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PubMed1991

Effects of 10 known or suspected spindle poisons in the in vitro porcine brain tubulin assembly assay.

We tested the 10 known or suspected spindle poisons (colchicine, econazole nitrate, chloral hydrate, hydroquinone, diazepam, thiabendazole, cadmium chloride, thimerosal, pyrimethamine and vinblastine) of the coordinated EEC programme for induction of aneuploidy with the in vitro porcine brain tubulin assembly assay. The influence of the compounds on different parameters [lag-phase, polymerization velocity, endabsorption (steady-state level), reversibility, influence on disassembly at 4 degrees C] was evaluated. Colchicine [IC30 (30% inhibition concentration): 0.002 mM), vinblastine (IC30: 0.002 mM), thimerosal (IC30: 0.03 mM), thiabendazole (IC30: 0.5 mM) and chloral hydrate (IC30: 60 mM) led to an inhibition of tubulin assembly in vitro. No influence on the steady-state level was obtained with econazole nitrate (up to 0.1 mM), diazepam (up to 2.5 mM), cadmium chloride (up to 1 mM), pyrimethamine (up to 1 mM) and hydroquinone (up to 25 mM), the highest dose tested being limited either by precipitation or by reaching the maximal solubility of the compound in the solvent used. Diazepam enhanced the lag-phase and slightly reduced the polymerization velocity dose-dependently; however, all the treated test mixtures reached the same end absorption levels as the control. The influence on the disassembly process was studied at 4 degrees C. Microtubules treated with colchicine, econazole nitrate, diazepam, thiabendazole, cadmium chloride, thimerosal and pyrimethamine reached the same end absorption level after disassembly as the untreated control. Chloral hydrate reduced the disassembly rate but the end absorption of the control was not reached, the 30% reduction concentration being 0.25 mM. Hydroquinone at very high doses (greater than 10 mM) stimulated the disassembly process.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneuploidy↗
PubMed1988

Separation of SH-modified myosin subfragment-1 (A1) isozyme into two distinct equimolar fractions by an affinity chromatography.

Our previous kinetic studies indicated that SH-modified myosin subfragment-1 A1 isozyme (S1(A1] contains at least two different types of active sites (Emoto, Y., Kawamura, T., & Tawada, K. (1985) J. Biochem. 98, 735-745). In those studies we have modified highly reactive SH-groups in S1(A1) with thimerosal. In this work, we separated the modified S1(A1) into two equimolar fractions by affinity chromatography with agarose-ADP. For the separation, Mg2+ in the elution buffer was indispensable. Although the two fractions appeared to have the same number of modified SH-groups per mol of S1, they had different enzymic and fluorescent properties. SH-modification with an excess of thimerosal for a much longer duration did not change any of the results: not the chromatographic profile, the properties of the two fractions, nor the number of modified SH-groups. Hence the two different populations were not generated by incomplete modification. After reduction with dithiothreitol, however, the differences between the two fractions disappeared. When we separately re-modified the reduced fractions and re-chromatographed them, in each case we again obtained two fractions, which had the same properties as the two fractions obtained from the original modification with thimerosal. These results demonstrate that the active site heterogeneity in SH-modified S1(A1) had no intrinsic origin in the unmodified S1: it was introduced by the SH-modification, but by an unknown mechanism(s) other than incomplete modification.

Adenosine Triphosphatases↗
PubMed1992

Patterns of intracellular Ca2+ concentrations in fertilized bovine eggs.

