scholarly journals Stimulation of liver 5-aminolaevulinate synthetase by drugs and its relevance to drug-induced accumulation of cytochrome P-450. Studies with phenylbutazone and 3,5-diethoxycarbonyl-1,4-dihydrocollidine

1972 ◽  
Vol 126 (5) ◽  
pp. 1149-1160 ◽  
Author(s):  
F. De Matteis ◽  
A. Gibbs
Keyword(s):  
Feedback Control ◽  
The Other ◽  
Synthetase Activity ◽  
Drug Induced ◽  
Microsomal Cytochrome ◽  
Primary Mechanism ◽  
Marked Enhancement ◽  
The One ◽  
Cytochrome P 450 ◽  
Stimulation Of

The relevance of the stimulation of 5-aminolaevulinate synthetase to the accumulation of cytochrome P-450 after administration of drugs was examined in rats treated with phenylbutazone and with 3,5-diethoxycarbonyl-1,4-dihydrocollidine. 3,5-Diethoxycarbonyl-1,4-dihydrocollidine alone stimulated 5-aminolaevulinate synthetase without increasing the concentration of cytochrome P-450, whereas phenylbutazone alone increased the microsomal cytochrome P-450 without significantly affecting the activity of the enzyme. When the two drugs were given together both effects were found. It is concluded that if an increased amount of 5-aminolaevulinate and haem must be made to provide for the accumulation of cytochrome P-450, it need only be a small amount. It is also concluded from these findings that stimulation of the drug-metabolizing system on the one hand and marked enhancement of 5-aminolaevulinate synthetase activity and porphyria on the other are likely to result from different actions of the drugs. Evidence is presented suggesting that porphyrogenic drugs stimulate markedly the activity of 5-aminolaevulinate synthetase by lowering the concentration of haem in the liver, thereby decreasing the normal feedback control. With 3,5-diethoxycarbonyl-1,4-dihydrocollidine a rapid inhibition of mitochondrial ferrochelatase and of liver haem synthesis may be the primary mechanism involved.

Drug-Induced Porphyrin Biosynthesis—XII. Levels of Cytochrome P-450 in Chick Embryo Liver following Administration of Allylisopropylacetamide and Propylisopropylacetamide

1974 ◽  
Vol 52 (4) ◽  
pp. 891-895 ◽  
Author(s):  
V. Krupa ◽  
J. C. Creighton ◽  
M. Freeman ◽  
G. S. Marks
Keyword(s):  
Chick Embryo ◽  
Aminolevulinic Acid ◽  
The Other ◽  
Synthetase Activity ◽  
Drug Induced ◽  
Liver Cytochrome ◽  
Time Period ◽  
Embryo Liver ◽  
Ala Synthetase ◽  
Cytochrome P 450

Allylisopropylacetamide caused a decrease in the level of chick embryo liver cytochrome P-450 1 h after administration, followed by an elevation above control levels at a later time period. Propylisopropylacetamide on the other hand did not produce an early decrease in cytochrome P-450 but produced an elevation of cytochrome P-450 at a later time period. Since propylisopropylacetamide is an inducer of δ-aminolevulinic acid synthetase activity and porphyrin accumulation in chick embryo liver, it was concluded that a loss of cytochrome P-450 is not a prerequisite for ALA-synthetase induction as is thought to be the case in rats.

Localization of Spontaneous Respiratory Neuronal Activities in the Medulla Oblongata of the Cat: A New Location of the Expiratory Center

1957 ◽  
Vol 190 (2) ◽  
pp. 350-355 ◽  
Author(s):  
Edgar Haber ◽  
Kurt W. Kohn ◽  
S. H. Ngai ◽  
D. A. Holaday ◽  
S. C. Wang
Keyword(s):  
Vagus Nerve ◽  
Reticular Formation ◽  
Medulla Oblongata ◽  
Electric Stimulation ◽  
The Other ◽  
Drug Induced ◽  
Other Hand ◽  
Twin Beam ◽  
New Location ◽  
Stimulation Of

Medulla oblongata of 80 vagotomized cats was explored with microelectrodes. Spontaneous respiratory neuronal activities and chest movements were recorded simultaneously with a twin beam cathode ray oscilloscope. It was found that inspiratory discharges are concentrated in the reticular formation between 3 mm rostral and 1 mm caudal to the level of the obex, which corresponds approximately to the inspiratory region of Pitts, Magoun and Ranson. On the other hand, expiratory discharges are not obtained in Pitts' expiratory area, but are found in a circumscribed region in the reticular formation from the level of the obex to 3 mm caudally. Electric stimulation of this region has been found recently by Ngai and Wang to yield marked expiratory spasm. It is concluded that the expiratory center is located caudally to the inspiratory center in the cat. The spontaneous respiratory neuronal discharges continue with no alterations of pattern of firing during drug-induced respiratory paralysis, and are increased both in number and in frequency during CO2 inhalation. Stimulation of the vagus nerve with 50 shocks/sec. reduces inspiratory discharges and prolongs the duration of expiratory discharges.

