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Biomedical subjects

W Feldberg

Publications and source records attributed to W Feldberg.

At least 55 records · Page 3Linked to original sources
PubMed1975

Lipid A fever in cats.

In unanaesthetized cats the effect of lipid A on rectal temperature and on prostaglandin E2 (PGE2) activity in cisternal cerebrospinal fluid (c.s.f.) was examined. Lipid A was injected either intravenously or into the cerebral ventricles. 2. Lipid A injected intravenously in a dose of 1--4 mug/kg produced longlasting fever which was more often biphasic than monophasic. With a second injection a much shorter but usually hither monophasic response was produced. The cat was then for a time insensitive to I.V. lipid A but when the injections were repeated at 24 hr intervals brisk monophasic fevers were again produced. The threshold dose of I.V. lipid A lay between 0-1 and 0-3 mug/kg. 3. Lipid A injected into the cerebral ventricles in a dose of 100 ng or 1 mug produced long-lasting monophasic fever. No tolerance developed; the same or only slightly diminished responses occurred on repeated injections. The threshold dose was between 5 and 20 ng. 4. A cat rendered insensitive to I.V. lipid A gave its normal fever response to injection of lipid A into the cerebral ventricles. 5. The fever produced by lipid A injected I.V. or into the cerebral ventricles was associated with the appearance of, or a rise in PGE2 activity in c.s.f. 6. Both the fever and the PGE2 activity in c.s.f. produced by lipid A injected intravenously or into the cerebral ventricles were brought down and prevented by I.P. injections of aspirin, paracetamol, or indomethacin.

Acetaminophen↗
PubMed1974

Morphine hyperglycaemia.

1. To find the site where morphine acts when producing hyperglycaemia on injection into the cerebral ventricles in unanaesthetized cats, morphine sulphate was infused or injected through an implanted Collison cannula into different parts of the liquor space in an amount of 0.75 mg except on microinfusion into the posterior hypothalamus, when the amounts were 80 or 160 mug. The glucose was determined in blood samples collected from the inferior vena cava.2. Microinfusions of morphine into the posterior hypothalamus did not produce hyperglycaemia.3. Infusion of morphine into the liquor space at the entrance of the aqueduct or of the fourth ventricle produced hyperglycaemia. Any structures in the walls of the third ventricle as well as the peri-aqueductal grey are thus excluded as the site of action.4. Infusion of morphine into the subarachnoid space just above the corpora quadrigemina or below the ventral surface of the brain stem produced hyperglycaemia. With these routes the morphine does not enter any part of the ventricular cavities and the action would appear to be on structures at the ventral surface of the brain stem.5. Injection of morphine into the cisterna magna produces hyperglycaemia when the doses are larger than those already effective on injection into the cerebral ventricles. This also suggests an action on structures at the ventral surface of the brain stem, as this surface is reached more readily from the ventricles than from the cisterna.6. It is concluded that on injection into the cerebral ventricles, the morphine has to pass into the subarachnoid space, through the foramina of Luschka, in order to produce hyperglycaemia. It then reaches the ventral surface of the brain stem and probably acts there on structures in the upper part of the medulla oblongata.7. Infusion of morphine into the corpora quadrigemina near the caudal end of the superior corpora can produce profound hypoglycaemia.8. Anaesthesia depresses the morphine hyperglycaemia, but when the dose injected into the cerebral ventricles is increased four times or more, hyperglycaemia is also produced in pentobarbitone sodium anaesthesia.

Anesthesia↗
PubMed1974

Further studies on the role of prostaglandin in fever.

1. Experiments were carried out in unanaesthetized cats to find out if a prostaglandin is the mediator (a) for the long lasting fever which often follows injections of phsyiological salt solutions into the cerebral ventricles or into the cisterna magna, as well as their perfusions through the cerebral ventricles, and (b) for the sodium fever which occurs during a perfusion of the cerebral ventricles with calcium-free artificial c.s.f. A fever mediated by prostaglandin should be accompanied by an increase of prostaglandin activity in cisternal c.s.f., and be abolished or prevented by antipyretics like paracetamol or indomethacin which inhibit prostaglandin synthesis. Both criteria were applied.2. The fever which follows injections or perfusions of physiological salt solutions appears to be mediated by a prostaglandin of the E series, probably E(2) (PGE(2)) because it was accompanied by increased prostaglandin E-like activity in the c.s.f. and abolished by paracetamol and indomethacin. During the first few days after pre-treatment of the cats with intramuscular chloramphenicol the injections were rarely followed by fever.3. The fever which occurs during a perfusion with calcium-free artificial c.s.f. appears not to be mediated by prostaglandin, because it was not associated with increased prostaglandin activity in the cisternal effluent, and not prevented by paracetamol or indomethacin, although these antipyretics usually attenuated the fever.4. A perfusion of the cerebral ventricles with artificial c.s.f. containing calcium in an abnormally high concentration (6.25 mM) brought down fever produced by PGE(1), or PGE(2), or bacterial pyrogen.

