Activity In Various Organs Research Articles

Correlation of T4 to T3 converting activity with T3 concentration in rat tissues.

The correlation between T4 5'-deiodinase activity and thyroid hormone concentration in rat tissues was sought. Studies with normal and thyroidectomized rats indicated a significant correlation of the hepatic T3 concentration with the enzyme activity in liver homogenate (r = 0.80, p less than 0.01) or in liver microsomes (r = 0.08, p less than 0.01). The correlation between the hepatic T4 concentration and activity of the enzyme was less significant (r = 0.55, p less than 0.05 for homogenate, and r = 0.66, p less than 0.01 for microsomes). The degree of T4 5'-deiodinase activity in various organs was found to increase in line with tissue concentration of T3. It seems likely that the level of T4 5'-deiodinase activity is controlled by the tissue concentration of T3.

Main trends in the search for new neuromuscular blocking agents

218 Main trends in the search for new neuromuscular blocking agents D. A. Kharkevich Department of Pharmacology, Fint Medica/Institute, .W'oscow, U.S.S.R. It is generally known that the neuromuscu­lar blocking agents are used in practically every field of surgery. Furthermore, they are applied for treatment of various neurological diseases which are accom­panied by an increased tonus of skeletal muscles and tetanus. The various demands of clinicians for neuromuscular blocking agents have made it necessary to create a set of such drugs with precise indications for the use of each drug. Defined in terms of the mode administration and the duration of action the required neuromuscular blocking drugs can be classified in the following groups: I. Drugs for parenteral (intravenous) administration 1. Of short duration of action ( 5-15 min) 2. Of moderate duration of action (20-60 min) (a) rapidly evoking apnea (b) weakly inhibiting respiration 3. Of long duration of action (more than 60 min) (a) rapidly evoking apnea (b) weakly inhibiting respiration II. Drugs for oral administration (of long duration of action, weakly inhibiting respiration). pharmacological antagonists. This may cause some difficulties cases when the inactivation succinylcholine is disturbed and the effect (myorelaxation, apnea) lasts for several hours. Such a situation may occur with genetically conditioned insuffi­ciency of pseudocholinesterase. Besides, succinylcholine, belonging to the depolariz­ing agents, increases the permeability of the endplate membrane, which is accompanied by release an excessive amount of Diadonium HO t:::O CH.OH HOH,C OH t:::02CI tH~CHr-0-o-Q-CH;_tH, Diplacinum Tercuronium TIPS-August 1981 potassium ions into the extracellular space. Their content increases in plasma and decreases in skeletal muscles. The altera­tion in the distribution of potassium ions may have an undesirable effect on the activity of various organs (heart, for ex­ample). Muscle soreness, which may be observed during the postanesthetic period is probably also caused by the potassium imbalance. Also the use of succinylcholine is contraindicated in galucoma. Thus, it is quite natural, that phar­macologists and chemists should aim at creating short acting neuromuscular block­ing agents with non-depolarizing mode of action. The general trends of their search are as follows. One lies in synthesis of agents, which are rapidly inactivated (for example, in the series of esters related to succinylcholine). Also, short duration of action can be based on the unstable fixation of the agent on acetylcholine receptor. In the series of his-quaternary ammonium compounds this may be achieved by chang­ing the character of radicals attached to quaternary nitrogen atoms. Proceeding a H.--'71 .#·rcHo ~ ~ ·2CI ·4H,Q --ICH·I·---N·-Qualidilum The drugs of short duration action are used for short manipulations- intubation, setting of dislocations, reposition of bone fragments, etc. The myorelaxation induced by the neuromuscular blocking agents of this group should not exceed 5-15 min. At the same time short acting agents can be useful for prolonged dripfeed or multi­ple intravenous administration. The drip infusion facilitates control of the degree of muscle relaxation. It is important that, after the discontinuance of the infusion the drug, initial tonus of skeletal mus­cles should be rapidly restored. Dioxonium Succinylcholine (lysthenon), a well known drug of depolarizing mode action, is a short acting neuromuscular blocking agent. However, it has a number of disadvantages. First all, it has no £; El~e\ler/~orlh-Holland B10medical Pre'' 1 Y~ I 0\65-fll47/81/0000- 0000/$02.50 H.c. oc~~N-CH, H,C,Nf'\N \__/ 'CH, H~C \___/ -2ar-H.C-OCO Arduan OCO-C.H.--N-CO--CH(CH,}-CH..-CO Fig. 1. Chemical structures o [some neuromuscular blocking agents. H,C,~ ~ Condelphinum

