Standardization of doctoral study in agricultural and extension education: is the field of study mature enough for achievement of the optimum degree of order?

Agricultural and extension education--or some derivative name--is a field of study leading to the doctoral degree in universities around the world. Is there are body of knowledge or a taxonomy of the knowledge--e.g., a knowledge domain--that one should possess with a doctorate in agricultural and extension education? The purpose of this paper was to synthesize the work of researchers who attempted to define the field of study, with a taxonomy comprising the knowledge domains (standards) and knowledge objects--structured interrelated sets of data, knowledge, and wisdom--of the field of study. Doctoral study in agricultural and extension education needs a document that provides for rules and guidelines--rules and guidelines that in turn provide for common and repeated use--all leading to achievement of an optimum degree of order in the context of academic, scholarly, and professional practice in agricultural and extension education. Thus, one would know in broad categories the knowledge, skills, and abilities possessed by one who holds a doctoral degree in agricultural and extension education. That is, there would exist a standard for doctoral degrees in agricultural and extension education. A content analysis of three previous attempts to categorize knowledge in agricultural and extension education served as the primary technique to create a new taxonomy--or to confirm an existing taxonomy--for doctoral study in agricultural and extension education. The following coalesced as nine essential knowledge domains for a doctorate in agricultural and extension education: (1) history, philosophy, ethics, and policy; (2) agricultural/rural development; (3) organizational development and change management; (4) planning, needs assessment, and evaluation; (5) learning theory; (6) curriculum development and instructional design; (7) teaching methods and delivery strategies; (8) research methods and tools; and, (9) scholarship and communications.

Pharmacological effects of intravenous melatonin: comparative studies with thiopental and propofol.

BACKGROUND: Possible utility of high-dose i.v. melatonin as an anaesthetic adjuvant has not been studied. This study compared its effects with thiopental and propofol. METHODS: Sprague Dawley rats were assigned to receive bolus or cumulative i.v. doses of melatonin, thiopental or propofol. Righting reflex, hindpaw withdrawal to a noxious stimulus, response to tail clamping and haemodynamic effects were assessed. RESULTS: Melatonin caused a dose-dependent increase in paw withdrawal threshold and the percent of rats displaying loss of the righting reflex. Melatonin was comparable to thiopental and propofol in terms of its rapid onset of hypnosis. The mean ED(50) values for loss of righting reflex were 5.4 (SEM 1.2), 12.5 (1.1) and 178 (1.1) mg kg(-1) for propofol, thiopental and melatonin, respectively. The percent of rats displaying loss of response to tail clamping was greater with propofol than with melatonin (P<0.05). Haemodynamic changes produced by melatonin or propofol were similar in onset and magnitude. CONCLUSIONS: I.V. melatonin can exert hypnotic effects similar to those observed with thiopental and propofol. Melatonin exhibited significant antinociceptive effects but was less effective in abolishing the response to tail clamping.

Not to be and then to be: visual representation of ignored unfamiliar faces.

Negative priming, the increase in response time and/or errors to targets previously encountered as distractors, is explained by inhibitory mechanisms that block the access of distractor representations to response systems. The processing of unfamiliar human faces was investigated using negative priming. Observers viewed a row of faces to decide whether 2 target faces were the same or different. Response latencies were longer when 1 or both targets had appeared as distractors on the immediately preceding trial--evidence that never-before seen faces are represented and require inhibition. Response latencies were shorter when face targets had appeared as distractors, either corrupted with high-frequency noise or contrast inverted--evidence that representations are facilitated. Finally, response latencies remained unaltered when face targets had appeared as upside-down distractors--evidence that not all distractor representations afford response priming. The visual system indeed represents ignored unfamiliar faces, but blocks these representations only if they vie with targets for the control of action.

The Reasons for Living Inventory for Adolescents (RFL-A): development and psychometric properties.