Sperm-induced calcium (Ca2+) changes were examined in zona pellucida-intact, mature bovine eggs injected with the fluorescent Ca2+ indicator fura-2 dextran (fura-2 D). Fifty four percent (37/68) of the dye-injected, inseminated bovine eggs were fertilized and 43% (16/37) of the fertilized eggs exhibited Ca2+ elevations during the time of measurement. All (16/16) of the eggs with Ca2+ elevations were fertilized but none of the unfertilized eggs (0/31) showed intracellular Ca2+ elevations. Six of 13 eggs that were later examined and found to be fertilized at the time of the Ca2+ recordings did not show sperm-induced Ca2+ elevations. Fifty percent (8/16) of the eggs with Ca2+ elevations exhibited a single Ca2+ rise as a response to sperm penetration during the 60-min period in which these eggs were monitored. Twelve percent (2/16) of the eggs responded with two Ca2+ elevations spaced by 50- and 51-min intervals and 38% (6/16) of the eggs exhibited multiple elevations with intervals of 15-29 min. In the latter group, one egg was polyspermic. The mean amplitude of the sperm-induced Ca2+ elevations was 564 +/- 58 nM. Eggs with single elevations reached higher peak concentrations than eggs with multiple elevations (p < 0.05). The mean duration of the Ca2+ elevations was 166 +/- 13 sec and was similar among eggs with different Ca2+ patterns. The first elevations detected occurred at a mean of 6.6 +/- 0.5 h after insemination. Fertilization in this study was confirmed by looking at pronuclear formation 16 h post-insemination or by DNA staining immediately after the fluorescence readings. Eggs exhibiting Ca2+ elevations ranged in stage of fertilization from just penetrated to pronuclear. Injection of inositol 1,4,5 trisphosphate (5 microM in the injection pipette) into 6 bovine eggs induced an immediate Ca2+ elevation with a mean peak Ca2+ value of 700 +/- 60 nM and a mean duration of 103 +/- 21 sec. Incubation of bovine eggs with 200 microM thimerosal induced periodic Ca2+ rises. The mean number of Ca2+ elevations observed in 35 min of recordings was 3.0 +/- 0.5 (n = 9, range 1-5). The mean peak Ca2+ value of the first thimerosal-induced Ca2+ elevation was 990 +/- 210 nM. The results of this study indicate that fertilization can evoke intracellular Ca2+ elevations in bovine eggs and that the periodicity of these Ca2+ elevations is different among eggs. Furthermore, both inositol 1,4,5-trisphosphate and thimerosal were able to induce intracellular Ca2+ release in bovine eggs.

Analysis of Variance↗
PubMed1995

Inositol trisphosphate-induced calcium release in the generation of calcium oscillations in bovine eggs.

Bovine eggs exhibit repetitive rises in intracellular calcium concentration ([Ca2+]i) in response to fertilization. The signaling pathways and Ca2 release mechanisms involved in their generation are not well characterized. This study examined the presence of a GTP-binding protein (G-protein) signaling pathway as well as the role of inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R)-mediated Ca2+ release and ryanodine receptor (RyR)-mediated Ca2+ release, the two Ca2+ receptors/channels most often thought to participate in the generation of [Ca2+]i oscillations, by injecting appropriate agonists and antagonists and monitoring their effects on Ca2+ release and pronucleus formation, injection of guanosine 5'-0-(3-thiotriphosphate) (GTP gamma [S]), which promotes G-protein-mediated phosphoinositide turnover, induced, at high concentrations, repetitive [Ca2+]i rises. Low concentrations of GTP gamma [S] were ineffective. Injection of inositol trisphosphorothioate (InsP3S3), a nonmetabolizable analogue of InsP3, evoked an immediate Ca2+ release followed by [Ca2R]i oscillations. The GTP gamma [S]- and InsP3S3-induced oscillations showed a rapid attenuation in amplitude and were terminated in about 30-60 min. Thimerosal, a thiol oxidizing agent, caused repetitive rises in [Ca2+]i by sensitizing Ca2+ injection-induced Ca2+ release. Injection of ryanodine, which stimulates Ca(2+)-induced Ca2+ release via the RyR, did not induce [Ca2+]i oscillations; and eggs into which it was preinjected exhibited normal [Ca2+]i oscillations in response to thimerosal. Preinjection of heparin, a competitive InsP3R antagonist, blocked in a dose-dependent manner the Ca2+ response to InsP3 and thimerosal, and its injection into fertilized oscillating eggs inhibited [Ca2+]i oscillations in all eggs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

An inositol 1,4,5-trisphosphate receptor-gated intracellular Ca(2+) store is involved in regulating sperm hyperactivated motility.

