Neuroplasticity in the smooth muscle of the myenterically and extrinsically denervated rat jejunum.

The objective of this study was to examine the effects of two different denervation procedures on the distribution of nerve fibers and neurotransmitter levels in the rat jejunum. Extrinsic nerves were eliminated by crushing the mesenteric pedicle to a segment of jejunum. The myenteric plexus and extrinsic nerves were eliminated by serosal application of the cationic surfactant benzyldimethyltetradecylammonium chloride (BAC). The effects of these two denervation procedures were evaluated at 15 and 45 days. The level of norepinephrine in whole segments of jejunum was initially reduced by more than 76% after both denervation procedures, but by 45 days the level of norepinephrine was the same as in control tissue. Tyrosine hydroxylase (noradrenergic nerve marker) immunostaining was absent at 15 days, but returned by 45 days. However, the pattern of noradrenergic innervating axons was altered in the segment deprived of myenteric neurons. Immunohistochemical studies showed protein gene product 9.5 (PGP 9.5)-immunoreactive fibers in whole-mount preparations of the circular smooth muscle in the absence of the myenteric plexus and extrinsic nerves. At 45 days, the number of nerve fibers in the circular smooth muscle increased. Vasoactive intestinal polypeptide (VIP)-immunoreactive fibers, a subset of the PGP 9.5 nerve fibers, were present in the circular smooth muscle at both time points examined. Choline acetyltransferase (CAT) activity and VIP and leucine enkephalin levels were measured in separated smooth muscle and submucosa-mucosal layers of the denervated jejunum. VIP and leucine-enkephalin levels were no different from control in tissue that was extrinsically denervated alone. However, the levels of these peptides were elevated two-fold in the smooth muscle 15 and 45 days after myenteric and extrinsic denervation. In the submucosa-mucosa, VIP and leucine enkephalin levels also were elevated two-fold at 15 days, but comparable to control at 45 days. CAT activity was equal to control in the smooth muscle but elevated two-fold in the submucosa-mucosa at both times. These results provide evidence for innervation of the circular smooth muscle by the submucosal plexus. Moreover, these nerve fibers originating from the submucosal plexus proliferate in the absence of the myenteric plexus. Furthermore, the myenteric neurons appear to be essential for normal innervation of the smooth muscle by the sympathetic nerve fibers. It is speculated that the sprouting of the submucosal plexus induced by myenteric plexus ablation is mediated by increased production of trophic factors in the hyperplastic smooth muscle.

Animals↗
PubMed1993

Proliferation of mast cells in the smooth muscle of denervated rat jejunum.

Mast cell hyperplasia and changes in phenotypic characteristics subsequent to myenteric and extrinsic denervation of a segment of rat jejunum were studied. The myenteric plexus and extrinsic nerves were ablated by serosal application of the cationic surfactant benzyldimethyltetradecylammonium chloride. There was a four-fold increase in the number of mast cells in the smooth muscle layers 15 days after denervation. This increase was sustained for at least 90 days after treatment. No increase in mast cell number was observed in the villus-crypt axis of the jejunum. Berberine sulfate fluorescent detection of heparin-containing mast cells demonstrated that a change in mast cell phenotype occurred between 20 and 90 days after the denervation procedure. The fact that myeloperoxidase activity was the same in denervated and control tissue within 5 days of denervation demonstrates the lack of a chronic inflammatory reaction. Our results suggest that mast cells might play a role in the gut wall re-modeling processes.

Animals↗
PubMed1993

Glucose-induced ion secretion in rat jejunum: a mucosal reflex that requires integration by the myenteric plexus.

We tested the hypothesis that the mucosa of rat jejunum is stimulated by intraluminal D-glucose, resulting in nerve-mediated ion secretion. We examined the D-glucose-induced secretory response in two ways. First, we measured the unidirectional fluxes of sodium and chloride ions, in vivo, during perfusion of segments of jejunum with solution that contained either D-glucose or mannitol. Second, we measured the net rate of absorption of D-glucose from sodium-free solution; this parameter is related to the rate of sodium ion secretion. We used the above two approaches in conjunction with techniques for destroying specific subsets of the intestinal nerves. Thus, we evaluated the subset of intestinal nerves that integrates the secretory response of the mucosa to D-glucose. Jejunal segments perfused with D-glucose solution exhibited significantly greater rates of sodium and chloride ion secretion than did segments perfused with mannitol. Intestinal segments in which the myenteric nerve plexus had been destroyed exhibited a significantly lower rate of sodium ion secretion in the presence of D-glucose than was seen in fully innervated segments. A role for the myenteric nerves in D-glucose-induced ion secretion was also indicated by experiments that involved absorption of D-glucose from sodium-free solution. It was concluded that exposure of the mucosa of rat jejunum to glucose increases the rate of secretion of both sodium and chloride ions. The myenteric nerve plexus is apparently involved in the integration of this mucosal reflex.

Animals↗