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At least 217 records · Page 12Linked to original sources
PubMedDate not supplied

[Use of antioxidants for preventing the hepatotoxic effect of acrylonitrile].

The authors examined the possibility of using antiooxidants in the chemoprophylaxis of poisonings with alkylating chemical compounds. It was demonstrated that vitamin E, ionol and low-molecular thiols (cystein, glutatione and unithiol) prevent the increased permeability of plasma membranes and impairment of the protein-synthesizing function of the endoplasmic reticulum of hepatoytes in acute and chronic acrylonitrile poisoning.

Acrylonitrile↗
PubMedDate not supplied

[Cysteine activity in the poisoning of animals by various aliphatic series halogenated hydrocarbons].

In poisoning animals with various aliphatic series haloid-hydrocarbons (LK99 and LD99) free cysteine was found to be a group antidote in rats poisoned with monohaloid-hydrocarbons. It was established that the therapeutic activity of cystein depends not on the nature of haloid and double bonds, but on the number of the haloid atoms in a molecule, the length, ramification and nature of the radical. A good durative action are shown by such cystein derivatives as acetyl-cysteine, glutathione and cystein salts. In poisoning with haloid-alkyls dithiol antidotes (unithiol, mecaptide, BAL) and other drugs proved ineffective.

Acetylcysteine↗
PubMedDate not supplied

[Thiol compounds in the combined therapy of prozerin poisonings].

The authors studied the protective action of dithiols (unithiol, dithiothreitol) and their combinations with atropine in proserine poisoning. With the use of the spatial-prospective plotting the antidote efficacy of dipyroxime, atropine, dithiothreitole, and their combinations was studied and compared. A new type of potentiation was discovered upon combined use of atropine, dipyroxime and dithiothreitol.

Animals↗
PubMed1981

[Method of determining human and animal plasma kallikrein inhibitors].

A method for determining blood plasma kallikrein inhibitors is suggested. It is based on inhibiting the kininogenase activity of kallikrein. The donors' dry plasma devoid of kininases, of other proteolytic enzymes and their inhibitors was used as source and reference of prekallikrein, kallikrein and high-molecular kininogen. Freshly centrifuged plasma was incubated in the presence of unithiol at 37 degrees C in amounts producing a 30-50% inhibition of the kininogenase activity of kallikrein. The values obtained reflected the activity of kallikrein inhibitors and might be of great importance in the study of the physiological role and biochemical properties of kallikrein inhibitors in different animal species, in the diagnosis and prediction of various diseases, as criterion for laboratory control over administering tissue inhibitors of proteolytic enzymes of animal origin.

Adolescent↗
PubMedDate not supplied

[Intensive intralymphatic and lymphotropic therapy in children].

Study of the effect of endolymphatic therapy with antibiotics and antioxidants on lipid peroxidation and endotoxicosis level in children in critical state showed that endolymphatic infusion of nonenzymatic antioxidants (vitamin E, unithiol) and wide-spectrum antibiotics noticeably reduced the activity of free-radical lipid peroxidation and accelerated detoxication in comparison with the control group.

Adjuvants, Immunologic↗
PubMedDate not supplied

[The effect of membrane-stabilizing and antioxidant preparations on the lipid peroxidation processes in cerebral stroke].

Changes in the concentration of the lipid peroxidation products in the blood of 152 patients in stroke were studied. 18 patients with LPO processes activation received supplementary treatment with antioxidant preparation (tocopheroli acetas, ascorbic acid, pyridoxalphosphate, glutaminic acid), which lowered significantly the blood content of LPO products; in 12 patients with reduced concentration of LPO products treatments with membrane-stabilizing preparations (lipostabyl, sodium hydroxybutyrate, ascorbic acid, unithiol) were administered, and restoration of LPO processes was established to have occurred. With the purpose of improving methods and assessment of the cerebral insult treatment efficacy, it is recommended that specific features of changes in the concentration of LPO products be used.

