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Biomedical subjects

R W Phillips

Publications and source records attributed to R W Phillips.

At least 127 records · Page 7Linked to original sources

Reduced hepatic blood flow does not limit gluconeogenesis in awake endotoxic minipigs.

Hypoglycemia associated with endotoxic shock is due to increased glucose utilization coupled with inadequate hepatic glucogenesis. Decreased hepatic blood flow is common in shock and could conceivably reduce hepatic gluconeogenic substrate and oxygen delivery, thereby limiting gluconeogenesis. A study was conducted to assess endotoxin-induced alteration of hepatic hemodynamics and its effect on glucose metabolism. Eight adult minipigs were fitted with jugular, portal, and hepatic vein and carotid artery catheters, and hepatic artery and portal vein flow cuffs for determination of transhepatic kinetics. Three days later they were infused with endotoxin at 15 micrograms/kg/hr. Hepatic blood flow and portal vein oxygen (O2) content became significantly (P less than or equal to 0.05) reduced thereby decreasing hepatic O2 input. Hepatic O2 extraction increased from 24 to 73% but never achieved the reported maximum of 97%. Therefore, reduction of O2 input did not seem to rate limit gluconeogenesis. Reductions in gluconeogenic substrate delivery were not involved since hepatic lactate and pyruvate input actually increased due to elevated blood lactate and pyruvate concentrations.

Animals↗

A comfortable, minimum stress method of restraint for Yucatan miniature swine.

For comfortable, minimal-stress restraint of Yucatan miniature swine, a heavy cotton duck sling reinforced with nylon webbing and covered with vinyl was used. The sling was designed with four leg openings and one hole for access to the anterior vena cava. Custom padding was used to line the leg holes and minimize chafing. Five sling sizes were developed for the restraint of any size Yucatan miniature pig (3 to 75 kg) or other pigs up to 150 kg. A steel frame on wheels was designed with or without a boat winch crank mechanism to support the interchangeable slings. The pig restraint was accomplished by lifting or hoisting the animal, depending on animal size.

Animals↗

Dissolution of amalgam in saline solution.

This experiment was designed to investigate the in vitro corrosion of several modern dental amalgams in saline solution over a six-month period by measuring changes in the soluble corrosion products. Based on the change of the electrical conductivity of the solution, the dissolution rate seemed to decrease gradually for the first three to four months. Then a rapid increase was observed, indicating a reactivated corrosion process. Larger dissolutions of copper and mercury were observed, especially for the high copper alloys, in these later stages. Zinc and indium, if present, were preferentially released at the earlier stages. Silver and tin could not be detected. Evidence exists that the corrosion of tin results in insoluble deposits of corrosion products.

Copper↗

Portal vein insulin response of glucose intolerant Yucatan miniature swine to common secretogogues.

A group of glucose intolerant miniature swine exhibiting an impaired portal vein insulin response to an IVGTT were examined with respect to their portal vein insulin response to the secretogogues: isoproterenol, arginine and leucine. Equivalent insulin responses to isoproterenol and leucine were noted on the part of the glucose intolerant animals when compared to control subjects. An impaired portal vein insulin response was evident during an infusion of 0.5 g/kg arginine and again when a pulse injection of .25 g/kg glucose was administered in the presence of isoproterenol (.05 microgram/kg . min). The close agreement of these results with those reported for human diabetics suggests that a similar pancreatic defect, most probably associated with the glucoreceptor, is present in this group of glucose intolerant miniature swine.

Animals↗

Dietary effects on metabolism of Yucatan miniature swine selected for low and high glucose utilization.

Yucatan miniature swine have been selected for increased (high K) or decreased (low K) ability to utilize glucose based on an intravenous glucose tolerance test (IVGTT). In this study we tested the effect of obesity in conjunction with ad libitum, high sucrose or high starch diets on IVGTT and the insulin response to glucose in these two lines of animals. Either diet caused increased glucose utilization and an increased insulin response in the low K animals. Neither diet caused a change in these parameters in the high K pigs. There were no differences in either line of animals due to sucrose vs starch diets. During an insulin impedance test both the mean steady state plasma glucose and plasma serum insulin concentration were significantly higher in the high K animals (P less than 0.01).

Animals↗

Influence of genetics and diet on the development of diabetes in Yucatan miniature swine.

The intent of this study was to examine the effect of a diet nutritionally similar to that consumed by most Americans on Yucatan miniature swine that have been bred for enhanced and impaired glucose tolerance. Seventeen Yucatan miniature pigs from the glucose-intolerant line (low K) and 17 from the glucose-tolerant line (high K) were selected. The oral glucose tolerance (OGT) of both groups of pigs was determined. After the OGT test (OGTT), 13 low K pigs and 12 high K pigs were placed on the American Swine Diet (ASD). The remaining animals were left on the regular swine diet. After 5 months, the pigs were again tested with an OGTT. Mean plasma glucose levels observed during the OGTT showed significant differences between the low K and high K groups on ASD at all time intervals from 60 to 150 minutes postdosing. Serum insulin levels in the high K group were significantLy elevated over those in the low K group during the OGTT at 10, 20, and 30 minutes prediet, and at 10 minutes after 5 months on diet. Both low and high K groups showed a dietary effect with aN elevated plasma glucose response to an OGTT, although the mean increase was not significant in the high K group. In the low K group, plasma glucose levels were significantly elevated (P less than 0.05) over prediet values at 20, 30, 60, 90 and 120 minutes. In addition, 7 out of the 10 low K pigs tested at 5 months developed insulin resistance, and noninsulin-dependent diabetes.

