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Biomedical subjects

J R Bailey

Publications and source records attributed to J R Bailey.

At least 55 records · Page 3Linked to original sources

Perfusion-independent oxygen extraction in myoglobin-rich hearts.

Cardiac myoglobin plays a role in oxygen consumption and has a protective effect during periods of hypoxia, but little is known about the role of myoglobin during periods of ischaemia. Myoglobin-rich sea raven hearts and myoglobin-poor ocean pout hearts were isolated and perfused at varying flow rates and under conditions of low and high oxygen demand to assess the role of myoglobin in oxygen extraction. In the myoglobin-rich hearts, oxygen extraction remained constant over the flow range. In the myoglobin-poor hearts, oxygen extraction was significantly elevated, relative to controls, at the lower flow rates but decreased as the flow rate increased. In hearts where myoglobin was inactivated by an oxidizing agent, oxygen extraction was similar to that observed in myoglobin-poor hearts. Under conditions of high oxygen demand, myoglobin-rich hearts again showed a constant oxygen extraction over the flow range. Myoglobin-inactivated hearts had a significantly elevated oxygen extraction at low flows, and this decreased as flow rate increased. These data suggest that myoglobin renders oxygen extraction by fish hearts independent of the rate of perfusion.

Animals↗

Enhancement of estradiol potency by the 17 beta-hydroxysteroid dehydrogenase inhibitor, 16-methylene E2 in vivo.

The ability of 16-methylene E2, a 17 beta-hydroxysteroid dehydrogenase inhibitor, to enhance estradiol 17 beta (E2) potency was assayed by 24-hr weight gain in the immature rat uterus. Initial studies demonstrated that 16-methylene E2 (1-100 micrograms s.c.) did not produce significant uterine weight gain 24 hr after administration, whereas E2 (0.1-10 micrograms s.c.) produced a significant uterine weight gain under the same experimental conditions. A subthreshold dose of E2 (0.01 microgram s.c.) when administered in combination with 100 micrograms (s.c.) of 16-methylene E2 produced a significant uterine weight gain. When rats were predosed with 16-methylene E2 at 72, 48, 24, 6 or 0 hr before the administration of 0.01 microgram of E2, the magnitude of the 24-hr uterine weight gain increased and attained maximal values for the 6-hr pretreatment time point. A subsequent dose-response study of 16-methylene E2 (1-100 micrograms s.c.) administered 6 hr before 0.01 microgram of E2 revealed that the 10, 50 and 100 microgram 16-methylene E2 dose significantly increased uterine weight gain in a dose-dependent manner. These results indicate that 16-methylene E2 is not a direct acting estrogen but acts synergistically with E2 to produce an enhanced uterine response. In a separate set of monkey experiments: 1) A trace dose of [3H]E2 was perfused through the in situ, term rhesus monkey placenta via the umbilical arteries and samples were collected from the umbilical vein of this open system.(ABSTRACT TRUNCATED AT 250 WORDS)

17-Hydroxysteroid Dehydrogenases↗

Acute effects of delta-9-tetrahydrocannabinol in rhesus monkeys as measured by performance in a battery of complex operant tests.

Acute effects of delta-9-tetrahydrocannabinol (THC) were assessed using a battery of food-reinforced complex operant tasks that included responding under delayed matching to sample (DMTS, n = 6), conditioned position response (CPR, n = 8) progressive ratio (PR, n = 8), temporal response differentiation (TRD, n = 3) and incremental repeated acquisition (IRA, n = 9) tasks. THC (0.003-0.3 mg/kg i.v.) given 15-min presession produced dose-dependent decreases in the number of reinforcers obtained in each task. TRD accuracy was decreased significantly at doses as low as 0.03 mg/kg, making TRD accuracy the most sensitive parameter measured. For PR, the break-point (number of responses emitted for the last reinforcer earned) was decreased significantly only at 0.3 mg/kg. Significant disruptions of performance in schedules other than PR were evident at doses of 0.1 mg/kg and above: response rates decreased or latencies to respond increased. Accuracy of responding was not altered in the IRA, DMTS or CPR tests at doses less than those that decreased response rates. The relative sensitivities of these tests for detecting THC behavioral effects were thus TRD greater than IRA = DMTS = CPR greater than PR. These results indicate that THC, at doses that produce plasma levels similar to those noted in humans after marijuana smoke exposure, produce acute behavioral effects on temporal differentiation in monkeys analogous to some effects reported in humans.

Animals↗

Fetal disposition of delta 9-tetrahydrocannabinol (THC) during late pregnancy in the rhesus monkey.

