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Biomedical subjects

B Norris

Publications and source records attributed to B Norris.

At least 55 records · Page 3Linked to original sources
PubMed1990

Use of nonradioactive 2-deoxyglucose to study compartmentation of brain glucose metabolism and rapid regional changes in rate.

A method is presented for measuring rapid changes in the rate of glucose phosphorylation in mouse brain with nonradioactive 2-deoxyglucose (DG). After times as short as 1 min after DG injection, the mouse is frozen rapidly, and selected brain regions are analyzed enzymatically for DG, 2-deoxyglucose 6-phosphate (DG6P), and glucose. The rate of glucose phosphorylation can be directly calculated from the rate of change in DG6P, the average levels of DG and glucose, and a constant derived from direct comparison of the rate of changes in glucose and DG6P after decapitation. Experiments with large brain samples provided evidence for a 2% per min loss of DG6P and at least two compartments differing in their rates of glucose metabolism, one rapidly entered by DG with glucose phosphorylation almost double that of average brain and another more slowly entered with a much lower phosphorylation rate. The method is illustrated by changes in phosphorylation within 2 min after injection of a convulsant or an anesthetic and over a 48-min time course with and without anesthesia. The sensitivity of the analytical methods can be amplified as much as desired by enzymatic cycling. Consequently, the method is applicable to very small brain samples. Examples are given for regions with volumes of 5 x 10(-4) microliters, but studies with samples as small as single large cell bodies are feasible.

Anesthesia, General↗
PubMed1990

Effect of microgravity on metabolic enzymes of individual muscle fibers.

Eleven enzymes were measured in individual fibers of soleus and tibialis anterior (TA) muscles from two flight and two control (synchronous) animals. There were five enzymes of glycogenolytic metabolism: phosphorylase, glucose-6-phosphate isomerase, glycerol-3-phosphate dehydrogenase, pyruvate kinase, and lactate dehydrogenase (group GLY); five of oxidative metabolism: citrate synthase, malate dehydrogenase, beta-hydroxyacyl-CoA dehydrogenase, 3-ketoacid CoA-transferase, and mitochondrial thiolase (group OX); and hexokinase, subserving both groups. Fiber size (dry weight per unit length) was reduced about 35% in both muscles. On a dry weight basis, hexokinase levels were increased 100% or more in flight fibers from both soleus and TA. Group OX enzymes increased 56-193% in TA without significant change in soleus. Group GLY enzymes increased an average of 28% in soleus fibers but underwent, if anything, a modest decrease (20%) in TA fibers. These changes in composition of TA fibers were those anticipated for a conversion of about half of the originally predominant fast glycolytic fibers into fast oxidative glycolytic fibers. Calculation on the basis of fiber length, rather than dry weight, gave an estimate of absolute enzyme changes: hexokinase was still calculated to have increased in both soleus and TA fibers, but only by 50 and 25%, respectively. Three of the OX enzymes were, on this basis, unchanged in TA fibers, but 3-ketoacid CoA-transferase and thiolase had still nearly doubled, whereas TA GLY enzymes had fallen about 40%. In soleus fibers, absolute levels of OX enzymes had decreased an average of 25% and GLY enzymes were marginally decreased.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1989

Inhibitors of immune complex-induced inflammation: 3-[1-(2-benzoxazolyl)hydrazino]propanenitrile derivatives.

The octanol-water partition coefficients (log P) and the dissociation constants (pKa) of 3-[1-(2-benzoxazolyl)hydrazino]propanenitrile analogues have been determined, and quantitative structure--activity relationships (QSAR) of the analogues as inhibitors of immune complex-induced inflammation have been studied. A significant correlation is observed between log P and pi substituent constants, and between pKa and inductive-field (F) and resonance (R) constants. The QSAR equations indicate that smaller substituents both at the 5-position and/or at the side chain tend to make the compound more potent, while an electron-withdrawing group at the side chain tends to make the compound less potent. The predicted potencies of 14 of 18 additional monosubstituted and all six disubstituted analogues agree reasonably well with the observed activities.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Stimulatory effect of angiotensin II on the electric properties of the isolated toad skin.

