Intragastrically Research Articles

Administration of Wine and Grape Juice Inhibits In Vivo Platelet Activity and Thrombosis in Stenosed Canine Coronary Arteries

Moderate daily consumption of alcoholic beverages is a negative risk factor for the development of atherosclerosis and coronary artery disease (CAD), especially in France and other Mediterranean areas where red wine is regularly consumed with meals. Platelets contribute to the development of atherosclerosis, CAD, and acute arterial thrombus formation. Anesthetized dogs were prepared with the Folts model of mechanically stenosed coronary arteries and intimal damage. Periodic acute platelet-mediated thrombus formation occurred, causing cyclic flow reductions (CFRs) in coronary blood flow. The CFRs were eliminated by the administration of 1.62 +/- 1.12 mL/kg red wine intravenously (IV) and 4.0 mL/kg intragastrically (IG). The CFRs were abolished by 2.04 +/- 1.42 mL/kg of grape juice IV and 10 mL/kg IG. White wine did not have significant results in eliminating the CFRs, either IV (2.0 mL/kg) or IG (4.0 mL/kg), decreasing the slopes of the CFRs only slightly. Pure ethanol has been shown to inhibit platelet aggregation in vitro, ex vivo, and in vivo, although a blood alcohol content (BAC) of > or = 0.2 g/dL is usually required. The BAC of dogs administered the red wine-saline solution intravenously was 0.028 g/dL, much less than is usually necessary for platelet inhibition with pure ethanol. Because red wine and grape juice, but not white wine, abolished the CFRs, this suggests there are compounds present in red wine and grape juice that are not present or are present in a lower concentration in white wine. Wine and grape juice contain a wide variety of naturally occurring compounds, including fungicides, tannins, anthocyanins, and phenolic flavonoids (including flavonols and flavones). These compounds have shown platelet inhibition in vitro by a variety of proposed mechanisms. Perhaps the biological activity of these compounds can explain the platelet-inhibitory properties of red wine and grape juice that are observed without high levels of ethanol.

Limited stimulus generalization between delta 9-THC and diazepam in pigeons and gerbils.

Pigeons trained to discriminate between the presence and absence of delta 9-THC (0.56 mg/kg, IM, intramuscularly) were tested with diazepam (5.6-30 mg/kg), administered IG (intragastrically), and were found to generalize the response associated with the THC training to the diazepam treatment only to a limited extent. Two groups of gerbils trained to discriminate between the presence and absence of IP (intraperitoneally) injected benzodiazepine agonists (5.6 mg/kg of diazepam and Ro 11-3128, respectively) generally did not generalize the drug response to IP administered THC (5.6 and 17.5 mg/kg). In addition, substitution testing with the dopamine autoreceptor blocker (+)-3PPP yielded non-drug responding in the pigeons. Hence neither proposed structural similarity between 3-PPP and THC, nor purported anxiolytic activity by 3-PPP (see Introduction) matched the THC-induced stimulus effects. The data are discussed with reference to the specificity of the THC cue or stimulus.

Intestinal Accumulation of Lead Salts and Milk Lead by Suckling Rats

Absorption of lead is known to be enhanced during infancy. In this study, the sites of intestinal accumulation of Pb by suckling rats have been determined under various conditions using 203Pb as a tracer. When 203Pb was administered intragastrically (IG) as a soluble salt, accumulation occurred primarily in the duodenum, regardless of dose and vehicle. In contrast, when rat pups suckled from a dam which had received 203Pb, the only region of the small intestine showing accumulation of radioactivity was the ileum. To confirm that these differences were not related to the route of administration, rat milk was labeled with 203Pb and was then used for IG administration. Once again, accumulation (4 hr post-administration) was confined to the ileum. When the dose was increased 10-fold, milk Pb displayed some accumulation in duodenal tissue, but very much less than that of soluble Pb at the same time and dosage. At 20 hr postadministration, there was negligible 203Pb in any region of the small intestine following administration as a soluble salt, but substantial retention in ileal tissue following administration in milk. The strikingly different patterns of intestinal accumulation obtained with Pb salts as compared with milk Pb suggest different modes of absorption of Pb ingested in these two forms.

Ethanol and current thresholds for brain self-stimulation in the lateral hypothalamus of the rat

Two groups of animals were implanted with stimulating electrodes in the lateral hypothalamus for intracranial self-stimulation (ICSS). Following surgery these animals were trained in the auto-titration, brain self-stimulation procedure which measured both the rate of responding and the reinforcement threshold for electrical stimulation. When behavior was stable, one group was given saline or ethanol (0.1–1.7 g/kg) administered intraperitoneally (IP) either 15 or 60 min before testing. The other group was given saline or ethanol (1.0–4.5 g/kg) administered intragastrically (IG) 15 or 60 min before testing. With IP administration, there was a graded decrease in lever-pressing at 15 min but the effect was less obvious at 60 min. There were no changes in threshold except at the highest dose when behavior was disrupted. With IG administration, a reduction in the rate of responding occurred at 15 min only. No changes in thresholds were observed at any dose level or injection-test interval. Thus, administration of ethanol either by the IP or IG route did not affect the reinforcement thresholds for ICSS in the lateral hypothalamus, and these results contrasted with those of other drugs of abuse such as amphetamine or morphine.

Effectiveness of DTPA therapy when administered intragastrically or intraperitoneally to remove Pu from adult or neonatal rats.

