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At least 1,387 records · Page 77Linked to original sources
PubMed1984

Effects of multiple putative anticarcinogens on the carcinogenicity of trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]-1,2,4-oxadiazole.

In an attempt to dissociate the chemotherapeutic from the carcinogenic properties of the antischistosomal and antitrypanosomal nitrovinylfuran trans-5-amino-3-[2-(5-nitro-2-furyl)vinyl]1,2,4-oxadiazole [(SQ18506) CAS: 28754-68-9; (E)-5-amino-3-(2-(5-nitro-2-furyl)vinyl)-1,2,4-oxadiazole], potential inhibitors of carcinogenesis were administered to female outbred CD-1 mice before and during exposure to SQ18506. The compounds tested were ascorbic acid, etretinate, butylated hydroxyanisole (BHA), cysteamine hydrochloride, cysteine hydrochloride, dimercaprol, disulfiram, 1,4-dithiothreitol, reduced glutathione, and spermidine phosphate. The primary types of tumors observed were squamous cell carcinomas of the stomach and thymic and nonthymic lymphomas. BHA reduced the incidence of malignant tumors to control levels, whereas cysteine hydrochloride, spermidine phosphate, and disulfiram reduced the incidence of chemically induced tumors by 42, 34, and 32%, respectively. Although cysteamine hydrochloride and disulfiram had no or only a modest effect on the overall incidence of tumors, the data suggested possible tissue-specific anticarcinogenic properties for these agents. Of the 8 antioxidants tested, only 1 had marked anticarcinogenic properties against SQ18506. These data indicate that antioxidant properties alone cannot account for the anticarcinogenic activity of the compounds tested. Coadministration of the anticarcinogen BHA with SQ18506 also blocked the chemotherapeutic effects of this agent on female CD-1 mice infected with Schistosoma mansoni.

5-Amino-3-((5-nitro-2-furyl)vinyl)-1,2,4-oxadiazol↗
PubMed1984

Effect of MPG on glucocorticoid-induced cataract formation in developing chick embryo.

Cataract in the developing chick embryo can be easily produced by administration of high doses of glucocorticoid and the cataract is preceded by a decreased level of glutathione in the lens (Nishigori et al, Exp Eye Res 36:617, 1983). In an attempt to prevent cataract formation, various natural and synthetic sulfhydryl compounds, glutathione, cysteine, ergothioneine, penicillamine, cysteamine and N-(2-mercaptopropionyl)glycine, were applied to hydrocortisone-treated developing chick embryos. N-(2-mercaptopropionyl)glycine showed the most potent delaying activity against cataract formation and also lessened the decrease of glutathione level in the lens. However, except for cysteamine, the other compounds tested had little or no effect.

Amino Acids, Sulfur↗
PubMed1995

[Bis((2,4-dioxo-1,2,3,4-tetrahydroquinazolin-3-yl)alkyl)disulfane and 3-(mercaptoalkyl)quinazolin-2,4(1H,3H)-dione: synthesis by ring transformation and antiviral activity. 42. Heterocyclic azines with heteroatoms in the 1- and 3- positions].

Reaction of N-(sulfonyloxy)phtalimide derivatives 1, 2, with cystamine and homocystamine, respectively, affords bis[2,4-dioxol-1,2,3,4-tetra-hydroquinazolin-3-yl)alkyl] disulfanes [sequence: see text] 3, which could be reduced to 3-(mercaptoalkyl)quinazoline-2,4(1H,3H)-diones. 5. (3-(2-Mercaptoethyl)quinazoline-2,4(1H,3H)-dione (5a) was also obtained in a one-pot reaction from 1 or 2 and cysteamine. 2-Ethoxy-4H-3,1-benzoxazin-4-ones 4a-c were converted with cysteamine to 3-(mercaptoethyl)quinazoline-2,4-diones 5a-c by a new ringtransformation reaction. 3-(2-Mercaptoethyl)quinazoline-2,4(1H,3H)dione (5a) and the corresponding disulfane 3a were evaluated for antiviral activity in vitro. Compounds 3a and 5a showed significant antiviral activity against some DNA- and RNA-viruses (vaccinia-, herpes simplex virus type 1; influenza A virus) at concentrations that were nontoxic to the host cell cultures.