In 1982 we showed that angiotensin II (Agt II) stimulates the bioelectric properties of the isolated toad skin and that this effect is blocked by pretreatment of the skin with indomethacine [J. B. Concha et al., IRCS Med. Sci. 10, 584 (1982)]. Ussing's technique and several inhibitors were used to continue this study on the isolated Pleurodema thaul skin. Serosal Agt II produced a dose-dependent increase in electrical parameters: a maximal concentration of 6 X 10(-6) M Agt II increased potential difference by 43 +/- 7.8% and short-circuit current by 51.5 +/- 7.7%. The responses were not affected by either alpha or beta blockers or by atropine. Indomethacine blocked responses to the calcium ionophore A23187 and to Agt II which were similar to each other. Additive effects of Agt II and of the calcium ionophore A23187 were found. No response to Agt II was obtained when Ca2+-free Ringer was used on the serosal side. Calcium channel blockers (nifedipine, verapamil, manganese), pentobarbitone and saralasin blocked the response to Agt II. This pharmacological evidence is in favour of the hypothesis that Agt II activates specific membrane receptors, leading to Ca2+ release and formation of prostaglandins which stimulate adenyl cyclase. This increases cAMP secretion, which in turn increases apical membrane permeability to sodium and enhances the active transport system.

Adrenergic alpha-Antagonists↗
PubMed1988

A novel method for measurement of triglyceride lipase activity: suitable for microgram and nanogram quantities of tissue.

The measurement of triglyceride lipase activity in microgram and nanogram quantities of tissue is reported. The method involves quantitation of glycerol released from a triglyceride substrate, which is shown to provide a value of approximately one-third of that obtained by quantitation of free fatty acid release. Influences on glycerol release, including pH optimum, NaCl inhibition, and activation by serum and heparin are characterized. Two separate assays are described for the measurement of glycerol that yield identical results with nanogram quantities of tissue. The advantage of one assay is its simplicity, while the advantage of the other is that it can be adjusted to measure very small tissue samples (nanogram) with the use of microanalytical procedures (i.e., enzymatic amplification of the NAD+ product of glycerol analysis). Sensitivity of the method is demonstrated by the analysis of triglyceride lipase activity in nanogram samples of single soleus muscle fibers. Measurement of picomole quantities of glycerol produced by lipase activity in single muscle fibers represents at least a 1,000-fold increase in sensitivity compared to currently available methods.

Animals↗
PubMed1984

Simultaneous determination of chloroprocaine hydrochloride and its degradation product 4-amino-2-chlorobenzoic acid in bulk drug and injection solutions by high-performance liquid chromatography.

A high-performance liquid chromatographic method has been developed for the simultaneous determination of chloroprocaine hydrochloride and its hydrolytic degradation product, 4-amino-2-chlorobenzoic acid. Separation is achieved using a mu-Bondapak C18 column and the eluant, water-acetonitrile-methanol-glacial acetic acid (74:20:5:1) containing 0.05-0.08% (w/v) sodium 1-heptanesulfonate, at a flow rate of 2 mL/min. Benzoic acid and p-nitroacetophenone were used as internal standards. A variable-wavelength UV detector (278 nm) was used for detection of the compounds. The method is simple, accurate, and precise.

Chromatography, High Pressure Liquid↗
PubMed1983

Effects of sodium pentobarbitone on the bioelectric properties of isolated toad skin.

