Biomedical subjects

M R Murphy

Publications and source records attributed to M R Murphy.

At least 55 records · Page 3Linked to original sources

PubMed1993

An integrated, dynamic model of feed hydration and digestion, and subsequent bacterial mass accumulation in the rumen.

Hydration of feeds and bacterial attachment to feed particles are thought to play major roles in rumen digestion of fibrous feedstuffs. The objective of the present study was to integrate these phenomena in a mechanistic model that could be used for data analysis. The proposed model was based on the conversion of biomass, where digestion end-products can be used for the synthesis of bacterial mass. Digestion of the potentially digestible fraction and subsequent accumulation of bacterial mass was based on a sequential, three-compartment model. These compartments represented substrate undergoing hydration, digestion, and bacterial mass accumulation. A fraction of the substrate was used for synthesis of bacterial mass. It was assumed that these bacteria associate either temporarily or permanently with the remaining substrate. Dacron bags containing either dry or fully-hydrated lucerne (Medicago sativa), maize (Zea mays) cobs, orchard grass (Dactylis glomerata), and wheat straw were incubated in the rumen of a steer that was infused continuously with (15NH4)2SO4. The 15N-enrichments of isolated particle-associated bacteria and residue remaining in the bags were used to estimate bacterial attachment. Substrate remaining and microbial mass accumulation were analysed simultaneously. Hydration did not appear to limit digestion. Fractional rate of digestion and appearance of attached bacterial mass was fastest for lucerne. For lucerne, 5% of the digestion end-products were used for synthesis of bacteria that associated with the substrate, whereas for maize cobs, orchard grass, and wheat straw this was 16, 14, and 19% respectively. Less than 2% of digestion end-products were used for synthesis of bacteria that permanently remained associated with the substrate. Permanent association can occur only with the indigestible fraction, and probably represents bacterial debris. Lysis and/or detachment of bacterial cells was highest for lucerne, and was indicative of the rapid dynamics of lucerne digestion.

Animal Feed↗

PubMed1993

Digestion kinetics of alfalfa and wheat straw assuming heterogeneity of the potentially digestible fraction.

Although it is recognized that the potentially digestible fraction of substrates in the rumen is heterogeneous in composition, most deterministic models that describe ruminal in situ digestion assume existence of only one or two homogeneous fractions of potentially digestible material. Alternatively, a stochastic model based on heterogeneity of substrate has been developed, although its validity has not been determined. To evaluate such a model, alfalfa hay and wheat straw were physically fractionated by dry sieving. Dacron bags containing these fractions were incubated in the rumen of a steer and the residue that remained was analyzed sequentially for DM, NDF, ADF, ADL, and acid detergent insoluble ash. Digestion kinetics of chemical fractions were determined by simultaneous analysis of the digestion profiles of DM, NDF, ADF, ADL, and acid detergent insoluble ash. The weighted mean and variance of the fractional digestion rate constant were .083 h-1 and 4.7 x 10(-4) h-2 for alfalfa and .021 h-1 and 2.4 x 10(-5) h-2 for wheat straw, respectively. In contrast, fitting DM data to a stochastic model assuming heterogeneous rates, the mean and variance of the fractional digestion rate were .078 h-1 and 8.3 x 10(-11) h-2 for alfalfa and .018 h-1 and 5.3 x 10(-12) h-2 for wheat straw, respectively. Because the estimates of the variance approached zero for the stochastic model, it is implied that this model reduced to a model involving a single fractional digestion rate. It is concluded that parameter estimates obtained from a stochastic model do not necessarily have a biological meaning.

Animal Feed↗

PubMed1993

Diazepam as a treatment for nerve agent poisoning in primates.

Diazepam is known to decrease organophosphate nerve agent-induced convulsions, neuropathology, and lethality in rhesus monkeys. We report that, when added to the previously fielded treatment regimen (pyridostigmine, atropine, and pralidoxime chloride), diazepam significantly protects the performance of rhesus monkeys trained in an equilibrium task, the Primate Equilibrium Platform (PEP), against deficits induced by the nerve-agent soman. If administered soon enough to minimize the occurrence of convulsions, diazepam should increase the probability of mission accomplishment and eventual complete recovery from nerve agent poisoning. Diazepam was fielded by the United States military services during Operations Desert Shield and Storm for the treatment of possible organophosphate toxicity.

Animals↗

PubMed1992

Use of cholinesterases as pretreatment drugs for the protection of rhesus monkeys against soman toxicity.

