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Biomedical subjects

J Knoll

Publications and source records attributed to J Knoll.

At least 109 records · Page 6Linked to original sources
PubMed1982

Seasonal variation in various blood indices of the kangaroo rat, Dipodomys panamintinus.

1. Various blood indices in the Panamint kangaroo rat revealed seasonal fluctuations. The red blood cell count during winter and summer averaged 7.2 +/- 1.0 X 10(6) and 9.2 +/- 0.2 X 10(6)/mm3 respectively. 2. The mean cell hemoglobin during winter and summer averaged 25 +/- 10.8 pg and 18.6 +/- 3.7 pg respectively. 3. These fluctuations may reveal a rapid rate of red blood cell destruction during winter in combination with a change in diet, concomitant to this, is an increase in mean cell hemoglobin of the surviving red blood cells.

Acclimatization↗
PubMed1982

Quantitative studies of the antagonism by naloxone and N-cyclopropylmethyl-norazido-dihydroisomorphine (CAM) of different opiates.

1. CAM--a new type of opiate antagonist [10, 11] was used to study the types of opiate receptors (OR) involved in the analgesic and narcosis potentiating effects of different opiates. The analgesic assays were: hot plate, algolytic test (rat) and acetic acid stretching test (mouse). 2. The in vivo equivalent of pA2 value (apparent pA2) for naloxone (NX) and CAM was determined with each opiate agonists. 3. The estimated pA2 values for analgesia did not differ significantly from those obtained for anesthesia in the case of NX, however, if CAM was used as antagonist the pA2 values were the same as with NX in the algolytic test, but different result was obtained when analgesia was measured by hot plate and stretching test, and narcosis potentiation was examined. 4. It was concluded that NX and CAM interact with the same OR when algolytic test was used, however different type of OR might be involved in hot plate and stretching assays and anesthesia potentiation, too.

Analgesia↗
PubMed1982

The selectivity of the anorectic effect of satietin. IV. The ineffectiveness of satietin on the sexual performance of male CFY rats.

Satietin a recently discovered potent endogenous anorectic agent was claimed to be a highly selective anorectic substance, devoid of any effect on other behavioral system. In the copulator male rats, in contrast to amphetamine, fenfluramine and fluoxetine it failed to influence the mating activity. This finding further supports the view that satietin has highly selective effect on feeding behavior.

Amphetamine↗
PubMed1982

The selectivity of the anorectic effect of satietin. I. The ineffectiveness of satietin on behavioral tests.

Satietin, a potent endogenous anorectic substance separated from human serum, plays a role of a rate limiting satiety signal in the negative feed back of food intake. The selectivity of satietin on some behavioral tests (unconditioned avoidance reaction, one-way as well as two-way conditioning, open field, consolidated conditioned reflex) was checked and compared to calcitonin. TRH and Glp-Leu-Pro-OH. Satietin seemed to be ineffective on all but one (open field) behavioral tests. Calcitonin and Glp-Leu-Pro-OH increased open field activity. Results indicate that satietin is an endogenous anorectic substance with a peculiar selectivity.

Animals↗
PubMed1982

The selectivity of the anorectic effect of satietin. II. Ineffectiveness of satietin on the water intake in food deprived rats. Effect of satietin in "conditioned aversion" paradigm.

The effect of satietin, a potent endogenius anorexigenic agent, on the water intake of fed and food deprived rats was studied and compared with the effects of calcitonin. In rats deprived of food for 96 h and supplied with water ad libitum, no change in the water intake of intracerebroventricularly (icvtr) administered satietin (2 units/rat), calcitonin (1 unit/rat) and saline (0.2 ml/rat), respectively, was observed. In animals deprived of food and water for 23 h, satietin (2 units/rat, icvtr) left water consumption unchanged, whereas calcitonin (1 unit/rat, icvtr) inhibited the intake of water significantly. The possible role of an aversive reaction in the anorexigenic effect of satietin was also studied using the "conditioned aversion" paradigm of Garcia et al. [3]. Satietin (250 units/kg, intravenously) did not elicit aversion for food.