Adult and neonatal rats were given 238Pu by gavage or parenterally and treated with 0.5 mmoles/kg of calcium diethylenetriaminepentaacetate (DTPA), by gavage or parenterally, to determine its effectiveness for removing Pu. Parenteral administration of DTPA to adult rats 2 h after an intravenous 238Pu injection was much more effective than intragastric treatment, removing nearly 70% of the retained dose. When 238Pu was given to adults intragastrically (IG), followed by DTPA given either intraperitoneally (IP) or IG 2 h later, 238Pu absorption increased while retention remained either unchanged, or increased. When neonates were given 238Pu IG and treated 2 h later with intraperitoneal or intragastric DTPA, removal of 238Pu was better than in adults: more than 80% of the 238Pu that was absorbed and retained was removed by intragastric DTPA. When neonates were injected IP with 238Pu, treatment with intraperitoneal DTPA was more effective for 238Pu removal than intragastric treatment.

Alteration in Lipoprotein Composition with Intravenous Compared to Intragastric Fat-Free Feeding in the Rat

Rats were fed continuously for 7 d with fat-free total parenteral nutrition solutions delivered intravenously (IV) or intragastrically (IG) to determine changes in plasma lipoprotein composition due to elimination of intestinal nutrient absorption. IV feeding resulted in significantly lower plasma levels of apoA-I and A-IV, which are synthesized by the intestine, and in a 40% reduction in the weight of intestinal mucosa. Higher apoE levels in plasma, a greater proportion of apoE-enriched HDL1 particles and proportionately more HDL cholesterol were observed in IV- than in IG-fed animals. IV feeding also resulted in lower apoC-II levels in the HDL fraction. These differences in plasma apolipoprotein and HDL composition suggest alterations in lipoprotein metabolism with IV compared to IG feeding in the rat.

Interaction of the discriminative stimulus properties of diazepam and ethanol in pigeons

One group of pigeons (n=5) was trained to discriminate between the effects induced by 5.6 mg/kg of diazepam (DZP) and the vehicle whereas other pigeons (n=5) had to discriminate between 3.0 g/kg of ethanol (ETOH) and the vehicle, administered intragastrically (IG) 10 and 40 min prior to the training sessions respectively. Once trained, the pigeons were tested with either diazepam or ethanol alone and in combination. The birds trained to discriminate between DZP and the vehicle mostly performed non-drug associated responses when tested with ETOH (0.56 to 3.0 g/kg). Tests with other doses of DZP (0.3 to 3.0 mg/kg) in the diazepam-trained birds resulted in an ED 50 value of 1.4 mg/kg. The birds trained to discriminate between ETOH and the vehicle generalized DZP to ETOH, the ED 50 value for diazepam being 3.0 mg/kg. Tests with other doses of ETOH (0.56 to 2.0 g/kg) in this latter group resulted in an ED 50 value of 1.3 g/kg. Tests with combinations of DZP and ETOH produced a shift of the dose-response curves to the left indicating drug additivity. The discrimination of 5.6 mg/kg of IG administered DZP but not that of ETOH (3.0 g/kg) was attenuated by injections of the analeptic bemegride (ED 50=5.5mg/kg), thus suggesting a difference in the cueing processes of the two drugs. When tested singly, bemegride induced non-drug responding or complete suppression of responding in the birds at the doses of 3.0 and 10.0 mg/kg respectively. In conclusion, the discriminable effects of DZP and ETOH are additive or even supra-additive, but the stimulus properties of the two drugs are not identical.

Small intestinal and colonic changes induced by a chemically defined diet.

Three groups of rats were fed, respectively, a chemically defined diet intragastrically (IG), an equivalent diet intravenously (IV) and solid food orally (CH) for 8 days, and their small intestines and colons compared. All received equal calories. The small intestine was divided into equal proximal (A), middle (B), and distal (C) segments for measurements. Mucosal weight per cm in segments A and B of IG were, respectively, 65 and 38% higher than in IV (P less than 0.01), but 27 and 33% lower than in CH (P less than 0.01). However, in the distal segment, C, mucosal weight in IG was similar to IV and CH was 79% higher (P less than 0.01). DNA and protein followed the same pattern. Segment A sucrase activities were similar in CH and IG and were much higher than in IV (P less than 0.01). Sucrase in IG dropped very rapidly distally so that it became much lower than in CH (P less than 0.05) and similar to IV. Mucosal weight, DNA, and protein in the colon were not significantly different in IG and IV, which were both significantly lower than in CH (P less than 0.01). The results indicate that a chemically defined diet maintains intestinal mass well in the proximal small intestine, but the effect diminishes rapidly in a distal direction so that distal small intestine and colon become atrophied and similar to those in intravenous feeding.

Tissue organ distribution and behavioral effects of platinum following acute and repeated exposure of the mouse to platinum sulfate.

Platinum sulfate was administered intragastrically (IG) to adult male Swiss mice in a single dose at the 7 day LD5 or LD25 level. Control groups received 0.25M H2SO4 (pH 0.85) or 0.14M NaCl. Open field behavior (ambulations, rearings) was measured, and tissue/organ Pt levels determined at 4 hr, or 1, 3, or 7 days post administration. At all times, the LD25 depressed ambulations significantly and rearings marginally. It did not effect exploratory ("hole-in-board") behavior. The LD25 resulted in disproportionately high tissue Pt levels relateive to the LD5. There were significant inverse correlations between behavior and tissue Pt levels for most tissues, but not for brain. In related experiments, adult male mice were subjected to repeated IG administration of Pt(SO4)2 at the LD1 level (one dose every 72 hr for up to 10 doses). Three days after administration of the final dose of each series, open-field and exploratory performance were measured and tissue/organ Pt levels determined. Tissue/organ Pt levels were variable but generally increased with dose number. No Pt was detected in the brain. Activity and explorations were marginally depressed. Only rearings correlated significantly with tissue Pt levels.