Hyperactivated motility, a swimming pattern displayed by mammalian sperm in the oviduct around the time of ovulation, is essential to fertilization. Ca(2+) has been shown to be crucial for the initiation and maintenance of hyperactivated motility. Nevertheless, how Ca(2+) reaches the axoneme in the core of the flagellum to switch on hyperactivation is unknown. Ca(2+)-releasing agents were used to determine whether an intracellular store provides Ca(2+) to the axoneme. Hyperactivation was induced immediately in bull sperm by thapsigargin, caffeine, and thimerosal. The responses were dose-dependent and were induced in both capacitated and uncapacitated sperm. When external Ca(2+) was buffered below 50 nM with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, the response to caffeine was significantly reduced; however, the responses to thapsigargin and thimerosal were not affected. This indicates caffeine-induced hyperactivation depends on external Ca(2+) influx, whereas hyperactivation by thapsigargin and thimerosal do not. Acrosome reactions were not induced by these treatments; therefore, an acrosomal store was probably not involved. Indirect immunofluorescence labeling showed type I inositol 1,4,5-trisphosphate receptors (IP(3)R) in the acrosome and neck region, but no ryanodine receptors (RyR) were found using anti-RyR antibodies or BODIPY FL-X ryanodine. These data indicate that there is an IP(3)R-gated Ca(2+) store in the neck region of sperm that regulates hyperactivated motility.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Toxic effects of ophthalmic preservatives on cultured rabbit corneal epithelium.

We investigated the effects of the ophthalmic preservatives thimerosal and sorbic acid on the proliferation and survival of rabbit corneal epithelial cells in tissue culture. Normally, explants of corneal epithelium grow vigorously during the first 7 days in culture. With 0.004% thimerosal present in the culture medium, the normal proliferation of corneal cells is suppressed completely. When 0.1% sorbic acid is present, proliferation is delayed and the lifespan of the corneal cells is reduced. After a 1-h exposure to concentrations of thimerosal of 0.0005% or greater, virtually all corneal cells present in established cultures are killed. These results suggest that use of ophthalmic preparations containing these chemicals may affect the metabolic and proliferative capacity of the corneal epithelium adversely.

Animals↗
PubMed2005

Chemical compounds that target thiol-disulfide groups on mononuclear phagocytes inhibit immune mediated phagocytosis of red blood cells.

BACKGROUND: Patients having immune cytopenias produce antibodies that target hematopoietic cells resulting in their phagocytosis and intracellular destruction. Early reports suggested that phagocytosis could be inhibited by interfering with membrane thiol (SH) groups on phagocytes. Thus, whether chemical compounds that interact with SH or disulfide (SS) groups on mononuclear phagocytes can inhibit phagocytosis of antibody-coated cells was examined. STUDY DESIGN AND METHODS: A monocyte monolayer assay (MMA), which examines the in vitro monocyte-macrophage (Mphi) interaction with anti-Rh(D)-coated red cells (RBCs), was used to study the ability of different SH and SS chemicals to inhibit the Fc receptor-mediated phagocytosis of sensitized RBCs. The compounds examined included thimerosal, dithiothreitol (DTT), pentane-1-thiol, and two recently described SH and two SS chemicals that have been synthesized. RESULTS: All compounds were found to be able to inhibit phagocytosis to varying degrees correlating to the structure of the molecule. In general, those compounds that interact with free SH groups to inhibit phagocytosis were found better than SH-containing compounds that interact with SSs. Thimerosal and p-nitrophenyl methyl disulfide were the most effective compounds inhibiting phagocytosis. Both chemicals showed greater than 50 percent inhibition at concentrations as low as 10(-9) mol per L. DTT was the least effective compound tested. Only thimerosal showed significant toxicity, as determined by decreased cell viability and increased apoptosis, but only at concentrations of 10(-8) mol per L. The effect of chemical treatment was on attachment rather than on phagocytosis itself. Fcgamma receptor-independent endocytosis was not affected by the chemical treatment. CONCLUSION: These studies indicate that pharmacologic strategies that target SH groups on mononuclear phagocytes may have future efficacy for the treatment of immune cytopenias.

Antibodies↗
PubMed2005

Incidence of autism spectrum disorders: changes over time and their meaning.