The effects of sodium pentobarbitone on the transepithelial potential difference and on the short-circuit current in the isolated toad skin were studied under different experimental conditions. Pentobarbitone was consistently effective when placed in the solution bathing the inside surface of the skin. The response to small concentrations (1.2, 3.6 and 6.0 x 10(-5) M) was a transient dose-related increase in the transepithelial potential difference and short-circuit current, and a decrease in both parameters at larger concentrations (3.6 x 10(-4) M). Total skin resistance decreased at small and increased at large concentrations. Analysis of the response in terms of the equivalent electrical circuit indicated that in small concentrations the effect was due to an increase in the driving force of the sodium (Na+) pump although the rate of entry of Na+ through the outer barrier was reduced. The activity of (Na+-K+)ATPase was increased within the first 7 min of the effect of pentobarbitone, thus confirming a direct action of the drug on Na+ transport. In large concentrations the electromotive force of the Na+ pump was decreased and inactivation of (Na+-K+)ATPase became evident. The effect of pentobarbitone was unchanged in six reserpinized toads, which would seem to rule out a catecholamine-mediated effect of the drug. The reduction of Na+-influx could indirectly increase transport efficiency since the rate of transport work should be reduced.

Amiloride↗
PubMed1982

Effect of colchicine on the electrophysiological properties of the toad sciatic-gastrocnemius preparations in vivo.

The effects of a single subepineural injection of colchicine on the toad sciatic-gastrocnemius preparation were studied in vivo. The resting membrane potential of the gastrocnemius muscle fibres declined by 15% at day 5. This was followed 2 days later by dispersion and reduction in the amplitude of the compound muscle action potential, decrease in the slope of the accommodation index curve (AI), and a decreased electromyographic interference pattern. These changes were progressive and led to blockage of electrical activity and appearance of pseudodenervation after 2 weeks. Pseudodenervation was confirmed on finding similar alterations in the AI profile in neurotomized toads. In contrast, the hind limbs of toads paralysed by d-tubocurarine had normal muscle AI. The decrease in the AI on the colchicine-treated side was dependent on the length of the severed nerve left attached to the muscle, indicating a centrifugal effect of the drug.

Action Potentials↗
PubMed1978

Effects of altered free fatty acid mobilization on the metabolic response to exercise.

This study was designed to evaluate the metabolic response to limitation of fat mobilization during severe exercise in man. To this end, we assessed the relationship between fat mobilization, lipid-ketone physiology, and exercise-induced elevations in the counter-regulatory hormones. Ten well trained athletes ran a 10-mile premeasured course in as short a time as possible during both a placebo and an experimental study. In the experimental study, fat mobilization was inhibited by the oral administration of 2 g of nicotinic acid. Blood samples for multiple substrate and hormonal assay were obtained 2 h before exercise, immediately before exercise, and immediately after exercise. In the experimental study, nicotinic acid effectively blocked the expected rise in plasma free fatty acid concentration observed in the placebo study. Although blunted, the exercise-induced rise in plasma ketone concentration persisted in spite of the reduced free fatty acid levels. The significance of the concommitant exagerated rise in glucagon and GH in stimulating ketogenesis is discussed. The inhibition of fat mobilization did not reduce the mean time required to run 10 miles. Since muscle uptake of free fatty acid is directly proportional to the plasma concentration of this substrate, our study suggests that the inability to mobilize fat does not prevent severe exercise for 70 min.

Amino Acids↗
PubMed1977

ECT versus chlorpromazine in mania.

The efficacy of ECT in the treatment of depression is well recognized. In mania its efficacy is less well acknowledged. This report compares ECT, chlorpromazine, and no active treatment in mania. Twenty-eight control patients diagnosed as manic were selected from consecutive admissions to the University of Iowa Psychiatric Hospital in the period 1935-1941 when there was no active treatment given. Twenty-eight patients treated with ECT were selected from the period 1945-1949, and 28 chlorpromazine-treated patients were selected from the period 1958-1964. Symptoms sufficient to fulfill a research diagnosis of mania had to be documented in the record for all patients. Results compare symptomatology, duration of hospital admission, discharge condition, discharge category, social recovery, and follow-up. Both ECT and chlorpromazine were superior to no active treatment for outcome measures considered. Ten chlorpromazine-treated patients did not respond satisfactorily to the chlorpromazine treatment but recovered with ECT treatment.

