Electrical contact and pregnancy.
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Biomedical subjects
Publications and source records attributed to A B Moore.
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The objective was to determine whether exogenous insulin and dietary energy interact to affect follicular development in gilts. In a 2 x 2 x 2 completely randomized design, main effects were level of dietary energy (5771 or 9960 kcal metabolizable energy/day beginning on Day 12 of the estrous cycle), insulin dosage (0 or 0.4 IU/kg twice daily beginning on Day 15 of the cycle), and day of cycle at ovary removal (Day 17 or Day 19). Percentage of follicles designated small (less than or equal to 3 mm diameter) decreased from Day 17 to Day 19 of the cycle, and the percentage of large follicles (greater than or equal to 7 mm) increased (p less than 0.05). Insulin interacted with day of the cycle (p less than 0.05) to affect distribution of medium (4-6 mm) and macroscopically atretic follicles. Percentage of atretic follicles increased from Day 17 to Day 19 in saline-treated (from 15.5% to 38.2%) but not in insulin-treated animals (6.3% to 10.7%). Percentage of medium (4-6 mm) follicles decreased from Day 17 to Day 19 in saline-treated gilts (from 41.7 to 16.6%) but not in insulin-treated gilts (39.8% to 35.1%). Intrafollicular testosterone and progesterone concentrations were not affected by treatments. In medium follicles, the ratio of estradiol to progesterone was greater (p less than 0.05) for insulin-treated gilts on Day 17 than for the other treatment combinations.(ABSTRACT TRUNCATED AT 250 WORDS)
Microcapsules made from a biocompatible, biodegradable polymeric excipient, poly(DL-lactide-co-glycolide) (DL-PLGA) that contained 22 weight percent (wt %) norethisterone (NET), were prepared by a solvent-evaporation microencapsulation process. The effects of changing both the lactide-to-glycolide ratio of the DL-PLGA and the size of the microcapsules on the rate of NET release and the rate of excipient biodegradation were determined in vivo. NET release rates were determined in baboons after injecting the microcapsule formulations intramuscularly. Serum samples obtained at various times following treatment were analyzed for NET, progesterone, and estrogen by radioimmunoassay (RIA). Biodegradation kinetics were determined by injecting NET microcapsules made from radiolabeled DL-PLGA intramuscularly into the hind legs of rats. Residual radioactivity at the injection site was determined at various times after treatment by combustion analysis of the muscle tissue. Changing the ratio of the comonomers to include more glycolide (DL-lactide:glycolide-96:4, 92:8, 87:13, 74:26) increased the rate of NET release and accelerated the biodegradation of the copolymer excipient. Decreasing the size of the microcapsules increased the rate of NET release. On the basis of these studies a NET microcapsule formulation has been identified for clinical testing which releases NET for 3 months and biodegrades completely within 6 months.
The value of naloxone (1 mg/kg of body weight/hr for 4 hrs), a beta-endorphin antagonist, was assessed in the management of endotoxin-induced shock in ponies. Three groups of 5 ponies each were used: controls, ponies given Escherichia coli endotoxin put untreated, and ponies given endotoxin and then treated with naloxone. Endotoxin-induced changes in hemodynamics, blood chemical values, regional blood flow, plasma enzymes, and energy supplies were measured at selected times during the first 6 hours after endotoxin was given. There was no evidence that beta-endorphins released during shock were responsible for the hemodynamic changes, blood flow changes, plasma enzyme changes, or energy deficits, because naloxone, at this dosage level, did not prevent these endotoxin-induced changes.