Amphetamine↗
PubMed1982

Satietin: a centrally acting potent anorectic substance with a long-lasting effect in human and mammalian blood.

An anorectic substance in human, mammalian (rat, guinea pig, rabbit, cat, dog, horse, cattle) and poultry (goose) serum, named satietin, was discovered recently. The substance was extracted and purified by gelchromatographic techniques. With an improved technique, a highly purified glycopeptide fraction, containing 87% carbohydrates (fucose, mannose, glucose and galactose) and 12.5% amino acids, was prepared from human serum and its anorectic effect was measured in fasting rats. A biological assay for satietin, expressing activity in units, was developed. The unit is equivalent to the anorectic activity of the amount of a sample which, when given intracerebroventricularly (icvtr) decreases the chow pellet consumption of rats deprived of food for 96 h, during the first day of feeding, from 24.04 +/- 0.76 g to 10 g. With higher icvtr doses of satietin (2-3 units/rat) the 24 h consumption of the fasting rats can be reduced below 4-5 g and the animals begin to eat on the second day of feeding only. With samples containing 100 units/mg, the anorectic effect was checked at various routes of administration. Satietin acts icvtr, proving that its site of effect is in the brain. A significant decrease in food intake was also observed in the deprived rats 1 h after the oral administration of satietin (100 units/100 g), 1 h after the intravenous or subcutaneous administration of satietin (40 units/100 g), the first hour consumption of food was completely blocked. The anorectic effect of satietin was compared to the endogenous peptides (CCK, calcitonin, pGlu-His-GlyOH), proved or claimed to have anorectic effect, and to the drug-pair, amphetamine and fenfluramine, which represent the two main types of anti-obesity agents. Satietin proved to be a highly specific anorectic substance different in its spectrum from hitherto known compounds inhibiting food intake.

Administration, Oral↗
PubMed1982

The selectivity of the anorectic effect of satietin. III. The ineffectiveness of satietin on metabolic rate, body temperature and blood pressure.

Satietin, a recently discovered endogenous anorectic substance, prepared from human serum was found to inhibit food intake in a very selective manner. As the hypothalamic satiety center was proposed to be the site of effect of satietin, its effect on other physiological processes (metabolic rate, body temperature, blood pressure) controlled by the hypothalamus was investigated. Satietin did not change the metabolic rate of rats, had no influence on the body temperature and did not affect blood pressure. For sake of comparison the effects of endogenous peptides, like calcitonin, known to inhibit food intake and the representatives of the two main classes of anorectics, amphetamine and fenfluramine, were also studied.

Amphetamine↗
PubMed1982

An improved method for the preparation of highly purified satietin samples from human serum.

Satietin, a highly selective anorectic substance, was prepared in highly purified form. A new isolation procedure is described for the preparation of human satietin. Serum proteins were removed by ultrafiltration and precipitation with trichloroacetic acid and the satietin active substances were then separated by gelchromatographic and electrophoretic techniques. The highly purified materials are proved to show carbohydrate properties. The carbohydrate and protein content of samples were determined by amino acid and sugar analysis after acid hydrolysis of samples. According to a specific bioassay these substances were found to contain 100 units/mg activity, and concluded to be glycoproteins having molecular weight around of 50,000.

Amino Acids↗
PubMed1981

A new model for the study of opiate B-receptors: isolated splenic strip of the cat.

Noradrenergic neurotransmission in the electrically stimulated isolated splenic strip of the cat was found to be modulated via opiate receptor. Pharmacodynamic parameters of morphine, methionine-enkephalin, azidomorphine, naloxone and N-cyclopropylmethyl-norazidomorphine (CAM) were determined. As CAM proved to be more potent than naloxone in this organ, the cat splenic strip is a useful model for the in vitro testing of opiate B-receptors.

Adrenergic Fibers↗
PubMed1981

Opiate agonists inhibit noradrenaline release via opiate B-receptors and N-cyclopropylmethylnorazidomorphine (CAM) blocks electrically evoked contractions via histamine in the mouse vas deferens.