Distribution of leucine 2,3-aminomutase activity in various organs of the rat and in subcellular organelles of rat liver

Leucine 2,3-aminomutase, the cobalamine-dependent enzyme involved in the conversion of β-leucine to leucine, has been shown to be widely distributed in rat organs. The activity is highest in skeletal and cardiac muscle, lower in brain, liver, and kidney, and very low in small intestine. In rat liver, the activity is nearly all in the cytosolic fraction.

Platelet kinetics during deep hypothermia

The effects of surface-induced deep hypothermia (20°C) on platelets in terms of their disappearance and location during cooling, recovery with rewarming, and subsequent survival were studied in splenectomized dogs utilizing 51Chromium-tagged autologous platelets. The curves for platelet counts and 51Cr activity were similar with both falling to about 10% of control value at 20°C and both returning to control levels within 1 hr of rewarming. No important differences were observed in the platelet count curves in groups of animals with or without a spleen, with or without 1 2 hr of circulatory arrest, and with or without administration of low molecular weight dextran. The mean platelet survival after hypothermia was somewhat longer (4.9 days) than in normothermic control dogs (4.2 days). The site of hypothermic sequestration was determined by counting 51Cr activity in various organs in animals sacrificed at 20°C; virtually all of the sequestered platelets were found in the liver. This was verified by electron micrographs of the liver. The results indicate that the thrombocytopenia of surface-induced deep hypothermia is due to completely reversible temporary sequestration of platelets in the liver and that the mean survival of platelets exposed to this procedure is not shortened.

THROMBOPLASTIC AND FIBRINOLYTIC ACTIVITIES IN VARIOUS ORGANS OF CONGENITALLY ATHYMIC NUDE MICE

Thromboplastic and fibrinolytic activities in various organs of congenitally athymic nude mice were estimated. These activities varied from one organ to another and the organs were divided into six groups of possible combinations of these activities. The lung revealed high thromboplastic and high fibrinolytic activities, while the liver showed low thromboplastic and low fibrinolytic activities. The pattern of distribution of these activities in various organs of nude mice was almost similar to that of rats and mice with normal thymus. No plasmin activity was found in all organs.

Effect of diet on adenylosuccinase activity in various organs of rat and chicken.

Adenylosuccinase activity of rat liver is depressed by prolonged starvation, cortisol administration, high protein diets, and alloxan diabetes. The loss of activity is not due to the accumulation of a dissociable inhibitor or loss of a cofactor. Starvation produces no loss in activity for 1 day; thereafter the activities of the liver and spleen enzyme decay with a half-life of about 0.9 day. Starvation produces no change in the activity of the kidney, brain, and skeletal muscle enzyme. Refeeding restores the activity of the liver enzyme to the fed level, with only a slight overshoot. The recovery of adenylosuccinase activity is equally rapid after refeeding a balanced diet, or corn oil, or glucose, and is not inhibited by injection of glucagon, in contrast to malic enzyme activity. Recovery is inhibited by cycloheximide, indicating the involvement of protein synthesis. Althouth adenylosuccinase is depressed in liver of starving rat it is elevated in liver of starving chicken. Starvation depresses malic enzyme activity and elevates alanine aminotransferase activity in both species. When rats are starved, the rate of de novo synthesis of adenine mononucleotide decreases in spleen and liver but not in kidney, suggesting a regulatory role for adenylosuccinase in purine biosynthesis. The low activity of adenylosuccinase in liver of severely starved rats is inconsistent with the proposal (Moss, K. M., and McGivan, J.D. (1975) Biochem. J. 150, 275-283) that the purine nucleotide cycle plays a major role in ammonia production for urea synthesis, at least under these conditions.