Animals↗
PubMed1995

Different molecular forms of basic fibroblast growth factor (bFGF) accelerate duodenal ulcer healing in rats.

UNLABELLED: Basic fibroblast growth factor is an angiogenic polypeptide that exhibits potent antiulcer activity without decreasing gastric acid or pepsin secretion. In this study, we investigated the effect of three acid-stable derivatives of human recombinant bFGF (hrbFGF) on the healing of chronic duodenal ulcer in rats. In Sprague-Dawley female rats, duodenal ulcers were induced by cysteamine-HCl. After laparotomy, rats were randomized to create six groups with homogeneously severe ulcers (perforated or penetrated into the liver or pancreas) and treated by gavage twice a day for 3 weeks with a) vehicle, b) cimetidine (10 mg/100 g), c) Ser78,96-hrbFGF (bioequivalent to rbFGF-CS23), d) CMC-hrbFGF, a carboxymethyl cysteine derivative of hrbFGF or e) PEG-hrbFGF, a polyethylene glycol derivative of hrbFGF. The peptides were administered at 100 ng/100 g. Autopsy was performed on the 21st day, and the ulcer size was measured. The ulcer sizes (mm2) were reduced from 10.3 +/- 1.8 in controls to 4.8 +/- 1.4* after cimetidine treatment and to 5.0 +/- 2.4, 4.2 +/- 1.1* and 0.5 +/- 0.2**, respectively, after administration of aforementioned hrbFGF derivatives (*P < .05; **P < .01 vs. vehicle group), which also significantly enhanced angiogenesis in the ulcer bed. CONCLUSIONS: 1) Oral administration of novel derivatives of hrbFGF accelerated the healing of cysteamine-induced chronic duodenal ulcer. 2) The PEG-hrbFGF derivative was more active than the other hrbFGF analogs. 3) The naturally occurring bFGF provides a good prototype to design new locally acting antiulcer drugs.

Animals↗
PubMed1993

The initiation of peptide formation in the biosynthesis of actinomycin.

Actinomycin Synthetase II (ACMS II), which activates threonine and valine by a thioltemplate mechanism during the synthesis of the actinomycin half-molecule 4-methyl-3-hydroxyanthranilic acid (4-MHA) pentapeptide lactone, was purified to near homogeneity from Streptomyces chrysomallus. It is a single polypeptide chain of M(r) 280,000 and contains 4'-phosphopantetheine as a covalently bound prosthetic group. ACMS II charges itself with threonine but not with the 4-MHA analogue p-toluic acid via a specific sulfhydryl group at the expense of ATP. Charging of ACMS II with p-toluic acid in thioester linkage took place, however, only when actinomycin synthetase I (ACMS I), a 4-MHA-AMP ligase, was present. In the additional presence of L-threonine, enzyme-bound p-toluyl-L-threonine was formed on ACMS II. The latter compound was also formed when chemically synthesized p-toluic acid adenylate was added instead of ACMS I and p-toluic acid. This indicates that p-toluic acid adenylate is a free intermediate in the reaction and that charging of the enzyme and acylation of threonine are both catalyzed by ACMS II rather than by ACMS I. Chemically synthesized thioesters of p-toluic acid and coenzyme A, pantetheine, or beta-alanyl-cysteamine reacted with ACMS II, threonine, and ATP with formation of enzyme-bound p-toluyl-threonine. In contrast, p-toluyl-cysteamine thioester was inactive, which indicates structural constraints in the reactivity of free thioesters of p-toluic acid with ACMS II. Such constraints obviously require structural similarity of the artificial substrate to a p-toluic acid thioester formed on the enzyme's surface in the course of the reaction. Since free coenzyme A was not involved in the charging of p-toluic acid or in p-toluyl-threonine formation, the sulfhydryl group of the 4'-phosphopantetheine cofactor is most likely the primary acceptor of p-toluic acid (or 4-MHA) in the initiation of peptide lactone formation.

Amino Acid Sequence↗
PubMed1996

Isolated rat gastric mucosal cells: optimal conditions for cell harvesting, measures of viability and direct cytoprotection.

