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Biomedical subjects

P Kourounakis

Publications and source records attributed to P Kourounakis.

At least 19 recordsLinked to original sources
PubMed1991

Anti-inflammatory and immunomodulating effects of the novel agent gamma-(2-aminoethylamino)-2-butyrothienone. 1st communication: inhibitory effects on mouse paw edema.

A series of 4-hydroxy-(or-amino)-ethyl-amino butyrophenones or butyrothienones were synthesized. For detail studies on antiinflammatory effects, gamma-(2-aminoethylamino)-2-butyrothienone (gamma-ABT) was chosen as representative of these new non-steroidal anti-inflammatories (NSAID). The effect on mouse paw edema induced by various phlogistic agents was first investigated. The inhibitory effect of gamma-ABT on carrageenin-induced edema was remarkable and nearly equal to that of indometacin. Similarly to indometacin, gamma-ABT inhibited the early and late stage of yeast-induced edema in contrast to concanavalin A (Con A) induced edema which was only inhibited by gamma-ABT. Both the above induced edema are supposed to be unrelated to prostaglandins in the rat system. gamma-ABT displayed an inhibitory effect on nystatin-induced edema similar to indometacin suggesting that gamma-ABT has significant membrane stabilizing action and a strong blocking action on synthesis of prostaglandins. gamma-ABT inhibited as well the sustained edema induced by mustard. In conclusion gamma-ABT is an effective agent not only on acute but also on subacute and chronic inflammation and its mode of action appears similar to other NSAID. gamma-ABT posses in addition the advantage of antioxidant activity which is not shared by selective cyclooxygenase inhibitors and thus should be potentially effective in autoimmune diseases.

Animals↗
PubMed1991

Anti-inflammatory and immunomodulating effects of the novel agent gamma-(2-aminoethylamino)-2-butyrothienone. 2nd communication: inhibitory effect on rat adjuvant induced disease.

The effect of the novel agent gamma-(2-aminoethylamino)-2-butyrothienone (gamma-ABT) on local and systemic changes of rats with adjuvant induced disease (AID) was investigated, gamma-ABT showed potent inhibitory effect on adjuvant primary inflammation and almost totally inhibited the secondary lesions. gamma-ABT improved the changes in lymphoid organ weight except of the thymus. gamma-ABT improved the change in albumin/globulin ratio, which is a parameter of systemic inflammatory reaction but did not improve the body weight gain in AID and normal rats. In addition gamma-ABT did not affect directly T or B lymphocytes as shown by the lymphocyte responses to mitogen (Con A) and a T cell dependent antigen (SRBC) but rather inhibited the suppressor cells found in AID. Although structurally gamma-ABT is completely different from known non-steroidal anti-inflammatories, immunosuppressive drugs behave to a great extent like them.

Adjuvants, Immunologic↗
PubMed1990

Antioxidant activity of and interleukin production affected by honey bee venom.

Honey bee venom is found to inhibit significantly nonenzymatic lipid peroxidation. It also possesses a considerable hydroxyl radical scavenging activity, evaluated by its competition with dimethyl sulfoxide for HO.. These results, in relation to the in vitro suppression mainly of interleukin-1 production offered by honey bee venom, may further support that antioxidant activity is involved in the anti-inflammatory activity of honey bee venom.

Animals↗
PubMed1989

Immunosuppression by a novel analgesic-opioid agonist.

The effect of a new, centrally acting analgesic, 2-n-pentyloxy-2-phenyl-4- methyl-morpholine (PM) on the humoral antibody isotype responses, mitogenic responses, and interleukin production and assay was studied. Treatment with this opioid agonist exerted a suppressive effect on the antibody responses to TD [sheep red blood cells (SRBC), fluoresceinated human gamma globulin (HGG-FITC)] and TI [fluoresceinated dextran (DEX-FITC), lipopolysaccharide (LPS)]antigens in mice. The suppression was found to be dose- and time-dependent for all antigens tested, suggesting that PM affected both T and B cells. PM impaired lymphocyte functions, as the in vitro T and B mitogen reactions were inhibited in a dose- and time-dependent manner in mice and rats. PM, even at the highest concentration used, could not completely inhibit the production of interleukin 1 (IL-1)-like activity, but it caused complete inhibition, in a dose-dependent manner, of the production of IL-2-like activity. In addition, PM inhibited the assays of both IL-1 and IL-2. Naloxone counteracted all immunosuppressive effects of PM in vivo and in vitro. From this it was concluded that PM operates on the immune system directly, via opioid receptor mechanisms. Our data suggest that immunosuppression by PM, an opioid agonist, may be exerted by an inhibition of interleukin action on lymphocytes, and they confirm the important role of opiate receptors in lymphocyte function.

