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Biomedical subjects

P Bass

Publications and source records attributed to P Bass.

At least 91 records · Page 5Linked to original sources

Method for the quantitation of gastric emptying time of gel test meals.

Isotopic markers were developed to allow measurement of the gastric emptying times of homogeneous and nonhomogeneous gel meals. Meals containing the dietary fibers psyllium and guar gum presented as homogeneous, viscous gels while meals containing the synthetic polymer polycarbophil presented as discrete gel particle-water mixtures. Fiber meals were labeled differently than polycarbophil meals. Fiber meals were labeled with 51Cr-CM-Sephadex. The marker was uniformly suspended in meals containing at least 1% guar or 2% psyllium. In contrast, polycarbophil particles were labeled by hydrating the dried granules with saline in which Na2(51)CrO4 had been dissolved. Use of the markers to measure gastric emptying was demonstrated in dogs fitted with duodenal cannulas. Half of the fiber meals emptied from the stomach in about 40 min without significant dilution by secretions. In contrast, only 8% of the polycarbophil particles emptied by 90 min. Particle-specific labeling of polycarbophil was important because the meal effluent was diluted extensively by secretions. We conclude that 51Cr-CM-Sephadex and soluble Cr-51 may be used as meal markers for estimation of the gastric emptying times of certain homogeneous and nonhomogeneous gel-type meals, respectively.

Acrylic Resins↗

Selective myenteric neuronal denervation of the rat jejunum. Differential control of the propagation of migrating myoelectric complex and basic electric rhythm.

Serosal application of benzalkonium chloride (BAC), a cationic surfactant, was used to selectively ablate the myenteric neurons of the rat jejunum. The myoelectric activity of the BAC-treated area and the areas both orad and caudad to it were assessed. In the jejunal segment devoid of myenteric neurons, the basic electric rhythm (BER) pattern was erratic and the amplitude of the BER was attenuated. The BER frequency of the jejunal area caudad to the BAC-treated area was 30.7 +/- 0.73 cycles/min, which was significantly reduced from the normal BER frequency (37.7 +/- 0.64 cycles/min). Spike activity was normal in areas both orad and caudad to the treated area, existing in regular cycling bursts (migrating myoelectric complex). Spiking in the treated area did not appear until approximately 13-17 days after BAC treatment. These spikes, though of greater duration and lower frequency than the adjacent areas, always appeared after an orad burst and were followed by a caudad burst. In addition, the following motility parameters of the regions orad and caudad to the treated area were not significantly different from control animals: burst duration, period, and burst propagation velocity. In conclusion, the present investigation has demonstrated that BAC-induced ablation of the myenteric neurons in the rat jejunum disrupts the BER but not the migrating myoelectric complex propagation. This suggests that the myenteric neurons play a modulatory role in the generation and propagation of the BER, whereas humoral factors or the submucosal neurons may be more important in the control of the migrating myoelectric complex.

Action Potentials↗

A bean alpha-amylase inhibitor formulation (starch blocker) is ineffective in man.

A commercial alpha-amylase inhibitor with potent inhibitory activity in vitro was used in a randomized double-blind, cross-over clinical trial in six nonobese, healthy adult males. In these subjects, this inhibitor had no effect on the response of blood glucose, insulin, or breath hydrogen to a standardized starch meal. It is concluded that this formulation has no effect on starch digestion in humans.

Amylases↗

Failure to demonstrate effectiveness of an anticholinergic drug in the symptomatic treatment of acute travelers' diarrhea.

Seventy adults in the United States with acute diarrhea who were attending classes in Guadalajara, Mexico, enrolled in a double-blind placebo-controlled treatment study of an anticholinergic drug, mepenzolate bromide (MZB). Thirty-five patients received MZB (50 mg) and 35 received placebo each taken 4 times daily for 48 hours. No significant difference was detected between the MZB- and placebo-treated patients in symptoms or in the frequency or character of stools. Recovery rates of 24.1% and 31% for placebo- and MZB-treated patients were similar. Despite the occurrence of anticholinergic side effects in 51% of MZB- versus 14% of placebo-treated patients (P less than 0.001), therapeutic efficacy was not detected. We do not recommend anticholinergic drugs for therapy in acute infectious diarrhea.