Controversial data have been obtained with direct cellular protection by prostaglandins and sulfhydryls. In the present studies, we compared the merits and liabilities of currently available cell viability assays, some of which have not been previously employed in studies of the gastric mucosa. We also tested the hypothesis that length of incubation of isolated cells with protective agents might influence the degree of cellular damage. Gastric mucosal cells were isolated from nonfasted rats and digested with various concentrations of pronase and/or EGTA. Cell viability was assessed by trypan blue and fast green exclusion, fluorescein diacetate hydrolysis, chromium release, LDH release, mitochondrial succinate dehydrogenase activity and nuclear fluorescence induced by ethidium bromide. The experiments revealed that both pronase and EGTA are needed to obtain mucosal cells with optimal yield and initial viability and that sequential additions of pronase (30 min) and EGTA (30 min), rather than their combination (60 min), increased viability without decreasing yield. Cell viability and yield were better when pronase was used in the first incubation. For LD50 determinations, a cell suspension was incubated with ethanol (0%-15%) for 5 min. For studying the effects of protective agents, the cells were pretreated with 16,16-dmPGE2 or cysteamine HCl at 37 degrees C for 30 min before a 5-min exposure to 7.5% or 15% ethanol. The LD50 value for ethanol injury was approximately 15% for all assays except LDH, where the LD50 value was 8.5%. Preincubating gastric mucosal cells for 30 min with 16,16-dmPGE2 or cysteamine resulted in no preservation of cell viability. However, when cells were preincubated with one of the protective agents for 60 min and then exposed to 8% or 10% ethanol for 5 min, partial protection was observed when assessed by succinate dehydrogenase activity and, in certain cases, by LDH release. We conclude that all seven cell viability assays yield a measurable LD50 value for ethanol-induced cell injury, but the results may vary by as much as 82%. Low concentrations of both pronase and EGTA are needed to obtain isolated mucosal cells with both high yield and initial viability. Biochemical measures of mitochondrial activity and nuclear damage provide reliable evidence of cell viability and should be used to complement membrane permeability assays. Long preincubation of cells (60 min) with protective agents resulted in only slight protection of mitochondrial function, in contrast to the rapid induction of gastroprotection seen with these compounds in vivo. We therefore surmise that processes that contribute to organ protection occur faster and more efficiently than those that control direct cell injury and protection.

Animals↗
PubMedDate not supplied

[Effect of a number of sulfur-containing radioprotective agents on the evacuatory function of the stomach in mice].

Tests staged on mongrel albino mice demonstrated that sulphur-containing radioprotectors used in doses two orders below those exercising a radioprotective action with their peroral administration are apt to significantly modify the evacuative function of the stomach. This properties of the sulphur-containing radioprotectors depends upon their chemical structure. A particularly strong influence on the evacuative function of the stomach in mice exerts cystamine dichlorohydrate, aminoalkylamino-alkylthiophosphates and mercaptoamidines. This property is less pronounced in cystaphos and cysteamine chlorhydrate. The least effect on the delayed evacuation was found in cysteamine bitartrate and in the disodium salt-4, 4(1)-trithiobis (butane-sulphonate). These data allow it to explain the specificity of the toxic and radioprotective action produced by diverse drugs with their peroral administration.

Animals↗
PubMed1991

Ocular manifestations of nephropathic cystinosis. The French-Canadian experience in a genetically homogeneous population.

A large spectrum of ocular pathologic features have been described in infantile cystinosis. Reported symptoms may require corneal transplantation and therapeutic efforts to solubilize cystine crystals with hourly administration of cysteamine (mercaptamine) drops. French Canada has the highest incidence of cystinosis in the world. We studied 18 patients with cystinosis who appeared to have much milder ocular involvement than that in other reported series. No operative interventions were required. Relatively mild photophobia was the most common ocular manifestation of cystinosis.

Adolescent↗
PubMed1998

Experimental induction of corpora amylacea in adult rat brain.