Three late-term (Gestational Days 146-151) rhesus monkeys were given 0.3 mg/kg delta 9-tetrahydrocannabinol (THC) intravenously via the maternal radial vein to quantify the placental transfer and fetal disposition of THC, the major psychoactive component of marijuana. Simultaneous blood samples were obtained from a maternal uterine vein and an intraplacental artery at 0, 3, 15, 30, 45, 60, 90, 120, and 180 min after dosing using an intraplacental cannulation technique. Samples of fetal plasma, spleen, testis, lung, brain, liver, bile, kidney, adrenals, thymus, and placenta were obtained at 180 min postdose. Samples were analyzed for THC and a major metabolite, 11-nor-9-carboxy-THC (11-nor), by radioimmunoassay (RIA). Peak plasma THC values were obtained 3 and 15 min after dosing in the mother (1419 ng/ml) and fetus (83 ng/ml), respectively. By 3 hr, maternal and fetal plasma THC levels were equal (37 ng/ml). Maternal plasma was sampled beyond 180 min at 24, 48, 72, and 96 hr postdose, times at which THC and 11-nor concentrations were either near or at the lower limit of sensitivity for the RIA (2 ng/ml). While maternal plasma 11-nor levels peaked at 1 hr (44 ng/ml), almost no 11-nor was detected in fetal plasma (less than 5 ng/ml). Fetal tissue concentrations of THC were 53 +/- 6 ng/g (SE) for brain and 114 +/- 10 ng/g for liver, while 11-nor was undetectable in placenta, fetal liver, and fetal brain. These data demonstrate that THC rapidly crosses the placenta and enters the fetus. The lack of 11-nor in fetal plasma and tissues suggests that this metabolite does not readily cross the placenta and that the fetus does not readily metabolize THC to 11-nor at this stage of development. A portion of this data was presented at the 1985 meeting of The American Society of Primatologists and at the 1986 meeting of The Teratology Society.

Animals↗

Function of myoglobin in oxygen consumption by isolated perfused fish hearts.

Myoglobin, an intracellular O2-binding protein, plays a protective role in maintaining performance of isolated fish hearts under hypoxic conditions. This study was designed to test the hypothesis that the protein contributes to O2 consumption under conditions of increased O2 demand or hypoxia. Isolated myoglobin-rich sea raven (Hemitripterus americanus) hearts and myoglobin-poor ocean pout (Macrozoarces americanus) hearts were perfused under conditions of changing partial pressure of O2 (PO2) and afterload. Sea raven hearts maintained O2 consumption and cardiac performance at low PO2 and high afterload, whereas ocean pout hearts did not. In other cases sea raven and ocean pout hearts were treated with hydroxylamine, which renders myoglobin incapable of binding O2, and subjected to changing PO2 and afterload. Sea raven hearts could not maintain O2 consumption and cardiac performance, whereas hydroxylamine treatment had no effect on O2 consumption in ocean pout hearts under these conditions. These data provide the first evidence to support the concept that myoglobin plays a role in O2 consumption of hearts.

Animals↗

Transplacental metabolism of dexamethasone and cortisol in the late gestational age rhesus monkey (Macaca mulatta).

The synthetic glucocorticoid dexamethasone (DEX) and endogenous cortisol were compared in 2 groups of pregnant monkeys of gestational age 143-148 days. In group I, a fetal intraplacental vein and a maternal femoral vessel were catheterized. 3H-Cortisol and 14C-DEX were administered intravenously along with 0.2 mg/kg unlabelled DEX to the mother. Blood and tissue samples were collected to 3 h and urine and feces to 96 h. In group II, 4 of the 7 animals were predosed with DEX 10 mg/kg s.c. for 3 days prior to surgery. The fetus was removed by cesarean section and the in situ placenta was perfused via the umbilical arteries at 15 ml/min X 8 min with 3H-cortisol/14C-DEX in Hanks' balanced salt solution. Samples were taken from the umbilical vein and uterine vein. In group I, HPLC analysis of paired maternal and fetal plasma samples taken at 10, 20, 60, 120 and 180 min after dosing indicated that the F/M DEX ratio was significantly greater than the F/M cortisol ratio. In fetal lung and liver tissues analyzed, less than 2% of the cortisol remained unmetabolized by 3 h, whereas greater than or equal to 76% DEX remained as parent compound. There was no significant difference between the percentage of DEX (83 +/- 7%) and cortisol (73 +/- 3%) recovery in maternal urine and feces. In group II, HPLC analysis of paired umbilical vein and uterine vein samples at 2, 4 and 8 min showed that by 8 min 24% of cortisol was converted to cortisone by the uteroplacenta, but only 2.5% of DEX was converted to a metabolite. In DEX-pretreated animals both uterine vein and umbilical vein samples indicated an increase in cortisol to cortisone conversion. A significant increase in DEX metabolism was evident in the uterine vein samples but not the umbilical vein. These data indicate that the fetus is exposed to a higher proportion of DEX than cortisol and that the uteroplacenta plays a larger role in cortisol than in DEX metabolism. In addition, these data suggest that DEX pretreatment enhances the ability of the uteroplacenta to convert cortisol to cortisone.

