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At least 145 records · Page 8Linked to original sources
PubMed1992

Antibody to the inositol trisphosphate receptor blocks thimerosal-enhanced Ca(2+)-induced Ca2+ release and Ca2+ oscillations in hamster eggs.

The sulfhydryl reagent thimerosal enhanced the sensitivity of hamster eggs to injected inositol 1,4,5-trisphosphate (InsP3) or Ca2+ to generate regenerative Ca2+ release from intracellular pools. A monoclonal antibody (mAb) to the InsP3 receptor blocked both the InsP3-induced Ca2+ release (IICR) and Ca(2+)-induced Ca2+ release (CICR). The mAb also blocked Ca2+ oscillations induced by thimerosal. The results indicate that thimerosal enhances IICR sensitized by cytosolic Ca2+, but not CICR from InsP3-insensitive pools, and causes repetitive Ca2+ releases from InsP3-sensitive pools.

Animals↗
PubMed1983

Rat brain (Na+-K+)ATPase: modulation of its ouabain-sensitive K+-PNPPase activity by thimerosal.

1. The (Na+ + K+) ATPase activity of a rat brain synaptic membrane preparation was inhibited by 10(-5) M thimerosal. 2. The ouabain inhibitable K+-PNPPase activity of thimerosal treated membranes was compared with that of untreated membranes with respect to sensitivity to temperature, ouabain, K+ and ATP. 3. All those kinetic characteristics were substantially altered by treatment with thimerosal.

4-Nitrophenylphosphatase↗
PubMed1994

Effect of thimerosal on cytosolic calcium and phosphatidylserine synthesis in Jurkat T cells.

1. We investigated the effect of the thiol reagent, thimerosal on calcium movements in the Jurkat T cell line. 2. Thimerosal induced a rise in cytosolic Ca2+ concentration due both to a release of Ca2+ from intracellular stores and a Ca2+ influx. 3. Thimerosal, released Ca2+ from the same intracellular stores than CD3 mAb and ionomycin. 4. Emptying the Ca2+ intracellular stores was accompanied by a marked decrease of phosphatidylserine synthesis indicating that phosphatidylserine synthesis occurs within or close to the endoplasmic reticulum Ca(2+)-stores as previously described in CD3-, ionomycin- or Ca(2+)-ATPase inhibitor-treated lymphocytes.

Calcium↗
PubMed1996

Reversed-phase high-performance liquid chromatographic study of thimerosal stability in Cuban recombinant hepatitis B vaccine.

Non-degraded thimerosal was determined in the presence of its decomposition products by directly assaying recombinant hepatitis B vaccine using a reversed-phase liquid chromatographic method. Methanol-water-orthophosphoric acid (65:35:0.9, v/v/v) was used as the eluent. Salicylic acid was employed as an internal standard. The calibration graph was linear (r = 0.99995) up to 2.5 micrograms of thimerosal. Interference from aluminium hydroxide was eliminated by centrifugation. Good stability of thimerosal in the hepatitis B vaccine was demonstrated. The results obtained were in agreement with the recently proposed mechanism of degradation.

Adsorption↗
PubMed2006

Immuno-biochemical evaluations of phenol and thimerosal as antigen preservatives in Montenegro skin test.

Montenegro skin test (MST) represents the main complementary diagnostic test for tegumentary leishmaniases (TL) in endemic regions. Most antigen formulations used for the MST contain thimerosal as preservative. The Food and Drug Administration (FDA), however, recommended reducing or eliminating thimerosal from vaccines and other biological reagents and the Agência Nacional de Vigilância Sanitária (ANVISA) in Brazil, prohibited the use of mercurial compounds in immunobiologicals. In the search for an alternative stabilizer, phenol and thimerosal were tested as antigen preservatives in MST. Formulations were tested when fresh and after a 12-month storage at 4 degrees C in TL confirmed mice and human patients, and were evaluated for protein constitution by SDS-PAGE, Western blot and anti-gp63 ELISA. In mice, a decrease in the diagnostic effectiveness in merthiolate formulation was observed after a 12-month storage. SDS-PAGE, Western blot and anti-gp63 ELISA analyses showed a degradation of antigen proteins in both formulations after 12-month storage and that phenol-preserved antigen was quantitatively and qualitatively better than the merthiolate-preserved one. In patients, the average of induration diameter was larger in fresh antigens (p<0.05). However, storage time did not jeopardize their diagnostic capacity. No non-specific reactions produced by phenol or merthiolate were observed neither in humans nor in mice. Phenol could be a good alternative to replace the merthiolate in MST, and despite the proteolytic activity, antigens remain viable for at least 12 months.