AIM: Several reviews have noted a huge increase in the rate of diagnosed autism spectrum disorders. The main aims of this paper are: 1) to use published empirical findings to consider whether the rise reflects a true increase in incidence, as distinct from the consequences of better ascertainment and a broadening of the diagnostic concept; and 2) to consider how epidemiological data may be used to test hypotheses about possible causal influences, using MMR and thimerosal as examples. METHODS: Search of the literature for studies with a large epidemiological base population, systematic standardized screening, a focus on an age group for which diagnostic assessments are reliable and valid, and diagnosis by trained professionals using high-quality research assessments. Also, search of a broader literature to consider the evidence from all epidemiological studies with respect to the hypothesized causal effect of MMR and thimerosal on autism spectrum disorders. RESULTS: The true incidence of autism spectrum disorders is likely to be within the range of 30-60 cases per 10 000, a huge increase over the original estimate 40 years ago of 4 per 10000. The increase is largely a consequence of improved ascertainment and a considerable broadening of the diagnostic concept. However, a true risk due to some, as yet to be identified, environmental risk factor cannot be ruled out. There is no support for the hypothesis for a role of either MMR or thimerosal in causation, but the evidence on the latter is more limited. CONCLUSION: Progress in testing environmental risk hypotheses will require the integration of epidemiological and biological studies.

Autistic Disorder↗
PubMed1995

Effects of thiol-modifying agents on KATP channels in guinea pig ventricular cells.

ATP-sensitive K+ (KATP) channels are thought only to open during conditions of metabolic impairment (e.g., myocardial ischemia). However, the regulation of KATP channel opening during ischemia remains poorly understood. We tested whether thiol (SH) group oxidation, which is known to occur during ischemia, may be involved in KATP channel regulation. Inside-out membrane patches were voltage clamped at a constant potential (O mV) in asymmetrical K+ solutions. The effects of compounds that specifically modify SH groups [p-chloromercuri-phenylsulfonic acid (pCMPS), 5-5'-dithio-bis(2-nitrobenzoic acid) [DTNB], and thimerosal] were tested. The membrane-impermeable compound, pCMPS (> or = 5 microM), caused a quick and irreversible inhibition of KATP channel activity. The reducing agent, dl-dithiothreitol (DTT) (3 mM) was able to reverse this inhibition. DTNB (500 microM) caused a rapid, but spontaneously reversible, block of KATP channel activity. After DTNB, no change was observed in single channel conductance. Oxidized glutathione (GSSG, 3 mM) did not block KATP channel activity. Thimerosal (100-500 microM) induced a DTT-reversible block of partially rundown KATP channels, or channels that underwent complete rundown; these channels were reactivated with trypsin (1 mg/ml). Thimerosal did not block KATP channels that had a high degree of activity. However, the ATP sensitivity was decreased; the concentration of ATP needed to half-maximally inhibit the channel (Ki) was increased from 47 +/- 12 to 221 +/- 35 microM (n = 6, P < 0.05). This was not due to a spontaneous change with time.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Chloromercuribenzenesulfonate↗
PubMed2000

Effects of inhibitors of arachidonic acid turnover on the production of prostaglandins by the guinea-pig uterus.

The supply of free arachidonic acid from phospholipids is generally regarded as the rate-limiting step for prostaglandin (PG) synthesis by tissues. Two enzymes involved in arachidonic acid uptake into, and release from, phospholipids are acyl-CoA:lysophospholipid acyltransferase (ACLAT) and phospholipase A2 (PLA2), respectively. PGF2 alpha produced by the endometrium induces luteolysis in several species including guinea-pigs. Thimerosal, an inhibitor of ACLAT, and aristolochic acid, an inhibitor of PLA2, both reduced, in a concentration-dependent manner, the output of PGF2 alpha from guinea-pig endometrium cultured for 24 h on days 7 and 15 of the oestrous cycle. This study showed that the continual production of PGF 2 alpha by guinea-pig endometrium is not only dependent upon the activity of PLA2 for releasing free arachidonic acid for PGF2 alpha synthesis, but also on the incorporation of arachidonic acid into the phospholipid pool by the activity of ACLAT. The inhibitory effects of thimerosal and aristolochic acid on the outputs of PGE2 and 6-keto-PGF1 alpha were less marked, particularly on day 7 when the low output of PGE2 was unaffected and the output of 6-keto-PGF1 alpha was increased at the lower concentrations of thimerosal. This finding indicates that there are different pools of arachidonic acid bound as phospholipid for the syntheses of PGF2 alpha and 6-keto-PGF1 alpha by guinea-pig endometrium.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1989

Effect of organic and inorganic mercuric salts on Na+K+ATPase in different cerebral fractions in control and intrauterine growth-retarded rats: alterations induced by serotonin.

