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Biomedical subjects

K Masek

Publications and source records attributed to K Masek.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Serotonin and treatment of mental disorders. Present status and future perspectives].

Serotoninergic system is involved in the regulation of diverse biological and psychological functions and a variety of serotonin receptor subtypes represent a possible target for a new generation of medications. 5-HT receptors play an important role in both schizophrenia and depression. Modern strategies for treating schizophrenia profit from the existence of interaction between serotonin and dopamine systems. New drugs called serotonin-dopamine antagonists (SDAs) offer wider spectra of activity and lower extrapyramidal side effects liability. The principle of the SDAs is that the drug should be a potent serotonin 5-HT 2A antagonist, with slightly less potent dopamine D2 receptor-blocking properties. New pharmacological agents with great therapeutic potential and fewer side effects were recently developed also for the treatment of depression. Among these new antidepressives the serotonin selective reuptake inhibitors (SSRIs) currently play the most important role.

Depressive Disorder↗
PubMed1996

Further evidence on the interaction of muramyl dipeptide with the serotonergic system.

The mode of interaction between muramyl dipeptide (MDP), a compound with immunopharmacological activities, and 5-hydroxtryptamine (5-HT, serotonin) was studied in isolated nerve-smooth muscle preparations of the carp stomach. Application of exogenous 5-HT evoked direct smooth muscle contractions; electric neurogenic stimulation evoked twitches due to release of 5-HT from nerve endings. Contractions evoked by a high concentration of 5-HT (3-30 microM) were resistant to atropine and potentiated in the presence of MDP. Isamoltan (5-HTID antagonist) decreased the amplitude of contractions, whereas ketanserin (5-HT2 antagonist) and MDL 72,222 (5-HT3 antagonist) had no effect. The addition of low concentrations (0.1-1.5 microM) of 5-HT did not contract the preparation but caused a decrease in the amplitude of neurogenic twitches, which might be due to the presynaptic inhibition of serotonin release. This effect of 5-HT was not changed by isamoltan or ketanserin, but it was largely reduced in the presence of 5-HT3 antagonists tropisetron and MDL 72,222. This inhibitory effect of 5-HT on twitch amplitude was potentiated by MDP. The interaction of MDP with the serotonergic system thus involved not only potentiation of the postsynaptic effect of higher 5-HT concentrations, which might have been mediated via the 5-HT1 subsystem, but also presynaptic inhibition. MDP enhancement of 5-HT's inhibitory effect, mediated via 5-HT3 receptors, might represent a new feature in mutual 5-HT-MDP interactions.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1996

Effect of adamantylamide dipeptide on reinfection resistance after primary infection eradication in experimental Schistosomiasis mansoni.

The immunomodulatory effect of adamantylamide dipeptide (AdDP) was tested in Schistosoma mansoni-infected challenged mice and infected praziquantel-treated (2 x 500 mg/kg) challenged animals. In AdDP-treated mice, the drug was given 58 days post infection of mice with 120 S. mansoni cercariae, challenged with 240 cercariae one day after treatment, while in praziquantel-treated mice, the drug was given 44 days post infection, two weeks post treatment (58 days post infection) they were given AdDP in the same dose and one day later challenged with the same cercarial load. AdDP increased the resistance against reinfection (90.3% vs. 83.5% in infected challenged control). The significant increase in resistance against reinfection was accompanied by significant increase in the percentage of lymphocytes forming EAC rosettes. Mice cured of their primary infection by praziquantel showed a significant reduction in percent resistance, hepatic granuloma size and intragranulomal Thy+ 1,2 and Lyt+ 1 T cells. In mice treated with both praziquantel and AdDP, resistance to reinfection was significantly higher than in mice treated with praziquantel only (89.29% vs. 62.13%) reaching a level comparable to that recorded in infected-challenged controls. Meanwhile granuloma size was not significantly different from that in the infected-challenged controls with a significant rise in Lyt+ 1 T cells. Data may suggest a role for granuloma as a mechanical obstacle and/or as a T cell-mediated reaction in maintenance of resistance to reinfection. A role for B lymphocytes should be considered as the rise of percent resistance to reinfection in mice treated with AdDP alone was accompanied by a significant increase in the percentage of B lymphocytes forming EAC rosettes. Moreover, findings may suggest the use of AdDP together with specific chemotherapy in endemic areas where reinfection and repeated treatment with its consequences are of common occurrence.