N-cyclopropylmethylnorazidomorphine (CAM) reduced slightly the stimulation evoked 3H-noradrenaline outflow from the mouse vas deferens and this effect was not antagonized by naloxone. Azidomorphine, however, inhibited potently the release of noradrenaline and the effect was completely antagonized by CAM and naloxone. The field stimulation induced release of acetylcholine remained unchanged in the presence of CAM. Atropine leaving the release of noradrenaline unchanged caused 50-60% inhibition of responses to electrical stimulation. Histamine and 48/80 inhibited the twitch responses to electrical stimulation and this effect was antagonized by H1-receptor antagonists (mepyramine, chloropyramine phenindamine, thenalidine, cyproheptadine), but not by cimetidine. H1-receptor antagonists increased the release of noradrenaline and facilitated neuromuscular transmission; cimetidine was ineffective. H1-blocking antihistamines completely inhibited the blockade of the electrically evoked contractions caused by CAM, whereas cimetidine left them unaltered. The effects of morphine and azidomorphine were only moderately antagonized by H1-blocking antihistamines and the effect of methionine enkephalin remained unchanged. In the presence of atropine and H1-blocking antihistamines CAM antagonized the effect of the opiate agonists competitively. It was concluded that in the mouse vas deferens opiate agonists inhibit noradrenaline release via opiate B-receptors. CAM inhibits the twitch responses in this test via histamine and H1-receptors were found to be involved in this mechanism.

Animals↗
PubMed1981

The fate of p-bromo-methylamphetamine (V-111) in the body.

The fate of p-bromo-methylamphetamine (V-111) in the body was studied by means of its radioactive labelled forms in mouse and rat experiments. It was found with the whole body autoradiographic method and liquid-scintillation measurements that the compound is rapidly absorbed by whatever routes of administration and it is rapidly taken up by the tissues from the blood stream. In the central nervous system, it reaches higher concentration than methyl-amphetamine and it leaves the central nervous system more slowly. We have shown with differential centrifugation that V-111 is bound much more avidly to the mitochondrial and microsomal fractions of rat brain than methyl-amphetamine and o-bromo-methyl-amphetamine (V-104). The intensity of binding is proportional to the lipid solubility of the compounds. V-111 and its metabolites are excreted mainly in the urine, and they can be found in small amounts also in the stool. In the case of V-111-3-14C a small amount of 14CO2 appeared in the expired air, too, which is a consequence of the disintegration of the molecule. It has been shown by the radiochromatographic and gas chromatographic, mass-spectrometric analysis of the metabolites that V-111 is excreted partly in unchanged form, nevertheless, the N-demethylated and subsequent products, viz. p-bromo-phenyl-acetone, p-bromo-phenylpropanol, p-bromo-benzoic acid and p-bromo-hyppuric acid are also excreted in the urine. The main metabolic pathway of amphetamine and of its methyl-derivative in rat is p-hydroxylation, which does not take place in the case of p-halogenated V-111. Thus the secondary metabolic pathway (demethylation, oxidative desamination) becomes the main metabolic route of V-111 in this species. The vigorous demethylation of V-111 was proved both in vivo and in vitro. In the rat, demethylating activity increases during prolonged treatment. The latter fact has to be taken into consideration when interpreting the pharmacological tolerance that develops during chronic administration of the compound.

Absorption↗
PubMed1980

The role of metabolic factors in the interaction between opiates and homopyrimidazoles in the central nervous system.

Both the analgesic and the antitussive effects of morphine, codeine and azidomorphine, azidocodeine and azidoethylmorphine are potentiated in rats and cats by Probon, a minor analgesic, with a homopyrimidazole structure. The analgesic effect of opiates and their toxicity are more strongly influenced by the N-methylhomopyrimidazoles than their antitussive effect. In the potentiation between Probon and morphine derivatives metabolic interference may play a role at the N-demethylation level, occuring in the liver microsomes.

Analgesics↗