The role of adaptive beliefs and attitudes against suicide has not been given adequate attention in the clinical or assessment literature. This article reports on the development and initial psychometric properties of a 32-item self-report inventory, the Reasons for Living Inventory for Adolescents (RFL-A). In Phase 1, we used exploratory and confirmatory factor analyses to identify five correlated factors: Future Optimism, Suicide-Related Concerns, Family Alliance, Peer Acceptance and Support, and Self-Acceptance. In Phase 2, we cross-validated the 5-factor oblique model in a different group of adolescents recruited from two high schools. In addition, we examined evidence for convergent, discriminant, and construct validities. The coefficient alpha indices for the RFL-A total and scales were satisfactory. In Phase 3, we evaluated additional evidence of reliability and validity using samples of high school and psychiatric inpatient adolescents. The results suggest that the RFL-A is a short, reliable, and valid measure that is potentially useful in the assessment of adolescent suicidal behavior.

Alu-repeat polymorphism in the gene coding for tissue-type plasminogen activator (t-PA) and risks of myocardial infarction among middle-aged men.

An Alu-repeat polymorphism in the gene coding for tissue-type plasminogen activator has been described recently, and it has been hypothesized that this polymorphism may predict risk of coronary thrombosis. In a prospective cohort of nearly 15,000 apparently healthy men, presence of an Alu-repeat insertion/deletion (I/D) polymorphism in the gene coding for tissue-type plasminogen activator was determined among 369 study participants who subsequently suffered a first myocardial infarction (cases) and among a group of 369 age- and smoking-matched study participants who remained free of reported cardiovascular disease during follow-up (controls). The distributions of the II, DI, and DD genotypes of the tissue-type plasminogen activator polymorphism among men who subsequently suffered myocardial infarction (0.30, 0.50, 0.21) were virtually identical to those who remained free of disease (0.29, 0.50, 0.21; P = .9). There was no evidence of association between the Alu insertion polymorphism and risks of future myocardial infarction in models assuming either allelic recessive (relative risk, 1.05; 95% confidence interval, 0.8 to 1.4, P = .8) or allelic dominant (relative risk, 1.04; 95% confidence interval, 0.7 to 1.5, P = .8) modes of inheritance, nor were associations found in analyses stratified by age, family history, hypercholesterolemia, or the presence of other risk factors for premature coronary disease. Multivariate analysis had no important effects on these relationships. In this cohort of middle-aged US men, the presence of the insertion allele of the Alu-repeat polymorphism of the tissue-type plasminogen activator gene is not associated with future risks of myocardial infarction.

The effects of plasma and brain magnesium concentrations on lidocaine-induced seizures in the rat.

Lidocaine and MgSO4 are often coadministered to patients with pregnancy-induced hypertension. This study examined whether MgSO4 alters the lidocaine-seizure threshold in the rat and, if so, whether systemic MgSO4 administration is as effective as intracerebroventricular MgSO4 infusion. In Experiment 1, rats were administered 50% MgSO4 or 0.9% NaCl intravenously (IV) (20 microL/h) for 5 days. In Experiment 2, rats were administered 0.9% NaCl, 0.8% MgSO4, or 2.0% MgSO4 (10 microL/h) via intracerebroventricular infusion for 24 h. All rats then underwent continuous IV lidocaine infusion until onset of electroencephalographic seizures. In Experiment 1, plasma [Mg2+] was greater in the MgSO4 group (5.1 +/- 1.5 mg/dL vs 1.8 +/- 0.3 mg/dL) but neither the dose of lidocaine required to induce seizures (MgSO4 = 19 +/- 2 mg/kg; saline = 23 +/- 5 mg/kg) nor brain [Mg2+] (MgSO4 = 794 +/- 17 micrograms/g; saline = 788 +/- 33 micrograms/g) were changed. In Experiment 2, intracerebroventricular MgSO4 increased both brain [Mg2+] (2% MgSO4 = 923 +/- 79 micrograms/g; saline = 788 +/- 35 micrograms/g) and the lidocaine seizure dose (2% MgSO4 = 39 +/- 7 mg/kg; saline = 26 +/- 3 mg/kg). Although intracerebroventricular administration of MgSO4 produces an anticonvulsant effect, chronic hypermagnesemia does not alter whole brain [Mg2+] and therefore offers no protection from lidocaine-induced seizures in this model.

Isoflurane and cytochrome b5 stimulation of 2-chloro-1,1-difluoroethene metabolism by reconstituted rat CYP2B1 and CYP2C6.