Corpora amylacea (CA) are glycoproteinaceous inclusions that accumulate in astroglia and other brain cells as a function of advancing age and, to an even greater extent, in several human neurodegenerative conditions. The mechanisms responsible for their biogenesis and their subcellular origin(s) remain unclear. We previously demonstrated that the sulfhydryl agent, cysteamine (CSH), promotes the accumulation of CA-like inclusions in cultured rat astroglia. In the present study, we show that subcutaneous administration of CSH to adult rats (150 mg/kg for 6 weeks followed by a 5-week drug-washout period) elicits the accumulation of CA in many cortical and subcortical brain regions. As in the aging human brain and in CSH-treated rat astrocyte cultures, the inclusions are periodic acid-Schiff -positive and are consistently immunostained with antibodies directed against mitochondrial epitopes and ubiquitin. Our findings support our contention that mitochondria are important structural precursors of CA, and that CSH accelerates aging-like processes in rat astroglia both in vitro and in the intact brain.

Aging↗
PubMed1981

Two new sulphur-containing amino acids in man.

Two unusual sulphur-containing amino acids have been isolated from urine of a baby who died with major physical malformations and failure of growth and development. Sensitive mass spectrometric methods were used to identify the nanomole quantities of the compounds available as S-(2-carboxypropyl)-cysteine and S-(2-carboxypropyl)-cysteamine. Incubation of fibroblasts in either [14C]Valine or [35S]cysteine resulted in radioactive labelling of the compounds, suggesting their origin from conjugation of methacrylic acid with cysteine and subsequent decarboxylation of the cysteine conjugate. Specific assay of methacrylyl-CoA hydratase is needed for final proof that this is a new inborn error of that enzyme, but these findings and parental consanguinity make this very likely. It seems possible that methacrylic acid or one of its derivatives may have caused the malformations present in the baby.

Abnormalities, Multiple↗
PubMed1992

Apolipoprotein E phenotyping by isoelectric focusing in immobilized pH gradients and silver staining.

A simple and high resolution procedure of apoprotein E (apo E) phenotyping by isoelectric focusing with immobilized pH gradients and silver staining is described. This method needs delipidated very low density lipoproteins (isolated from 1 mL of serum) but obviates immunoblotting as well as neuraminidase treatment in routine applications because the sialylated forms are clearly separated. Immunoblotting (with polyclonal and monoclonal anti-apo E antiserum), cysteamine and neuraminidase treatment, and pI markers allowed the localization of three main alleles, xi 2, xi 3, xi 4 and the detection of variants or rare alleles (6/450 determinations). The serum amyloid A (SAA) apolipoproteins (SAA1,SAA2) could be characterized unequivocally (especially with E3 and E4). Silver staining proved more sensitive than Coomassie Brilliant Blue and needs only 5 micrograms of protein in the sample. The results of 403 normo-or hyperlipidemic patients are shown. In the group of 191 normolipidemic patients (cholesterol less than 6.40 mmol/L triglycerides less than 2 mmol/L), the relative frequency of the xi 3 allele (0.83) is higher than in other reports on Caucasians (about 0.77) whereas the xi 4 allele is lower. As previously described, we find a high frequency of the 4/3 phenotype in hypercholesterolemia and 3/2 in hypertriglyceridemia. The high frequency of the E2/E2 phenotype, usually associated with hyperlipidemia, and variants in complex hypertriglyceridemia makes the apo E phenotyping necessary in many cases of dyslipidemias.

Acrylamides↗
PubMed2001

Structure-activity analysis of the potentiation by aminothiols of the chromosome-damaging effect of bleomycin in G0 human lymphocytes.

The radioprotective aminothiols 2-[(aminopropyl)amino] ethanethiol (WR-1065) and cysteamine (CSM) potentiate the induction of chromosomal damage by the radiomimetic compound bleomycin (BLM) in G0 human lymphocytes. To investigate the mechanism of potentiation, we measured the clastogenic activity of BLM in the cytokinesis-block micronucleus assay in the presence and absence of amines, thiols, and aminothiols. The hydroxy analog of WR-1065, 2-(3-aminopropylamino) ethanol (WR-OH), potentiates BLM only slightly, indicating the critical nature of the thiol group. As thiols, WR-1065 and CSM may donate electrons for the activation of Fe(+2)-BLM or for the regeneration of Fe(+2)-BLM from inactive Fe(+3)-BLM. The amines putrescine, spermidine, and spermine all potentiate BLM, but they are weaker potentiators than the aminothiols, and they are effective only at high concentrations. Their activity, like that of WR-OH, is probably a consequence of conformational alteration of DNA. Dithioerythritol (DTE) and 2-mercaptoethanol (2-ME), thiols lacking an amino group, are less effective potentiators of BLM than are the aminothiols. The thiol group of WR-1065 and CSM is therefore essential, but insufficient, for explaining the strong enhancement of BLM activity. The cationic nature of CSM and WR-1065, conferred by the amino groups, evidently concentrates the active thiol function at the site of BLM action on DNA. As expected on this basis, the diamine WR-1065 is a more effective potentiator of BLM than is the monoamine CSM, whereas cysteine and N-acetylcysteine (NAC), which lack a net positive charge, potentiate BLM only weakly. These studies suggest that potentiation of the clastogenic action of BLM by aminothiols can be explained by the combination of a thiol-mediated redox mechanism and an amine-mediated targeting of the thiol function to DNA.