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One minute after instillation of 14C-estradiol-17 beta (14C-E2 17 beta) into selected sections of the gastrointestinal tract of swine, radioactive estradiol metabolites were present in blood collected from the portal and jugular veins. Ether was used to extract free but not conjugated estrogens. The percentage of plasma radioactivity that was ether extractable (EE) was low in portal plasma and even lower in jugular plasma following instillation of 14C-E2 17 beta into the stomach, ileum and colon. EE radioactivity was not detectable in either portal or jugular plasma when estradiol was instilled into the duodenum or jejunum. Therefore, estrogens were conjugated either in the lumen of the gastrointestinal tract or as they crossed the intestinal mucosa. The liver played only a minor role in conjugation of these steroids, since the estrogen metabolites present in portal plasma were very similar to those in jugular plasma, and metabolites in the urine were similar to those in plasma. The principal estrogen conjugate found in both portal and jugular plasma, regardless of the gastrointestinal section into which 14C-E2 17 beta was instilled, was estrone glucuronide. There was no uniform metabolic pattern observed in the metabolites of estradiol that remained in the lumen of each gastrointestinal section; however, many metabolic transformations occurred. We concluded that almost all estrogens absorbed were metabolized during the absorption process. The liver was active only in the metabolism of estrogens that escaped conjugation in the intestinal mucosa.
Studies were conducted to determine the absorption and metabolic fate of orally administered 3H-estradiol-17 beta-glucuronide (3H-E2-G) in swine. Xylazine-tranquilized female pigs (5 to 6 wk old) were given .04, .4 or 4 mumol 3H-E2-G via stomach tube, and blood samples were collected from previously implanted jugular cannulas for 12 or 72 h. The entire gastrointestinal tract was removed from gilts euthanatized 12 h post-treatment, and free and conjugated estrogens were isolated from plasma and intestinal chyme by diethyl ether extraction and adsorption to Amberlite XAD-2 resin columns. After preparative thin layer chromatography of the conjugate fractions, the conjugates were cleaved by enzyme hydrolysis, solvolysis or acid hydrolysis. The freed estrogens were identified by thin layer chromatography. Plasma radioactivity peaked between 6 and 8 h after administration of the conjugate. None of the radioactivity in plasma was ether extractable. There was evidence for a decrease in absorption rate of radioactive estrogen in the high dosage group. The pattern of metabolites and urinary excretion or orally administered 3H-E2-G was similar to that reported for 14C-E2, except for the greater proportion of polar metabolites and delayed absorption, probably reflecting the need for the conjugate to be hydrolyzed first. The greater proportion of polar metabolites found in this study may have been due to the longer treatment period rather than the administration of the conjugated form of estradiol.
Studies were conducted to determine the absorption and metabolic fate of 3H-estradiol-17 beta-glucuronide (3H-E2-G) in swine. The conjugate, 3H-E2-G (48.7 x 10(6) DPM, 45.5 Ci/mmol), was injected into ligated 15-cm sections of duodenum, proximal jejunum, distal jejunum, ileum and spiral colon of 10 kg female pigs. Blood from the jugular and portal veins and urine were collected at .5-h intervals for 5 h. Absorption from the colon was rapid and radioactivity peaked in both portal and jugular plasma by .5 h postinjection. In contrast, the highest plasma estrogen concentration from most other sections was reached at 5 h, the last sampling time. The urinary excretion patterns were nearly identical to those seen in plasma, with the radioactivity peaking early (1.5 h) after instillation of 3H-E2-G into the colon, but still rising at the end of the experiment after instillation into the duodenum, distal jejunum and ileum. The proximal jejunum, which produced low plasma estrogen concentrations, also produced low urine concentrations. The slower absorption of 3H-E2-G compared to 14C-estradiol-17 beta is consistent with the view that the limiting factor for the absorption of the conjugate is hydrolysis to a free estrogen. The predominant metabolites in portal venous plasma from all sections of the intestine at the end of the experiments were the monoglucuronides of estrone and estradiol. Because the administered 3H-E2-G was conjugated at C-17, the presence of estrone glucuronide in portal plasma indicates that, at least in the duodenum, ileum and colon, 3H-E2-G undergoes cleavage, followed by the oxidation of estradiol to estrone, which is subsequently reconjugated by the intestinal mucosa.
