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Biomedical subjects

S H Roth

Publications and source records attributed to S H Roth.

At least 163 records · Page 9Linked to original sources
PubMed1980

Mechanisms of anaesthesia: a review.

Anaesthesia is a drug-induced reversible perturbation of neuronal activity. Since a wide variety of structurally unrelated substances are capable of producing this phenomenon, it has been generally accepted that anaesthetics produce their effects through non-specific hydrophobic interactions. Results of recent studies in whole animal and cellular (membrane) preparations demonstrate that a unitary theory of action does not exist. Anaesthetics can produce a spectrum of activity in the central nervous system, and different agents produce different patterns of activity. At the cellular and membrane level, differential effects have been observed, structural dependent differences occur and optical isomers display very different activities. The perturbation (fluidity change) of membrane components does not appear to be uniform for all anaesthetics. It is concluded that anaesthetics are selective agents, and produce their effects at multiple sites and through a variety of mechanisms.

Anesthesia↗
PubMed1980

Benoxaprofen: once a day vs twice a day in patients with rheumatoid arthritis or osteoarthritis.

This multicenter clinical trial was conducted in patients with rheumatoid arthritis and osteoarthritis in an effort to evaluate and compare the efficacy and safety of benoxaprofen when taken as a single 600 mg dose in the evening or when taken in 2 300 mg doses. The results of the double-blind crossover studies demonstrated the effectiveness of the qd and bid dose and revealed no significant difference between the 2 dose regimens. They also showed the once-daily dose, a dose that is more convenient and easier to comply with, to be as effective as the twice-daily dose.

Adult↗
PubMed1980

Membrane and cellular actions of anesthetic agents.

It is generally accepted that anesthetics affect most biological cells in a nonspecific fashion. A similar or unitary mechanism of action has been proposed for all anesthetics. This may be the rule for general anesthesia; however, evidence exists which suggests that all anesthetics may not act via the same mechanism or at the same site. It is well recognized that various anesthetic agents can affect peripheral systems in a selective manner that is often clinically relevant. In addition to the nonspecific requirement of lipid solubility, specific molecular structure may determine the selectivity of an anesthetic and thus its pattern of anesthesia. Recent studies on an isolated neuronal preparation, the stretch receptor of the crayfish, are presented which demonstrate that anesthetics can differentially alter neuronal behavior in addition to producing biphasic effects of excitation and depression. It is yet to be resolved whether these effects are relevant to the mechanism of anesthesia.

Action Potentials↗
PubMed1979

Combination bronchodilators: antagonism of airway smooth muscle contractions in vitro.

The component drugs of fixed-dose combination bronchodilators may interact in a synergistic manner to antagonize airway contractions. To examine this hypothesis, combinations of ephedrine (E) and theophylline (Th) or salbutamol (S) and theophylline were tested for their ability to relax contracted guinea-pig airway smooth muscle in vitro. The combination bronchodilator effect was compared to the summed effects of the component drugs given individually (i.e. a theoretical additive response, Ta). Relaxation responses to combination bronchodilators were considered less-than-additive if significantly less than Ta, additive if non-significant and greater-than-additive or synergistic if the values were significantly greater than Ta. It was found that the E-Th combinations interacted primarily in an additive fashion to relax contractions induced by histamine, acetylcholine and 5-hydroxytryptamine at concentrations that produced one-half maximal contractile response (ED50). Similarly S-Th combinations interacted in an additive manner to reverse histamine and acetylcholine contractions. In the case of both E-Th and S-Th combinations, the drugs were more effective in reducing the smooth muscle contractions when given during rather than prior to the response. It may be concluded that beta-sympathomimetics and methylxanthines when combined do not interact in a synergistic fashion to produce relaxation of contracted airway smooth muscle.

Acetylcholine↗
PubMed1979

The non-specific membrane binding properties of delta9-tetrahydrocannabinol and the effects of various solubilizers.

