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S Todorov

Publications and source records attributed to S Todorov.

At least 19 recordsLinked to original sources
PubMed2007

In vivo effects of amtolmetin guacyl on lipid peroxidation and antioxidant defence systems in different models of gastrointestinal injury.

1. The in vivo effects of the non-steroid anti-inflammatory drug (NSAID) amtolmetin guacyl (AMG) on lipid peroxidation (LP) and on antioxidant enzyme and non-enzyme defence systems were investigated in models of stomach and colon damages, induced by other NSAIDs, by ethanol or by 2,4,6-trinitrobenzenesulfonic acid (TNBS). 2. Indomethacin increased LP, glutathione peroxidase (GSH-PX) and glucose-6-phosphate dehydrogenase (Glu-6-P-DH) activities and decreased glutathione levels in gastric mucosa. Pretreatment with AMG normalized some of the parameters affected by indomethacin. 3. Treatment of rats with ethanol for 0.5 h led to a decrease in glutathione levels as well as activities of glutathione reductase and Glu-6-P-DH in gastric mucosa. AMG, administered 0.5 h before ethanol, limited the adverse actions of ethanol. 4. Amtolmetin guacyl failed to abolish the TNBS-induced changes in the followed-up parameters in colon mucosa and liver, but additional alterations (as with tolmetin) were not observed. 5. The beneficial profile of AMG in the various experimental models of free radical-induced damage investigated in this study suggests the possibility that this drug might possess antioxidant activity.

Animals↗
PubMed2007

Potential antioxidant activity of celecoxib and amtolmetin guacyl: in vitro studies.

1. In vitro studies of the potential antioxidant activity of the selective cyclo-oxygenase-2 inhibitor celecoxib and the non-steroid anti-inflammatory drug amtolmetin guacyl (AMG) were carried out. The study included experiments on the ability of these drugs to affect some indices of the oxidative stress [lipid peroxidation (LP), activity of antioxidant enzymes, glutathione (GSH) level] in rat stomach and colon mucosa and in liver. 2. Celecoxib and AMG did not change the activity of the enzymes GSH-peroxidase, oxidased glutathione (GSSG)-reductase and glucose-6-phosphate-dehydrogenase, as well as the GSH level in all tissue preparations. An increased superoxide dismutase (SOD) activity and a tendency to a decreased Fe/ascorbic acid-induced LP in stomach and colon mucosa were found, but only in the presence of AMG. 3. In the liver, both celecoxib and AMG decreased spontaneous and Fe/ascorbic acid-induced LP. SOD activity was enhanced only in the presence of AMG. 4. Experiments aimed at studying celecoxib and AMG in free oxygen radical-generating systems were also carried out. AMG and tolmetin (the main metabolite of AMG) inhibited OH*-provoked deoxyribose degradation in a Fenton system. Celecoxib had no effect on free radicals when tested in the same system. 5. In conclusion, the results of the present in vitro studies suggest that AMG and celecoxib possess antioxidant and metal-chelating abilities, which might contribute to their beneficial effects.

Animals↗
PubMed2003

Prejunctional modulation of non-adrenergic non-cholinergic (NANC) inhibitory responses in the isolated guinea-pig gastric fundus.