Animals↗

Dexamethasone increases UDP-glucuronyltransferase activity towards bilirubin, oestradiol and testosterone in foetal liver from rhesus monkey during late gestation.

We previously showed that in perinatal rhesus monkeys hepatic UDP-glucuronyltransferase activities appear to develop differentially in two clusters, analogous to those of the rat. We demonstrate here that hepatic UDP-glucuronyltransferase activities differ between the rat and the rhesus monkey in their response to glucocorticoids. Treatment of pregnant rhesus monkeys with dexamethasone during late gestation increases UDP-glucuronyltransferase activities towards bilirubin, oestradiol and testosterone in the foetal-liver microsomal fraction to 25, 4 and 4 times their low control values respectively. Analogous dexamethasone treatment in rat fails to increase these activities significantly in the foetal liver. These findings suggest that maternal glucocorticoid therapy in late gestation could greatly increase the newborn primate's capacity to glucuronidate bilirubin.

Animals↗

Renal handling of sodium chloride and its control in birds.

Avian kidneys show features of both mammalian and non-mammalian kidneys, possessing cortical reptilian-type (RT) and medullary mammalian-type (MT) nephrons, blood supplies from renal arterial and renal portal systems, and a primitive macula densa. To determine how these morphological characteristics contribute to unique renal functions, we examined first a possible functional link between the renal tubules and the preglomerular vasculature and, second, the function of the loop of Henle of the MT nephrons. Infusion of 5% NaCl (2.0 ml/kg/h) into the renal portal system of the pullet Gallus domesticus caused diuresis and natriuresis in the infused side, whereas infusion of the same dose into the systemic circulation showed no effect. Infusion of 10% NaCl at a higher flow rate into either the renal portal or systemic routes caused hypernaturemia and a prolonged antidiuresis, presumably due to a release of arginine vasotocin. Plasma renin activity (PRA) decreased during renal portal infusion of hypertonic saline, suggesting that increases in intratubular or peritubular NaCl levels may suppress PRA. The thick limb of the loop of Henle (TLH) isolated from the MT nephron of the quail Coturnix coturnix revealed a lumen-positive, furosemide-sensitive transepithelial voltage (Vt) that requires the presence of both Na and Cl. Net water flux (Jv) was nearly zero when the TLH was perfused and bathed with isosmotic solution. Net water flux increased only slightly and osmotic water permeability (Lp) was low when the osmotic gradient was imposed. Vasotocin altered neither Vt, Jv, nor Lp. Chloride efflux was higher than Cl influx, and net Cl absorption was comparable to that of the TLH of the mammalian kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Renal response of fowl to hypertonic saline infusion into the renal portal system.

The avian kidney has a dual blood supply: one arising from the renal arteries and the other from the renal portal system. In anesthetized pullets (Gallus gallus) two major shunt pathways bypassing the kidney were occluded to ensure the venous blood returning from the leg suffuses the peritubular sites before it enters the systemic circulation. Urine was collected from the ureteral orifices. When 5% NaCl (2.0 ml X kg-1 X h-1) was infused for 20 min into the renal portal system, urine flow and urinary NaCl concentrations and excretion rates increased immediately in the infused side. Infusion of 5% NaCl into the systemic circulation produced no natriuresis. Infusion of 10% NaCl (4.0 ml X kg-1 X h-1), into either the systemic or renal portal route, caused a prolonged antidiuresis. Plasma renin activity (PRA) decreased after portal infusion of 5% NaCl and after both portal and systemic infusion of 10% NaCl. These results suggest that 1) infusion of hypertonic saline into the renal portal system produces local renal effects and 2) increases in tubular or peritubular NaCl levels may suppress PRA.

Animals↗

UDP-glucuronyltransferase activity exhibits two developmental groups in liver from foetal rhesus monkeys.

UDP-glucuronyltransferase was assayed in liver from adult rhesus monkeys and foetuses during late gestation. Activities toward 2-aminophenol, 5-hydroxytryptamine, 1-naphthol and 4-nitrophenol in the foetal liver ranged from 46 to 114% of adult values, whereas activities toward bilirubin, oestradiol and testosterone were less than 5% of adult values. This suggests that in primates UDP-glucuronyltransferase develops differentially in two clusters analogous to that in the rat.

Animals↗

Maternal, fetal, and neonatal elimination of ethanol in nonhuman primates.