Purified fetal bovine serum acetylcholinesterase (FBS AChE) and horse serum butyrylcholinesterase (BChE) were successfully used as single pretreatment drugs for the prevention of pinacolyl methylphosphonofluoridate (soman) toxicity in nonhuman primates. Eight rhesus monkeys, trained to perform Primate Equilibrium Platform (PEP) tasks, were pretreated with FBS AChE or BChE and challenged with a cumulative level of five median lethal doses (LD50) of soman. All ChE-pretreated monkeys survived the soman challenge and showed no symptoms of soman toxicity. A quantitative linear relation was observed between the soman dose and the neutralization of blood ChE. None of the four AChE-pretreated animals showed PEP task decrements, even though administration of soman irreversibly inhibited nearly all of the exogenously administered AChE. In two of four BChE-pretreated animals, a small transient PEP performance decrement occurred when the cumulative soman dose exceeded 4 LD50. Performance decrements observed under BChE protection were modest by the usual standards of organophosphorus compound toxicity. No residual or delayed performance decrements or other untoward effects were observed during 6 weeks of post-exposure testing with either ChE.

Acetylcholinesterase↗

PubMed1992

Evaluation of the preruminant calf as a model for the study of human carotenoid metabolism.

This study evaluated the preruminant calf as an animal model for the study of human carotenoid metabolism. Fifteen newborn male Holstein calves were fed a carotenoid-free milk replacer diet to maintain them in the preruminant state. After a 7-d adjustment period, three calves were killed and 12 calves received a single oral dose (20 mg) of beta-carotene in the form of water-soluble beadlets. Blood samples were collected periodically and samples of various tissues were collected when the calves were killed. Three animals each were killed by exsanguination at 1, 3, 6 and 11 d post-dosing. Serum beta-carotene concentrations peaked between 12 and 30 h post-dosing and declined slowly afterwards. Serum data were fitted to a two-compartment model and yielded an elimination constant (k2) that was similar to reported human values. Adrenal tissue showed significant concentrations of beta-carotene by 24 h post-dosing, and levels were still elevated at 264 h. Liver, spleen and lung beta-carotene concentrations were significantly elevated by 24 h and rapidly declined thereafter. Adipose and kidney peak beta-carotene concentrations were observed at 72 and 144 h, respectively. Heart and muscle did not display significant changes in beta-carotene concentrations. The preruminant calf shows promise as an animal model for the study of absorption and metabolism of carotenoids by humans.

Adipose Tissue↗

PubMed1992

Reduction of the MAC of desflurane with fentanyl.

Opioids are known to affect the MAC of inhalational anesthetics. We have determined the interaction between fentanyl and desflurane, following a bolus injection of fentanyl at induction in 134 adult patients. Five groups of patients were studied. Four groups received desflurane or isoflurane in oxygen with either fentanyl 3 or 6 micrograms/kg and thiopental 2-5 mg/kg given as a bolus injection at the time of induction. An additional group received desflurane in oxygen alone. Groups were stratified by age. MAC determination, in response to the stimulus of skin incision, was made using the "up-down" method and logistic regression. The MAC desflurane in oxygen was 6.3% (5.3-7.6%, 95% confidence interval [CI]). Fentanyl 3 micrograms/kg produced a fentanyl plasma concentration of 0.78 +/- 0.53 ng/ml at skin incision and resulted in a MAC for desflurane of 2.6% (2.0-3.2%, 95% CI) %. Fentanyl 6 micrograms/kg produced a fentanyl plasma concentration of 1.72 +/- 0.76 ng/ml at skin incision and resulted in a MAC for desflurane of 2.1% (1.5-2.6%, 95% CI). To compare recovery times to eye-opening and response to commands, patients were grouped according to the plasma fentanyl concentrations at the time of awaking. Recovery was faster in patients who received desflurane than in those who received isoflurane. The authors conclude that the MAC of desflurane is significantly reduced 25 min following a single dose of 3 micrograms/kg of fentanyl and that increasing the fentanyl dose to 6 micrograms/kg produces little further decrease in MAC. Desflurane is also associated with faster recovery from anesthesia than is isoflurane.

Adult↗

PubMed1992

Technical note: mineral deposits on Dacron bags during ruminal incubation.