Acetaminophen↗
PubMed1973

Pyrogen fever and prostaglandin-like activity in cerebrospinal fluid.

1. In the unanaesthetized cat, rectal temperature was recorded and c.s.f. was collected from a Collison cannula implanted into the third ventricle with its opening lying in close proximity to the anterior hypothalamus. Samples of c.s.f. were collected from the same cat, during normal temperature, during fever produced by Shigella dysenteriae injected into the third ventricle and during the fall in temperature which occurred when the antipyretic paracetamol was injected intraperitoneally during the pyrogen fever.2. The samples of c.s.f., when tested on the rat stomach fundus preparation, caused contractions which were not due, or at most to a small degree only, to 5-hydroxytryptamine, as they were resistant to BOL. They were therefore probably due to a prostaglandin-like substance.3. When assayed against PGE(1), the activity of c.s.f. collected from cats when their body temperature was normal corresponded to between 1.3 and 10 ng/ml. The values, whether low or high, rose over 2.5-4 times to between 4 and 35 ng/ml. in c.s.f. collected during pyrogen fever; they were again low, between 1.5 and 6 ng/ml., in samples collected when the fever had been brought down by paracetamol, but rose again with the return of fever.4. The results provide direct evidence for the theory that fever produced by pyrogens results from their ability to increase synthesis and release of prostaglandins, and that antipyretics bring down the fever because they inhibit the increased synthesis.

Acetaminophen↗
PubMed1973

Effect of pyrogen and antipyretics on prostaglandin acitvity in cisternal c.s.f. of unanaesthetized cats.

1. Samples of cisternal cerebrospinal fluid (c.s.f.) were collected from unanaesthetized cats while rectal temperature was continuously recorded. From the same cat, samples were collected during normal body temperature, during pyrogen fever and when the fever was brought down by an I.P. injection of an antipyretic. Fever was produced by injection of the bacterial pyrogen of Shigella dysenteriae either into the third ventricle, cisterna magna or I.V. The samples of c.s.f. were assayed for PGE(1)-like activity on the rat stomach fundus strip preparation rendered insensitive to 5-HT.2. In samples of c.s.f. collected during normal body temperature, usually either no PGE(1)-like activity was detected, or its activity was low. Higher values were obtained in only a few cats.3. In each experiment the PGE(1)-like activity increased, often many-fold, in samples collected during the pyrogen fever, irrespective, of the route of administration of the pyrogen. However, on I.V. injection, about 1000 times larger doses of the pyrogen were required than on injection into the liquor space to produce fever and the increase in PGE(1)-like activity of cisternal c.s.f.4. The antipyretic drugs indomethacin, paracetamol and aspirin, injected I.P. during the pyrogen fever, brought down temperature, and the PGE(1)-like activity of the cisternal c.s.f. again became low.5. When samples of cisternal c.s.f. were subjected to thin layer chromatography the prostaglandin-like activity was solely or mainly found in the zone corresponding to the prostaglandins of the E series.6. These findings support the theory that pyrogens produce fever by increasing synthesis and release of prostaglandin in the preoptic anterior hypothalamic area, and that antipyretics of the aspirin type bring down this fever because they inhibit this synthesis.7. It is concluded that pyrogen increases prostaglandin synthesis not only in the preoptic anterior hypothalamic area. When injected into the liquor space increased synthesis of prostaglandin probably occurs in many regions near the surface of the brain stem, and when injected I.V. may occur in other parts of the C.N.S. as well. But to produce fever the prostaglandin has to act on the preoptic anterior hypothalamic area.

Acetaminophen↗
PubMed1972

The hyperglycaemic effect of morphine.