Adjuvants, Immunologic↗
PubMed1996

Which type of 5-hydroxytryptamine receptor mediates relaxation of the longitudinal muscle of guinea pig proximal colon in vitro?

Concentration-dependent 5-hydroxytryptamine (5-HT) relaxations of guinea pig proximal colon were evoked in the presence of atropine (0.2 microM). 5-HT effect was neuronally mediated since it was blocked by tetrodotoxin (TTX) (0.5 microM). The type of 5-HT receptor mediating the relaxations was investigated using both 5-HT agonists and antagonists. Selective 5-HT3 antagonists tropisetron (10, 50, 500 nM) and ondansetron (1 microM) shifted the concentration-response curves for 5-HT to the right. Another 5-HT3 antagonist MDL 72222 (0.5 microM), 5-HT1/5-HT2 antagonists methiothepin (0.1 microM) and metergoline (0.1 microM), 5-HT(1A,B) antagonist propranolol (l microM) and 5-HT1B antagonist isamoltane (10 nM) were ineffective. Specific agonist of 5-HT3 receptors 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) and agonist of 5-HT1 receptors 5-carboxamidotryptamine (5-CT) also relaxed the preparation, although the relaxation was not 5-HT relaxation. Neither was it neurogenic because it persisted in the presence of TTX (0.5 microM). The concentration-response curve for 2-methyl-5-HT was not affected by ondansetron (1 microM) or tropisetron (0.5 microM), but it was shifted to the right in the presence of 5-HT1/5-HT2 receptor antagonists methiothepin (0.1 microM) and metergoline (0.1 microM) and in the presence of 5-HT(1Da)/5-HT2A receptor antagonist ketanserin (1 microM). Methiothepin (0.1 microM) also inhibited the relaxations evoked in the presence of 5-CT. Specific agonist of 5-HT4 receptors 5-methoxytryptamine did not exert any effect on the preparation. It is suggested that there are two different mechanisms of relaxation in the guinea pig proximal colon. One is neurogenic and involves the activation of 5-HT3 receptors located on inhibitory neurons to the muscle; the other is myogenic and might be mediated via yet unclassified 5-HT receptors located on the muscle.

Animals↗
PubMed1994

The effect of immunomodulator muramyl dipeptide on serotoninergic responses of isolated neuromuscular preparations.

The mode of action of muramyl dipeptide (MDP), a compound with immunopharmacological properties, was studied in isolated nerve smooth muscle preparations with different receptor systems. The amplitudes of contractions evoked directly by stimulants as well as neurogenic twitches or relaxations were registered. In the rat stomach strip EC50 of acetylcholine, serotonin (5-HT) and KCl was estimated. MDP (50 nmol/l) but not levamisole potentiated selectively the contractions evoked by 5-HT and significantly (p < 0.01) lowered the respective EC50. In the rat vas deferens MDP selectively potentiated the twitches enhanced by 5-HT but not those enhanced by noradrenaline. Such potentiation was blocked by 5-HT3 antagonists tropisetron and MDL 72,222 (1 alpha H,3 alpha,5 alpha-H-tropan-3-yl 3,5-dichlorobenzoate) but not by the 5-HT2 antagonist ketanserin. The antagonist methiothepin nonselectively abolished the potentiation by MDP as well as the enhancement of twitches by 5-HT and noradrenaline, whereas l-propranolol and isamoltan influenced neither the enhancement of twitches by 5-HT nor the potentiation by MDP. In the isolated longitudinal muscle of guinea pig proximal colon, 5-HT caused a biphasic response in the presence of atropine; the initial neurogenic relaxation was potentiated in the presence of MDP and was suppressed in the presence of tropisetron. Thus, the potentiating effect of MDP in the isolated organs studied was selective with respect to the serotoninergic system and might be mediated by 5-HT3 receptors.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1993

Some cellular and pathophysiological correlates of the inflammatory effects of a synthetic immunomodulatory agent, muramyl dipeptide (MDP).