Acute Disease↗

Surfactants selectively ablate enteric neurons of the rat jejunum.

Surfactants, a group of nonspecific membrane perturbating substances, can cause nerve damage. Various concentrations of the cationic surfactants benzalkonium chloride (BAC) and benzethonium chloride, the anionic surfactants sodium ricinoleate, dioctyl sodium sulfosuccinate and sodium lauryl sulfate and the nonionic surfactant Triton X-100 were applied to the serosal surface of the rat jejunum every 5 min for 0.5 hr and then rinsed off with saline. Thirty days after surfactant application, the treated and an untreated segment of jejunum were removed and examined histologically. All surfactants which were tested significantly reduced the number of ganglion cells in the myenteric plexus. In addition, sodium ricinoleate significantly reduced the number of ganglion cells in the submucosal plexus. Higher concentrations of the cationic agents BAC and benzethonium chloride caused a generalized tissue damage including disruption of the smooth muscle, lymphocytic infiltration, intestinal perforation and death. Using BAC as a prototype surfactant, peptidergic neuron distribution and gut electrical activity were examined. BAC treatment markedly reduced the immunoreactivity of somatostatin, substance P, met-enkephalin and vasoactive intestinal peptide in the myenteric plexus. In addition, the electric properties of the smooth muscle were altered. BAC treatment resulted in an erratic, markedly distorted basic electric rhythm and an alteration in spike potential generation. These studies demonstrate that surfactants in appropriate concentrations selectively ablate the myenteric neurons and alter peptidergic neuron distribution and gut electrical parameters in the rat jejunum.

Animals↗

Antagonism of gut, but not central effects of morphine with quaternary narcotic antagonists.

Naltrexone methylbromide and naloxone methylbromide, quaternary derivatives of naltrexone and naloxone respectively, are assumed to act peripherally. Both compounds reversed the intestinal stimulating effect of morphine in the dog. Naltrexone methylbromide 5 mg/kg s.c. blocked morphine-induced intestinal spike potentials for 50 min while intravenous doses caused antagonism for only 25 min. The antagonism by the s.c. route approximated that produced by naltrexone 0.2 mg/kg s.c. In morphine-dependent dogs, naltrexone methylbromide did not appear to antagonize morphine centrally in doses ranging from 0.25 to 50 mg/kg s.c. since it did not induce behavioral signs of narcotic withdrawal. Similarly, i.v. naloxone methylbromide was also able to reverse morphine-induced intestinal spike potential in dogs but the protection lasted only 25 min. In rats, naltrexone methylbromide 10 and 30 mg/kg i.p. neither reversed morphine block of PGF2 alpha-induced diarrhea nor antinociception. This suggests a lack of CNS narcotic antagonism in both test. In mice, naltrexone methylbromide, 60-720 mg/kg orally and 3-140 mg/kg i.p. failed to block morphine inhibition of prostaglandin F2 alpha-induced diarrhea. Paradoxically, in this species, 30 mg/kg s.c. of naltrexone methylbromide appeared to cross the blood-brain barrier since this dose reversed morphine-induced antinociception. In conclusion, naltrexone methylbromide effectively antagonizes the acute gut stimulating effect, but not the chronic behavioral effect of morphine administration in dogs. Based upon the antinociception test, naltrexone methylbromide does not cross the blood-brain barrier in rats but may in mice. Morphine inhibits prostaglandin F2 alpha-induced diarrhea by a central mechanism in rodents.

Animals↗

Laxative-like effects of nonsteroidal anti-inflammatory drugs on intestinal fluid movement and membrane integrity.