Adenylate kinase activity in various organs and tissues of mice with the obese-hyperglycemic syndrome (gene symbol Ob/Ob).

The activities of adenylate kinase (ATP:AMP phosphotransferase, EC 2.7.4.3) in lyophilized cryostat sections of various organs from mice with the obese-hyperglycemic syndrome (gene symbol ob/ob) were measured fluorometrically. Skeletal and heart muscle tissues had the highest enzyme activities, i.e. 258 and 155 mmoles substrate converted per kg dry weight and per hr (MKH), respectively. Pancreatic islet specimens, which were composed mainly of B-cells, possessed the highest activitty of all parenchymatous cells studied, with 18 MKH as compared to 16 MKH for the cortical tubules of the kidney and 7 and 6 for the exocrine pancreas and liver cells, respectively. The granular layer of the cerebellum had enzyme activity of 31 MKH. The adenylate kinase activity in the B-cells was apparently not influenced by hyperglycemia since it was similar both in obese-hyperglycemic mice of different ages and in lean mice, although the blood sugar concentrations in such animals are much different.

Thyromimetic activity of methylene-bridged thyroid hormone analgos.

Methylene—bridged thyroid hormone analogs, in which a methylene group replaces the oxygen atom bridging the two aromatic rings, were evaluated for thyromimetic activity in the rat. All five analogs tested resembled qualitatively the corresponding diphenyl ethers with respect to their ability to increase mitochondrial glycerophosphate dehydrogenase (GPD) activity in various organs and tissues. The methylene—bridged compounds exerted effects typical of the diphenyl ethers on body wt and on the wts of various organs and tissues. The methylene-bridged analogs of T4 and T3 were tested for effects upon metabolic rate and were found to increase oxygen consumption. The analog corresponding to T4 was evaluated in thyroidectomized rats and was found to elevate GPD activity, to increase oxygen consumption, and to exert T4-like effects on the wts of various organs. The methylene-bridged compounds resembled qualitatively the diphenyl ethers with respect to their ability to inhibit lipid peroxidation in vitro. Although...

Rat folic acid reductase activity during the perinatal period, in newborns, and after trimethoprim administration.

The folic acid reductase activity in various organs of adult rats was studied in comparison to pregnant females (20th day of gestation) and fetal rats. The enzyme activities in the tissues of pregnant rats were in general about 30% higher than in normal adults. Fetal rats also possess the ability to catalyze the reduction of dihydrofolic acid, but it is evident that the liver and kidney have a considerably reduced capacity to form tetrahydrofolate. The folic acid reductase activity in liver and kidney rises for 10 days after birth and then declines to normal enzyme levels by the 4th week of life.

Protein methylation in rat brain in vitro.

Abstract— Protein‐methylation activity in various organs of the rat was studied with S‐adenosyl‐L‐[methyl‐14C]methionine ([methyl‐14C](SAM) as methyl donor. Activity of the enzyme was highest in brain and lowest in liver. Histones comprised approximately 20 per cent of the total radioactivity incorporated, and lysine‐rich histone was the most active. Analysis of amino acids of the methylated proteins of rat brain showed arginine to be the amino acid most extensively methylated, but some methylation occurred in lysine residues. An additional [methyl‐14C]‐labelled amino acid was found near histidine on the amino acid column chromatogram.

Diurnal Changes in Livers and Digestive Systems of Coturnix as Related to Three Photoperiodic Regimens

THE effect of photoperiod on the cyclic nature of eating and muscular activity of animals is generally recognized, but its effects on the physiologic activity of various organs are not fully appreciated. Tyler (1958) reported the variation in the quantity of gastrointestinal excretion that occurred in poultry and related the variations to the influence of the starting time (zero hour) and to the length of a time unit.In a study of red-winged blackbirds and starlings collected by shooting or netting, Fisher and Bartlett (1957) observed a difference in liver weight and in color of birds killed at different times during the natural daily photoperiod. While relatively small samples were used, the differences between day and night samples were significant. Changes in energy storage of fat in the liver preparatory to migration have been reported by Farner et al. (1961) and by Odum (1960).The present investigation was made to…

Vitamin A esterase activity in various organs of the chick.