Acute, fully reversible paw edema was produced in mice after systemic administration of muramyl dipeptide (MDP, i.e. N-acetylmuramyl-L-alanyl-D-isoglutamine). Its stereoisomer N-acetylmuramyl-D-alanyl-D-isoglutamine (MDP-D,D) was much less effective. The swelling of paws occurred very soon (1 h) after MDP injection, reached the maximum severity at an interval of 6 h and declined afterwards. While no substantial quantitative differences were found in the sensitivity of the various inbred strains of mice to edemagenic activity of MDP, athymic nude mice were completely resistant to the induction of edema. Formation of edema was blocked by silica, indomethacin (partially also by nordihydroguaiaretic acid), monoclonal antibodies against T-cells and their TH-subpopulation. It is suggested that the MDP-induced edema is a macrophage- and T-cell-dependent, prostaglandin- (and partially leukotriene)-mediated acute reaction associated with increased vascular permeability. Possible engagement of immune/inflammatory cytokines like IL-1 has been discussed. The data support the view that this type of edema is a consequence of changes in the activity of important cellular components of the immune system.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1993

T-cell-dependent immunobiological activity of a desmuramyl analog of muramyl dipeptide, adamantylamide dipeptide (AdDP), and D-isoglutamine.

The present experiments demonstrate that, similar to immunomodulatory muramyl dipeptide, its desmuramyl analog adamantylamide dipeptide is able to induce mild and fully reversible paw edema in mice. This effect is an immune-related phenomenon depending on the activation of T-cell/macrophage interactions and on production of prostaglandins. Possible involvement of certain immunoregulatory/inflammatory cytokines (e.g. IL-1, IL-2) has been suggested. The most probable intrinsic moiety of the adamantylamide dipeptide molecule responsible for triggering the edema formation is obviously D-isoglutamine.

Adjuvants, Immunologic↗
PubMed1992

An introduction to the possible role of central nervous system structures in neuroendocrine-immune systems interaction.

The involvement of different regions of the brain in the immune response was investigated with the aid of small electrolytic lesions. The lesions were placed in such a way that they covered different areas of the brain stem, basal ganglia, but also some parts of the frontal cortex. The cellular immune response as well as DNA synthesis with the aid of labelled precursors was measured. The results suggest the possibility of the existence of three circuits. One circuit represents catecholaminergic cell group A1-7 in reticular formation, nucleus parabrachialis and central ncl. amygdalae. The second circuit represents serotonergic rapheal groups B6.8, hypothalamus and ncl. basomedialis of amygdala. The third circuit represents ncl. amygdalae and the medial part of frontal cortex, namely the cingulate cortex area 1-2. The close correlation between the changes of the immune response and the CNS activity was also investigated in the experiments with immunosuppressed and immunostimulated animals by measuring of the turnover of some neurotransmitters but also by recording electrocephalographic activity.

Animals↗
PubMed1991

The effect of lentinan on proliferative processes in parenchymal organs of rats--I. The effect on pyrimidine and nucleic acid syntheses.

The present study investigated the effect of Lentinan on the biochemical events associated with the pyrimidine and nucleic acid syntheses in the liver, kidney, thymus and spleen of rats. Lentinan was used at a dose of 4 mg/kg/day (twice) and in a single dose of 20 mg/kg. The following changes were observed. (1) The utilization of (14C)orotic acid for the synthesis of uridine components of liver acid-soluble extract and RNA uracil was activated after the administration of both doses of the drug. The specific activity of cytidine components of the acid-soluble extract and RNA were, on the other hand, not affected. The same holds true for the kidney. The ratio of the specific activity of cytidine:uridine components of the acid soluble extract as well as RNA decreased after the administration of both doses of the drug. The specific activity of DNA cytosine and thymine are slightly suppressed in the liver after the administration of a high dose of Lentinan; no effect was observed in the kidney. (2) The uptake of (14C)cytidine by the liver was not affected; the specific activity of DNA cytosine and thymine were increased after the administration of a high dose of Lentinan. (3) The uptake of (14C)thymidine by the liver was not affected; the specific activity of liver DNA thymine was increased after the administration of both doses of the drug. In the thymus an increase of specific activity of DNA thymine has also been observed. (4) Repeated doses of the drug (4 mg/kg for 6 consecutive days) increased the weight of the spleen. The specific activity of DNA thymine of the liver and spleen were significantly increased.