The binding of [3H]delta9-tetrahydrocannabinol to crude and purified synaptosomal membrane suspended in either Krebs solution or 10 mM sodium phosphate buffer was examined. The membrane/buffer partition coefficient was found to be 12,500, and was constant over a free concentration range of 10(-8) to 10(-6)M. Binding was similar in both suspending media, and to both crude and purified synaptosomal membrane. The solubilizing agent Cremophor E.L. (8 microgram ml-1) decreased the partition coefficient by one-half, and by greater than 99% at 0.4 mg ml-1. Similar effects were observed with Tween 80, while ethanol caused a maximum decrease of 60%. Membrane concentrations of THC were calculated at various effective concentrations reported in the literature, and were within the range predicted by the Meyer-Overton rule of anaesthesia. An apparent non-specific interaction with neuronal membranes and effective membrane concentrations of the order 2 x 10(-4) to 1 x 10(-2) mol kg-1 suggests THC may exert some of its effects by a mechanism analogous to the general anaesthetics, and thus may be classified as a partial anaesthetic.

Animals↗
PubMed1979

Effects of atropine on secretion and motility in isolated gastric mucosa and attached muscularis externa from ferret and cat.

1. A combined in vitro preparation of gastric mucosa and adjacent muscle from young ferrets and kittens has been used to study the effects of atropine on acid secretion and motility produced by acetylcholine (ACh) and pentagastrin.2. The minimal dose of atropine required to abolish a maximum secretory response to ACh also prevented the associated motility response. This dose of atropine also blocked the motility response to pentagastrin, but was without influence on the secretory effect of this agent. A 10(3) times larger dose of atropine reduced the secretory effect of pentagastrin by half, probably not by anti-muscarinic effect. The results exclude the possibility that the acid secretory response to pentagastrin necessarily involves a cholinergic receptor.3. The results support the view that the response of the fundic smooth muscle to pentagastrin depends on the excitation of cholinergic nerves.4. No evidence has been found of any cholinergic component in the acid secretory response to pentagastrin. In assessing the significance of this result, however, it must be remembered that the Auerbach plexus has been removed over the major part of the mucosa, and the Meissner plexus deprived of input and probably damaged.5. The results are compatible with the hypothesis that the depressant effect of atropine on acid secretion produced by gastrin and its derivatives is due to the elimination of a cholinergic potentiating influence arising in the intramural plexuses. The residual Meissner plexus elements in this in vitro preparation appear inadequate to sustain this effect.

Acetylcholine↗
PubMed1978

The guinea pig tracheobronchial spiral strip: responses to selected agonists.

The guinea pig tracheal spiral strip is a useful preparation for studying bronchoconstrictor and bronchodilator compounds. Employing a simple and rapid modification of this technique, experiments were performed in vitro to quantitate the effects of selected bronchospastic agents on guinea pig tracheobronchial smooth muscle. Three sections of the main airways were prepared from each animal: an upper tracheal, a lower tracheal, and a bronchial segment. The dose-dependent contractile responses of the three tissue segments were determined for carbachol, acetylcholine, histamine, 5-hydroxytryptamine, and bradykinin. Differences were observed amongst the agonists in magnitudes of contraction, effective concentration ranges, and slopes of dose-response curves. ED25, ED50, and ED75 values were calculated from regression analysis of dose-response data. The relative order for these agents to produce maximum contractions was found to be carbachol congruent to acetylcholine greater than histamine greater than 5-hydroxytryptamine greater than bradykinin. Furthermore, it was found that there was no significant difference between the three tissue segments in their responses to the various agonists.