1. In the unanaesthetized cat, an injection of 0.75 mg of morphine into a lateral cerebral ventricle produced strong hyperglycaemia; on intravenous injection, 10 to 30 times larger doses were required. Other effects produced with both injections were shivering, pupillary dilatation, opening of the eyes, miaowing, periods of excitation, and analgesia. Between the periods of excitation the cat did not react to objects moving in front of its eyes and it had a vacant stare.2. Noradrenaline, adrenaline, and 5-hydroxytryptamine (5-HT) injected intraventricularly (250 mug, twice) depressed the hyperglycaemia due to intraventricular morphine, and noradrenaline also depressed the hyperglycaemia due to intravenous morphine. Adrenaline produced the strongest and 5-HT the weakest depression. 5-HT did not depress the other effects of morphine, but the catecholamines depressed most of them; only analgesia and the vacant stare appeared to be unaffected.3. Reserpine injected intraventricularly (0.5 mg, twice) greatly accentuated the hyperglycaemia as well as the other effects produced by intraventricular morphine, but pupillary dilatation and opening of the eyes no longer occurred; the protrusion of the nictitating membranes produced by the reserpine persisted.4. Pentobarbitone sodium injected intraperitoneally in an anaesthetizing dose practically abolished the morphine hyperglycaemia, but injected intraventricularly in a dose of a few milligrammes, it had a two fold effect: depression followed by enhancement of the morphine hyperglycaemia. The enhancement may be due to sensitization of the effect of the adrenaline released by morphine, since adrenaline hyperglycaemia was enhanced as well.5. Morphine did not seem to act on structures in the walls of either the lateral or third ventricle when producing its hyperglycaemic effect on intraventricular injection. The action may therefore be on more caudally situated parts of the neuro-axis, on the central grey, on structures in the floor of the fourth ventricle or of the lateral recesses, or even on structures near the ventral surface of the brain stem.

Analgesia↗
PubMed1972

A vasodepressor effect of pentobarbitone sodium.

1. In anaesthetized cats under artificial ventilation, a few milligrams of pentobarbitone sodium injected into the cerebral ventricles produced a pronounced fall in arterial blood pressure, which was central in origin and resulted from inhibition of vasomotor tone.2. Pentobarbitone sodium was more effective in lowering blood pressure when injected into the cerebral ventricles than when injected into the cisterna magna, yet the pentobarbitone sodium did not act on structures in the ventricular wall, but acted on structures reached from the subarachnoid space.3. To produce its vasodepressor effect, the pentobarbitone sodium had to pass through the foramina of Luschka into the subarachmoid space beneath the medulla oblongata and to penetrate its ventral surface in a region caudal to the trapezoid bodies and lateral to the pyramids. This was the outcome of experiments in which the pentobarbitone sodium was injected into or perfused through the cerebral ventricles with or without an outflow cannula inserted into the aqueduct or into the fourth ventricle, and of experiments in which pentobarbitone sodium solutions were applied by means of Perspex rings to this region of the exposed ventral surface of the medulla. Whereas the application of pentobarbitone sodium to this region on one side had a weak vasodepressor effect only, its application on both sides produced a pronounced fall in arterial blood pressure.4. The region where pentobarbitone acted on topical application covers the region where nerve cells are found in the marginal glia immediately under the pia mater. The possibility is discussed that these cells are the morphological substrate on which the pentobarbitone acts, that arterial blood pressure is maintained by their activity which is suppressed by the pentobarbitone sodium.

Animals↗
PubMed1971

Effects of adrenoceptor blocking agents on body temperature.

1. The effect on rectal temperature of adrenoceptor blocking agents, injected through a cannula chronically implanted into a lateral cerebral ventricle, was examined in unanaesthetized rabbits, cats and rats, kept at room temperature (19-22 degrees C).2. In rabbits, the alpha-adrenoceptor blocking agent phenoxybenzamine (50 or 100 mug) produced marked hypothermia when injected intraventricularly but not when injected intravenously. In some rabbits as little as 1 mug was effective on intraventricular injection. Phentolamine and ergotamine, the other alpha-adrenoceptor blocking agents examined, had a much weaker hypothermic action when injected intraventricularly, whereas the beta-adrenoceptor blocking agents propranolol, pronethalol and Trasicor had no effect.3. In rabbits in which the noradrenaline stores of the hypothalamus were depleted by intraventricular injections of reserpine, the hypothermic effect of phenoxybenzamine was abolished and remained abolished for a few days.4. In cats, an intraventricular injection of phenoxybenzamine (200 mug) produced long-lasting hyperthermia, but not in all cats, and only with the first, or the first two or three injections. Injected intraperitoneally, this dose had no effect on temperature. Phentolamine (100 or 200 mug) had a very weak hyperthermic effect and phentolamine (500 mug), a hypothermic effect, but only on intraventricular injection, whereas ergotamine (100 and 200 mug) had a weak hyperthermic effect both on intraventricular and intraperitoneal injection. Propranolol and Trasicor had no effect on temperature when injected intraventricularly.5. In rats, phenoxybenzamine (5 or 20 mug) produced long-lasting hypothermia on intraventricular injection.6. Some of the temperature effects produced by intraventricular injections of the alpha-adrenoceptor blocking agents are explained on the assumption that they prevent the effect on temperature produced by a continuous release of noradrenaline from adrenergic neurones innervating the anterior hypothalamus.

Amino Alcohols↗