Certain nonsteroidal anti-inflammatory drugs (NSAID) of the fenamate chemical class are known to cause diarrhea in clinical use. Paradoxically, this action is shared by prostaglandins, against whose syntheses are inhibited by NSAID. This study was done to investigate the laxative potential of 5 NSAID (meclofenamate, flufenamate, mefenamate, indomethacin and aspirin). The ability to produce a laxative response was assessed by determining effects on fluid absorption in vitro in hamster everted sacs and by the enteropooling assay in hamster small intestine. In addition, the lytic action of these drugs on the erythrocyte membrane was determined to arrive at a possible mechanism of action. All of the NSAID, except aspirin, produced dose-related inhibition of fluid transport, similar to prostaglandin E1 and E2. The order of inhibition was flufenamate greater than meclofenamate greater than mefenamate greater than indomethacin. Like results were obtained when enteropooling was measured in vivo. Flufenamate and meclofenamate produced lumenal fluid accumulation comparable to two laxatives, dioctyl sodium sulfosuccinate and ricinoleic acid. Finally, the effects of these NSAID on fluid movement paralleled their lytic action on the erythrocyte membrane model, suggesting that NSAID may produce diarrhea in a manner similar to certain laxatives, by increasing mucosal permeability through membrane damage.

Alprostadil↗

Canine intestinal ulcer: myoelectric components and the effect of chronic hypergastrinemia.

The effects of jejunal ulcer and chronic endogenous hypergastrinemia on canine gastrointestinal myoelectric activity were investigated in three groups of dogs. All dogs were chronically implanted with electrodes on the stomach and either the duodenum or jejunum. Fasted-state myoelectric activity was monitored before and after gastroenterostomy. Two groups of dogs underwent autotransplantation of the gastric antrum to the midcolon with either gastroduodenostomy or gastrojejunostomy. The third group of dogs underwent diversion of the antroduodenum with gastrojejunostomy. Chronic hypergastrinemia was observed postoperatively in the dogs of each of the three models. Only dogs with gastrojejunostomy and antrocolic transplant developed intestinal ulcers. None of the dogs, despite the presence of ulcers in one group, demonstrated significant changes in myoelectric activity. In both gastrojejunostomy models, a trend toward lengthened interdigesive phase 2 at the expense of phase 1 was seen. No other myoelectric changes were observed and chronic hypergastrinemia had no effect on myoelectric activity in these models. We conclude; (a) experimental jejunal peptic ulcer is not marked by significant changes in interdigestive myoelectric activity and (b) chronic hypergastrinemia is not accompanied by the gastrointestinal muscle, effects reported after acute treatment with gastrin, suggesting a tolerance.

Animals↗

The laxative effects of lactulose in normal and constipated subjects.

We compared lactulose syrup to a placebo (5% sucrose syrup) in 42 normal and 24 chronically constipated volunteers. The study in normal subjects was double-blind and had a crossover design of two dose levels, 30 and 60 ml/day, whereas the study in constipated subjects was a double-blind parallel study of 60 ml/day dose. Lactulose syrup produced clinically and statistically significant increases in the frequency, weight, volume, and water content of stools and produced stools of softer consistency compared to baseline values, as well as to a sucrose-treated control group in both normal and constipated subjects. The study in normals suggests that the laxative effects are dose-related. Adverse effects reported were tolerable and were extensions of the pharmacologic effects of the drug. We concluded that lactulose is an effective laxative that affects the character of the colonic fecal content, thereby inducing evacuation of feces in people with constipation.

Adolescent↗

Electrical arrhythmias in gastric antrum of the dog.