Extensive DM contamination was found on Dacron bags that were incubated for prolonged periods of time in the rumen of steers fed alfalfa hay. The ash content of the contaminant was high, and most of it was acid-soluble X-ray analysis indicated the presence of hydroxylapatite and synthetic calcium magnesium phosphate or whitlockite. The contaminant appeared as a smooth coating on the Dacron fiber, suggesting that contamination was a gradual process rather than the result of entrapment of dislodged crystals from plant material. Contamination seemed to occur exponentially within the range of observations (0 to 42 d). Contamination also occurred in steers fed orchardgrass, although to a lesser extent than in steers fed alfalfa hay. The DM contamination was less than .04 g per bag (average bag weight was 1.2 g) during the first 10 d of incubation. However, correction for contamination might be required for studies involving longterm incubation or mineral digestion.

Animal Feed↗

PubMed1992

Water metabolism of dairy cattle.

Lactating dairy cows metabolize large amounts of water and are affected rapidly by water deprivation. Total body water, half-life of body water, size of component pools, and exchanges among them have been quantitated in several studies. The data underscore the dynamic nature of water metabolism in lactating cows. Water is lost in milk, urine, feces, and various forms of evaporation. Sources of water include drinking, feed, and metabolic (oxidation) water. Factors that have been shown to influence drinking behavior include eating pattern, water temperature, whether water is given in a trough or water bowl, flow rates into water bowls, animal dominance if water bowls are shared, and stray voltage. Important environmental factors modulating water consumption of dairy cattle are DMI, nature of the diet, milk production, temperature, and humidity. Equations have been proposed to predict water consumption based on measures of some of these variables. Water is of paramount importance both physiologically and nutritionally; therefore, it is not surprising that its metabolism indirectly may affect many feeding and management decisions. Ample water of acceptable quality must be provided to maximize milk production.

Animal Feed↗

PubMed1992

Supplementation of dairy cow diets with calcium salts of long-chain fatty acids and nicotinic acid in early lactation.

Forty multiparous Holstein cows were assigned to one of four treatments 15 d postpartum according to milk yield during wk 2 postpartum to examine the effects of supplementing niacin, Ca salts of long-chain fatty acids, and their interaction. Treatments were control, niacin (12 g/d), Ca salts of long-chain fatty acids (3% of dietary DM), or a combination of niacin and Ca salts. On d 99 postpartum, all cows were fed the control treatment for 2 wk to evaluate residual effects. Milk and FCM yields, blood plasma NEFA and beta-hydroxybutyrate concentrations, and apparent total tract hemicellulose digestibility were increased; milk protein percentage, milk SNF percentage, and blood plasma glucose concentrations were reduced by treatments containing the Ca soaps. Niacin supplementation increased milk protein content and yield but reduced blood plasma beta-hydroxybutyrate concentration. During the residual period, in which all cows received the control treatment, milk yield and plasma NEFA concentration remained elevated, milk protein and SNF contents remained depressed, and milk fat content was reduced for cows previously supplemented with Ca salts of long-chain fatty acids. Methionine and phenylalanine uptakes by the mammary gland were enhanced by niacin supplementation. Results indicated that dairy cattle in early lactation yielded more milk when their diets were supplemented with Ca salts of long-chain fatty acids and that niacin supplementation increased milk protein content and yield.

3-Hydroxybutyric Acid↗

PubMed1991

Analysis of centromere function in Saccharomyces cerevisiae using synthetic centromere mutants.

We constructed Saccharomyces cerevisiae centromere DNA mutants by annealing and ligating synthetic oligonucleotides, a novel approach to centromere DNA mutagenesis that allowed us to change only one structural parameter at a time. Using this method, we confirmed that CDE I, II, and III alone are sufficient for centromere function and that A + T-rich sequences in CDE II play important roles in mitosis and meiosis. Analysis of mutants also showed that a bend in the centromere DNA could be important for proper mitotic and meiotic chromosome segregation. In addition we demonstrated that the wild-type orientation of the CDE III sequence, but not the CDE I sequence, is critical for wild-type mitotic segregation. Surprisingly, we found that one mutant centromere affected the segregation of plasmids and chromosomes differently. The implications of these results for centromere function and chromosome structure are discussed.

Base Sequence↗

PubMed1991

Differential sensitivity of CNS regions to acetylcholinesterase inhibition following chronic low-dose soman treatment in the rat.

Several discrete brain regions were analyzed for regional brain sensitivity to acetylcholinesterase (AChE) inhibition following administration of repeated low-dose soman (39 micrograms/kg, SC; once daily for 5 days). The same brain regions were also assayed on days 3 through 7 after the last injection of soman, to examine possible recovery of AChE. The observed regional brain sensitivity to AChE inhibition can be described in the following order: frontal cortex = piriform cortex greater than hippocampus = cerebellum = thalamus greater than striatum = hypothalamus. Most brain areas showed only a small recovery from this inhibition through the seventh day following the last soman injection. The progressive nature of the AChE inhibition during the week of soman administration and the failure to find a significant interaction between injection and day indicates that tolerance to soman exposure did not develop in this paradigm. The protocol described here appears to provide a useful method to study prophylactic measures for low-dose repeated soman exposure and evaluation of differential CNS inhibition and recovery from AChE inhibition.