An intrauterine growth-retarded (IUGR) model based on restriction of blood supply to the rat fetus at the 17th day of pregnancy was studied. We investigated in vitro the effects of thimerosal and mercuric chloride on Na+K+ATPase activity in total brain homogenate, synaptosomes and myelin at weaning. In addition, we evaluated the reversal effect of serotonin on mercury-inhibited Na+K+ATPase activity. The toxicity, in terms of inhibition of Na+K+ATPase activity was greater with mercuric chloride than with thimerosal. Synaptosomes and principally myelin were more sensitive to the metal salts than total homogenate. Serotonin stimulated the Na+K+ATPase activity in total brain homogenate and synaptosomes but inhibited the enzyme in the myelin fraction. This effect was more marked in the IUGR group than in the control group. Serotonin (1 mM) added to total homogenate pretreated with the mercury salts produced variable reversal effects. In the synaptosomal fraction reverse effect was noted with serotonin. In myelin fraction, added serotonin increased inhibition caused by thimerosal.

Animals↗
PubMed1987

Immunological complications of soft contact lenses.

Immunologic reactions may be the basis of some complications associated with the use of soft contact lenses. In the case of giant papillary conjunctivitis, the antigen causing the problem is not known but is presumed to be protein adherent to the lenses. Superior limbic keratoconjunctivitis and dendritic corneal lesions related to soft contact lenses are associated with thimerosal, but occlusive patch tests do not demonstrate consistent delayed hypersensitivity responses to this preservative in these patients, suggesting that a toxic response may be involved. The association of corneal infiltrates and conjunctival hyperemia with delayed hypersensitivity to thimerosal probably represents the strongest immunologic association to date. These patients consistently show delayed hypersensitivity reactions to thimerosal in occlusive patch tests and intradermal tests.

Conjunctival Diseases↗
PubMed1994

ATP-sensitive K+ channels of skeletal muscle fibers from young adult and aged rats: possible involvement of thiol-dependent redox mechanisms in the age-related modifications of their biophysical and pharmacological properties.

In the present work, we have investigated whether thiol-dependent redox mechanisms play a role in the regulation of ATP-sensitive K+ (KATP) channels present on the surface membrane of skeletal muscle fibers from 5-7-month-old ("young adult") and 24-26-month-old ("aged") rats. The KATP channels were surveyed by using patch-clamp techniques. Continuous recordings of channel activity were performed in the inside-out configuration at a constant voltage at 20 degrees, in the presence of 150 mM KCl on both sides of the membrane. As expected, the excision of cell-attached patches from young adult rat fibers, into ATP-free solution, dramatically increased KATP channel activity. In contrast, when patches were excised from aged rat fibers no increase of channel activity was detected. Open probability (Popen) analysis in the range of potentials from -70 mV to +60 mV revealed that the Popen of the channels of aged rat fibers was about 7.5 times lower than that of young adult rat fibers. Moreover, a decrease in the number of functional channels present in the patches of aged rat fibers was also observed. No change with aging was found in the single-channel conductance, which was 60 pS. The application of increasing concentrations of the sulfhydryl group-reducing agents L-cysteine (5 microM to 5 mM) and N-acetyl-L-cysteine (0.5-5 mM) restored the Popen of the channels of aged rat fibers without increasing the number of functional channels. Thimerosal, a sulfhydryl group-oxidizing agent, and glybenclamide applied to the cytoplasmic face of KATP channels from fibers of either young adult or aged rats dramatically abolished channel openings. However, the KATP channels of aged rat fibers were 30-200 times more sensitive to the inhibitory effects of these chemicals. In both young adult and aged rat fibers the effect of thimerosal was reversed only by addition of L-cysteine. In contrast, the effect of glybenclamide was fully reversible. Moreover, after preincubation of aged rat channels with 1 mM L-cysteine, the blocking effect of glybenclamide was reduced and was similar to that observed in young adult rat fibers. These observations lead us to conclude that, in rat skeletal muscle, the KATP channel proteins contain thiol groups essential for channel activity. Oxidation of these groups occurs during aging and prolonged channel closure. This modification may explain the altered pharmacological response to both thimerosal and glybenclamide observed in aged rat skeletal muscle fibers.