Antral electrical arrhythmias were investigated in 32 unanesthetized chronic dog preparations implanted with serosal electrodes and transducers. Five of these animals underwent surgical removal of the duodenal cap and the adjacent hypomuscular segment. In the intact dogs two distinct types of arrhythmias of the basic electric rhythm (BER) were observed. During phase I (basal activity) arrhythmias were recorded in 17 of 32 dogs. In 9 of the 32 dogs, arrhythmias were present in more than 10% of recorded phase I activity. These arrhythmias included tachygastria as well as mixed gastric rhythms. A second type of arrhythmia consisting of premature and delayed BER occurred in all dogs during phase III (burst activity). In all five dogs, duodenal cap removal produced a marked increase in antral arrhythmias as well as the disruption of normal interdigestive motor and electrical patterns. The changes in terminal antral electrical rhythmicity after surgery may be due to an interaction with the higher frequency duodenal pacemaker tissue. Antral frequencies of 15-18 cycles/min in two of five dogs several days after cap removal were evidence of a duodenal influence. Antral arrhythmias may be present during both normal and pathophysiological states. Their importance is as an indicator of the functional status of the antral smooth muscle and its responsiveness to normal physiological and pharmacologic stimuli.

Action Potentials↗

Electromotor feeding responses of primate ileum and colon.

Serosal bipolar electrodes to record spike discharges and strain gauge force transducers to record circular muscle contractions were placed in pairs on the terminal ileum, cecum, right colon at the ileocecal valve, ascending colon, and proximal transverse colon of sixteen primates. After an overnight fast, electromotor responses to continued fasting or to ingestion of a meal (randomized order) were recorded in awake animals. Feeding led to increased spike discharges and increased frequency of muscle contractions at all sites. The onset of these responses usually was within 6 minutes after feeding; the responses increased progressively during 30 to 45 minutes and then remained more or less at a constant plateau of increased activity. Atropine completely blocked the postcibal responses of ileum and proximal colon for up to 30 minutes. Transit time data of labeled meals excluded direct stimulation by a food bolus as the mechanism of the observed postcibal colonic response. The pattern of response was consistent with humoral mediation.

Animals↗

A unique distribution of laxative-induced spike potentials from the small intestine of the dog.

The effects of castor oil and ricinoleic acid on small bowel electrical activity were studied in the fasted conscious dog and were compared to the effects elicited by two nonlaxative oils (triolein and oleic acid). Spike potential activity was monitored at two jejunal sites using unipolar recording electrodes. Castor oil, ricinoleic acid, and triolein produced an increased incidence of basic electrical rhythm (BER) with associated spike potentials when compared to a fasted control; however, the total electrical spiking activity produced by these oils was not statistically different from that induced by feeding. No treatment altered any of the characteristics of BER. A novel pattern of electrical spiking activity was observed in response to the laxatives. This pattern consisted of short repetitive bursts of spike potentials which migrated the length of the recording site. The laxative-induced electrical pattern persisted for several days after treatment with ricinoleic acid or castor oil, and interdigestive patterns were occasionally interrupted for as long as 72 hr. Electrical activity following feeding or the nonlaxative oils consisted of random spike potentials, and normal interdigestive electrical activity resumed within 24 hr. The laxative-induced electrical pattern was shown to be quantitatively distinct from those produced by feeding, fasting, or nonlaxative oils. This pattern may reflect an action of these laxatives on intestinal motility during a diarrheal state.

Animals↗

A miniature transducer for recording intestinal motility in unrestrained chronic rats.

An extraluminal strain gage force transducer has been developed for recording gastrointestinal motility in small animals such as rats. Two commercial strain gages are bonded and wires attached to form half a Wheatstone bridge. The device is placed between silicone sheeting and prepared for implantation. As many as six implanted transducers can record simultaneously contractions and tone variations of circular or longitudinal gastrointestinal muscles. The transducers have been implanted in more than 20 rats, with some units lasting up to 4 mo. Furthermore, good relationships exist between intraluminal pressure waves registered by a small intraluminal balloon and gut contractions registered by the transducer. The transducers are a useful and accurate tool for rodent gut motility studies.

Animals↗