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Biomedical subjects

J J Stewart

Publications and source records attributed to J J Stewart.

At least 37 records · Page 2Linked to original sources

Intestinal myoelectrical activity and transit time in chronic portal hypertension.

This study was designed to determine the effects of portal hypertension on intestinal myoelectrical activity and propulsion. In a single surgery, adult rats were implanted with a serosal electrode at each quarter of the small intestine, and portal hypertension was produced by calibrated constriction of the portal vein. To determine intestinal transit, portal vein-stenosed (PVS) and sham-operated animals were chronically implanted with a catheter in the proximal small intestine. Transit time was determined by measuring the progression of radioactive chromium along the bowel. Studies were conducted 6, 9, and 14 days after surgical preparation. Portal hypertension was associated with both transient and persistent changes in intestinal myoelectrical activity during the experimental period. Slow wave frequency was significantly reduced in the proximal small intestine on all test days and in the distal small intestine on day 14. Occurrence of the migrating myoelectric complex was reduced on days 6 and 9. Phase III amplitude was significantly reduced in the distal small intestine on all test days. Changes in intestinal myoelectrical activity in PVS animals were not associated with measurable changes in intestinal propulsion. The results suggest that both transient and persistent changes in intestinal myoelectrical activity occur during the 2-wk period after portal vein stenosis. The functional significance of the changes is unknown.

Action Potentials↗

A comparison of peripheral and central effects of clonidine on rat intestinal transit.

This study was designed to examine the effects of centrally or peripherally administered clonidine on small intestinal transit (SIT) in rats with diarrhea. Adult, male rats weighing 200 to 250 grams were surgically implanted with a silicone catheter in the proximal small intestine. Some animals were additionally implanted with a cannula in the right lateral cerebroventricle. SIT was determined by measuring the progression of an intraduodenally administered radioactive marker (Na2CrO4, 0.5uCi) along the small intestine. In most experiments, the effects of clonidine or saline were determined in animals challenged with sodium ricinoleate (100 mg) intraduodenally, the active ingredient in castor oil except treatment with reserpine. Given subcutaneously (s.c.) clonidine significantly inhibited SIT at doses between 25 and 200 micrograms/kg. The effects of s.c. clonidine were antagonized by yohimbine, but not by reserpine or subdiaphragmatic truncal vagotomy. In contrast, given intracerebroventricularly (i.c.v.) clonidine produced a more long lasting effect at total doses greater than 20 micrograms. Intestinal antipropulsive effects of i.c.v. clonidine were blocked by yohimbine, but not by prazosin. Reserpine (s.c.) or 6-hydroxydopamine (i.c.v.) did not affect the actions of central clonidine. However, effects of i.c.v. clonidine were abolished after vagotomy. The results indicate that clonidine inhibits rat intestinal transit in similar total doses when given s.c. or i.c.v. Inhibition of SIT by clonidine results from alpha-2 adrenergic receptor activation. In the case of i.c.v. clonidine, the receptors appear to be located postsynaptically and the response is dependent upon intact vagal innervation.

Adrenergic alpha-Antagonists↗

Effects of ginger on motion sickness susceptibility and gastric function.

This study was designed to evaluate the antimotion sickness activity of ginger root (Zingiber officinale) and to characterize the effects of ginger on gastric function. Twenty-eight human volunteers participated in the project. Subjects made timed head movements in a rotating chair until they reached an endpoint of motion sickness short of vomiting (malaise III or M-III). Each subject was tested with either ginger or scopolamine and a placebo. A substance was judged to possess antimotion sickness activity if it allowed a greater number of head movements compared to placebo control. Gastric emptying of a liquid was measured by nuclear medicine techniques in normal and motion sick subjects. Gastric electrical activity was monitored by cutaneous (surface) electrodes positioned over the abdominal area. Powder ginger (whole root, 500 or 1,000 mg) or fresh ginger root (1,000 mg) provided no protection against motion sickness. In contrast, subjects performed an average of 147.5 more head movements (p less than 0.01) after scopolamine (0.6 mg p.o.) than after placebo. The rate of gastric emptying was significantly (p less than 0.05) slowed when tested immediately after M-III but was inhibited less when tested 15 min after M-III. Powdered ginger (500 mg) had no effect on gastric emptying in normal or motion-sick subjects. Gastric motility was also changed during motion sickness. The frequency of the electrogastrogram (EGG) was increased after M-III (tachygastria) and the normal increase in EGG amplitude after liquid ingestion was reduced in motion sick subjects. Although powdered ginger (500 mg) partially inhibited tachygastria in motion sickness, it did not enhance the EGG amplitude in motion sick subjects. We conclude that ginger does not possess antimotion sickness activity, nor does it significantly alter gastric function during motion sickness.