Animals↗
PubMedDate not supplied

Thimerosal-dependent agglutination complicating the serologic evaluation for unexpected antibodies.

Thimerosal (merthiolate) is a preservative present in several low-ionic-strength blood bank reagents. Thimerosal-dependent panagglutinins were found in the serum of a hospitalized patient during serologic testing for unexpected red cell antibodies. The agglutinins behaved like a mixture of IgG and IgM and reacted with all red cells tested. Once the true nature of the serum panagglutinins was determined, blood bank reagents free of thimerosol were used, and no further serologic problems were encountered. Agglutination of this type should be considered whenever sera appear to contain panagglutinins and thimerosal is present in the test system.

Aged↗
PubMed1996

Effects of protein kinase C activation and inhibition on sperm-, thimerosal-, and ryanodine-induced calcium responses of human oocytes.

Previous data have shown that protein kinase C (PKC) participates in the mechanism of sperm-induced calcium oscillations in mammalian oocytes, but the actual role of this enzyme in the oscillation mechanism is still unknown. In this study we show that drugs modulating PKC activity disturb the oscillations induced by spermatozoa, thimerosal and ryanodine, but in a different way for each of the three oscillogenic agents. Moreover, PKC inhibition interferes with the return of the intracellular free calcium concentration to basal values during the sperm- and ryanodine-induced calcium oscillations, but not during the thimerosal-induced calcium oscillations. When the PKC-modulating drugs were applied before any of the three oscillogens, the subsequent calcium oscillations were also disturbed. However, the first calcium spike induced by spermatozoa and thimerosal was little influenced by PKC activation or inhibition. On the other hand, ryanodine failed to produce any calcium response when the PKC activity was clamped to a high level. These data suggest that sustained high PKC activities impede calcium oscillations by interfering with the opening of the ryanodine-sensitive calcium release channel, whereas sustained low activities of the enzyme paralyse the channel in the open state.

Alkaloids↗
PubMed2001

Skin reactions to thimerosal and Leishmania in dogs from a leishmaniasis endemic area: it is better to keep them apart.

Positive Montenegro's skin test is a delayed type hypersensitivity reaction widely used as indicative of previous infection with Leishmania in both humans and dogs. Montenegro's antigen consists of a crude Leishmania antigen solution, usually containing thimerosal as preserving agent. In this work it is shown that a large proportion of dogs (11 out of 56) examined in an endemic area of leishmaniasis presented induration at the site of injection of a diluent containing thimerosal alone. This clearly demonstrates that thimerosal leads to a high number of false positive skin reactions in dogs and that its use in Montenegro's skin test antigenic preparations should be avoided.

Animals↗
PubMed1999

Thimerosal in vaccines: a joint statement of the American Academy of Pediatrics and the Public Health Service.

The Food and Drug Administration (FDA) Modernization Act of 1997 called for FDA to review and assess the risk of all mercury-containing food and drugs. In line with this review, U.S. vaccine manufacturers responded to a December 1998 and April 1999 FDA request to provide more detailed information about the thimerosal content of their preparations that include this compound as a preservative. Thimerosal has been used as an additive to biologics and vaccines since the 1930s because it is very effective in killing bacteria used in several vaccines and in preventing bacterial contamination, particularly in opened multidose containers. Some but not all of the vaccines recommended routinely for children in the United States contain thimerosal.

Legislation, Drug↗
PubMed2003

Safety of thimerosal-containing vaccines: a two-phased study of computerized health maintenance organization databases.