Animals↗
PubMed1991

Non-synaptic cholinergic modulation of neurogenic twitches of the guinea-pig ileum.

The effect of cholinergic and anticholinergic compounds on conduction of neuronal excitation has been studied in myenteric plexus-longitudinal muscle strips from the guinea-pig ileum. A preparation in a special triple bath was drawn through two rubber membranes dividing the strip into three segments. Neurogenic stimulation of the oral segment set up nerve action potentials propagating aborally across the middle segment (10 mm) so that the aboral segment might be also invaded, eventually. Drugs were added to the middle segment to affect neuronal propagation (non-synaptic effects) which was monitored by twitch height of the aboral segment. The application of acetylcholine to the middle segment augmented aboral twitches. The effects of nicotine, pilocarpine and oxotremorine were selectively blocked by (+)-tubocurarine, pirenzepine and atropine, respectively. The effect of acetylcholine was suppressed by pirenzepine and atropine and mimicked by doubling of KCl concentration. The effect of acetylcholine may be thus explained by the facilitated propagation of nerve action potentials in partially depolarized cholinergic terminals via stimulation of muscarinic receptors. The adenylate cyclase system is not directly involved in the mechanism of muscarinic facilitation of neuronal propagation in the terminals; however, it may participate in the modulation of a final common effector mechanism.

Acetylcholine↗
PubMed1991

Pharmacokinetic profile of the immunomodulating compound adamantylamide dipeptide (AdDP), a muramyl dipeptide derivative in mice.

A pharmacokinetic profile of 14C-AdDP with uniformly labelled alanine was investigated. It was shown that the distribution phase after an i.v. administration is very short with a half-life of 2.1 min. The half-life of elimination phase after the i.v. administration is about 2.85 hours, that is longer than those of MDP and its derivatives. The total body clearance (30 ml/min/kg) is caused predominantly by metabolism of the compound. All the radioactivity found in urine in a 48 hours interval after a s.c. administration represents only 3.1% of the administered dose. Only a smaller part of the excreted radioactivity is formed by unmetabolised AdDP. The concentration curve after a s.c. administration is characterized by a very fast absorption with a half-life shorter than 1 minute. The distribution and elimination phases are prolonged (20 min, 11 hours respectively) in comparison with an i.v. injection. The decreased absolute bioavailability after a s.c. administration (65%) is probably not biologically significant because of a slower release of the compound from the site of the s.c. administration. A relatively very high radioactivity was found in liver, kidney, thymus, spleen and brain very soon which suggest a very good penetration into tissues. It is an agreement with the high apparent distribution volume of peripheral compartment and higher lipophilicity of AdDP as compared to MDP.

Adjuvants, Immunologic↗
PubMed1991

The effect of some immunomodulators administration to rats on palmitic and oleic acids incorporation into the lipids of liver cell organelles.

The incorporation of equimolar doses of [14C]-palmitic and [3H]-oleic acids into the lipid moiety of hepatocytes after muramyl dipeptide (MDP), adamantylamide dipeptide (AdDP) and levamisole (LM) administration were investigated. The utilization of [14C]-palmitic acid for the synthesis of neutral lipids and phospholipids of crude nuclear fraction increased significantly after MDP and AdDP administration and to a lesser extent after LM. While the incorporation of [3H]-oleic acid did not change significantly after MDP and AdDP, LM significantly increased the incorporation of this acid into the phospholipids of nuclear and microsomal fractions. The changes in the incorporation of saturated palmitic and unsaturated oleic acids suggest a possible influence on deacylation-reacylation mechanisms. These changes could alter the physical properties of membrane and affect certain membrane functions, including the activity of membrane bound enzymes and transport mechanisms.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Effect of immunomodulator adamantylamide dipeptide on antibody response to influenza subunit vaccines and protection against aerosol influenza infection.