Acute Disease↗
PubMedDate not supplied

[The new anti-alcohol preparation medikhronal: changes in the level of ethanol, acetaldehyde and monoamines during the treatment of alcoholism patients].

Treating patients with stage-II alcoholism with medichronal and unithiol sharply decreases blood levels of alcohol and acetaldehyde. Medichronal restores the decreased level of norepinephrine excretion in 25% of patients and the increased level of epinephrine in 43%. The high baseline concentration of serotonin dropped in 41%, however, its level remained higher than in the controls. There was a negative correlation between the changes of ethanol concentrations and the excretion of norepinephrine. There was a direct dependence between the changes in the norepinephrine/epinephrine ratio and the serotonin concentration.

Acetaldehyde↗
PubMedDate not supplied

[Free radical mechanisms of memory disorders of toxic origin and experimental therapy of the condition].

Influence of the pesticides deltametrin and dichlophos on memory processes and activity of the antioxidative enzymes superoxide dismutase (SOD) and catalase in the brain and blood of female rats was studied. Xenobiotics disturbed processes of formation and storage of signs of memory, which were tested in the conditional reaction of passive avoidance and in the conditional reaction of active avoidance; they also lowered SOD activity (but not catalase) in the brain (deltametrin by 25%, dichlophos by 21%) 3 h after their injection to the animals. Indices of SOD activity and blood catalase didn't change. SOD inhibition is suggested to be a result of the action of biotransformation product of deltametrin and dichlophos molecules on it, since in in vitro experiments pesticides don't exert influence on the inhibition kinetics of epinephrine autooxidation by brain homogenates. Prophylactic use of alpha-tocopherol or unithiol optimizes the processes of learning and memory in rats, intoxicated with these toxicants; a more marked antiamnestic, effect is observed in the combined injection of these preparations.

Animals↗
PubMed1996

[The effect of different concentrations of saline solutions on the proteolytic activity of trypsin and microbial proteases].

Laboratory investigations were carried out to study the influence of certain medical substances and saline solutions of various concentrations upon activity of trypsin and microbial proteases under similar conditions and regimens of action. Based on the results obtained with regard for the inhibiting effect of medicamentous substances and concentrations of saline solutions upon trypsin and microbial proteases the authors made up a prescription of the saline solution with unithiol, sodium thiosulphate, calcium chloride, sodium chloride. This composition is optimal for the elimination of microbial toxicosis in the injury focus, and facilitates natural development of the wound process.

Dose-Response Relationship, Drug↗
PubMed2002

Quantification of the Raf-C1 interaction with solid-supported bilayers.

By use of the quartz crystal microbalance technique, the interaction of the Raf-Ras binding domain (RafRBD) and the cysteine-rich domain Raf-C1 with lipids was quantified by using solid-supported bilayers immobilized on gold electrodes deposited on 5 MHz quartz plates. Solid-supported lipid bilayers were composed of an initial octanethiol monolayer chemisorbed on gold and a physisorbed phospholipid monolayer varying in its lipid composition as the outermost layer. The integrity of bilayer preparation was monitored by impedance spectroscopy. For binding experiments, a protein construct comprising the RafRBD and Raf-C1 linked to the maltose binding protein and a His tag, termed MBP-Raf-C1, was used. Dissociation constants and rate constants of the association and dissociation were obtained for various 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/1,2-dimyristoyl-sn-glycero-3-phosphoserine (DMPS) lipid mixtures. Independently of the phosphatidylserine (PS) content, the dissociation constants were in the order of 5x10(-7) M, while the on-rate constants were in the range of 2x10(3) (M s)(-1) and the off-rate constants in the range of 1x10(-3) s(-1). The maximum frequency shift increased significantly with increasing amounts of DMPS; this indicates that this negatively charged lipid is the primary binding site for MBP-Raf-C1. Exchange of DMPS for 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) did not alter the thermodynamics and kinetics of protein binding, which implies that the protein interaction is mainly electrostatically driven. Scanning force microscopy (SFM) was employed to render protein adsorption visible and to confirm the assumption of a protein monolayer on the lipid layer. SFM images clearly revealed that the protein binds preferentially, but not solely, to negatively charged phosphatidylserine headgroups. We hypothesize that PS-enriched domains are initial binding sites with high affinity for Raf-C1, but that lateral interactions may account for protein domain growth.