OBJECTIVE: To assess the possible toxicity of thimerosal-containing vaccines (TCVs) among infants. METHODS: A 2-phased retrospective cohort study was conducted using computerized health maintenance organization (HMO) databases. Phase I screened for associations between neurodevelopmental disorders and thimerosal exposure among 124 170 infants who were born during 1992 to 1999 at 2 HMOs (A and B). In phase II, the most common disorders associated with exposure in phase I were reevaluated among 16 717 children who were born during 1991 to 1997 in another HMO (C). Relative risks for neurodevelopmental disorders were calculated per increase of 12.5 micro g of estimated cumulative mercury exposure from TCVs in the first, third, and seventh months of life. RESULTS: In phase I at HMO A, cumulative exposure at 3 months resulted in a significant positive association with tics (relative risk [RR]: 1.89; 95% confidence interval [CI]: 1.05-3.38). At HMO B, increased risks of language delay were found for cumulative exposure at 3 months (RR: 1.13; 95% CI: 1.01-1.27) and 7 months (RR: 1.07; 95% CI: 1.01-1.13). In phase II at HMO C, no significant associations were found. In no analyses were significant increased risks found for autism or attention-deficit disorder. CONCLUSIONS: No consistent significant associations were found between TCVs and neurodevelopmental outcomes. Conflicting results were found at different HMOs for certain outcomes. For resolving the conflicting findings, studies with uniform neurodevelopmental assessments of children with a range of cumulative thimerosal exposures are needed.

Cohort Studies↗
PubMed1990

Effect of thimerosal in leukemia, in leukemic cell lines, and on normal hematopoiesis.

Anti-thymocyte globulin (ATG), a horse antiserum to human thymus tissue, has been shown to induce granulocytic differentiation of the HL-60 human leukemia cell line. In this paper we describe the effect of ATG on leukemic blasts and its effect on other human leukemia cell lines in vitro. The in vitro differentiation effect of ATG was observed in blasts from two patients with leukemia and the human leukemia cell line K562. The differentiation effect of ATG was attributable to its preservative, thimerosal, separable from ATG by high pressure liquid chromatography or dialysis. Subsequent studies with thimerosal alone showed it to induce differentiation in leukemic blasts from three patients and the human leukemia cell lines U937, K562, and KG-1. The differentiation effect of thimerosal is blocked by a sulfhydryl-protective agent, dithiothreitol, suggesting that the mechanism of differentiation may be mediated via a sulfhydryl group-dependent process.

Antilymphocyte Serum↗
PubMed1987

Thimerosal, an inhibitor of endothelial acyl-coenzyme A: lysolecithin acyltransferase, stimulates the production of a nonprostanoid endothelium-derived vascular relaxing factor.

Thimerosal stimulates the production of a labile, smooth-muscle-relaxing substance in native and cultured endothelial cells. This substance is not prostacyclin (or any other prostaglandin) but has properties similar to the EDRF released by ACh or bradykinin. The production of EDRF in response to thimerosal is slower in onset, and may involve biochemical mechanisms different from those stimulated by other endothelium-dependent relaxants. The above results suggest that inhibition of acyl-CoA:lysophosphatide acyltransferase (by interaction with thiol groups of the enzyme) is the mechanism underlying the thimerosal-induced EDRF production.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1975

Teratogenicities of ophthalmic drugs. II. Teratogenicities and tissue accumulation of thimerosal.

Under the conditions of this study, systemically or topically applied thimerosal was found to have no teratogenic effect even when given in concentrations approaching the 50% lethal dose of these compounds. A comparison of topical and subcutaneous administration of thimerosal to rabbits shows that a substantial concentration of mercury was present in blood and tissues of the treated animals and their offspring. Thimerosal was found to cross the blood-brain and placenta barriers.

Administration, Topical↗
PubMedDate not supplied

Neurotoxic character of thimerosal and the allometric extrapolation of adult clearance half-time to infants.