Isoflurane stimulates the metabolism of 2-chloro-1,1-difluoroethene (CDE) in liver microsomes from phenobarbital-treated rats or rabbits. The P450 isozymes involved and the mechanism by which such stimulation occurs have not been clarified. The present study examined the effects of isoflurane and cytochrome b5 on CDE metabolism in reconstituted systems containing purified rat CYP2B1 or CYP2C6. Under similar incubation conditions, CYP2B1 defluorinated CDE at approximately five times the rate of CYP2C6. Isoflurane was a potent stimulator of CDE metabolism, increasing it nearly 5-fold when catalyzed by CYP2B1, but only 2-fold when catalyzed by CYP2C6. Isoflurane had no stimulatory effect on benzphetamine metabolism by CYP2B1 or CYP2C6. Cytochrome b5 was not required for isoflurane-facilitated CDE metabolism; however, the addition of cytochrome b5 to CYP2B1 increased CDE metabolism 71 and 44%, in the absence and presence of isoflurane, respectively. In reconstituted CYP2B1, isoflurane generated a type I difference spectrum of approximately twice the magnitude of CDE and stimulated NADPH consumption more so than CDE. The same quantity of NADPH was consumed when CDE was present with isoflurane as compared with isoflurane alone. These data support the hypothesis that isoflurane stimulates CDE metabolism by a mechanism involving increased P450 reduction via direct isoflurane interaction with P450.

Isoflurane-chlorodifluoroethene interaction in human liver microsomes. Role of cytochrome P4502B6 in potentiation of haloethene metabolism.

Short-chain saturated halocarbons, including isoflurane and the chlorofluorocarbon substitute HCFC-123, can strongly potentiate the cytochrome P450-dependent oxidation of gaseous haloethenes, such as 2-chloro-1,1-difluoroethene (CDE) and vinyl chloride, in vivo and in vitro. P450 isozyme specificity in this effect is suggested by the fact that the interaction is pronounced in microsomes from rats treated with phenobarbital, but does not occur in microsomes of isoniazid- or beta-naphthoflavone-treated animals. We examined the effect of isoflurane on CDE defluorination in liver microsomes from 10 human organ donors to determine whether saturated halocarbon/haloethene interactions also occur in humans and, if so, to determine the cytochromes P450 involved. Three of the samples exhibited isoflurane-stimulated increases (24, 32, and 41%) in CDE defluorination; isoflurane either inhibited or had no effect on CDE metabolism in the other seven samples. Two samples in which isoflurane potentiated CDE metabolism to the greatest rates had higher coumarin 7-hydroxylase (indicative of CYP2A6), 7-ethoxycoumarin O-deethylase (CYP2B6), and nifedipine oxidase (CYP3A4) activities than the other eight samples. However, all 10 subjects had similar rates of phenacetin O-deethylation (CYP1A2) and chlorzoxazone 6-hydroxylation (CYP2E1). In microsomes from cells transfected with cDNAs coding for individual human P450s, CDE metabolism by CYP2B6 was stimulated (216%) by isoflurane, whereas isoflurane did not stimulate CDE metabolism by human CYP2A6, CYP3A4, CYP2D6, or CYP2E1. Isoflurane highly increased CDE defluorination in purified rat CYP2B1 (470%).(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of volatile sevoflurane degradation product formation in an anesthesia circuit by a reduction in soda lime temperature.