Adamantylamide dipeptide (AdDP) is a novel synthetic compound combining the antiviral properties of amantadine and the essential adjuvant activity of immunomodulator muramyl dipeptide. Mice were immunized with influenza A/Taiwan/1/86 (H1N1), A/Sichuan/2/87 (H3N2) and influenza B/Beijing/1/87 subunit vaccines containing AdDP or aluminium hydroxide (Al(OH)3). Induction of homologous haemagglutination-inhibition (HI) antibodies and correlation to protection against lethal aerosol influenza A/PR/8/34 (H1N1) infection were investigated. Subunit vaccine containing A/Sichuan (H3N2) and Al(OH)3 stimulated high HI antibody titres but failed to provide protection against heterologous influenza A (H1N1) challenge infection following either the primary or the secondary immunizations. In contrast, similar treatment with A/Sichuan subunit vaccine containing AdDP conferred significant protection against heterologous challenge despite low levels of circulating antibody. Primary immunization with even influenza B/Beijing subunit vaccine containing AdDP, but not Al(OH)3, provided partial protection against influenza A challenge. These results suggest that appropriate immunomodulators like AdDP can convert restricted homotypic immunity induced by inactivated influenza subunit vaccines to advantageous cross-reacting type of heterologous response.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Non-junctional modulation of neurogenic twitches of the guinea-pig ileum by some peptides and other compounds in the triple bath.

The effects of some neuropeptide transmitter candidates and of some other neurotoxins or drugs on conduction of neural excitation were studied in myenteric plexus-longitudinal muscle strips from the guinea-pig ileum. A preparation in a special triple bath was drawn through two rubber membranes dividing the strip into three segments. Neurogenic stimulation of the oral segment set up nerve action potentials propagating aborally across the middle segment so that the aboral segment might also be invaded. Drugs were added to the middle segment to affect neuronal propagation (non-junctional effects) which was monitored by twitch amplitude of the aboral segment. The application of bradykinin and cromakalim did not affect aboral twitches although strong contractile and relaxatory effects were observed when the drugs were applied directly to the aboral segment; no neurogenic effects thus manifested. Capsaicin and neurotensin, when applied both to the middle and aboral segments, elevated the tone of the preparations accompanied with a decrease in twitch amplitude; these effects may have been due to neurogenic stimulation and release of other motor neurotransmitters. The application of VIP, apamin and dendrotoxin to the middle as well as to the aboral segments augmented aboral twitches, which might be at least partly due to facilitation of nerve action potential propagation in nerve terminals of cholinergic motor fibres.

Action Potentials↗
PubMed1990

The effect of cyclosporine A on renal and hepatic microsomal mixed function oxidase systems in rats.

The effect of cyclosporine A (CsA), the immunosuppressant used in transplantation and also in the treatment of some autoimmune diseases, on the microsomal mixed function oxidase (MFO) systems in rat kidney and liver was studied. Since CsA given intragastrically (50 mg/kg/day) for three consecutive days decreased body, liver and kidney weights, in rats, the results were compared not only with the control untreated animals but also with the group of fully starved rats. In the liver the cytochrome P-450 level and aniline-hydroxylase activity were slightly higher than in the control rats but not as high as in the fully starved animals. This suggests that in the liver the effect might be the result of the antagonism between the CsA action and partial starvation of the CsA-treated animals. On the other hand, in the kidney the cytochrome P-450 level was as high as in the fully starved animals and the aniline-hydroxylase activity was significantly increased as compared to both the control and fully starved animals. Thus, in the kidney the microsomal MFO system seems to be induced after short-term CsA treatment. The activities of aminopyrine-N-demethylase and the levels of cytochrome bs did not change significantly after CsA treatment in both organs.

Animals↗