1. The distribution of vitamin A esterase activity for vitamin A acetate, palmitate, and alcohol was studied in various tissues of the chick.2. Liver and kidneys were highly active in the hydrolysis of acetate, and showed only slight activity in the hydrolysis of palmitate or in the synthesis of vitamin A esters.3. Pancreas was highly active in both acetate and palmitate hydrolysis and in the synthesis of vitamin A esters.4. The small intestine showed a moderate and equal activity in all three reactions.5. Sodium taurocholate enhanced the hydrolysis of vitamin A palmitate by pancreas and small intestine. It also enhanced the hydrolysis of vitamin A acetate by pancreas, but had no effect on the hydrolysis of acetate by liver, and even inhibited this reaction in kidneys and intestine. It also inhibited the synthesis of vitamin A esters by pancreas and small intestine.

EXPERIMENTAL STUDIES ON THE CARBONIC ANHYDRASE ACTIVITY IX. THE MODE OF ACTION OF ADRENOCORTICAL STEROIDS, ESPECIALLY ALDOSTERONE, ON THE CARBONIC ANHYDRASE IN MICE AND RATS

In the present experiments we investigated the effects of adrenalectomy and aldosterone, DOCA and hydrocortisone replacement on carbonic anhydrase activity in various organs of rats and mice. At the same time we reviewed all the experimental results hitherto obtained, and discussed the mechanism of action of aldosterone on the kidney. The characteristic feature of the action of aldosterone on renal carbonic anhydrase activity of normal or adrenalectomized mice and rats is that the effects in these two animal species are contrary to each other, being accelerative in the former species and inhibitory in the latter, whereas the effect of adrenalectomy on the renal enzymic activity is inhibitory in the former species and accelerative in the latter. This is an example of a difference in hormonal action between animal species. To explain the results the following hypothesis is offered: Presumably there is a species difference in the synthesis of renal carbonic anhydrase after aldosterone treatment. This difference may be dependent on the amount of other synthesized enzymes participating in Na metabolism, for example, ATP ase. That is, in mice the increase in carbonic anhydrase synthesis affected by aldosterone may cause the decrease in ATPase synthesis. The situation is reversed in rats.

ENZYME ACTIVITIES IN VARIOUS ORGANS OF HYPOPHYSECTOMIZED RATS AND RABBITS.

AbstractThe activities of nine different enzymes (glucose‐6‐phosphatase, combined activities of glucose‐6‐phosphate dehydrogenase and 6‐phosphogluconate dehydrogenase, phosphohexose isomerase, aldolase, iso‐citric dehydrogenase, lactic dehydrogenase, glutamic‐oxalacetic transaminase, glutamic‐pyruvic transaminase and glutamic acid dehydrogenase) were measured in liver, skeletal muscle, cerebral cortex, hypothalamus, adrenal cortex and thyroid gland of hypophysectomized rats and rabbits. The water and fat contents were determined in liver and muscle. DNA and protein were measured in all tissues. After hypophysectomy the activities of the Embden‐Meyerhof enzymes were unaffected when the values were expressed per unit wet weight or per unit protein. When calculated on unit DNA the activities of almost all enzymes were in most tissues significantly decreased after hypophysectomy. This finding is due to the fact that except for cerebral cortex and hypothalamus in rabbits the DNA content of all tissues studied is significantly increased after hypophysectomy. The observed changes in enzyme activities and DNA content in the tissues are discussed in relation to hormonal and dietary influences on enzyme activities.