The decomposition rate of organomercurials and the potency of the blood-brain barrier increase with the size of the organic radical. Thus methylmercury damages the brain more than thimerosal does, and when intake limits set for methylmercury are applied to thimerosal the safety margin is increased even if the clearances were the same. However, the clearance half-time of ethylmercury in adults is about one-third of the 50 days' clearance half-time of methylmercury given for 60 kg body weight. Moreover, because metabolic rates (e.g. basal metabolism, daily loss of mercury in per cent of body burden) in different weight groups are related to the fractional power of body weight (rule of allometry), mercury clears from the infant body faster than from the adult body. Blood mercury concentrations observed after vaccination showed agreement with allometrically extrapolated concentrations.

Adult↗
PubMedDate not supplied

Detection of antinuclear and antilaminin antibodies in autistic children who received thimerosal-containing vaccines.

Autism, a neurodevelopmental disorder, may involve autoimmune pathogenesis. Since mercury is potentially a risk factor for autoimmunity, we conducted a study of mercury-induced antinuclear and antilaminin antibodies in autistic and normal children who had been pre-administered with thimerosal-containing vaccines. Laboratory analysis by different immunoassays showed that the serum level of these two autoimmune markers did not significantly differ between autistic and normal children. This finding suggests that the mercury as in thimerosal-containing vaccines is likely not related to autoimmune phenomenon in autism.

Antibodies, Antinuclear↗
PubMed2002

The oxidant thimerosal modulates gating behavior of KCNQ1 by interaction with the channel outer shell.

Thimerosal (o-Ethylmercurithio)benzoic acid, TMS), a membrane-impermeable, sulfhydryl-oxidizing agent, has been described to increase the K+ current IKs in KCNE1-injected Xenopus laevis oocytes. Since there are no cysteine residues in the extracellular domain of KCNE1, it has been proposed that TMS interacts with its partner protein KCNQ1. The aim of this study was therefore to investigate the interaction of TMS with KCNQ1 and the respective K+current IK. In CHO cells stably transfected with KCNQ1/KCNE1, TMS increased IKs, whereas in CHO cells expressing KCNQ1 alone, TMS initially decreased IK. TMS also affected the cytosolic pH (pHi) and the cytosolic Ca2+ activity ([Ca2+]i) in these cells. TMS slowly decreased pHi. With a short delay, TMS increased [Ca2+]i by store depletion and capacitative influx. The time course of the effects of TMS on pHi and [Ca2+]i did not correlate with the effect of TMS on IK. We therefore anticipated a different mode of action by TMS and investigated the influence of TMS on cysteine residues of KCNQ1. For this purpose, KCNQ1wt and two mutants lacking a cysteine residue in the S6 or the S3 segment (KCNQ1C331A and KCNQ1C214A, respectively) were expressed in Xenopus laevis oocytes. A sustained current decrease was observed in KCNQ1wt and KCNQ1C331A, but not in KCNQ1C214A-injected oocytes. The analysis of tail currents, I/V curves and activation kinetics revealed a complex effect of TMS on the gating of KCNQ1wt and KCNQ1C331A. In another series we investigated the effect of TMS on IKs. TMS increased IKs of KCNQ1C214A/KCNE1-injected oocytes significantly less than IKs in KCNQ1wt/KCNE1- or KCNQ1C331A/KCNE1-injected cells. These results suggest that thimerosal interacts with the cysteine residue C214 in the S3 segment of KCNQ1, leading to a change of its gating properties. Our results support the idea that not only the inner shell, but also the outer shell of the channel is important for the gating behavior of voltage dependent K+ channels.

Animals↗
PubMed1993

Evaluation of the capability of different chromatographic systems for the monitoring of thimerosal and its degradation products by high-performance liquid chromatography with amperometric detection.

Several liquid chromatographic systems using electrochemical detection on carbon electrodes were compared for the analysis of thimerosal and its degradation products, thiosalicylic acid and dithiodibenzoic acid. The studied separation systems included reversed-phase ion-suppressed chromatography, reversed-phase ion-pair chromatography and ion chromatography. Amperometry and coulometry were evaluated as electrochemical detection techniques. The best method for thimerosal determination in ophthalmic solutions in terms of selectivity and sensitivity was ion-pair chromatography.

Benzoates↗