Adult↗
PubMed1971

Actions of bretylium tosylate at the neuromuscular junction.

1. The actions of bretylium tosylate on neuromuscular transmission in the rat phrenic nerve diaphragm preparation have been investigated by electrophysiological methods. Additional experiments have been made on the effect of the drug on the frog rectus preparation and on the acetylcholinesterase of erythrocytes.2. After bretylium, there was a reduction in the amplitudes of miniature end-plate potentials (mepps), endplate potentials (epps) and acetylcholine potentials recorded in the diaphragm, and also in the contractures of the rectus in response to acetylcholine (ACh) and to carbachol.3. After bretylium, there was a prolongation of the time courses of epps and ACh potentials. Under certain circumstances there was enhancement of the amplitudes of epps and ACh potentials and of the contractile responses to ACh but not to carbachol.4. Bretylium reduced the velocity of hydrolysis of ACh by erythrocyte ghosts. This inhibition was competitive and the Ki of bretylium was 0.053 mM.5. Bretylium did not cause a reduction in the mean quantal content of the epp in junctions blocked with Mg(++).6. It is concluded that bretylium exerts both facilitatory and inhibitory influences on neuromuscular transmission, which, exerted simultaneously, may give the false appearance that the drug has little action at this synapse.

Acetylcholine↗
PubMed1968

Studies on renal vasomotion.

1. The present investigation was made on the left kidney of the dog. The animals were anaesthetized intravenously with pentobarbitone (30 mg/kg) and the kidneys were perfused with saline at room temperature (20 degrees -22 degrees C). The renal innervation was untouched.2. Stimulation of the left splanchnic major nerve at T10-T12, and of the renal nerves, consistently caused renal vasoconstriction.3. Repeated stimulation of both supradiaphragmatic vagi failed to induce any vasomotion in the kidney.4. The vasoconstrictor effect was not blocked by either nicotine or hexamethonium even in enormous doses (30,000 mug). This may indicate that renal ganglia do not exist, for these ganglion blockers would prevent transmission across the ganglia.5. Kidney perfusate, re-injected into the kidney after vasoconstriction induced by stimulation of the renal nerves, brought about a notable reduction in outflow. This effect was not observed when perfusate from a non-stimulated kidney was used. This points to the release of a vasoconstrictor substance after nervous stimulation.6. Acetylcholine (ACh) in concentrations ranging from 0.001 mug/ml. caused a reduction in renal outflow. Thresholds were extremely variable. Higher concentrations of ACh (100-1,000 mug/ml.) often induced vasodilatation. The vasoconstrictor effect of ACh was not blocked by atropine.7. Nicotine and hexamethonium (10,000-30,000 mug) induced blockade which elevated the threshold for ACh to values of 1,000 mug/ml.8. Noradrenaline (0.0001 mug/ml.) induced a strong renal vasoconstriction.9. Hydergine (5-10 ml. solutions in concentrations ranging from 15 to 30 mug/ml.) blocked the renal response to nerve stimulation. This suggests that the nature of the renal innervation is adrenergic.10. In diseased kidneys which show reduction of the lumen of the arterioles, the thresholds for ACh, nicotine and noradrenaline are greatly increased, which might explain why we failed to show any effect of these drugs on renal vasomotion in several kidneys, many of which were not examined histologically.11. The collision technique was applied in an attempt to discover the nature of the fibres activated by ACh. It was found that ACh greatly reduced the size of the action potentials generated by splanchnic stimulation. This would seem to indicate that these impulses are conducted antidromically by sympathetic postganglionic fibres.12. These findings are discussed in relation to the hypothesis that the renal innervation is chiefly adrenergic and that ACh acts as a sympathetic transmitter, liberating noradrenaline, and that this effect is blocked at postganglionic endings, or at some structure intervening between adrenergic nerve endings and the effector cells, or at sensory nerve endings.

Acetylcholine↗