Three cynomolgus and 6 rhesus monkeys (106-160 days gestational age) were administered ethanol (0.8-1.5 g/kg i.v.) over a 30-min period. Blood samples were drawn under anesthesia from catheters in the maternal femoral artery, fetal umbilical circulation and/or neonatal umbilical artery. Comparison of maternal/fetal blood sample pairs from 60 to 300 min after initiation of the ethanol infusion revealed a significant correlation of blood ethanol concentration (r = 0.968, p less than 0.001). Thus, during the elimination phase, maternal blood ethanol concentrations are predictive of fetal blood ethanol concentrations. In three studies where the fetus was delivered 2 h after the infusion of ethanol, the neonatal rates of elimination were observed to be approximately 1/4 those of the mother. These data indicate that during the last third of nonhuman primate pregnancy, the maternal component of ethanol elimination appears to be the predominant factor in the overall rate of fetal ethanol elimination.

Animals↗

Differences in eye-hand motor coordination of video-game users and non-users.

The recent proliferation of electronic video games has caused an outcry from those who question the merits of the games, while others maintain the games improve eye-hand coordination. At present, no empirical data are available to indicate whether there are differences in eye-hand coordination between video game users and non-users. Comparing 31 video game users and 31 non-users showed users have significantly better eye-hand motor coordination on a pursuit rotor. However, no relationship was found between an individual's eye-hand motor coordination and the amount of time spent weekly playing video games or the length of experience with video games.

Adult↗

Hepatotoxic effects of estradiol-17 beta-D-glucuronide in the rat and monkey.

The steroid D-ring glucuronide conjugate estradiol-17 beta-D-glucuronide (E217G) but not the A-ring conjugate E23-glucuronide (E23G) has been shown to inhibit bile flow in the rat. To determine if primates are also sensitive to E217G-induced cholestasis, a noninvasive approach with the use of indocyanine green (ICG), a dye eliminated primarily by biliary excretion, was first validated in the rat and then applied to the rhesus monkey. ICG (16 mg/kg rat; 4 mg/kg monkey) was administered i.v. 10 min after an i.v. bolus dose of either E217G (5.5 or 11 mumol/kg), E23G (11 mumol/kg) or vehicle alone. In the rat, the elimination T1/2 of ICG was increased by the 11 mumol/kg dose of E217G (P less than .025), whereas E23G produced no significant change from vehicle control values. In the monkey, the 5.5 and 11 mumol/kg doses of E217G increased the T1/2 of ICG in a dose-related manner (P less than .005), whereas E23G was without effect. Plasma levels of total radioactivity demonstrated dose-dependent kinetics after the administration of a tracer dose and 11 mumol/kg of [3H]E217G. A rebound of plasma radioactivity was seen at 11 mumol/kg of [3H] E217G, the time course of which mimicked the time course of E217G-induced cholestasis. High-performance liquid chromatographic analysis of rat bile and plasma after the administration of [3H]E217G revealed primarily E217G and estradiol-3-sulfate-17 beta-D-glucuronide together with small amounts of three unidentified metabolites. In the monkey, only E217G and estradiol-3-sulfate-17 beta-D-glucuronide were observed in the plasma after the administration of [3H]E217G. In contrast to E217G, estradiol-3-sulfate-17 beta-D-glucuronide was choleretic in the bile duct-cannulated rat model. These data indicate that E217G is hepatotoxic in both rodents and nonhuman primates.

Animals↗

Intrarenal renin-angiotensin system in primitive vertebrates.

Teleost fishes, which have a simpler nephron structure and lack the macula densa, respond to lowered blood pressure by releasing renin. Inhibition of the angiotensin-converting enzyme decreases the resting level of blood pressure, suggesting that the RAS may participate in control of blood pressure in fish. Glomerulotubular balance is poorly developed, and GFR is readily increased by an increase in renal perfusion pressure. It is not clear at present whether angiotensin is involved physiologically in intermittency of glomerular filtration, or whether it controls GFR through its action on systemic blood pressure. Birds appear to have an intermediate form between primitive vertebrates and mammals in terms of morphologic structure of the JG apparatus and nephrons, and in renal function. Fowl, in which angiotensin causes biphasic depressor and pressor responses, do not respond to acute hypotension or hypovolemia by releasing renin unless blood pressure remains low. Unilateral infusion of hypertonic saline into the renal portal system, which perfuses the peritubular sinusoid, increases urinary excretion of sodium chloride in the infused kidney, accompanied by mild diuresis. The slight but significant decrease in PRA occurs after portal infusion of hypertonic saline. Further investigation will be necessary to determine on an individual nephron basis whether an increased tubular sodium or chloride load may alter GFR by a possible tubuloglomerular feedback mechanism.

Angiotensins↗