Bleomycin↗
PubMed1994

Effect of environmental conditions on radiation target size analyses.

Target size determinations from radiation inactivation of proteins is dependent on the physical and chemical environment of the sample during radiation exposure. Effects of temperature and physical state have already been described. Buffers, the effects of protein concentration, and the addition of small molecules are examined for several enzymes. Phosphate buffer is found to have major effects on the rate of inactivation of certain, but not all, proteins. The amount of protein in irradiated samples is significant for all enzymes studied; the nature of the specific protein used is unimportant. Neither sucrose nor other glycitols could substitute for protein in target size determinations. Certain small molecules, especially cysteamine, were effective in sparing the need for high protein levels in radiation inactivation studies of four enzyme systems.

Acetylcholinesterase↗
PubMed2000

Direct electrochemistry of horseradish peroxidase immobilized on a colloid/cysteamine-modified gold electrode.

Direct electron transfer of immobilized horseradish peroxidase on gold colloid and its application as a biosensor were investigated by using electrochemical methods. The Au colloids were associated with a cysteamine monolayer on the gold electrode surface. A pair of redox peaks attributed to the direct redox reaction of horseradish peroxidase (HRP) were observed at the HRP/Au colloid/cysteamine-modified electrode in 0.1 M phosphate buffer (pH 7.0). The surface coverage of HRP immobilized on Au colloid was about 7.6 x 10(-10) mol/cm(2). The sensor displayed an excellent electrocatalytic response to the reduction of H(2)O(2) without the aid of an electron mediator. The calibration range of H(2)O(2) was 1. 4 microM to 9.2 mM with good linear relation from 1.4 microM to 2.8 mM. A detection limit of 0.58 microM was estimated at a signal-to-noise ratio of 3. The sensor showed good reproducibility for the determination of H(2)O(2). The variation coefficients were 3. 1 and 3.9% (n = 10) at 46 microM and 2.8 mM H(2)O(2), respectively. The response showed a Michaelis-Menten behavior at higher H(2)O(2) concentrations. The K(app)(M) value for the H(2)O(2) sensor was found to be 2.3 mM.

Biosensing Techniques↗
PubMed1997

Depletion of cerebral D-serine in non-ketotic hyperglycinemia: possible involvement of glycine cleavage system in control of endogenous D-serine.

Tissue concentrations of D-serine and other chiral and non-chiral amino acids were measured post-mortem in the cerebral cortex of the neonatal or infantile individuals with (three cases) or without (seven cases) non-ketotic hyperglycinemia (NKH) using high performance liquid chromatography with fluorometric detection. In the cortical tissues of the NKH patients lacking activity of glycine cleavage system, there was a marked reduction and elevation of the contents of D-serine and glycine, respectively, compared to non-NKH controls. Systemic administration of an inhibitor of glycine cleavage system (GCS), cysteamine, mimicked the changes in the cortical concentrations of these amino acids in the 8-day-old rats. Augmentation of brain glycine levels by means of intraperitoneal injection of glycine itself resulted in an increase in cortical D-serine contents in the neonatal rats with normal activity of GCS. These findings provide the first evidence that GCS might be implicated in the biosynthesis or content regulation of endogenous D-serine in the mammalian brain.

Amino Acid Oxidoreductases↗
PubMed2001

Oxidation and generation of hydrogen peroxide by thiol compounds in commonly used cell culture media.