BACKGROUND: Sevoflurane reacts with carbon dioxide absorbents, such as soda lime, to release the volatile products compounds A and B. These two products, which have been detected in anesthesia circuits, are among five formed when sevoflurane is degraded by soda lime at increased temperature; the others, compounds C, D, and E, have been detected only in heated sealed systems. The current study attempted to determine the influence of soda lime temperature on compounds A and B generation in an anesthesia circuit and whether a decrease in soda lime temperature could eliminate product formation in the circulating gases. METHODS: Sevoflurane (1.5% in oxygen) was circulated (6 l/min) in a partially closed, low-flow (215 ml/min fresh gas) anesthesia circuit that included a canister containing 1.2 kg fresh soda lime. Carbon dioxide was introduced into the circuit at 200 ml/min, and gas samples for analysis of sevoflurane, compounds A, B, C, and D, and carbon dioxide were taken at the opening of an attached artificial lung. The circuit was operated for 8 h under conditions whereby the soda lime temperature could increase freely or the soda lime was chilled with ice. RESULTS: A maximum core soda lime temperature of about 46 degrees C was measured when the experiment was run under conditions whereby the soda lime temperature was allowed to increase. Compounds A and B increased with time to a maximum of 23 and 9 ppm, respectively. At 4.5 h of circuit operation, compound C/D was found. Chilling of the soda lime canister, which produced a maximum core soda lime temperature of 25 degrees C, resulted in neither compound B nor C/D being detected during the 8-h period. Compound A was present in the circuit at all times at approximately 10 ppm; however, its concentration did not increase as occurred when the experiment was conducted under nonchilled conditions. Carbon dioxide levels at the opening of the lung remained at a constant 5% for 8 h with or without soda lime chilling. CONCLUSIONS: This study demonstrates that the release of volatile sevoflurane degradation products in an anesthesia circuit is highly dependent on soda lime temperatures. A reduction of the temperature of soda lime may be a feasible method of preventing the release of significant levels of sevoflurane degradation products without interfering with carbon dioxide absorption or altering the sevoflurane concentration.

Interaction of fluoroethane chlorofluorocarbon (CFC) substitutes with microsomal cytochrome P450. Stimulation of P450 activity and chlorodifluoroethene metabolism.

The abilities of halothane and the fluoroethane chlorofluorocarbon (CFC) substitutes, FC-123, FC-133a, FC-124, FC-134a and FC-125, to stimulate cytochrome P450 activities and 2-chloro-1,1-difluoroethene (CDE) defluorination in hepatic microsomes from phenobarbital-treated rabbits were compared. At 1% (v/v) each, halothane and FC-123 similarly increased the consumption of NADPH and O2 by 300 and 100%, respectively, over that in microsomes without substrate. FC-133a and FC-124 were less effective, increasing NADPH and O2 consumption by 150-200 and 70%. FC-134a and FC-125 were the least effective, increasing NADPH and O2 consumption by only 70 and 50%, respectively. No metabolism of any fluoroethane could be detected under the incubation conditions used. Halothane and FC-123 were most effective in stimulating CDE metabolism with increases of CDE defluorination ranging from 1.5- to 2-fold. FC-133a and FC-124 enhanced CDE oxidation 89 and 74%, respectively, and FC-134a and FC-125 had no effect. While CDE metabolism was enhanced in the presence of the fluoroethanes, no additional NADPH or O2 was consumed when halothane or FC-124 was incubated with CDE compared with incubations containing only halothane or FC-124. Log-log plots of NADPH consumption and CDE metabolism with the olive oil/gas partition coefficients of each fluoroethane showed linear relationships. These data demonstrate that the activity of the fluoroethanes in stimulating P450 activity and CDE metabolism is a function of their lipid solubility, and fluoroethane-enhanced CDE metabolism is related to the ability of these compounds to increase uncoupled P450 activity.

Inhibitory effects of propofol on cytochrome P450 activities in rat hepatic microsomes.

The effects of propofol on cytochrome P450 activity in rat hepatic microsomes were evaluated to determine the potential influence of this anesthetic on the metabolism of coadministered agents. In microsomes from untreated and isoniazid-treated rats, propofol was a weak inhibitor of enflurane metabolism, inhibiting activity only at 0.35 mM propofol. In contrast, toluene, a related compound, effectively impaired enflurane defluorination in microsomes from untreated, and isoniazid- and phenobarbital-treated rats at concentrations as low as 0.025 mM. Propofol, in contrast to toluene, was an effective inhibitor of benzphetamine demethylation where it inhibited this activity at propofol concentrations as low as 0.025 mM in microsomes from phenobarbital-treated rats. In microsomes from phenobarbital-treated rats, propofol potently inhibited the metabolism of aniline. Sixty-four percent inhibition was achieved at 0.03 mM propofol, whereas toluene had no effect at 1 mM. These data demonstrate that propofol does not effectively inhibit enflurane metabolism performed by the isoniazid-inducible cytochrome P450IIE1 but effectively impairs activities of the phenobarbital-inducible cytochrome P450 isozymes.