scholarly journals The influence of homodromous and heterodromous electric currents on transmission of excitation in plant and animal

1915 ◽  
Vol 88 (607) ◽  
pp. 483-507 ◽  
Keyword(s):  
Electric Current ◽  
The Other ◽  
Muscle Preparation ◽  
Mimosa Pudica ◽  
Electric Currents ◽  
Joint Effects ◽  
Conducting Tissue ◽  
The One ◽  
Conduction Of Excitation ◽  
Stimulation Of

I have in a previous paper described investigation on the conduction of excitation in Mimosa pudica . It was there shown that the various characteristics of the propagation of excitation in the conducting tissue of the plant are in every way similar to those in the animal nerve. Hence it appeared probable that any newly found phenomenon in the one case was likely to lead to the discovery of a similar phenomenon in the other. A problem of great interest which has attracted my attention my attention for several years is the question whether, in a conducting tissue, excitation travels better with or against the direction of an electric current. The experimental difficulties presented in the prosecution of this enquiry are very numerous, the results being complicated by the joint effects of the direction of current on conductivity and of the poles on excitability. As regards the latter, the changes of excitability in the animal nerve under electrotonus have been demonstrated by the well-known experiments of pflüger. In a nerve-and-muscle preparation, the presence of a pole P is shown to induce a variation of excitability of a neighbouring point S. When P is kathode, the excitability of the point S, near it, is enhanced; stimulation of S, previously ineffective, now becomes effective, and the resulting excitation is transmitted to M, causing response of the muscle. Conversely, the application of anode at P causes a depression of excitability of S. Stimulus previously effective now becomes ineffective. In this manner the transmission of excitation may be indirectly modified by the polar variation of excitability of the stimulated point (fig. 1 a ).

scholarly journals EXPERIMENTS ON THE RELATION OF THE INHIBITORY TO THE ACCELERATOR NERVES OF THE HEART

1897 ◽  
Vol 2 (2) ◽  
pp. 151-179 ◽  
Author(s):  
Reid Hunt
Keyword(s):  
Mode Of Action ◽  
Inhibitory Effect ◽  
Relative Strength ◽  
The Other ◽  
Maximal Stimulation ◽  
The One ◽  
Considerable Period ◽  
Minimal Stimulation ◽  
Ventricular Beat ◽  
Stimulation Of

The experiments described in Part IV of this paper show that in whatever manner the problem of the relation of the vagus to the accelerators is approached, whether the accelerators are stimulated during a stimulation of the vagus, or the vagus during a stimulation of the accelerators, or both are stimulated simultaneously, either for a short or for a longer period, the result is the same, viz., the effect upon the rate of the heart is determined entirely by the relative strength of the stimuli applied to the two nerves. If the stimuli are of approximately the same strength, as judged by the effect of stimulating the nerves separately, the rate of the heart is but slightly affected; if the stimulus applied to the vagus is the stronger, the heart is slowed; if it is weaker, the heart is accelerated. In all cases the result of stimulating the two nerves simultaneously is approximately the algebraic sum of the results of stimulating them separately; sometimes the inhibitory effect slightly predominates, but not more frequently than does the accelerator effect. Moreover, the two nerves may be stimulated simultaneously for a considerable period of time without either completely overcoming the effect of the other. Thus as far as their effect upon the rate of the ventricular beat is concerned, the vagus and accelerator nerves seem to be purely antagonistic; the statement that a minimal stimulation of the one can completely overcome a maximal stimulation of the other is undoubtedly incorrect, and the hypotheses as to the mode of action of these nerves upon the heart, based upon this statement, lose their chief support.

scholarly journals ON THE RELATION OF DIRECT CURRENTS TO CONDENSER DISCHARGES AS STIMULI

1935 ◽  
Vol 18 (5) ◽  
pp. 755-766 ◽  
Author(s):  
H. A. Blair
Keyword(s):  
Differential Equation ◽  
Electrical Stimulation ◽  
The Other ◽  
The One ◽  
Stimulation Of

Data on the electrical stimulation of sciatic-gastrocnemius preparations of the frog by both direct currents and condenser discharges at the same time are discussed in relation to the validity of the differential equation See PDF for Equation where p is the local excitatory process, V the stimulating current or voltage, and K and k are constants. It is concluded that the constant k is the same whether it is derived from the data of the one stimulus or the other when the same fibres are being stimulated.

scholarly journals Exposed Pedagogy: Architecture as (a) Medium (of communication)

2021 ◽  
Author(s):  
◽  
Michael Smith
Keyword(s):  
Public Discourse ◽  
The Other ◽  
Social Implications ◽  
The Public ◽  
The Social ◽  
The One ◽  
Stimulation Of ◽  
Three Components

