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Clearance rate of gonadotrophin releasing hormone in peripheral plasma of the pig.

Gonadotrophin releasing hormone was administered as an intravenous bolus injection into four boars and four ovariectomized sows. Radioimmunoassay of concentrations of gonadotrophin releasing hormone in blood collected periodically after injection indicated a biexponential decline suggesting a rapid distribution to the extracellular fluid and a slower elimination by metabolism. A mean half-life value of 2.12 +/- 0.95 (SD) minutes was calculated for the first component and of 13.15 +/- 2.55 minutes was calculated for the second component of the decline in gonadotrophin releasing hormone concentrations. No significant difference was detected between boars and sows for half-life value of either component. In the four boars, luteinizing hormone values reached a peak in plasma 20 minutes after injection and that of testosterone at 90 minutes after gonadotrophin releasing hormone treatment.

Animals↗

Arthritis inflammation monitored by subcutaneous millimeter wave thermography.

A new technique for remote, noninvasive mapping of temperature elevations of the human joints is described; it uses the mm wave radiation emitted by the human body. A solid state switched scanner for 68 GHz is described which overcomes the depth limitations of conventional, infrared thermographs and can measure to subcutaneous depths of several mm with a temperature resolution of 0.25 degrees C. Measurements on rheumatoid arthritic knee joints are presented which show little correlation with simultaneously measured skin temperatures. Significant longterm thermographic changes induced by steroid injection indicate a potential for objective patient monitoring and development of new treatment methods.

Adult↗

Studies on intestinal absorption by single-injection technique and continuous measurement of portal vein blood electrolyte concentration and hematocrit in the alert rat.

Whole blood and ultrafiltrate conductivity in the portal vein (as a measure of hematocrit and total electrolyte concentration, Cel, respectively) and arterial pressure of alert rats were measured continuously. Single intraduodenal injections of solutions iso- and hyperosmotic to blood (0.5 or 1 per cent of body weight) produced characteristic changes which were compared with those after the application of water. Whereas H2O and isosmotic passively absorbed substances (sorbose and urea) caused a very variable Cel drop, isosmotic actively absorbed nutrients elicited individually constant but interindividually different (glucose greater than alanine++ greater than arginine) changes due to solute coupled electrolyte free water transport. This was taken as evidence of variable paracellular shunt permeability playing a role in passive, but not in active absorption. The magnitude of Cel changes was related to absorption rate, which was confirmed by behaviour with hypertonic solutions, where osmotic activity in the gut was lost the sooner, the more rapid absorption rate was. Shunt permeability was temporarily blocked by arginine. Hct changes immediately after injections indicated fluid loss from portal vein blood, which could be evaluated in the case of mannitol. The thickness of the absorptive layer, obtained from latency of Cel change after urea, delivered values not exceeding 0,51 mm for the unstirred layer. The latencies after glucose and alanine were usually not much greater than after urea. Cel rise after hypertonic solutions had the same latency as Cel drop after water. Small arterial pressure changes after nutrient solutions, mostly absent after injections of water and NaCl, indicated circulatory effects originating in the gut in association with the former.

Alanine↗

Removal of Pu and am from beagles and mice by 3,4,3-LICAM(C) or 3,4,3-LICAM(S).