The inhibitory neurotransmission of the stomach was investigated in isolated guinea-pig gastric fundus. In preparations treated with guanethidine (1 micro mol L-1) and p-fluoro-hexahydro-sila-difenidol (1 micro mol L-1), electrical stimulation evoked neurogenic inhibitory responses not modified by hexamethonium (100 micro mol L-1), suggesting that inhibitory postganglionic non-adrenergic non-cholinergic (NANC) nerve fibres are involved. The nitric oxide (NO)-synthase inhibitor Nomega-nitro-l-argininine-methyl-ester hydrochloride (1-100 micro mol L-1) and the soluble guanylyl cyclase inhibitor ODQ (0.1-3 micro mol L-1) also abolished such relaxant response, suggesting the involvement of NO/Cyclic Guanosine 3',5' monophosphate (cGMP) system as the final mechanism of muscle relaxation. The alpha2-adrenoceptor agonist, UK 14 304 (10 nmol L-1-10 micro mol L-1) did not influence the electrical field stimulation (EFS)-evoked NANC responses. These latter responses were also refractory to a variety of receptor agonists and antagonists, acting at Gamma Aminobutyric Acid (GABA), serotonin 5HT1a, opioid micro , delta and kappa, muscarinic M1 and M2, histamine H2 and H3 and cannabinoid receptors. The NANC response was insensitive to the P/Q-type Ca2+-channel blocker omega-agatoxin TK (1 nmol L-1-0.1 micro mol L-1), but partially inhibited by the N-type Ca2+-channel blocker omega-conotoxin GVIA (0.1 nmol L-1-0.1 micro mol L-1), and by the L-type Ca2+-channel blockers nifedipine and calcicludine (0.1 nmol L-1-0.1 micro mol L-1). These data suggest that the NANC relaxation of the isolated guinea-pig gastric fundus is mediated by NO as the final inhibitory (neuro)transmitter at the longitudinal smooth muscle cells. The mechanism(s) promoting NO production is/are Ca2+-dependent, but apparently insensitive to presynaptic modulation. Both N- and L-type channels seem to occur in nitrergic nerve endings, where they contribute to trigger NO diffusion at the synaptic cleft.

Animals↗
PubMed2003

Involvement of H2-receptors in the mechanism of analgesic action of Tyr-MIF-1.

The antinociceptive effects of H2-agents cimetidine (CIM) and dimaprit (DMP) as well as their effects on the Tyr-MIF-1-evoked analgesia have been studied after intraperitoneal (i.p.) administration in rats. In the paw-pressure (PP) test Tyr-MIF-1 (1 mg/kg), CIM (50 and 100mg/kg) and DMP (5 and 10mg/kg) induced analgesia. Injected before DMP, naloxone (NAL) and CIM diminished or completely prevented the pain-relieving effect of H2-agonist DMP. The antinociceptive effect of Tyr-MIF-1 has been potentiated by DMP dose-dependently. CIM (50mg/kg) decreased the antinociceptive action of the combination Tyr-MIF-1 + DMP, while CIM (100mg/kg) expressed a weaker inhibitory effect on it. The data obtained clearly show that H2-receptor activation is involved in the mechanism of the Tyr-MIF-1 antinociceptive action.

Analgesics↗
PubMed1999

Detection and characterization of a novel antibacterial substance produced by Lactobacillus plantarum ST 31 isolated from sourdough.

Lactobacillus plantarum ST31 isolated from sourdough produced an antimicrobial substance inhibiting other strains of the genera Lactobacillus, Leuconostoc, Pediococcus, Streptococcus, Bacillus and some foodborne pathogens including Staphylococcus aureus. This antimicrobial substance was inactivated by proteolytic enzymes. Consequently, it was characterized as a bacteriocin and was designated plantaricin ST31. This bacteriocin was stable in the pH range 3-8 and it was not affected by amylolytic enzymes. Production of plantaricin was pH and temperature dependent, and maximum yields were obtained in MRS broth cultures maintained at pH 6 and incubated at 30 degrees C in the exponential phase to the early stationary growth phase of the producer organism. This bacteriocin was purified by using consecutive ammonium sulfate and reversed-phase chromatography. It is a peptide of 20 amino acid residues with a mass of 2755+/-0.3 Da, as determined by electrospray mass spectrometry. The sequence of Plantaricin ST31 showed no similarity to those of other bacteriocins. Plantaricin ST31 production appeared to be chromosomally encoded.

Adsorption↗
PubMed1998

Effect of diphenylhydramine on the Tyr-MIF-1 antinociception in rats.