Acetylcholinesterase↗

PubMed1991

Behavioral toxicity of anticholinesterases in primates: chronic pyridostigmine and soman interactions.

Dose rates for continuous infusion of pyridostigmine bromide required to inhibit 30% and 60% of normal serum cholinesterase activity in rhesus monkeys were determined. The effects of continuous pyridostigmine infusion at these dose-rates on the behavioral toxicity of 5 daily repeated low-dose exposures to a toxic organophosphate (soman) were determined not be deleterious; in fact, they were slightly (and variably) protective. Relative to controls (5-day soman ED50 = 0.89 micrograms/kg/day), pyridostigmine infusions producing 30% and 60% inhibition produced 5-day ED50s of 1.25 and 1.11 micrograms/kg/day, respectively. Variability in response to the pyridostigmine-soman combinations appeared to be greater than in response to daily soman exposure without pyridostigmine infusion.

Animals↗

PubMed1991

Effects of three reputed carboxylesterase inhibitors upon rat serum esterase activity.

Rats have very high endogenous levels of serum carboxylesterase (CAE) compared to primates. This difference accounts for the lower sensitivity of rats to toxic organophosphates, which interact with CAE instead of the more critical acetylcholinesterase. Pretreatment of rats with CAE inhibitors potentiates the effects of organophosphates. In this study, the effects of three putative CAE inhibitors, 2-(o-Cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide (CBDP), bis-p-nitrophenyl-phosphate (BNPP), and tetraisopropyl pyrophosphoramide (Iso-OMPA), on the hydrolysis of several commercially available substrates were determined. Respective kinetic constants Km and Vmax were derived and effects of inhibitors compared using saturating amounts of substrate. Data presented here indicate significant differences in substrate affinity (Km), reactivity (Vmax), as well as effects of inhibitors. CBDP inhibits hydrolysis of specific naphthyl and paranitrophenyl esters at relatively low concentrations (1-10 microM). In contrast, significantly higher concentrations (mM) of BNPP and Iso-OMPA were required for inhibition of serum esterase activity. Of the inhibitors tested, Iso-OMPA in general exhibited the smallest inhibitory effect on ester hydrolysis. Although inhibition of hydrolysis of specific paranitrophenyl and naphthyl esters occurred in the presence of similar amounts of CBDP, the degree of inhibition differed significantly (50-75% vs. greater than 90%, respectively). These data suggest that there exists in rat serum, a pool of naphthyl ester esterase activity that is very sensitive ex vivo (greater than 90% inhibition) to CBDP and may be very useful in validating a rodent model for soman toxicity.

Animals↗

PubMed1991

Manganese turnover in chicks as affected by excess phosphorus consumption.

A repletion-depletion assay was conducted to evaluate the effect of Mn status and excess dietary P provided as dicalcium phosphate on Mn excretion and turnover. Chicks were fed either Mn-adequate (30 mg Mn/kg) or high Mn (1000 mg Mn/kg) casein-dextrose diets for 7 d. Following this loading period, the chicks were fed a Mn-deficient casein-dextrose diet (1.4 mg Mn/kg) with or without 0.5% excess P supplied from dicalcium phosphate. Whole body (without feathers) and selected body tissues (liver, kidney, gut, tibia and feathers) were assayed for Mn content at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 15 and 20 d after initiation of the Mn-deficient diet. Excess P had little effect on Mn turnover. All tissues showed significantly reduced biological half-lives (P less than 0.05) as a result of loading chicks with a high level of Mn (1000 mg/kg) during the 7-d loading period. However, there was wide variation in Mn turnover rates among tissues. Liver, kidney and whole body contained readily exchangeable manganese in much higher proportions than did bone.

Animals↗

PubMed1991

Psychomotor performance after desflurane anesthesia: a comparison with isoflurane.