Airway Resistance↗
PubMed1978

Stereospecific presynaptic inhibitory effect of delta9-tetrahydrocannabinol on cholinergic transmission in the myenteric plexus of the guinea pig.

delta9-Tetrahydrocannabinol (THC) is very lipid soluble, as are many anesthetic agents. The action of anesthetics is nonspecific; isomers are equieffective. THC is optically active; therefore, the effects of its stereoisomers were studied on the electrically and chemically stimulated longitudinal muscle strip of guinea pig ileum. The results demonstrate that both isomers depress the response to electrical stimulation in a dose-related manner. The maximum effect is gradually reached in approximately 20 min. The (-) isomer is 24.6-fold more active than the (+) isomer (ED50 for (-) THC is 1.25 X 10(-7) M, for (+) THC, 3.08 X 10(-6) M) and the site of action appears to be presynaptic because responses to ACh are not significantly depressed. The depressant effects are relatively nonreversible. Membrane concentrations calculated at the ED50 values for the (-) isomer are of the order of 0.5 mM/kg dry membrane, well within the range for anesthesia. Thus THC may be regarded as a partial anesthetic since some of its actions are similar to those of the classical anesthetics, yet it possesses selective action at the neuronal membrane or tissue level.

Animals↗
PubMed1978

Acid secretion and motility of isolated mammalian gastric mucosa and attached muscularis externa.

A procedure is described for the setting up of a preparation of mammalian gastric mucosa from kitten or ferret. The mucosa is stripped of its outer muscle coats except for a 2-mm strip of circular muscle fibers running across the diameter of the preparation. The connections of this strip to the underlying mucosa are undisturbed. The preparation is immersed on the nutrient side in Krebs-Henseleit solution, gassed with 95% O2 and 5% CO2, and the secretory side contains 5% dextrose, both at 37 degrees C. Acid secretion is determined by a pH stat method and motility is recorded by a strain gauge attached to one end of the muscle strip. Secretory and motility responses are recorded for the three main parietal cell agonists, acetylcholine (ACh), pentagastrin, and histamine. In all cases, concentrations adequate to produce secretory effects also produced modulation of motor activity. In both animals the similarity between the motility responses produced by cholinergic stimulation and pentagastrin was notable.

Acetylcholine↗
PubMed1976

Pressure antagonism of anaesthetic-induced conduction failure in frog peripheral nerve.

Experiments to investigate pressure-induced antagonism of the effects of general anaesthetics in isolated peripheral nerve from the frog are described. The doses of four gaseous general anaesthetic agents required to reduce electrically evoked action potentials by 50% (mean +/- SEM) were nitrous oxide 490 +/- 40.4 kPa, ethylene 665 +/- 212 kPa, dichlorodifluoromethane 108 +/- 17.2 kPa and cyclopropane 70 +/- 5 kPa. The combination of high pressure and the anaesthetic agent partially or completely restored the action potential amplitudes for the gaseous and some of the volatile agents (chloroform, diethyl ether, helothane). However, reversal of the effects of other volatile agents (ethanol, butanol), sodium pentobarbitone and two local anaesthetic agents (procaine, dibucaine) did not occur. The pressures used to effect a reversal were less than anticipated. This apparent inconsistency with the critical volume hypothesis for anaesthesia is discussed.

Anesthesia, Inhalation↗
PubMed1976

Effects of a series of alcohols on the binding of a fluorescent dye to erythrocyte membranes.

1. The effects of a series of aliphatic alcohols (methanol to octanol) on membrane proteins of erythrocytes were studied by monitoring the flueorescence of a dye (1-anilino-8-naphthalenesulfonic acid (ANS)) that adsorbs to erythrocyte ghost membranes. Low concentrations of all the alcohols reduced the ANS fluorescence of the membrane-ANS suspensions; lent to those which protect against hypotonic hemolysis on intact erythrocytes; higher concentrations markedly increased the fluorescence. Ethanol and methanol decreased ANS fluorescence at all concentrations. 2. Lytic concentrations of saponin did not increase ANS fluorescence and did not modify the membrane action of the alcohols. 3. None of these effects were observed in liposomes prepared from lipid extracts of the erythrocyte membrane. 4. Since the apparent dissociation constant for the ANS-membrane interaction was unchanged in the presence of the alcohols, it was assumed that the fluorescence changes anesthetic concentration of the alcohols alter the conformation of membrane proteins, as indicated by the decreased number of ANS binding sites.

Alcohols↗