<p>Architecture schools are often isolated from the profession and the public they serve both pedagogically and physically, and often this is justified. Schools are not typically very public. However, schools could play a much greater role in the stimulation of a public discourse around architecture. The intent of this thesis is to examine how architecture can stimulate that discussion and ultimately how architecture could frame that discourse. The thesis proposes that an architecture school can and should be a vehicle for public discourse by way of framing that discourse on the one hand and overtly stimulating it on the other. Specifically, an architecture school has the capacity to contribute to public discourse through the visual affects of form making and the social implications of that same form. The research is divided into three components that chronicle an argument from contextualisation, through investigation to application.</p>

scholarly journals II. On the rhythm of the heart of the frog, and on the nature of the action of the vagus nerve

1882 ◽  
Vol 33 (216-219) ◽  
pp. 199-203
Keyword(s):  
Vagus Nerve ◽  
The Body ◽  
The Other ◽  
Micrometer Screw ◽  
Lower Lever ◽  
The One ◽  
Stimulation Of

The method of investigation employed by the author is as follows:— The heart with the vagus nerve intact having been removed from the body together with a portion of the oesophagus, a thread is tied to the very apex of the ventricle and another to the loose flap which is dis­closed at the junction of the two auricles when the two aortic trunks are cut away. The piece of the oesophagus removed with the heart is held firmly in a suitable holder and the heart suspended between two horizontal levers by means of the two threads which are attached to the auricles and ventricle. Between the two levers a clamp is placed, the edges of which can be approximated to any degree by means of a fine micrometer screw j the two limbs of this clamp are placed one on each side of the suspended heart, and by means of the micrometer screw, the tissue between the two edges can be simply held firm or compressed to any extent required. In this way, with the clamp in the auriculo-ven­tricular groove, the beats of both auricles and ventricle are registered simultaneously and separately; the contractions of the auricles pull the upper lever downwards, those of the ventricle the lower lever upwards. Similarly by varying the position of the clamp the con­tractions of any two adjacent portions of the heart can be studied, as for example, sinus and 'auricles, base and apex of the ventricle, &c.; heat, cold, and poisons can be applied to the tissue on the one side of the clamp and not on the other; and under all these various condi­tions the effects of stimulation of the vagus can be observed.

Involvement of nitroxide radicals in cocaine-induced hepatotoxicity

1982 ◽  
Vol 60 (12) ◽  
pp. 1614-1620 ◽  
Author(s):  
Elmer J Rauckman ◽  
Michelle W Kloss ◽  
Gerald M Rosen
Keyword(s):  
Hydrogen Peroxide ◽  
Reduced Glutathione ◽  
Cellular Proteins ◽  
Lipid Hydroperoxides ◽  
Pyridine Nucleotides ◽  
Futile Cycle ◽  
The One ◽  
Cytochrome P 450 ◽  
Stimulation Of

Cocaine administration can produce hepatotoxicity in non-induced mice of at least one strain, DBA/2Ha and hepatotoxicity in induced mice of several strains. Metabolic studies and the administration of metabolites indicate that the minor metabolic pathway, cocaine → norcocaine → N-hydroxynorcocaine → norcocaine nitroxide, is responsible for the observed cocaine-induced hepatotoxicity. In vitro experiments show that cytochrome P-450 can oxidize N-hydroxynorcocaine to norcocaine nitroxide. Norcocaine nitroxide is unreactive towards cellular proteins or glutathione but does react directly with reduced pyridine nucleotides and is rapidly reduced enzymatically by the microsomal flavoproteins, NADPH-cytochrome P-450 reductase and FAD-containing monooxygenase. These reactions constitute a futile cycle in which NADPH is consumed and superoxide and hydrogen peroxide are generated. We postulate that the destruction of hydrogen peroxide by glutathione peroxidase results in the accumulation of excess oxidized glutathione which is actively excreted by the cell, since insufficient NADPH is available for glutathione reductase to maintain the GSH/GSSG ratio at an acceptable level. As reduced glutathione levels diminish, the cell can no longer protect itself against toxic lipid hydroperoxides which accumulate as a result of stimulation of lipid peroxidation (caused by the one electron cycling reaction, N-hydroxynorcocaine to norcocaine nitroxide cycle). Finally, as glutathione is depleted below a certain level, the cell loses the ability to maintain the GSH/GSSG ratio in a range consistent with homeostasis resulting in loss of cellular function. Ultimately, necrosis results. This mechanism is consistent with all the information available concerning cocaine-induced hepatotoxicity.

Quine on Meaning and Translation

Philosophy ◽  
1979 ◽  
Vol 54 (209) ◽  
pp. 329-346
Author(s):  
D. E. Bolton
Keyword(s):  
The Other ◽  
Set Up ◽  
The One ◽  
Verbal Stimulation ◽  
Stimulation Of

In Word and Object Professor Quine formulated his Principle of Indeterminacy of Translation as follows:Manuals for translating one language into another can be set up in divergent ways, all compatible with the totality of speech dispositions, yet incompatible with one another. In countless places they will diverge in giving, as their respective translations of a sentence of the one language, sentences of the other language which stand to each other in no plausible sort of equivalence however loose. The firmer the direct links of a sentence with non-verbal stimulation, of course, the less drastically its translations can diverge from one another from manual to manual.

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