Decorporation of Pu and Am by tetrameric catechoylamide (CAM) ligands has been investigated in beagles and mice. Eight dogs were injected intravenously (iv) with 237 + 239Pu(IV) + 241Am(III) citrate, and 30 min later, pairs of dogs were injected iv with 30 mumole/kg of 3,4,3-LICAM(C) [N1,N5,N10,N14-tetrakis(2,3-dihydroxy-5-sulfobenzoyl)tetr aazatetradecane, tetrasodium salt], 3,4,3-LICAM(S) [N1,N5,N10,N14-tetrakis(2,3-dihydroxy-4-carboxybenzoyl)te traazatetradecane, tetrasodium salt], CaNa3-DTPA, or each of the latter two ligands. Blood was sampled, and excreta were collected for 7 days, at which time the dogs were sacrificed and nuclide retention in liver and nonliver tissue was measured. Groups of five mice were each given 238Pu(IV) or 241Am(III) citrate iv; 3 min later 30 mumole/kg of a CAM ligand was injected intraperitoneally, mice were killed at 24 hr, and separated excreta and tissues were analyzed. In the dogs, average retention at 7 days of the injected Pu and Am, respectively, was as follows: 12 and 70% after treatment with a CAM ligand alone; 30 and 20% after DTPA; 12 and 20% after LICAM(S) plus DTPA; 90 and 89% without a ligand. In the mice, mean retention of the injected Pu and Am, respectively, was as follows: 14 and 66% after treatment with LICAM(C); 21 and 54% after LICAM(S); 91 and 87% without a ligand. In both species, about 99% of net Pu excretion (excretion with ligand - excretion without ligand) promoted in 24 hr by DTPA or LICAM(S) was in the urine, whereas about 10% of net Pu excretion promoted by the less hydrophilic LICAM(C) was in feces. Delayed excretion of both Am and Pu was significant in all ligand-treated dogs. Comparison of the nuclide content of tissues of ligand-treated mice with those of mice killed 3 min after nuclide injection indicated that the CAM ligands chelated circulating Pu and Am and prevented further deposition. In addition, the CAM ligands removed much of the presumably loosely bound Pu present in liver and skeleton at the time of ligand injection. LICAM(C) was more effective in removing Pu from liver and LICAM(S) was more effective in the skeleton. Moderate to severe uremia and histological evidence of cell killing in the distal tubules of the kidney were observed in the four dogs injected once with 30 mumole/kg of LICAM(S).(ABSTRACT TRUNCATED AT 400 WORDS)

Americium↗

D-penicillamine-induced angiopathy in rats. The effect of high dose D-penicillamine treatment on aortic permeability to albumin and on the ultrastructure of the vessel.

Male Sprague-Dawley rats were treated with D-penicillamine (D-pen) 500 mg/kg/day for 10 or 42 days. Pair fed rats served as controls. Changes in aortic morphology were examined by light- and transmission-electron microscopy (TEM). In addition, the endothelial permeability and the penetration through the aortic wall of albumin were studied 10 minutes, 24 and 48 hours after i. v. injection of human serum 131I-albumin (131I-HSA). TEM revealed extensive elastolysis in the arterial wall of D-pen-treated rats, consistent with an inhibitory effect on crosslink formation. In experimental animals excess deposition of collagen and glycoaminoglycans was observed in the subendothelial and medial layer of the aortic wall, together with prominent basal membrane substance around aortic smooth muscle cells. The aorta/serum-ratio and the radioactive build-up 24 and 48 hours after injection of 131I-HSA was reduced in animals treated with D-pen for 42 days, indicating an impeded transmural transport of tracer which may be caused by a steric exclusion effect of abundant hyaluronate. The endothelial ultrastructure was unaffected by D-pen, and no differences in aortic 131I-HSA radioactivity or aorta/serum-ratio were recorded between experimental and control groups 10 minutes after tracer injection, indicating that the permeability of the endothelial barrier to albumin remained unaffected by D-pen treatment. These observations support the hypothesis that treatment with high doses of D-pen may induce a fibroproliferative response in rat aorta, possibly by an inhibitory effect on the cross-linking of collagen and elastin.

Animals↗

Effects of scopolamine and methylscopolamine on classical conditioning of the rabbit nictitating membrane response.

Classical conditioning of the rabbit nictitating membrane response was accomplished by presenting tone- and light-conditioned stimuli for 800 msec before delivery of a 100-msec shock as the unconditioned stimulus. Scopolamine significantly retarded the rate of acquisition and final asymptotic performance of conditioned responses to the tone- and light-conditioned stimuli. Methylscopolamine was approximately 20 times less potent than scopolamine in retarding the rate of acquisition, and had no effect on the final asymptotic performance of conditioned responses. The retardation in acquisition of conditioned responses produced by scopolamine could still be detected 5 days after cessation of drug injections, indicating that the effects of scopolamine were on acquisition and not performance. In contrast, scopolamine and methylscopolamine had no affect on the development of long-term habituation produced by the unpaired presentations of tone, light and shock stimuli. Control experiments indicated that the acquisition of conditioned responses by animals injected with saline, scopolamine or methylscopolamine was not contaminated by the presence of changes in base-line responding, sensitization or pseudoconditioning. In addition, scopolamine and methylscopolamine did not affect the unconditioned nictitating membrane reflex. In previously trained animals, scopolamine produced a significant, approximately 25-db elevation in the intensity threshold of a tone-conditioned stimulus for elicitation of conditioned responses. It was concluded that scopolamine blocks the excitatory properties of tone stimuli and this accounts for its ability to retard the rate of acquisition of conditioned responses.