A study was made of flunixin meglumine (FM), an analgesic agent with antiprostaglandin activity, in the management of endotoxin-induced changes in ponies. Three groups of 5 ponies each were used: A--controls, B--nontreated ponies with endotoxin-induced shock, and C--ponies with endotoxin-induced shock treated with FM. Shock was induced in anesthetized ponies with IV injections of Escherichia coli endotoxin. Disruption of glucose homeostasis, insulin levels, hemograms, aerobic metabolism, and cell damage as indicated by plasma enzymes were observed. Treatment with FM (5 minutes) after shock was induced did not prevent general tissue damage as indicated by plasma enzymes, but separation of creatine phosphokinase into its 3 isoenzymes revealed a significant increase in the amount of the creatine phosphokinase isoenzyme bb in group B ponies, but not in FM-treated ponies (group C). The source of this isoenzyme is believed to be brain tissue. Acidosis as indicated by lactic acid and venous pH was less in FM-treated ponies than in nontreated (group B) ponies. Blood glucose and insulin concentrations changed in both groups B and C (endotoxin-induced shock), but the patterns of change were different. The only effect of FM on hematologic values was a significant decrease in blood platelet counts. The results of these experiments indicate that FM improved cellular metabolism and reduced brain damage. These effects were believed to be the result of the maintenance of mean arterial blood pressure and enhanced perfusion of vital organs by preventing extensive vasodilation in the gastrointestinal tract.
The effects of dexamethasone (1 mg/kg of body weight) on hematologic, blood gas, and blood coagulation values in anesthetized ponies during endotoxin-induced shock were evaluated. Fifteen ponies were assigned to 3 groups of 5 ponies each: group 1, anesthetized nontreated and dexamethasone-treated controls; group 2, endotoxin, nontreated; group 3, endotoxin, dexamethasone treated. The hematologic changes in this endotoxin shock model included leukopenia and hemoconcentration. Significant hematologic effects were not seen in ponies after administration of dexamethasone. However, dexamethasone treatment resulted in an increased trend in total WBC counts and neutrophils. The blood gas changes reflected a respiratory component resulting from anesthesia and a greater metabolic component from the endotoxemia. The plasma lactate increase was significantly (P less than 0.05) less in ponies treated with dexamethasone, compared with plasma lactate in non-treated ponies. During endotoxin shock, the changes observed in the blood coagulation values included a significant (P less than 0.05) prolongation of the activated partial thromboplastin time and thrombin time and an insignificant prolongation of the prothrombin time. Dexamethasone treatment prevented prolongation of thrombin time and permitted only a mild prolongation of activated partial thromboplastin time. Seemingly, corticosteroids are useful in the treatment of clinical endotoxin shock in horses as indicated by their desirable effects on total WBC, neutrophils, cellular metabolism, and blood coagulation.
External cardiac massage and concomitant respiratory support were used successfully 6 of 8 anesthetized ponies sustaining unexpected cardiac arrest while being used in a study of shock. Approximately 20 thoracic compressions/min maintained systolic and diastolic aortic blood pressures in excess of 50% of the corresponding base-line values in 5 ponies. The high success rate was attributed to early recognition of the problem, the small size of the patient, and the relatively short duration of cardiopulmonary resuscitation (average, 2.9 minutes). It was concluded that external cardiac message can be effective for cardiopulmonary resuscitation in selected equine patients that have sustained cardiac arrest.
A study was made of flunixin meglumine, an analgesic agent with antiinflammatory and antiprostaglandin activity, for the management of endotoxin-induced cardiovascular derangements. Three groups of 5 ponies each were used: controls--group 1; given endotoxin but not treated--group 2; and given endotoxin and treated with flunixin meglumine--group 3. Shock was induced in anesthetized ponies with IV injection of Escherichia coli endotoxin. Hemodynamic changes were monitored, and regional blood flow was determined at 4 different times, using microspheres labeled with 1 of 4 nuclides. There were extensive vasodilation and decreased blood return to the heart of group 2 ponies, as indicated by decreased mean arterial blood pressure and central venous pressure and by increased heart rate and cardiac output. Blood flow, as determined by radioactive microspheres, to gastrointestinal regions, skeletal muscle, and skin was increased and that to the CNS was decreased. Treatment with flunixin meglumine (group 3 ponies) exerted selective microvascular actions which helped to reverse endotoxin-induced changes. This included the maintenance of mean arterial blood pressure and the enhanced perfusion of vital organs (eg, brain and heart) by preventing extensive vasodilation in the gastrointestinal tract.
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