Tyr-MIF-1 is a representative of the MIF's family of endogenous peptides. It has been isolated from bovine hypothalamus and human parietal cortex that suggests its involvement in nociception. Tyr-MIF-1 can bind to the mu-receptors as well as to its specific non-opiate receptors in the brain. Data in the literature rise the idea that histamine (HA), a well known nociceptive agent, and Tyr-MIF-1 might have a common pathway in their effects on nociception. We tested that possibility by investigation of the combined action of diphenhydramine (DPH, an H (1) -antagonist) and Tyr-MIF-1 on nociception. The changes in the nociceptive effects were examined in the male Wistar rats by the Randall-Sellito paw-pressure (PP) and the tail-flick (TF) tests. Tyr-MIF-1 in a dose of 1 mg/kg exerted strong naloxone-reversible analgesic effects. DPH (100 microg/kg, i.p.) had an antinociceptive action, too. The co-administration of Tyr-MIF-1 and DPH enhanced the antinociceptive effect, as compared to DPH (PP) and to TYR-MIF-1 alone (TF). These effects were reversed when methylene blue (MB, 500 microg/rat) was applied 1h before the combination. However, naloxone (1 mg/kg, i.p.) only slightly affected the antinociceptive effect of DPH and TYR-MIF-1, compared to that of MB. The results obtained confirmed the hypothesis that cyclic nucleotides are involved in the realization of nociceptive effects of both HA and Tyr-MIF-1.

Analgesics↗
PubMed1998

Neuropeptides of the cholecystokinin group: effects and mechanisms of action on the gastro-intestinal and gall bladder motility.

The neuropeptides of the cholecystokinin (CCK) group belong to the substances usually referred to as "brain-gut" neuropeptides. They are synthesized in neurons of the central nervous system, in the peripheral and in the autonomous nervous systems, in endocrine cells (types "I", "K" and "A"), as well as in the enteric nervous system of the gastro-intestinal tract and of the pancreas. The CCK-group peptides realize their effects via several different mechanisms (Fig. 1): endocrine or neuroendocrine (classic hormonal mechanism)--the peptide, released by the endocrine cell or by the nerve terminal, is carried by the circulation to the remote target organs; paracrine or neuroparacrine--the peptide, released in the intercellular space, reaches the target effector cells via diffusion. Similarly to the classic neurotransmitters, CCK and its analogues could play a neurotransmitter role, also modulating the release of acetylcholine (ACh) and of other neurotransmitters in enteric and CNS neurons. In the present review article some smooth-muscle and neuromodulatory effects of CCK are described and compared to the results of the authors' studies on the problem.

Acetylcholine↗
PubMed1998

Effects of newly synthesized amino acids containing thiazole residues on electrically evoked smooth muscle contractions.

New amino acids containing thiazole residues have been synthesized and in vitro experiments were performed to study their action on neurotransmission in target tissues with adrenergic and cholinergic neurotransmission. Acetaminothiazoles, structurally related to the novel class, are known to act as H1 agonists, therefore, the effects of the newly synthesized Ala- and Pro-thiazole derivatives on smooth muscle contractile activity were compared to those of histamine (HA). The experiments were carried out on electrically stimulated prostatic part of rat and rabbit vasa deferentia and proximal guinea pig ileum. HA had biphasic effect on electrically evoked neurogenic contractions of guinea pig ileum, Pro(Thz) had a stimulating effect, while Ala(Thz) had no effect. The histamine H1-receptor antagonist diphenhydramine inhibited the Pro(Thz)-induced spontaneous contractile activity in the longitudinal layer of guinea pig ileum. HA had a biphasic effect on electrically induced neurogenic contractions of rat and rabbit vasa deferentia while Pro(Thz) and Ala(Thz) inhibited the ES-contractions. The present results show that the newly synthesized compounds might affect the electrically evoked smooth muscle contractions. Some similarity in the effects of HA and of the new substances was observed.

Amino Acids↗
PubMed1995

Different effects of H1 and H2 blockers on the tone and the contractile activity of guinea pig stomach fundus.