Acoustic Stimulation↗

Concurrent inductions of avian hepatic lipogenesis, plasma lipids, and plasma apolipoprotein B by estrogen.

The inductions of hepatic fatty acid synthesis, estrogen-specific plasma proteins, plasma lipids, and apolipoproteins by a single subcutaneous injection of diethylstilbestrol (40 mg/kg body weight) have been examined in immature male turkeys. Estrogen induced the appearance of phosvitin, lipovitellin, and apoVLDL-II in the blood plasma. The highest concentrations of these estrogen-specific plasma proteins were observed 48 hr following hormone administration. Estrogen increased the concentration of triglyceride in the liver, predominantly those molecular species containing 16 carbon fatty acids (triglycerides with 53 and 55 carbon atoms). Liver cholesterol was present predominantly as free cholesterol. Although estrogen did not affect the concentrations of free or esterified cholesterol in the liver, the hormone increased the amount of cholesterol esterified with 20-carbon fatty acids and caused a corresponding decrease in cholesterol esterified with 18 carbon fatty acids. Estrogen treatment elevated the plasma triglycerides 55-fold, tripled the plasma phospholipid, and approximately doubled the plasma cholesterol. The de novo synthesis of fatty acids in the liver in vivo was stimulated by estrogen administration, as exhibited by increased 3H2O incorporation into the phospholipids and triglycerides of both liver and plasma. In contrast, hepatic cholesterol synthesis was unaffected. The amounts of newly synthesized triglyceride in the liver and plasma and the specific radioactivities of the plasma triglyceride following 1-hr in vivo labeling periods, 0, 24, 48, and 72 hr after estrogen injection indicate that increased hepatic fatty acid synthesis is a primary and major casuative factor in the development of estrogen-induced hyperglyceridemia in this avian species. The concentration of apolipoprotein B in the plasma increased in parallel with hepatic fatty acid synthesis and the appearance of newly synthesized triglyceride in the plasma, whereas the plasma apolipoprotein A-I level decreased. These observations indicate that in the avian liver estrogen causes a coordination of inductions in the conversion of carbohydrate to triglyceride and in the production of proteins (apolipoprotein B and apoVLDL-II) involved in the assembly of triglyceride-rich lipoprotein particles, leading to hypersecretion of these lipoproteins into the circulation.

Animals↗

High dose netilmicin therapy of severe or chronic infections.

Sixteen patients with chronic or recurrent urinary tract infections, 14 with septicaemia, 2 with salmonellosis, 2 with pneumonia and 1 with acute mastitis were treated with 200 mg (2.2-3.6 mg/kg) netilmicin intramuscularly every 8 hours for 7-10 days (mean 8.8 days). 28 patients were cured, 5 showed marked improvement and 2 patients with septicaemia and severe underlying diseases failed to respond to treatment. The bacterial isolates were inhibited by 4.0 mg netilmicin/l or less. Antibiotic serum level determinations were performed in 32 patients. Mean serum concentrations of netilmicin 1 and 8 hours after injection were 12.6 and 2.0 mg/l respectively in 27 patients with normal serum creatinine levels. In 5 patients with elevated serum creatinine, mean peak and trough values were 21.5 and 5.8 mg/l, respectively. Mean netilmicin concentrations in serum and skin blister fluid obtained from 4 patients were equal 2-3 hours after injection, indicating appropriate tissue penetration. Nephrotoxicity occurred in 2 patients. Ototoxicity was not demonstrated. Netilmicin appears to be an effective and safe drug in the treatment of a variety of bacterial infections.

Adult↗

Effects of gastrin on emptying and composition of digesta of the omasum of sheep.

Three adult sheep were prepared with a denervated pouch of fundus of the abomasum and a reentrant fistula system that connected the remaining proximal and distal portions of the abomasum. The proximal cannula of the reentrant system was close to the omasoabomasal orifice, allowing for easy collection of fluid leaving the omasum. Intravenous injection of 0.5, 1.0, or 2.0 microgram/kg/hr of synthetic human gastrin I caused a marked decrease in flow rate of fluid from the omasum. The concentration of particulate matter in the digesta was inversely related to rate of omasal outflow. An increase in acid output from the denervated abomasal pouch during gastrin injection indicated that the hormone was given at pharmacologically effective doses. Results indicate that gastrin has a modulating effect on the flow of ingesta through the ruminant forestomachs. Actual sites of action were not identified.