Adsorption↗
PubMedDate not supplied

Pharmacokinetics of 14C-DMPS (sodium-1,3 14C-2,3-dimercaptopropane-1-sulphonate) in beagle dogs.

The pharmacokinetics of labelled DMPS (sodium-1,3 14C-2,3-dimercaptopropane-1-sulphonate) have been studied in four beagle dogs following bolus intravenous injection (65.7 mumol kg-1) and oral administration (197 mumol kg-1). Following intravenous injection the main kinetic parameters were t 1/2 = 43 min, V beta = 160 ml kg-1, and plasma clearance Clp = 2.6 ml min-1 kg-1. Following oral administration 14C-DMPS is rapidly absorbed with peak concentrations (478 +/- 25 mumol l-1) measured after 30-45 min. About 60 per cent of the oral dose was absorbed. Estimates of t 1/2, V beta, and Clp after oral administration were in close agreement with the values obtained in the intravenous study. 14C-DMPS is eliminated from the body by the kidneys. About 70 per cent of 14C-DMPS in dog plasma are bound to proteins. Binding is even higher in plasma from rat and man.

Administration, Oral↗
PubMedDate not supplied

Evaluation of three antidotes on arsenic toxicity in the common earthworm (Lumbricus terrestris).

The common earthworm (Lumbricus terrestris) is being evaluated in our laboratories as a substitute for mice in metal toxicity studies. These two disparate species have enzymes in common, such as catalase, superoxide dismutase and glutathione-S-transferase. Also, worms respond similarly to these rodents for selenium and nickel toxicity. Worms are less sensitive, however, to metal toxicity. In this study earthworms were challenged with three different arsenic compounds: arsenite, arsenate and the vesicant phenyldichloroarsine (PDA). The median lethal dose for each arsenic compound was determined. The order of toxicity of the arsenic compounds to the worms was PDA > arsenite > arsenate (24 h LD50 values were 189.5, 191.0 and 519.4 mumol kg-1, respectively). Individual mammalian dithiol antidotes, namely the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS), meso-dimercaptosuccinic acid (DMSA) or 2,3-dimercapto-1-propanol (BAL), were injected into the worms 5 min after various doses of the arsenic compound were administered. The decreases in acute toxicity values were recorded. All three antidotes protected the worms against arsenic toxicity with varying degrees of effectiveness. The protective action for the inorganic arsenic compounds was in the order DMPS > DMSA > BAL. For the organic arsenical, PDA, the most effective antidote was BAL.

Animals↗
PubMedDate not supplied

Beryllium-induced biochemical alterations and their prevention following co-administration of meso-2,3-dimercaptosuccinic acid or 2,3-dimercaptopropane sulphonate in rats.

The effects of meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane sulphonate (DMPS) on body beryllium burden, hepatic lipid peroxidation, glutathione, alkaline and acid phosphatase and some biochemical variables of porphyrin metabolism were studied in beryllium-poisoned rats. It was observed that beryllium poisoning is associated with a slight increase in lipid peroxidation, significant depletion of alkaline phosphatase and elevation of acid phosphatase activities in the liver and increased beryllium concentration in blood and other soft organs. Evidence is presented that both DMSA and DMPS during concomitant administration prevented most of the above beryllium-induced biochemical alterations. Tissue beryllium concentration and histopathological lesions in liver and kidneys were also significantly less marked following simultaneous administration of DMPS compared to beryllium-exposed controls; DMSA was comparatively less effective.

Animals↗
PubMedDate not supplied

Chelation in metal intoxication: influence of cysteine or N-acetyl cysteine on the efficacy of 2,3-dimercaptopropane-1-sulphonate in the treatment of cadmium toxicity.