Effects of Gibberellin and Growth-retarding Chemicals on Respiration and Catalase Activity in Various Organs of Cucumber Seedlings

Cucumber seedlings were grown in darkness on filter paper saturated with water, gibberellin (GA), growth-retarding chemicals (mainly Amo-1618) or both GA and Amo-1618. The effects on oxygen consumption and catalase activity were studied on cotyledons, radicles, and hypocotyl tips. GA increased respiration and catalase activity of hypocotyl and cotyledons, decreased radicle respiration, and had no significant effect on its catalase activity. Amo-1618 decreased respiration of hypocotyl and cotyledons and increased that of the radicles. It stimulated catalase activity in all three organs. The inverse effects of GA and Amo-1618 on oxygen uptake and catalase activity were mutually antagonized when both compounds were applied at concentra tions counteracting their opposite effects on hypocotyl elongation. No stimulating effect on catalase activity was found with most other growth retarding chemicals. Some of them had no significant effect on the enzyme, and one even decreased its activity.

Effect of dietary fat on the disposition of cholesterol-4-C14 in rats.

SummaryRats were maintained for 30 to 76 days on a purified diet containing 20% fat as hydrogenated cottonseed oil, corn oil, or coconut oil and then injected intravenously with a tracer dose of cholesterol-4-C14. In the 6 days following injection higher excretion of C14 was observed in animals maintained on hydrogenated cottonseed oil. Of the activity extracted by petroleum ether after saponification, a lower percentage was present in the digitonin-precipitable fraction in animals fed coconut oil. Smaller amounts of cholesterol were excreted by the coconut oil-fed rats. No consistent differences were observed in total C14 activity of various organs of the different dietary groups at any time period. Neither serum cholesterol nor serum C14 activity was affected by variation of the type of dietary fat given these rats.

Receptor apparatus of the stomach for peptic ulcer disease

Numerous works of Russian physiologists (K.M.Bykov, 1947; K.M.Bykov and V.N. Chernigovsky, 1947; and others) provide objective evidence in favor of the existence of specialized nerve endings in the stomach (chemo-, mechano-, termo-, osmo-, baroreceptors), the function of which under pathological conditions changes sharply, as a result of which interoceptive influences from the stomach on the activity of various organs and systems are disrupted. The issue of the afferent innervation of the human stomach has been little studied. The interest of the morphological study of the afferent innervation of the stomach is associated, first of all, with the question of the functional significance of the detected sensory nerve endings and with the changes that they undergo during pathological processes.

Histochemistry of Cholinesterase-Devices of Counterstaining and Specific Distribution

From the study of distribution of ChE activity in various organs, it was showed that in order to detect the peripheral cholinergic fibre, the histochemical demonstration of ChE was very useful. Such histochemical preparation may even be more demonstrative than silver impregnations. Further more suitable counterstaining adding to this (e. g. counter staining with sudan black B.) may contribute to clarification of the functional properties of peripheral neurons.

Pernicious Anemia and Liver Therapy

O N banks of Nile and its canals, more than a thousand years before birth of Christ, priest-doctors of ancient Egyptians prescribed for their patients various parts of animal body, dried and powdered. Their remedies were derived from elephant, lion, camel, crocodile, and some seventy-nine were prepared from hyena. This practice was widely prevalent down through Middle Ages, and the pharmacopoeia of seventeenth and even of eighteenth century contains many extraordinary ingredients.' Why such empirical organotherapy should have held sway for so many centuries it is difficult to say. The therapeutic results must have been negligible. But patients will have medicine, and I suppose that powdered hyena's liver did just as much for plague as any of thousand pills and draughts which received higher recommendation. Successful organotherapy, as we conceive it today, must be directed in such a way that specific organ is administered to particular person in whom this organ is absent or functioning at too slow a rate. Diseases which are susceptible to cure by organotherapy are in true sense of word deficiency diseases, and our ability to cure them depends entirely upon our ability to overcome deficiency. The first brilliant success in therapy of this type was instituted in 1891, when Dr. George Murray in England began to administer thyroid extract to a woman with hypothyroidism (myxedema). Since then we have discovered other diseases which are due to deficient activity of various organs, and addition of new dis1 Osler, The Evolution of Modern Medicine.