Adolescent↗

Therapeutic effects of antimotion sickness medications on the secondary symptoms of motion sickness.

In addition to nausea and vomiting, motion sickness involves slowing of brain waves, loss of performance, inhibition of gastric motility and the Sopite Syndrome. The therapeutic effects of antimotion sickness drugs on these reactions were evaluated. The subjects were rotated to the M-III end-point of motion sickness. Intramuscular (IM) medications were then administered. Side effects before and after rotation were reported on the Cornell Medical Index. Brain waves were recorded on a Grass Model 6 Electroencephalograph (EEG), and gastric emptying was studied after an oral dose of 1 mCi Technetium 99m DTPA in 10 oz. isotonic saline. An increase in dizziness and drowsiness was reported with placebo after rotation. This was not prevented by IM scopolamine 0.1 mg or ephedrine 25 mg. EEG recordings indicated a slowing of alpha waves with some thea and delta waves from the frontal areas after rotation. IM ephedrine and dimenhydrinate counteracted the slowing while 0.3 mg scopolamine had an additive effect. Alterations of performance on the pursuit meter correlated with the brain wave changes. Gastric emptying was restored by IM metoclopramide. Ephedrine IM but not scopolamine is effective for some of the secondary effects of motion sickness after it is established.

Adolescent↗

Oral absorption of sodium pentobarbital and effects on gastrointestinal function.

An anaesthetic dose (40 mg/kg) of sodium pentobarbital (SP) was administered intragastrically to adult, fasted male rats at total dosing volumes of 1, 2, or 3 ml. Area under the plasma concentration-time curve did not differ for the various dosing volumes. During the initial (rapid) phase of gastric emptying all solutions containing drug appeared to empty at a faster rate than distilled water (2 ml). However, solutions containing drug emptied much more slowly than water during the terminal (slow) phase of gastric emptying. Drug solutions moved along the small intestine at approximately the same rate as distilled water. SP significantly lowered rectal temperature and slowed the propagation velocity of the migrating myoelectric complex (MMC) recorded from four serosal electrodes chronically implanted along the proximal small intestine. In addition, the drug significantly decreased the rate of MMC recurrence, extended the duration of MMC phases, and decreased slow wave frequency at all sites monitored. The results suggest that: 1) the relative oral bioavailability of sodium pentobarbital is not influenced by dosing volume within the range tested, 2) the various dosing volumes of SP tested moved through the gastrointestinal tract at an equal rate, and 3) orally administered SP significantly decreases the propagation velocity and periodicity of the MMC in the small intestine.

Administration, Oral↗

Electrogastrograms during motion sickness in fasted and fed subjects.

Seven human volunteers were subjected to stressful Coriolis stimulation (rotating chair) either during the fasted state or following the ingestion of yogurt (6 oz). Subjects tested after yogurt reached a Malaise-III (M-III) endpoint of motion sickness after significantly (p less than 0.01) fewer head movements than subjects tested in the fasted state. Surface electrogastrogram (EGG) recordings at M-III were similar for both dietary states and consisted of a brief period of tachygastria, followed by a period of low amplitude EGG waves. Ingestion of yogurt enhanced susceptibility to motion sickness but did not affect the associated pattern of EGG.

Adolescent↗

Responsiveness of genetically epilepsy-prone rats to intracerebroventricular morphine-induced convulsions.