Recovery and psychomotor performance were studied in 80 ASA physical status I-III adult patients undergoing outpatient surgery. Patients were divided into four equal groups: thiopental induction of anesthesia followed by desflurane in nitrous oxide and oxygen (Th-DES-N2O/O2), thiopental induction of anesthesia followed by isoflurane in nitrous oxide and oxygen (Th-ISO-N2O/O2), thiopental induction of anesthesia followed by desflurane in oxygen (Th-DES-O2), and desflurane inhaled induction followed by desflurane in oxygen (DES-DES-O2). Patients were excluded from analysis if they required opioids or antiemetics postoperatively. The use of desflurane was associated with more rapid awakening compared with isoflurane (time to eye opening 9.45 +/- 0.67 min [Th-DES-N2O/O2] and 13.8 +/- 1.59 min [Th-ISO-N2O/O2], P less than 0.05). Psychomotor performance was measured using the choice reaction time and critical flicker fusion threshold. At 30 min after discontinuing anesthesia, five patients in the Th-ISO-N2O/O2 group and one patient in the Th-DES-N2O/O2 group were too sleepy to perform psychomotor tests. In addition, five patients who received Th-DES-O2 and one patient who received the inhaled induction and maintenance of anesthesia with desflurane in oxygen were too sleepy to perform tests at 30 min. Patients receiving Th-DES-N2O/O2 showed less impairment of choice reaction time than those receiving Th-ISO-N2O/O2. Critical flicker fusion threshold, however, showed no difference between groups. The use of thiopental was associated with delayed recovery. Compared with isoflurane, desflurane anesthesia is associated with more rapid initial awakening and less impairment of choice reaction time.

Adult↗

PubMed1991

Comparison of ocfentanil and fentanyl as supplements to general anesthesia.

Three doses of ocfentanil (1, 3, and 5 micrograms/kg), a new narcotic, were compared with fentanyl (5 micrograms/kg) as a supplement to general anesthesia. Sixty adult ASA I-III patients undergoing elective surgery were studied. The drugs were given as a bolus injection during induction of anesthesia in a double-blind manner. With the stimulus of tracheal intubation, systolic arterial blood pressure increased (mean +/- SE) from 127 +/- 6.9 to 183 +/- 7.4 mm Hg and heart rate increased from 82.1 +/- 4.8 to 104 +/- 6.4 beats/min in patients who had received 1 microgram/kg of ocfentanil intravenously. In comparison to patients who received 1 microgram/kg of ocfentanil, the increases in heart rate and systolic arterial blood pressure at the time of tracheal intubation were less with 3 and 5 micrograms/kg of ocfentanil and 5 micrograms/kg of fentanyl (P less than 0.05). At incision, heart rate decreased after the intravenous administration of 5 micrograms/kg of ocfentanil when compared with patients who received 1 microgram/kg of ocfentanil. There were differences between study groups in the mild increase in arterial blood pressure observed at incision. The authors conclude that ocfentanil and fentanyl appear to be similar in action, with 3 micrograms/kg of ocfentanil being approximately equivalent in effect to 5 micrograms/kg of fentanyl.

Adjuvants, Anesthesia↗

PubMed1991

A compartmental model to analyze ruminal digestion.

In contrast to digestion models that include a discrete lag phase, a compartmental digestion model was proposed. It assumed the existence of a lag compartment and a digestion compartment. Substrate present in the digestion compartment was subject to first-order kinetics digestion. Flow of substrate from the lag compartment to the digestion compartment was proposed to be a first-order process and likely was affected by hydration of substrate, bacterial attachment, and colonization. The proposed model was compared with models that assumed the existence of a discrete lag phase. Parameter estimates for these models were obtained either through logarithmic transformation of data or nonlinear regression. Statistically, there was no difference between the compartmental model and the nonlinear model with a discrete lag phase. Differences in parameter estimates between these two models were small. Residual mean squares were higher for the logarithmically transformed models. Differences in parameter estimates between these models and the compartmental model depended on the structure of the experimental data. In a number of cases, the nonlinear parameters of the compartmental model converged to the same value, resulting in a different interpretation of the model. Residual mean squares for predicting rate of disappearance were lowest for the compartmental model.

Animals↗

PubMed1991

Niacin absorption from the rumen.

Absorption of niacin from the rumen was tested in vivo using a buffer solution that contained either nicotinic acid or nicotinamide. The experimental design was a 3 X 3 Latin square with three midlactation, ruminally cannulated Holstein cows. Orthogonal comparisons were control versus niacin and nicotinic acid versus nicotinamide. Nicotinamide was more rapidly absorbed from the rumen than nicotinic acid; this may have been caused by differences in the dissociation constants of the compounds. The effects that differential absorption may have on ruminal fermentation and animal metabolism require further study.

Absorption↗