The influence of cysteine or N-acetyl cysteine administration on the efficacy of 2,3-dimercaptopropane-1-sulphonate (DMPS) in the treatment of cadmium intoxication was investigated in cadmium-pre-exposed rats. Cysteine, N-acetyl cysteine, DMPS, DMPS + cysteine or DMPS + N-acetyl cysteine were about equal in effectiveness in mobilizing hepatic cadmium mainly from its supernatant cytosolic fraction (SCF) and both of the combinations were more effective than either of them alone in mobilizing cadmium from its nuclear mitochondrial fraction (NMF). The DMPS was apparently more effective than cysteine or N-acetyl cysteine in mobilizing renal cadmium from its SCF or NMF and it was more effective than even their combinations in mobilizing cadmium from renal SCF. The treatment with cysteine or N-acetyl cysteine reduced cadmium-induced hepatic and renal metallothionein (MT) and the treatment with DMPS reduced renal MT only, probably due to removal of hepatic and renal SCF cadmium by these agents. However, MT levels were high in animals treated with DMPS + cysteine or DMPS + N-acetyl cysteine, despite lowering of cadmium in these tissues, suggesting a contribution of MT induced by cysteine or N-acetyl cysteine itself. The cadmium exposure increased hepatic and renal zinc and renal copper levels, probably as a result of cadmium-induced MT, and some of the levels were normalized considerably by the subsequent treatment with cysteine, DMPS or to a lesser extent N-acetyl cysteine and their combinations, showing their protective effects against cadmium toxicity. The increase in blood cadmium and the decrease in blood zinc and copper levels due to cadmium exposure also were reversed appreciably by some of these treatments. The results have shown a limited benefit of cysteine or N-acetyl cysteine administration on the efficacy of DMPS in the treatment of cadmium intoxication.

Acetylcysteine↗
PubMed2004

Lead-induced oxidative stress and hematological alterations and their response to combined administration of calcium disodium EDTA with a thiol chelator in rats.

The therapeutic efficacy of calcium disodium ethylenediaminetetracetic acid (CaNa(2)EDTA) and the two thiol chelators, 2,3-dimercaptopropane 1-sulfonate (DMPS) and monoisoamyl dimercaptosuccinic acid (MiADMSA) was studied, both individually and in combination, in reducing lead concentration in blood and soft tissues and in restoring lead induced altered biochemical variables in rats. Exposure to subacute dose of lead implicated a critical role of reactive oxygen species (ROS) and oxidative stress in altering the normal values of these variables. Exposure to lead caused a significant inhibition of blood delta-aminolevulinic acid dehydratase (ALAD), an important enzyme in the haem synthesis pathway and glutathione (GSH) level. These changes were also accompanied by inhibition of ALAD activity in kidney, delta-aminolevulinic acid synthase (ALAS) activities in liver and changes in platelet counts in whole blood suggesting disturbed haem synthesis pathway. Lead exposure also led to a pronounced depletion of brain GSH contents, superoxide dismutase (SOD) activity, an increase in thiobarbituric acid reactive substances (TBARS), and activity of glutathione S-transferase (GST). Specific activities of membrane-bound enzymes, acetylcholinesterase (AChE) and monoamine oxidase (MAO), were significantly inhibited on lead exposure. These biochemical changes were correlated with increased uptake of lead in blood and soft tissues. Post lead exposure treatment with MiADMSA in particular provided significant recovery in altered biochemical variables besides significant depletion of tissue lead burden. Treatment with CaNa(2)EDTA and DMPS individually had only moderate beneficial effects on tissue oxidative stress, although they were equally effective in the removal of tissue lead burden. Tissue zinc and copper levels did not depict any significant depletion, although changes like marked depletion of zinc following CaNa(2)EDTA and copper after MiADMSA administration were of some concern. Combined administration of CaNa(2)EDTA, particularly with MiADMSA, was the most effective treatment protocol compared to all other treatments. It can be concluded from our present results that combined therapy with CaNa(2)EDTA and MiADMSA proved significantly better in restoring biochemical and clinical variables over monotherapy with these chelating agents against subacute lead exposure in adult rats.