Animals↗

Phospholipid metabolism changes in rat tissues in vitro after injections of propranolol.

When added to incubations in vitro. (+/-)-propranolol, a cationic amphiphilic drug, causes profound alterations in incorporation of [32P] orthosphosphate into rat cerebral cortex phospholipids. These include increases in the labeling of phosphatidic acid and polyphosphoinositides abd a decrease in the labeling of phosphatidylcholine. Similar changes occurred in a dose-dependent manner in incubations of cerebral cortex mince, prepared from animals injected i.p. 30 min before death with doses of propranolol ranging from 7.5 to 45 mg/kg. All changes in total incorporation and in labeling pattern had disappeared 3 hr after injection, indicating the reversibility of the effect. Repeated injections of low doses of propranolol (7.5 mg/kg) brought about significant changes in the labeling of brain cortex mince phospholipids, and especially a reduction in total incorporation. Addition of propranolol to kidney and liver minces caused reductions in the labeling of phosphatidylcholine and phosphatidylethanolamine and selective increases in the labeling of acidic lipids, restricted to phosphatidic acid in liver and phosphatidylinositol in kidney. After injection of 45 mg of propranolol per kg, but not at 15 mg/kg, some alterations in the labeling pattern were observed in liver and kidney minces. The differential response of tissues to propranolol injections can be explained on the basis of the pharmacokinetics of drug distribution and clearance and metabolic capacities of the tissues. Changes in phospholipid metabolism may be in part responsible for deleterious side effects that can occur during therapy with high doses of propranolol.

Animals↗

Defleecing effect of betamethasone and other long-acting corticosteroids, their influence on wool growth and some physiological processes in sheep.

The defleecing effects of the long-acting derivatives of prednisolone, triamcinolone and dexamethasone were compared with those of betamethasone alcohol when these steroids were administered at the rate of 3.3 mg/kg liveweight in three equal intramuscular injections of 1.1 mg to Merino wethers. Prednisolone showed no defleecing activity whereas the other steroids produced positive but variable responses. Prolonged depression of wool growth was evident following treatment with dexamethasone esters. Betamethasone alcohol injected intramuscularly at 1.1 mg/kg daily for 3 days produced a similar defleecing response to intravenous infusion of 3.3 mg/kg betamethasone phosphate over 8 days. A range of dose rates (0.3-3.3 mg/kg) of betamethasone as multiple and single intramuscular injections indicated that the minimum effective defleecing dose was approximately 2.1 mg/kg. The response to simultaneous administration of betamethasone and insulin or chlorpropamide (to increase glucose utilization) and glucose or xylazine (to increase hyperglycaemia) suggested that the gluconeogenic role of this steroid had little effect on fibre shedding. Thyroxine (300 micrograms per sheep) administered on the first day with an injection of betamethasone (0.9 mg/kg), and alone daily for 20 days thereafter, did not influence the changes in wool production resulting from betamethasone treatment. These results are discussed in relation to the molecular structure and physiological characteristics of a potentially specific defleecing steroid.

Adrenal Cortex Hormones↗

Disposition of oxytetracycline in the bovine genital tract: systemic vs intrauterine administration.

The distribution of oxytetracycline (OTC) in genital tissues, uterine secretions, milk, and plasma was examined after systemic (IM) and intrauterine (IU) administration at various intervals after administration in normal-cycling diestrous cows and in cows with chronic endometritis. The IM route resulted in OTC concentrations in endometrium and uterine secretions that were higher than were concentrations in plasma and milk over 72 hours. Twenty-four hours after IM administration, OTC concentrations in tissues of the genital tract (ovaries, oviducts, myometrium, serosa, cervix, and vagina), muscles, and udder were 100% higher than were concentrations in plasma. The IU administration resulted in a high concentration in the endometrium and uterine cavity over the 72-hour posttreatment period. The plasma concentrations were considerably lower than after the IM injection, indicating a lesser absorption from the uterus than from the IM injection site. This was more pronounced in cows with endometritis. Elimination from plasma and milk occurred in 24 hours. Contrary to results of the IM route, the IU route did not result in detectable concentrations in genital tissues apart from the endometrium 24 hours after administration.