Animals↗
PubMed1987

Effect of age on the induction of in vitro drug metabolism by pregnenolone-16 alpha-carbonitrile (PCN); effect of age and PCN on immune responses.

The drug metabolizing capacity and the immune responses of normal and PCN treated young, adult and old rats were studied. In normal young and old rats the drug metabolism in general and the immune responses were reduced in comparison to adult animals. PCN treatment caused significant increase of drug metabolism in all age groups of animals due to induction of the microsomal enzymes of the liver. However, there were certain drug dependant variations in the different age groups of rats. PCN given in vivo affected differently the responses of T and B-cells in the young, adult and old animals. PCN is a non-hormonal microsomal enzyme inducer and the question a-rises as to whether there is any connection between this process and the immune system.

Aging↗
PubMed1987

In vivo interaction of spironolactone and phenobarbital with cholesterol; effect on cholesterol organ concentration.

In this work, the effect of pretreatment with spironolactone or phenobarbital on female Wistar rats after a chronic administration of cholesterol, upon the cholesterol concentration in blood, brain and liver was examined. It was found that the pretreatment reduced cholesterol in all tissues in the order, brain - plasma - liver. The findings were attributed to an increased biodegradation and disposition of cholesterol. It could also be concluded that after the pretreatment we may have a predominance of the catabolic and/or the disposition rather than of the synthetic and/or absorption processes for the steroid.

Animals↗
PubMed1979

Fine structural changes in the liver of young and old rats as influenced by microsomal enzyme inducers.

When given orally to young and old rats, pregnenolone-16 alpha-carbonitrile, spironolactone, or phenobarbital, known microsomal enzyme inducers, caused an increase in smooth endoplasmic reticulum. Dexamethasone, while a potent microsomal enzyme inducer, did not cause smooth endoplasmic reticulum increase. In both untreated and treated old rats, there was dilatation and vesiculation of rough endoplasmic reticulum with occasional granular material present in vesicles. Cytoplasmic lipid droplets of various sizes were frequent. Some mitochondria exhibited polymorphism and a variation in matrical density. Lysosomes and autophagic vacuoles as well as lipid droplets of various sizes were frequent in all groups. These results show that microsomal enzyme inducers influence the subcellular structure of hepatocytes in old rats.

Aging↗
PubMed1979

Effect of steroids and diethylstilbestrol on cocaine toxicity, plasma concentrations and urinary excretion.

Comparative experiments were performed on female rats given pregnenolone-16 alpha-carbonitrile (PCN), spironolactone, triamcinolone, estradiol or diethylstilbestrol to study correlations between the toxic effect of cocaine, its blood clearance and its urinary excretion. PCN and estradiol significantly reduced the toxicity of the drug as well as its plasma levels and urinary excretion. Diethylstilbestrol and spironolactone, unlike triamcinolone, also diminished cocaine toxicity and plasma concentrations.

Animals↗
PubMed1979

The synthesis of some bridgehead N,O-heterocycles of biological interest.

The preparation of 5-aryl-6-oxa-1-azabicyclo[3,3,0]octanes, 6-aryl-5-oxa-1-azabicyclo[4,3,0]nonanes and 7-aryl-6-oxa-1-azabicyclo[5,3,0]decanes from the corresponding substituted omega-chlorobutyrophenones and aminoalcohols is described; and the ring opening reactions are studied. A preliminary biologic activity study has also been conducted, and demonstrated that the 5-(2,5-dimethyl)phenyl-6-oxa-1-azabicyclo[3,3,0]octane possesses antiinflammatory activity.

Analgesics↗
PubMed1978

Synthesis of 2-aryl-4,4-spiro-morpholinium compounds of possible biologic interest.

The preparation of some 2-hydroxy-2-aryl-4,4-polymethylenemorpholinium bromides (II) by ring closure of the corresponding N-phenacyl-N-hydroxy-ethylpiperidinium (pyrrolidinium) bromide (III) and the synthesis of 2-ethoxy (IV) and of 2,3-dehydro derivatives (VI) are described. The synteshis of 2-phenyl-4,4-pentamethylene-morpholinium bromide (VII) from the hydrogenation of either the 2-phenyl or 2-p-bromophenyl-2,3-dehydromorpholinium derivativies (VI) is also reported. Proof of the chemical structures is provided by IR, UV, and NMR spectroscopy. The synthesized compounds did not present any significant pharmacologic activity.