Many studies have examined the effects of thiol compounds upon cells in culture (e.g., upon signal transduction and regulation of gene expression), but few have considered how thiols can interact with cell culture media. A wide range of thiols (cysteine, GSH, N-acetylcysteine, gamma-glutamylcysteine, cysteinylglycine, cysteamine, homocysteine) were found to interact with three commonly used cell culture media (RPMI, MEM, DMEM) to generate hydrogen peroxide with complex concentration-dependencies. Thiols added to these media rapidly disappeared, although less H(2)O(2) was generated on a molar basis than the amount of thiol lost. Studies on cellular effects of thiols, especially those on redox regulation of gene expression or protein function, need to take into account that thiols are rapidly lost, and that their oxidation generates H(2)O(2), which can have multiple concentration-dependent effects on cell metabolism.

Acetylcysteine↗
PubMed1997

Progression of mouse buthionine sulfoximine cataracts in vitro is inhibited by thiols or ascorbate.

Mouse lens cultures were employed to study the progression of cataracts initiated by injection of buthionine sulfoximine, an inhibitor of glutathione (GSH) biosynthesis. Culture of lenses removed from untreated mice on postnatal day 7, for 48 hr in the presence of 4 mm BSO, resulted in only limited cataractous changes. To enable substantial progression of cataracts in vitro, it was therefore necessary to pretreat the mice with BSO prior to lens culture. A single injection of BSO (4 nmol mg-1 lens), administered on day 7, resulted in >90% depletion of lens GSH within 3 days, but no visible cataractous changes. The clear lenses were incubated for 29+/-1 hr at 37 degrees C in Medium HL-1, supplemented with EGF, insulin and Ca2+, in the presence or absence of BSO, and were scored for cataract development by previously described criteria. In the absence of BSO, only 4 of 10 lenses developed large opacities. However, in the presence of 4 mm BSO, 40 out of 45 experimental lenses developed opacities affecting at least 50% of the lens visual field and were scored as stages 1C-4, depending upon the extent and density of the cataracts. In addition, three lenses had opacities involving 20-50% of the field (stage 1B). By contrast, less than 10% of lenses from untreated mice incubated in the absence of BSO developed opacities. The cataracts developed in 4 mm BSO were accompanied by reduction of lens glutathione levels to <0.010 nmol mg-1 lens. They were almost completely prevented by 1 mm ascorbate, 2 mm GSH, 2 mm GSH monoethyl ester and 2 mm cysteamine. GSH and GSH ester maintained lens glutathione content between 0.1 and 0.2 nmol mg-1 in the presence of BSO, whereas ascorbate did not prevent near-total GSH depletion. The prevention of cataracts by thiols and ascorbate was confirmed by lens Na/K ratios not significantly different from those in control lenses. The above combination of GSH depletion in vivo by a single injection of BSO, followed 3 days later with lens culture in the presence of BSO, may yield a useful system to elucidate and control the biochemical mechanisms involved in oxidative cataract induction by this GSH-depleting agent.

Animals↗
PubMed1989

Effect of omega-conotoxin GVIA on release of 3H-gamma-aminobutyric acid from slices of rat neostriatum.

omega-Conotoxin GVIA (omega-CT) diminished the potassium-induced in vitro release of 3H-gamma-aminobutyric acid (3H-GABA) from slices of rat neostriatum in a manner which depended on the concentration of potassium. omega-CT (0.1 mmol/l) decreased the release of 3H-GABA induced by 25 mmol/l K+ from 11.6% to 6.1% of tissue content, ie. by 48%, while it did not affect the release of 3H-GABA caused by 20 mmol/l K+, which was 4.8% of tissue content. However, in the presence of a polyclonal antiserum or cysteamine (600 mumol/l), both of which diminish the effects of endogenous somatostatin, 0.1-10 nmol/l omega-CT decreased the release of 3H-GABA induced by 20 mmoles/l K+ by 40%. It is concluded that omega-CT did not only inhibit GABA-neurones, but had an additional inhibitory effect on somatostatin neurones which are known to depress the release of 3H-GABA. It is further concluded that neuronal interactions, which are possible in brain slice preparations, may impede the interpretation of effects of drugs, especially if agents are used which affect basic mechanisms of transmitter release and thus the release of various transmitters from neurones.

Animals↗