Contrasting effects of 1,1,1-trichloroethane on [14C]vinyl chloride metabolism and activation in hepatic microsomes from phenobarbital- and isoniazid-treated rats.

The interaction of 1,1,1-trichloroethane (TCE), a widely used chlorocarbon solvent, on the metabolism and activation of [14C]-vinyl chloride in rat hepatic microsomes was investigated to determine the effects of combined exposures to these compounds. In microsomes from phenobarbital (PB)-treated rats, TCE increased vinyl chloride-protein binding and vinyl chloride aqueous metabolite formation over twofold when vinyl chloride 0.32% (v/v) and TCE (0.65%) are incubated together. In contrast, under similar incubation conditions, TCE inhibited vinyl chloride metabolism and protein binding up to 45% in microsomes from isoniazid-treated animals. TCE also inhibited vinyl chloride metabolism and binding in microsomes from untreated rats, but to a lesser degree. Like the effect of TCE on vinyl chloride-protein binding, TCE increased vinyl chloride binding to DNA approximately 130% in microsomes from PB-treated rats, yet inhibited vinyl chloride-DNA binding in microsomes from isoniazid-treated and untreated animals. Consistent with TCE effects on vinyl chloride binding and aqueous metabolite production, TCE further increased cytochrome P450 loss due to vinyl chloride metabolism in microsomes from PB-treated rats, but was inhibitory to cytochrome P450 loss due to vinyl chloride metabolism in microsomes from isoniazid-treated and untreated rats. These data demonstrate that the relatively metabolically inert solvent, 1,1,1-trichloroethane, can directly increase vinyl chloride metabolism and activation catalyzed by the phenobarbital-inducible isozymes, but is inhibitory toward vinyl chloride metabolism catalyzed by the isoniazid-inducible CYP2E1.

NADPH and oxygen consumption in isoflurane-facilitated 2-chloro-1,1- difluoroethene metabolism in rabbit liver microsomes.

2-Chloro-1,1-difluoroethene (CDE) metabolism can be facilitated by isoflurane in microsomes. In an effort to elucidate the mechanisms of increased CDE metabolism, NADPH and oxygen consumption during CDE metabolism were measured in the absence and presence of isoflurane in rabbit liver microsomes. In microsomes from phenobarbital-treated rabbits, isoflurane (1-4 mumol, 0.6-2.3%) enhanced CDE (2 mumol, 1.1%) metabolism, increasing fluoride release up to 2.5 times compared with CDE alone. Fluoride release increased with increasing amounts of CDE (1-4 mumol). Isoflurane alone strongly increased NADPH consumption (3.78 +/- 0.4 to 9.65 +/- 0.23 nmol/mg/min +/- SD) and oxygen consumption (3.27 +/- 0.03 to 6.62 +/- 0.75 nmol/mg/min) compared with control when incubated for 5 min at 30 degrees C. No isoflurane metabolism was detected by fluoride release. Incubation of CDE alone resulted in CDE metabolism (0.70 +/- 0.15 nmol/mg/min) and lesser, but significant increases in NADPH (4.79 +/- 0.14) and oxygen consumption (4.44 +/- 0.24) compared with control. Incubation of isoflurane with CDE at 30 degrees C for 5 min caused a 3-fold increase of CDE metabolism (2.18 +/- 0.25 nmol/mg/min); however, no more NADPH (8.59 +/- 0.95) or oxygen (7.22 +/- 0.16) was consumed compared with isoflurane incubation. No significant changes in H2O2 production were observed between all groups. These data indicate that isoflurane is an efficient uncoupler of cytochrome P-450, and suggests that increased CDE metabolism by isoflurane may result from a coupling of isoflurane-stimulated cytochrome P-450 activity to CDE oxidation.

Central nervous system toxicity of local anesthetic mixtures in the rat.