The sensitivity to intracerebroventricular morphine-induced convulsions was determined in members of the severe seizure (GEPR-9) and moderate seizure (GEPR-3) colonies of genetically epilepsy-prone rats as well as in non-epileptic control rats. GEPR-9s were more sensitive to morphine-induced wet-dog shakes, rearing with bilateral forelimb clonus and generalized clonus than controls of GEPR-3s. GEPR-3s were less sensitive to morphine-induced wet-dog shakes and rearing with bilateral forelimb clonus than controls. Both high and extremely low doses of morphine in GEPR-9s elicited tonic extensor convulsions resembling the characteristic sound-induced convulsion of GEPR-9s. The results suggest that opiotergic systems may contribute to the pathophysiology of the seizure-prone condition in GEPR-9s. Further, differences in responsiveness of opiotergic systems in GEPR-3s and GEPR-9s may partially account for differences in seizure severity in the characteristic sound-induced seizures of these two types of GEPRs.

Animals↗

In vitro adsorption of sodium pentobarbital by SuperChar, USP and Darco G-60 activated charcoals.

This study was designed to examine the in vitro adsorption of sodium pentobarbital by three activated charcoals. Solutions of sodium pentobarbital (20 mM) were prepared in distilled water and in 70% sorbitol (w/v). Radiolabeled (14C) sodium pentobarbital was added to each solution to serve as a concentration marker. Two ml of each drug solution was added to test tubes containing 40 mg of either Darco G-60, USP, or SuperChar activated charcoal. The drug-charcoal mixtures were incubated at 37 degrees C for O, 2.5, 5, 7.5 or 10 min. Equilibrium, indicated by a constant percentage of drug bound for two consecutive time periods, was established immediately for the aqueous mixtures and for Darco G-60 in sorbitol. The time to equilibrium was prolonged for USP (2.5 min) and SuperChar (5 min) in the presence of sorbitol. In the second series of experiments, solutions of sodium pentobarbital (1.25 to 160 mM) were prepared in either distilled water or sorbitol. Amount of drug bound by 10 to 320 mg of activated charcoal within a 10 min incubation period was determined. Scatchard analysis determined maximum binding capacity (Bmax) and dissociation constants (Kd) for each activated charcoal. In water, Bmax (mumoles/gm) was greatest for SuperChar (1141), followed by USP (580) and Darco G-60 (381), while the Kd's did not differ. Sorbitol did not change the Bmax or Kd of USP or Darco G-60, but the additive significantly decreased the Bmax (717) and increased the Kd for SuperChar (3.3 to 10.1 mM). The results suggest that relative binding capacity of activated charcoal is directly proportional to surface area, and that sorbitol significantly reduces sodium pentobarbital binding to SuperChar.

Adsorption↗

Effects of activated charcoal and sorbitol on sodium pentobarbital absorption in the rat.

Three activated charcoals were tested for their ability to reduce the oral absorption of sodium pentobarbital (SP) in rats. Fasted adult, male rats were given 40 mg/kg of C-14 labelled SP by gavage (2 ml). Five minutes after drug administration, the animals were given 40 mg of either Darco (G-60), United States Pharmacopeia (USP) or SuperChar (SC) activated charcoals. The charcoals were administered as a slurry in either 1 ml of water, or 1 ml of 70 percent (w/v) sorbitol solution. Water (control) and sorbitol given alone were tested separately. Various pharmacokinetic parameters were calculated from the plasma concentration of SP determined at various time intervals after drug administration. When given in water, only SC significantly (p less than .01) reduced the peak plasma concentration and oral bioavailability of SP. Sorbitol given alone produced diarrhea but did not affect drug absorption. However, sorbitol selectively enhanced the effectiveness of G-60 and USP charcoals and, as a result, all charcoals significantly reduced SP absorption when given along with the cathartic. The results suggest that when given in water, charcoal antidotal effectiveness is proportional to absorptive surface area, and that sorbitol may enhance the antidotal effectiveness of some charcoals but not others.

Administration, Oral↗

Translocation of indigenous bacteria from the gastrointestinal tract of mice after oral ricinoleic acid treatment.