The action of H1 and H2 blockers on the spontaneous and evoked contractile activity of gastric fundus smooth muscles as well as the effects of H2 antagonists on the release of acetylcholine (ACh) from gastric myenteric neurons were studied. The experiments were performed on smooth muscle strips (25 x 3 mm) cut out in circular direction from guinea pig fundus region. In concentrations of 1 x 10(-7) M to 1 x 10(-4) M, the H1 blockers diphenhydramine (DPH), mepyramine (MEP) and dimethpyrindene (DMPD), but not the H2 blockers ranitidine (RAN), cimetidine (CIM) and roxatidine (ROX), increased in a concentration-dependent manner the smooth muscle tone, the maximum contractions being about 50% of the contractile effects of 1 x 10(-5) M ACH and 5 x 10(-5) M histamine (HA). The concentration-dependent contractions of the stomach fundus strips in response to electrical field stimulation (EFS) were enhanced by RAN, CIM and ROX (but not by MEP and DPH), all in concentrations of 1 x 10(-7) M to 1 x 10(-4) M. EFS increased the resting [3H]-ACh release by 67.8%, the S2/S1 ratio being 0.85 +/- 0.04. ROX in a concentration of 1 x 10(-5) M significantly increased (by 16.1%) the EFS-induced release with a S2/S1 ratio of 1.22 +/- 0.04. The ROX effect on the [3H]-ACh release was reduced or even abolished by 1 x 10(-6) M tetrodotoxin (TTX) and 1 x 10(-6) M scopolamine or in Ca(2+)-free medium, while 1 x 10(-6) M hexamethonium did not change it. It might be concluded that H2 blockers have no direct myogenic effect and do not interfere with muscarinic receptors in guinea pig stomach fundus. The H2 antagonists enhance the EFS-evoked contractions of the gastric smooth muscle most probably by increasing the release of ACH.

Acetylcholine↗
PubMed1994

Presynaptic histamine H2 receptors modulate the sympathetic nerve transmission in the isolated rat vas deferens; no role for H3-receptors.

The modulatory activity mediated by histamine receptors on the sympathetic nerve transmission was investigated in the rat vas deferens. Agonists and antagonists acting at the different histamine receptor subtypes (H1, H2 and H3) were tested on electrically-driven preparations in vitro. Low-frequency stimulation (0.1 Hz) evoked muscle contractions almost completely-sustained by ATP release, while at high-frequency stimulation (5-10 Hz) norepinephrine was mainly involved. The H1 receptor agonists, pyridilethylamine and 2-(2 aminoethyl)thiazole, enhanced the electrically evoked twitch responses, but not contractions induced by exogenously-applied norepinephrine and ATP. These effects were prevented by the H1-blocking drugs, mepyramine and phenyramine, but only at high concentrations (10 mumol/l). All these H1-antagonists strongly enhanced muscle response to electrical stimulation. The H2 receptor agonists, dimaprit, amthamine and impromidine, reduced the contractions evoked by field stimulation, but not by exogenously applied norepinephrine and ATP, the effect being antagonised by H2-blocking drugs, ranitidine and famotidine. The H3 receptor agonist, R(alpha)-methylhistamine, reduced the electrically evoked muscle contractions, the effect being not modified by the selective H3-blocking drug, thioperamide, but prevented by famotidine. These data suggest that rat vas deferens contains presynaptic histamine H2 receptors, able to mediate inhibitory effects on the sympathetic transmission, while histamine H3 receptors are apparently not involved. On the contrary, the role of H1 is still unclear, since both agonists and antagonists may have the same effects.

Animals↗
PubMed1994

[The reactivity of canine colonic and ileal smooth muscle to carbachol (Jestryl)].

Experiments were carried out on longitudinal and circular smooth-muscle strips isolated from the ileum and colon of healthy dogs (controls) and of dogs with local peritonitis. The changes in the contractile responses of the strips to carbachol administered cumulatively were studied, and the EC50 and pD2 values were calculated from the dose-response curves. For the colonic longitudinal strips the EC50 was 6 x 10(-8)M and the pD2 was 7.58. The pD2 for the ileal longitudinal strips was 7.83. The pD2 value for the circular strips from the ileum and colon was 7.19 and 8.87 respectively. In the dogs with local peritonitis, the sensitivity of the longitudinal strips to carbachol was higher (the pD2 for the ileum was 7.86 and for the colon-7.21) as compared to the circular strips (the pD2 for the ileum was 6.22 and for the colon-6.65). The affinity of the cholinoreceptors in the ileal circular strips to carbachol was decreased as compared to controls.