Local anesthetics are often administered as mixtures during regional anesthesia. This study investigated whether a synergistic or antagonistic interaction between amide/amide or amide/ester local anesthetic combinations is present with respect to central nervous system toxicity. For surgical preparation, rats were anesthetized with 0.8% halothane in 30% O2/balance N2O and mechanically ventilated. Mean arterial blood pressure and the electroencephalogram were continuously monitored. After surgery, the halothane was discontinued for 15 min. An intravenous infusion of solutions containing lidocaine alone, bupivacaine alone, or any of three mixtures of the two drugs was then begun and continued at a fixed rate until seizure activity was observed on the electroencephalogram. Total administered doses of both drugs were compared by isobolographic analysis. After a similar protocol, a second experiment was performed evaluating lidocaine, tetracaine, or any of three mixtures of those two drugs. In both experiments, normocapnia, normoxia, and normothermia were maintained for all rats. For mixtures of lidocaine/bupivacaine (P = 0.40) and lidocaine/tetracaine (P = 0.24), there was no evidence that a significant degree of either synergism or antagonism was present. At the onset of seizures, mean arterial pressure was lowest in the lidocaine-alone groups in both experiments. Increasing doses of either bupivacaine or tetracaine (with correspondingly decreasing doses of lidocaine) were associated with greater mean arterial pressure values at onset of seizures. We conclude that central nervous system toxic effects of amide/amide or amide/ester anesthetic combinations, such as might occur during accidental intravascular injection, are no more than when the drugs are administered alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute stimulation of trifluoroethene defluorination and cytochrome P450 inactivation in the rat by exposure to isoflurane.

The effect of isoflurane on trifluoroethene (TFE) defluorination and cytochrome P450 inactivation was examined in rats to determine the influence of this anesthetic on in vivo fluoroethene metabolism. Exposure of rats to TFE (0.5%, v/v) or a mixture of TFE and isoflurane (0.5% each) in oxygen for 60 min resulted in plasma fluoride increased over that in nonexposed or isoflurane (0.5%)-exposed animals. In untreated rats plasma fluoride levels following TFE and TFE-isoflurane exposures were approximately equal. In rats treated with phenobarbital, however, isoflurane increased plasma fluoride over two times that in rats exposed to TFE alone. Likewise cytochrome P450 levels declined 24% in TFE-exposed animals and 64% in rats exposed to TFE-isoflurane. The ability of microsomes from fluorocarbon-exposed animals to metabolize (R)- and (S)-warfarin indicates that TFE exposure inactivated the phenobarbital-inducible isozymes P450IIB1, P450IIC6, and P450IIIA to approximately equal degrees (21-35%). TFE-isoflurane exposure further inhibited P450IIB1 and PB450IIC6 to 50-70%, but had only a minor effect on P450IIIA activity. These data demonstrate that the defluorination of TFE in vivo by the phenobarbital-inducible cytochrome P450 isozymes is increased by isoflurane, and that isoflurane enhances the ability of TFE to inactivate cytochromes P450 in an isozyme-selective manner.

Nitric oxide generation from nitroprusside by vascular tissue. Evidence that reduction of the nitroprusside anion and cyanide loss are required.

Nitric oxide (NO) was produced from sodium nitroprusside in the presence of vascular tissue but was not released spontaneously from the nitroprusside anion. In the absence of tissue in the dark nitroprusside did not release NO. When solutions of nitroprusside alone were irradiated with visible light, nitric oxide was released at rates linearly proportional to nitroprusside concentration and light intensity. Nitric oxide was produced from solutions of nitroprusside in the dark after the addition of vascular tissue, including lengths of rabbit aorta, subcellular fractions of aorta, and human plasma. NO was also released from nitroprusside after reaction with various reducing agents including cysteine and other thiols, ascorbic acid, sodium dithionite, ferrous chloride, hemoglobin, myoglobin, and partially purified cytochrome P450 with an NADPH-regenerating system. HCN was simultaneously produced in these solutions, and addition of KCN blocked NO release. Iodine oxidized intermediate cyanoferrates and blocked nitric oxide release. KCN or iodine also blocked NO production by tissue, but had no effect upon photochemical NO release. These results show that, apart from photolysis which makes no physiological contribution, release of nitric oxide from nitroprusside, in simple solutions and in biological tissue, occurs after nitroprusside has undergone reduction and lost cyanide.