Acetylcysteine↗
PubMed1996

[Allergic reaction to merthiolate (a disinfectant) based on material from the Occupational Medicine Institute in Lodz].

Incidence and causes of allergy to merthiolate (thimerosal) was studied in 685 patients, examined in the Nofer Institute of Occupational Medicine, during the period from 1 September 1993 to 15 October 1995. Allergy to thimerosal was diagnosed in 39 persons (5.7%) including 25 (6.3%) females and 14 (4.9%) males. Health service workers predominated among those sensitized (13.8% of all medical personnel examined during that period). In 19 persons only allergy to mercury was observed. Among them 7 showed no skin changes, 6 manifested symptoms of hand dermatitis, in 4 patients atopic dermatitis and in 2 dermatitis diseminata were diagnosed. Two patients suffered from allergic rhinitis. It was found that the general vaccination of health service workers against viral hepatitis as well as immunotherapy with pollen preparations containing thimerosal (Catalet, Biomed, Poland) were the main causes of allergy to mertiolate. Allergy to thiosalicyclic acid was not observed and two persons reacted positively to mercuric chloride.

Adolescent↗
PubMed1993

Transmucosal delivery of leucine enkephalin: stabilization in rabbit enzyme extracts and enhancement of permeation through mucosae.

Leucine enkephalin (Tyr-Gly-Gly-Phe-Leu; Leu-Enk) is a naturally occurring peptide that has been shown to have pain modulating properties. To evaluate the feasibility of using various absorptive mucosae as a route of systemic delivery, the stability of Leu-Enk and the effect of enzyme inhibitors (e.g., amastatin, EDTA, and thimerosal) on stabilization and permeation of Leu-Enk through rabbit mucosae in the presence of dihydrofusidates were investigated. Enzymes in the nasal, rectal, and vaginal mucosae were extracted and Leu-Enk (50 micrograms/mL) was added to each of the enzyme extracts and incubated to determine the kinetics and mechanism of degradation. The rate of degradation in the extracts in the absence of inhibitors followed the order: rectal > vaginal > nasal. Whereas EDTA had the best stabilizing effect on Leu-Enk, thimerosal was the best stabilizer for the degradation intermediates. A combination of amastatin (50 microM), EDTA (5 mM), and thimerosal (50 microM) had the greatest stabilizing effect on Leu-Enk and its degradation intermediates. For permeation studies, each mucosa was mounted onto a Valia-Chien permeation cell with Leu-Enk (200 micrograms/mL) in isotonic phosphate buffer (as donor solution). The enhancers used for the study were sodium tauro-dihydrofusidate (STDHF), sodium glycodihydrofusidate (SGDHF), and phosphato-dihydrofusidate (PHDHF). The greatest effect was achieved by PHDHF for all the mucosae. STDHF had a significant effect only on the rectal permeation, whereas SGDHF had significant effects on rectal and vaginal mucosae. Mechanisms by which the dihydrofusidates enhance permeating may involve micelle formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1983

Kinetic studies on the (Na+ + K+)-dependent ATPase evidence for coexisting sites for Na+, K+ and Mg2+.