Animals↗
PubMed1991

Involvement of calcium ions in the modulation of electrically-induced rat vas deferens contractions by histaminergic drugs.

1. The modulatory action of histaminergic drugs: histamine; 2-(2-aminoethyl)thiazole (H1-agonist); dimaprit (H2-agonist); diphenhydramine (H1-receptor antagonist); and cimetidine (H2-receptor antagonist) on rat vas deferens contractions induced by electrical field stimulation (0.1 Hz, 1 pulse, 1 msec duration, supramaximal voltage) was studied either at different calcium concentrations in the nutrient fluid or after verapamil. 2. Histamine and 2-(2-aminoethyl)thiazole inhibited the electrically-evoked contractions (EEC). This effect was unchanged after verapamil. 3. Diphenhydramine potentiated the EEC. Verapamil added before the H1-receptor antagonist inhibited this action. 4. The effects of agonists and antagonists of H-receptors decreased with the increasing of calcium concentration. 5. The results obtained suggested the existence of heterogeneity of prejunctional H-receptors. The function of histaminergic drugs on adrenergic neurotransmission in field stimulated rat vas deferens is Ca(2+)-dependent.

Animals↗
PubMed1991

Changes in the responsiveness of the colonic smooth muscle to carbachol in Hirschsprung's disease.

In vitro experiments were performed on smooth-muscle strips cut out in longitudinal and circular direction from the colon of Hirschsprung's patients who underwent an operation and from patients operated on for tumors of the sigmoid colon and rectum, serving as controls. The changes in the contractile activity of the smooth-muscle strips after carbachol applied cumulatively were examined and dose-response curves were plotted. The EC50 values for the circular strips from the aganglionic part of the colon were 6 x 10(-7) M in Hirschsprung's patients and 3.7 x 10(-8) M in control patients: the pD2 values were 6.23 and 7.43, respectively. This showed that the affinity of cholinoreceptors in the aganglionic part of the colon for carbachol was 16 times lower in Hirschsprung's patients as compared to control patients. The EC50 values for longitudinal strips from the ganglionic part of the colon were 2.6 x 10(-7) M in Hirschsprung's patients and 4 x 10(-8) M in control patients; pD2 values were 6.6 and 7.4, respectively. The affinity of cholinoreceptors in the smooth muscle of the ganglionic part of the colon for carbachol was also decreased (nearly 6.5 times) in Hirschsprung's patients as compared to controls.

Atropine↗
PubMed1991

Comparative study of the hypotensive effect of a group of structural derivatives of glaucine.

A comparative study was made on the hypotensive effect of a group of dehydrogenated structural derivatives of the alkaloid glaucine. The compounds studied induced a slowly occurring marked decrease in the blood pressure. Applied intravenously, they did not manifest the initial brief and very pronounced phase of the hypotensive effect, typical of glaucine, and failed to change substantially the respiration and the cardiac activity of the experimental animals. The most marked hypotensive effect was demonstrated by 7-benzoyl-dehydroglaucine (DG4), which reduced the blood pressure by about 50 and 60% respectively, when applied in doses of 1 mg/kg and 2.5 mg/kg. Applied duodenally, the dehydrogenated glaucine derivatives also manifested a gradually occurring hypotensive effect, whereby DG4 again caused the most pronounced blood pressure drop. Depending on the DG4 and glaucine doses used, the pressor effects of noradrenaline (NA) and nicotine (NIC) were moderately to strongly suppressed or completely inhibited. In experiments on cat membrana nictitans glaucine also suppressed moderately (2.5 mg/kg) or markedly (5 mg/kg) the contractile effects of NIC and NA, while DG4 did not influence (1 mg/kg) or potentiated (2.5 mg/kg) these effects.

Animals↗
PubMed1990

Interaction of histaminergic drugs with adrenergic neurotransmission in rabbit ear central artery.