Animals↗
PubMed1978

Induction of hepatic RNA-and protein synthesis by pregnenolone-16alpha-carbonitrile in rats.

Repeated administration of pregenolone-16alpha-carbonitrile (PCN) induced hepatic microsomal RNA-synthesis in female rats. The RNA that appeared with 14C-orotate in the microsomes after a 12-h pulse had maximal specific activity. Deoxycholate-soluble RNA demonstrated a higher specific activity than did its ribosomal counterpart, and both were significantly more radioactive than in the respective controls. Examination of the rate of 14C-leucine incorporation into microsome-bound polypeptides showed that the enhanced RNA-synthesis after PCN treatment resulted in an augmentation of protein-synthesis. Administration of this cyanosteroid was also associated with a significant decrease in glucose-6-phosphatase activity and an increase in the cholesterol content of rat hepatocellular microsomes, which correlate well with the degranulation of rough endoplasmic reticulum and the synchronous proliferation of smooth endoplasmic reticulum.

Animals↗
PubMed1978

Effect of pregnenolone-16 alpha-carbonitrile on bilirubin-and sulfobromophthalein-binding to hepatic Y and Z proteins in the rat.

Pregnenolone-16 alpha-carbonitrile (PCN), administered twice daily p.o. for 3 days at a dose level of 20 mumol/100 g body weight, significantly enhances in vivo binding of 14C-bilirubin and sulfobromophthalein (BSP) to hepatic Y and Z proteins in female Charles River CD rats. 14C-bilirubin-binding to Y protein showed a 61% increase, while binding of the same moiety to the Z protein fraction was augmented by 59%. BSP-binding in vivo demonstrated rises of 114 and 71% in relation to Y and Z proteins, respectively. These data correlate well with previous investigations in which PCN was found to have a beneficial influence on experimentally induced hyperbilirubinemias and, furthermore, there is an indication that phenobarbital, another potent microsomal enzyme inducer, acts via a similar mechanism.

Animals↗
PubMed1978

Dehydration of 2-hydroxy(ethoxy)-2-aryl-N.N-penta(tetra) methylenemorpholinium bromides.

Dehydration of 2-hydroxy(ethoxy)-2-aryl-N.N-penta(tetra) methylenemorpholinium bromide was achieved either by heating (175 degrees C) the compound with catalytic amounts of hydrobromic acid, or by refluxing the compound in a glacial acetic acid-hydrogen bromide mixture or by treating it with phosphorus tribromide at room temperature. In the acetic acid-hydrogenbromide method, the product was accompanied by N-bromoethyl(carbethoxy)-N-phenacylmorpholinium bromide, while strong heating (210 degrees C) of the title compounds or reflux in xylene yielded N-2-bromoethylpiperidine hydrobromide. Under the latter conditions, N-methyl-N-phenacylpiperidinium bromide gave similarly N-methylpiperidine hydrobromide. A preliminary biologic activity study in the synthesized compounds has also been conducted.

Analgesics↗
PubMed1978

Hepatic intracellular distribution of pregnenolone-16alpha-carbonitrile and its influence on adenyl cyclase activity in rat liver cells.

Pregnenolone-16alpha-carbonitrile (PCN) enhanced adenyl cyclase activity in the liver cells of female Sprague-Dawley rats. Injection of 14C-PCN and fractionation of hepatocytes into nuclei, mitochondria, total ribosomes, endoplasmic reticulum (ER) membranes, cytosol and plasma membranes revealed that after 4 h there was a preferential localization of the cyanosteroid in ER membranes. Total ribosomes and cytosolar proteins seemed to contain less PCN after 4 h, the optimal time for maximal penetration and intracellular establishment. On the other hand, PCN was localized preferentially in plasma membranes after 2 h and this diminished with time. Only trace amounts of the cyanosteroid were found in the nuclei and mitochondria, from the time of its intracellular introduction to the time of its apparent removal from the hepatocyte.

Adenylyl Cyclases↗
PubMed1977

Temperature-dependence of stress-induced hepatic autophagy.

In rats, restraint for 48 h elicits hepatic glycogen depletin, autophagy and other ultrastructural changes (e.g. mitochondrial enlargement and rough endoplasmic reticulum disorganization) associated with marked hypothermia. By restoring the body temperature of these animals, all the hepatocytic alterations are abolished.

Adrenal Glands↗