Animals↗

Yucatan miniature swine as a model for the study of human diabetes mellitus.

Two lines of Yucatan miniature swine have been developed by genetic selection for decreased and increased glucose clearance during an i.v. glucose tolerance test. The decreased glucose clearance is due to low peripheral insulin levels usually from a decrease in insulin secretion. In two pigs the decreased peripheral insulin resulted from increased hepatic uptake of insulin. During gestation and lactation, an increased insulin resistance and a diabetic-like state occurs in some animals. When fed a low fiber diet that contains 40% of calories from saturated fat (a typical American diet), Yucatan swine become more glucose intolerant. Seven to ten animals on the diet from the glucose intolerant line showed a glucose tolerance curve that would have been classified as diabetic if they were humans utilizing both intravenous and oral glucose tolerance tests. Miniature swine from this line are available to interested researchers.

Animals↗

Assessment of pancreatic and hepatic function in Yucatan miniature swine exhibiting impaired glucose tolerance.

A group of Yucatan miniature swine exhibiting impaired glucose tolerance (Kq = .91 +/- .04), were examined with respect to their portal and hepatic vein insulin levels following a fasting intravenous glucose tolerance test. The majority of these animals (9 of 11) were found to exhibit the expected portal vein insulin deficiency. This deficiency was found to encompass all phases of the insulin response and was not limited to the acute secretory phase. The remaining two animals were found to have normal portal vein insulin concentrations while exhibiting reduced hepatic vein insulin levels, and impaired glucose tolerance. An excessive rate of hepatic insulin extraction is proposed to explain the etiology of the insulin deficiency and glucose intolerance observed in these latter two animals.

Animals↗

Prostaglandins and their metabolites in the gastrointestinal tract of Yucatan miniature swine.

Concentration of prostaglandins E1, E2, F2alpha, and 15 keto, 13, 14-dihydro F2alpha (MPF2alpha), were measured in gastric, duodenal, jejunal, and ileal mucosa, and in the luminal contents of these gastrointestinal segments in miniature swine at 30, 60, and 120 min after they ingested a liquid nutrient meal. Large quantities of E1 and F2alpha were present in gastric contents at 30 min with lesser amounts of E2 and MPF2alpha. The concentrations of E1, E2, and F2alpha in the gastric contents decreased progressively with time after feeding. The total quantity and the concentrations of E1 and F2alpha decreased with passage of ingesta through the duodenum and jejunum. Mucosal concentrations of E1 and F2alpha were greatest in the duodenum and proximal jejunum and lowest in gastric mucosa. These results indicate that there is considerable production and metabolism of prostaglandins in the gastrointestinal tract, with major amounts secreted into the luminal contents of the stomach and duodenum after food intake.

Alprostadil↗

Effects of osmolality of liquid nutrient diets on plasma equilibration of water and carbohydrate in Yucatan miniature swine.

Osmolality of a liquid diet was varied from 250 to 700 mOsm/kg by altering the amount of sucrose and corn syrup solids, while maintaining the same level of calories, protein, and electrolytes. The appearance of 3H and 14C in blood plasma were monitored during a 4-h period after pigs voluntarily consumed one of five diets labeled with 3H2O and U-14C-sucrose. Plasma osmolality and sodium and potassium concentrations in plasma did not differ among the diets. Postprandial plasma glucose concentration response to the diets varied both between and within treatments. The rates of radioactive tracer appearance in plasma suggest that water and carbohydrate absorption were accelerated with increasing osmolality of diet up to 700 mOsm/kg.

Absorption↗

Effects of osmolality of liquid nutrient diets on meal passage and nutrient absorption in Yucatan miniature swine.

The effects of varying the osmolality of liquid nutrient diets on the absorption of water, electrolytes, and carbohydrate from the small intestine were studied in Yucatan miniature swine. Pigs were killed and their gastrointestinal contents recovered at either 30 or 60 min after consuming liquid diets adjusted to 340, 450, 540, or 700 mOsm/kg and labeled with 3H2O, 22NaCl, U--14C-sucrose, and 51Cr-EDTA as a passage marker. Intragastric dilution and gastric emptying were not effected by diet osmolality. Gastric contents of all pigs converged toward 450 mOsm/kg, and osmolality of small intestine contents did not differ between diets. The absorption of carbohydrate, water, sodium, and potassium from jejunal contents increased with increasing osmolality of the diets. The rates of appearance of 3H, 22Na, and 14C in plasma also increased with increasing diet osmolality. These findings suggest that moderately hyperosmotic liquid diets may be beneficial, as compared with isoosmotic diets.

Absorption↗