The interaction of histamine and other histaminergic agents with adrenergic neurotransmission in blood vessels was studied in vitro. The experiments were carried out on ear central arteries isolated from male Chinchilla rabbits. The proximal segment of the artery was perfused with Krebs-Henseleit solution at a rate of 3.0 ml/min and was allowed a 120-min adaptation before the experiments. Contractions of the arterial smooth muscle were evoked either by noradrenaline (NA) or by low-frequency electrical stimulation (LFES). The effects of histamine and the other histaminergic agents on the arterial tone and on the NA- or LFES-induced contractions were studied. When applied extralumenally in concentrations higher than 1 x 10(-12) M histamine and 2-(2-aminoethyl) thiazole (2-AET) enhanced the LFES-induced smooth-muscle contractions. Dimaprit (DMP) did not markedly change the LFES-contractile effects. Diphenhydramine (DPH) and mepyramine (MEP) in higher concentrations potentiated the contractions in response to LFES. Ranitidine (RAN) moderately potentiated and cimetidine (CIM) did not affect the LFES-evoked contractions of the artery. None of the drugs tested significantly changed the NA-induced contractions. The results only partly confirm the assumption that histamine exerts its modulatory effects on adrenergic neurotransmission via postsynaptic excitatory H1-receptors and presynaptic inhibitory H2-receptors.

Animals↗
PubMed1990

Effects of histaminergic drugs on the contractile activity of smooth muscles from imipramine-treated rats.

The effects of histaminergic drugs and their interaction with adrenergic neurotransmission in smooth muscles from imipramine-treated animals were studied. The experiments were performed on isolated preparations (vasa deferentia and segments from terminal ileum and proximal colon) from male Wistar rats which were given imipramine, 10 mg/kg orally, twice daily for 2 weeks. The effects of histamine (HIST) and diphenhydramine (DPH) on the tone and phasic contractions of ileum and colon were investigated. The action of the histaminergic drugs on the vas deferens contractions evoked by low-frequency electrical stimulation (LFES) was also studied. In imipramine-treated animals LFES elicited much stronger contractions than in the controls. HIST modulatory action on the LFES-induced contractions was not markedly changed. The potentiation of the vas deferens contractions by DPH was strongly decreased. Imipramine reduced the potentiating action of both histaminergic agents on the ileum phasic contractions as well as the enhanced effects of HIST applied 10 min after DPH. Imipramine had opposite effects on the potentiating action of HIST and DPH on the colon phasic contractions: the HIST effects were slightly reduced and those of DPH were enhanced. After H1-blockade HIST exerted a stronger potentiation of the colon spontaneous contractions as compared to the controls. Present data show that imipramine could change the modifying action of histaminergic agents on adrenergic neurotransmission and also their interaction with histaminergic receptors in smooth muscles.

Animals↗
PubMed1990

[The effects of isotheoline (IST) on the nonvascular smooth musculature].

The influence of IZT on nonvascular smooth musculature in experiments in vitro was studied: on isolated intestine of the rabbit, ileum of the guinea pig, an uterine horn of the rat and guinea pig, vas deferens of the rat; as well as in vivo: on an experimental model of bronchospasm of guinea pigs, induced by acetylcholine, histamine and serotonin. Isometric contractions were recorded, and in the experiments in vivo--the tonus of the bronchial smooth musculature by a piston recorder. The obtained results showed that in experiments in vitro IZT increased the dose dependent tonus of intestinal smooth musculature; inhibited predominantly at low concentrations like clonidine the contractions of vas deferens of the rat by low frequent field stimulation--0.1 Hz and its influence was weak in respect to contractions of this organ, induced by high frequent field stimulation (10 Hz); inhibited the contractions of vas deferens in response to exogenously administered NA. IZT inhibited only bronchoconstrictor effect of serotonin in experiments in vivo. It was established that the effects of IZT both in respect to the vascular and to the nonvascular smooth musculature were Ca++ dependent and were connected with pre- and postsynaptic alpha-adrenergic receptors.

Animals↗