A single dose of ricinoleic acid, the active component of castor oil, administered intragastrically to specific pathogen-free mice produced significant alterations in the proximal small intestinal mucosa. Two hours after drug administration, the duodenal villi were markedly shortened with massive exfoliation of columnar and goblet cells. This disruption of the mucosal barrier resulted in continuity between the intestinal lumen and the lamina propria of the villi. Because of the loss of the mucosal barrier, bacteria of the indigenous gastrointestinal flora translocated from the gastrointestinal lumen to the mesenteric lymph nodes, spleen, and liver. The peak incidence of bacterial translocation occurred 4 days after the ricinoleic acid treatment. Strictly anaerobic bacteria, which normally colonize the gastrointestinal tract at greater levels than aerobic or facultatively anaerobic bacteria, were translocated at a greater incidence to the mesenteric lymph nodes than were the other indigenous bacteria. The mucosa began regenerating within 4 h after the ricinoleic acid treatment and viable translocated bacteria were no longer cultured from the mesenteric lymph nodes by 7 days after treatment.

Animals↗

Absorption of sodium pentobarbital by three types of activated charcoal.

The in vitro adsorption of sodium pentobarbital by activated charcoal (USP), Darco G-60 and SuperChar was studied. Various solutions of sodium pentobarbital, ranging in concentration from 2.5 to 10 mg/ml (pH = 9), were prepared in distilled water. Radiolabeled (14C) sodium pentobarbital was added to serve as a concentration marker. Two millimeters of each solution was added to from 5 to 350 mg of each charcoal in a test tube. The resulting charcoal-drug slurries were mixed thoroughly and incubated at 37 C for 10 min. Analysis of supernatant allowed calculation of percentage of drug bound. Plots of percentage of drug bound vs log quantity of charcoal necessary to bind 50% of the drug (B-50) were constructed. B-50 was lowest for SuperChar (indicating highest binding capacity), followed by USP and Darco G-60 activated charcoals. In a second series of experiments, drug adsorption was determined at various pH's, or when sodium pentobarbital was dissolved in various volumes of distilled water. Adsorption of the drug from solutions buffered at pH 8.1, 9, 9.7, 11 and 12 did not differ from adsorption in aqueous solution. Adsorption of sodium pentobarbital by 50 or 100 mg of each charcoal did not change when 5 mg of the drug was dissolved in 1, 2, 4, 6, 8 or 10 ml of water. The results suggest that sodium pentobarbital is most readily adsorbed by SuperChar under all conditions studied, followed by USP and Darco G-60 activated charcoals. Changes in pH, or in the initial mixture volume, did not influence the degree of drug adsorption to activated charcoal.

Adsorption↗

Effects of methotrexate on intestinal transit in rats.

A study was designed to determine the effects of methotrexate (MTX) on rat intestinal transit. Adult male rats were implanted with indwelling cannulas in the proximal duodenum 5 to 7 days prior to experimentation. After recovery from surgery, groups of animals were treated with either saline (1.0 ml/kg/day) or MTX at 0.5, 1.25, 3.125, or 7.8 mg/kg/day (ip) for 3 consecutive days (Days 1-3). On each of the next 5 consecutive days (Days 4-8) weight and intestinal transit determinations were made in animals from each test group following a 24-hr fast. Intestinal transit was determined by measuring the progression of an intraduodenally administered bolus of radioactive chromium (Na2(51)CrO4, 0.5 mu Ci) through the small intestine. When compared with saline-treated controls, intestinal transit was significantly (p less than 0.05) increased on 1 or more of the 5 test days in animals treated with doses of MTX greater than 0.5 mg/kg/day. When compared with animals treated with saline, animals treated with MTX lost a greater percentage of their initial body weight after the fast period. Plasma concentrations of MTX, determined at various time intervals after 3.125 mg/kg given daily for 1 to 3 consecutive days, peaked at 15 and 30 min after each injection and diminished to undetectable levels after 4 hr. The results indicate that 3 days of parenteral therapy with MTX significantly increases rat intestinal transit. The intestinal effects appear to be transient and are proportional to the total dose of drug administered over the 3-day period. The intestinal effects of MTX occur from 1 to several days after peak plasma concentrations of drug and are associated with a reduced ability to sustain body weight after a 24-hr fast.

Animals↗

Disseminated superficial actinic porokeratosis: appearance associated with photochemotherapy for psoriasis.

A patient with chronic psoriasis treated with psoralens plus ultraviolet A (PUVA) developed characteristic lesions of disseminated superficial actinic porokeratosis (DSAP). Since other processes associated with ultraviolet irradiation, including epidermal dysplasia, actinic keratoses, squamous cell carcinomas, and keratoacanthomas, have been reported to result from PUVA, it is possible that her DSAP lesions were induced by this therapy.