Animals↗
PubMed1998

Involvement of tyrosine phosphorylation in inhibition of fMLP-induced PLD activation by N-acetyl-L-cysteine in differentiated HL60 cells.

N-acetyl-L-cysteine (NAC), which is known as a multipotential agent; an antioxidant, a thiol reagent, or a tyrosine kinase inhibitor, inhibited N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced phospholipase D (PLD) activation in HL60 cells in a concentration-dependent manner (IC50 = 2 mM). Its inhibitory mechanism was examined in this study to gain insight into the regulation of PLD activity. NAC had no direct effect on membrane PLD activity in an in vitro assay system. fMLP-induced formation of inositol phosphates via phospholipase C (PLC) was not affected by the drug, suggesting that the receptor-G protein coupling was not inhibited. H2O2, which is known to induce PLD activation in several types of cells, failed to activate PLD in HL60 cells. Pretreatment of 3-amino-1,2,4-triazole (ATZ), a catalase inhibitor, did not enhance fMLP-induced PLD activation. NAC inhibited fMLP-induced tyrosine phosphorylation of several protein bands (42, 44, 64, and 138 kDa) in a concentration-dependent manner. The temporal and concentration-dependent inhibitory profiles for tyrosine phosphorylation of 64- and 138-kDa proteins were well correlated with PLD activation. However, thiol reagents, 1 mM 2,3-dimercapto-l-propanol (2,3-DMP), 1 mM dithiothreitol (DTT), and 2 mM cysteine also did not suppress protein tyrosine phosphorylation or PBut formation by fMLP. Wortmannin, a selective phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, inhibited these two tyrosine phosphorylation bands. These results suggest that NAC inhibits fMLP-induced PLD activation through blockage of protein tyrosine phosphorylation, which is located at the downstream of PI-3 kinase.

Acetylcysteine↗
PubMed1995

Exact power computation for dose-response studies.

The toxicity of an agent or the therapeutic effect of a drug may be assessed by a dose-response study. We present a method for computing the exact power of exact and large sample statistical tests employed for binary response data from such a study. This method, based on recursive polynomial multiplications, enables fast computation of exact power for studies with up to a moderately large sample size. We demonstrate the efficiency of our method using three examples. The method is suitable for the design and power analysis of dose-response studies in which the usual asymptotic approximations are suspect.

Adenoma↗
PubMed1995

Characterization of the antifungal protein secreted by the mould Aspergillus giganteus.

An antifungal polypeptide (AFP) of 51 amino acid residues, secreted by the mould Aspergillus giganteus, has been purified to homogeneity and characterized. The inhibitory effect of this protein on the growth of different microorganisms has been studied. Whereas the growth of many of the filamentous fungi assayed is inhibited, no effect has been observed against yeasts or bacteria. The minimal concentration for total inhibition of the growth is in the range 6 to 25 microM. The antifungal polypeptide does not produce any effect on the growth of the producing mould. The polypeptide promotes aggregation of acidic phospholipid vesicles. A remarkable resistance to proteolysis and a low hydrogen x deuterium exchange have been observed for this protein. The protein does not show any thermal transition up to 80 degrees C when studied by differential scanning calorimetry and infrared spectroscopy. The uv absorbance, fluorescence emission, and circular dichroism (CD) characteristics of this protein have been studied. The protein exhibits a strong positive band at 230 nm as a prominent feature of the CD spectrum in the far uv region. All the spectroscopical properties of the antifungal protein are highly influenced by the abundance of tyrosine residues. These can be grouped in two different populations, buried and exposed, based on the results of pH-titration experiments. Fourier-transform infrared spectroscopy reveals a high content of beta-structure in AFP. Reduction and carboxy-amidomethylation produces a rather unstructured polypeptide as deduced from its spectroscopical properties.

Aspergillus↗