Animals↗

[Epidural application of opiates in chronic pain due to malignoma (author's transl)].

In 75 patients epidural opiates were applied for relief of chronic cancer pain. In order to avoid local infection during long-term therapy part of the catheter was placed subcutaneously. Different opiates were used separately or in combination with local anaesthetics to define the degree and duration of pain relief after epidural opiate application. Haemodynamic and respiratory parameters, changes in lower extremity blood supply and other side-effects were recorded during epidural pain therapy. Epidural opiate application cause a long-lasting reduction of pain, which may become restricted during long-term or repeated use, especially after a period of systemic opiate therapy. Side-effects, for example slight respiratory depression in the first hour after injection, indicate an initial phase of resorption beeing followed by a long-lasting reduction of pain without attendant symptoms. Keeping in mind certain precautions epidural opiate therapy is superior to systemic opiate application.

Adult↗

Muscle irritation caused by different products containing oxytetracycline.

Muscle irritation studies were done in rabbits using 9 different commercial products. Eight products had propylene glycol and 1 had polyvinylpyrrolidone as a vehicle. Macroscopical examination 3,6 and 10 days after intramuscular injection indicated that the irritation caused by the 8 products with propylene glycol as a vehicle were very similar. The product with polyvinylpyrrolidone caused much less damage and healing took place more quickly. Saline used as a control caused no tissue damage.

Animals↗

Induction of canine in vitro reactivity to alloantigen following intralymphatic immunization.

An experimental model has been developed using the dog to study the induction of systemic cell-mediated immunity following intralymphatic immunization (ILI) with allogenic cells. As detected in one-way mixed lymphocyte cultures, blastogenically-reactive immune peripheral blood lymphocytes were observed after the third ILI with 10(7) cells. The in vitro reactivity was augmented by a fourth ILI to a node not previously injected indicating that a response in one node was followed by the trafficing of memory cells to other nodes. No immune PBL were detected after four ILI with lower doses of 10(3) cells. However, these dogs subsequently responded to a single injection of 10(7) cells with high levels of immune lymphocytes which were detectable for up to 24 days. Apparently, ILI with 10(3) or 10(5) cells, while insufficient to produce detectable levels of alloreactive lymphocytes were sufficient for lymphocyte priming. Results obtained with this model will aid in ongoing human trials of intralymphatic immunotherapy of malignant disease.

Animals↗

Half-life of 13,14-dihydro-15-keto prostaglandin f2 alpha in peripheral plasma of the pig.

The metabolite of prostaglandin F2 alpha (PGF2 alpha ) namely 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM), was administered as an intravenous bolus injection into five adult pigs. Concentrations of PGFM in blood collected periodically after injection indicated a biexponential decline suggesting a rapid distribution to the extracellular fluid and a slower elimination by metabolism. A mean half-life value of 14.97 +/- 1.33 (SD) minutes was calculated for the second component of the decline in PGFM concentration.

Animals↗

Practical considerations for the use of a pulmonary artery thermistor catheter.

The use of a pulmonary artery thermistor catheter for pressure measurement and thermodilution cardiac output determination was evaluated in 11 dogs. Pulmonary artery wedge pressure was a reliable index of left atrial pressure at end-expiratory pressures less than 10 cm. H2O. Fluctuations in pulmonary artery temperature occurred at a frequency equal to the respiratory rate and an amplitude of 0.010 to 0.086 degrees C. Changes in amplitude were associated with changes in ventilatory waveform, respiratory rate, and level of anesthesia. Intermittent and continuous positive-pressure ventilation generally dampened and reversed the pulmonary artery temperature pattern exhibited during spontaneous breathing. This suggested that when end expiration is used to time indicator injection, cardiac output will be underestimated during spontaneous breathing and overestimated during continuous or intermittent positive-pressure ventilation. When indicator was injected at the same point in the ventilatory cycle, successive values of cardiac output deviated from one another by 0.0 to 6.7 percent. Deviations as large as 14 percent resulted if sequential injections were out of phase by half a respiratory cycle. These deviations can be minimized by injecting indicator at the same point in the respiratory cycle, if it is not feasible to measure cardiac output during apnea. The clinical utility of a pulmonary artery thermistor catheter can be optimized through appreciation of its specific strengths and limitations.

Animals↗