Adult↗

Antipropulsive effects of central and peripheral morphine in the rat gastrointestinal tract.

The antipropulsive effects of centrally or peripherally administered morphine have been examined at three levels of the rat gastrointestinal tract. Adult male rats were anaesthetized with pentobarbitone (50 mg kg-1 i.p.) and were implanted with an intraluminal catheter in either the proximal duodenum or mid-jejunum. Other animals were also implanted with a cannula in the right lateral cerebral ventricle. Gastric emptying and transit were determined selectively by measuring the progression of a radioactive chromium (CR-51) solution, given intragastrically for tests of gastric emptying or instilled into the proximal or distal intestinal catheter for determination of intestinal transit, 30 min after administration of morphine or saline given either subcutaneously (s.c.) or intracerebroventricularly (i.c.v.). Morphine given either s.c. (5 mg kg-1) or i.c.v. (30 micrograms, total dose) significantly inhibited gastric emptying and transit through bulk portions of the small intestine indicating that by either route it inhibits propulsion at all three levels of the gastrointestinal tract.

Animals↗

Temporal effects of morphine on rat intestinal transit.

Rat intestinal transit was determined 30, 60, 150 and 270 min after morphine sulfate or saline given either subcutaneously (s.c.), intraduodenally (i.d.) or intracerebroventricularly (i.c.v.). In addition, two popular methods of quantifying the progression of a radioactive marker along the bowel, the intercept and geometric center methods, were compared. Morphine (5 mg/kg) given s.c. and i.d. produced two distinct periods of reduced intestinal transit, an early phase at 30 min and a late phase at 150 min. Neither phase of the response was influenced by transection of the vagus nerve. The late phase was not affected by cannulation of the bile duct but was completely extinguished when animals were treated with saline instead of the ricinoleic acid, a cathartic agent used in the original experimental protocol. Given i.c.v., morphine (30 micrograms, total dose) inhibited intestinal transit 30 and 60 min after administration. The results indicate that the temporal effects of morphine on rat intestinal transit differ after central and peripheral administration, and in animals treated and not treated with a cathartic agent. Both methods of calculating intestinal transit produced similar statistical results.

Animals↗

Effects of emetic and cathartic agents on the gastrointestinal tract and the treatment of toxic ingestion.

Emetic drugs and saline cathartics produce direct or reflex changes in gastrointestinal motility. The changes in gastrointestinal smooth muscle function may be important in the rapid oral or rectal expulsion of gastrointestinal contents, effects which serve as a basis for emetic and cathartic drug use in the treatment of toxic ingestion. Because of difficulties in recording gastrointestinal smooth muscle contractile activity from the intact, unanesthetized animal or man, relatively few studies have attempted to characterize the changes in gastrointestinal motility preceding vomiting. Limited results from past studies and the results of more recent studies employing improved technology suggest that pharmacological activation of the emetic reflex is accompanied by characteristic movements of the stomach and small intestine. The gastric response consists of initial muscle relaxation and an expansion of gastric volume. The intestine responds with a contraction, which begins in the distal ileum and migrates orad over the entire small intestine immediately before active retching. The changes in gastric and intestinal motility may be initiated by structures in the central nervous system and may be an important component of the emetic reflex. This article urges more active research to characterize the gastrointestinal emetic response and to investigate more generally the therapeutic value of emesis in the treatment of toxic ingestion. Emphasis should be placed on the clinically important emetic drugs apomorphine and syrup of ipecac. Studies comparing the efficiency of removal of gastrointestinal contents, resultant blood levels of orally administered drugs with and without emesis, differences in the gastrointestinal emetic response between agents and the pharmacology of the gastrointestinal emetic response should be performed. Studies should also be conducted to determine the pharmacology of the emetic sensory receptors in the gastrointestinal tract and the intraluminal physical-chemical or gastrointestinal physiological factors influencing gastrointestinal emetic sensory receptor activation. The results would demonstrate the value of emesis in various poison cases and help establish criteria for use and selection of emetic drugs. No less experimental attention should be devoted to the cathartic drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