Na+-ATPase activity of a dog kidney (Na+ + K+)-ATPase enzyme preparation was inhibited by a high concentration of NaCl (100 mM) in the presence of 30 microM ATP and 50 microM MgCl2, but stimulated by 100 mM NaCl in the presence of 30 microM ATP and 3 mM MgCl2. The K0.5 for the effect of MgCl2 was near 0.5 mM. Treatment of the enzyme with the organic mercurial thimerosal had little effect on Na+ -ATPase activity with 10 mM NaCl but lessened inhibition by 100 mM NaCl in the presence of 50 microM MgCl2. Similar thimerosal treatment reduced (Na+ + K+)-ATPase activity by half but did not appreciably affect the K0.5 for activation by either Na+ or K+, although it reduced inhibition by high Na+ concentrations. These data are interpreted in terms of two classes of extracellularly-available low-affinity sites for Na+: Na+-discharge sites at which Na+-binding can drive E2-P back to E1-P, thereby inhibiting Na+-ATPase activity, and sites activating E2-P hydrolysis and thereby stimulating Na+-ATPase activity, corresponding to the K+-acceptance sites. Since these two classes of sites cannot be identical, the data favor co-existing Na+-discharge and K+-acceptance sites. Mg2+ may stimulate Na+-ATPase activity by favoring E2-P over E1-P, through occupying intracellular sites distinct from the phosphorylation site or Na+-acceptance sites, perhaps at a coexisting low-affinity substrate site. Among other effects, thimerosal treatment appears to stimulate the Na+-ATPase reaction and lessen Na+-inhibition of the (Na+ + K+)-ATPase reaction by increasing the efficacy of Na+ in activating E2-P hydrolysis.

Animals↗
PubMed2003

Immediate allergy to tetanus toxoid vaccine: determination of immunoglobulin E and immunoglobulin G antibodies to allergenic proteins.

BACKGROUND: Adverse reactions to tetanus toxoid (TT) vaccine are mostly mild and limited to the injection site. However, immunoglobulin (Ig)E-mediated reactions may occur, and the incidence of anaphylactic responses to TT immunization is 0.001%. When TT induces an allergic reaction, the potential causative agents can be TT antigens, thimerosal or aluminum phosphate. OBJECTIVE: We studied four children who developed immediate urticaria after TT vaccine, soon after the reaction and 5 years later. METHODS: Skin tests were performed separately with TT vaccine and two vaccine components, thimerosal and aluminum phosphate, and the diagnosis was confirmed by provocation test. IgE and IgG antibodies to TT and their specificities were determined. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting were performed to characterize the antigenic proteins. RESULTS: All four children were immediate skin test-positive to TT, but negative to thimerosal and aluminum phosphate; 3 developed a reaction after intramuscular provocation using increasing doses of TT vaccine; and 1 refused to be tested. All these tests were negative in five controls, all of whom received TT vaccine and developed only local swelling at the site of application 24 hours after vaccine administration. After 5 years the IgG antibodies were still high in all cases and the IgE antibody values fell by 50%. Patients allergic to TT vaccine produced IgE and IgG antibodies, which decreased at different rates but remained for at least 5 years. The pattern of antibody decrease was confirmed by radioallergosorbent test, enzyme-linked immunoadsorbent assay, or immunoblotting assay. IgE and IgG antibodies recognized two proteins derived from TT, of 150 and 50 kDa, corresponding to the intracellular form and to a chain of the extracellular form of the tetanus neurotoxin. CONCLUSIONS: In children with immediate allergic reactions to TT vaccine, antibodies may persist for at least 5 years, requiring evaluation by skin and/or in vitro tests before subsequent treatment.

Adolescent↗
PubMed1992

Photosensitivity to piroxicam: absence of cross-reaction with tenoxicam.

We studied 2 groups of patients. One group of 10 patients had a photosensitive eruption to piroxicam. Another group of 24 patients had positive patch test reactions to thimerosal and thiosalicylic acid and had never taken piroxicam or tenoxicam. Patients were patch tested with thimerosal 0.1% pet., thiosalicylic acid 0.1% pet., salicylic acid 2.0% pet., piroxicam 1 and 5% pet. and tenoxicam 1 and 5% pet. Photopatch tests were also performed with piroxicam and tenoxicam. All 10 patients with photosensitivity to piroxicam had positive patch tests to thimerosal and thiosalicylic acid and 9 of them had positive photopatch tests to piroxicam. 20 out of 24 patients with positive patch tests to thiosalicylic acid also had positive photopatch tests to piroxicam. All the patients tested with salicyclic acid were negative. Out of the 29 patients with positive photopatch tests to piroxicam, none reacted to tenoxicam. In countries with a high incidence of contact sensitivity to thimerosal/thiosalicylic acid, the use of piroxicam should be avoided and replaced by tenoxicam, a drug without reported photosensitivity.

Adult↗