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PubMed1989

A human liver alcohol dehydrogenase enzyme-linked immunosorbent assay method specific for class I, II, and III isozymes.

A sensitive and convenient method for the quantitative measurement of human alcohol dehydrogenase (ADH) isozymes based on enzyme-linked immunosorbent assay has been devised. The procedure was optimized with respect to antigen coating density, antiserum dilution, and incubation times with rabbit antisera raised against beta 1 beta 1-ADH to achieve a limit of sensitivity of 1 ng/ml for this isozyme when purified. Using the optimal conditions established, quantitative measurement of alpha beta 1, alpha gamma 1, beta 1 gamma 1, pi, and chi-ADH were obtained with antisera raised in rabbits toward these individual isozymes. The incorporation into the procedure of thimerosal (ethyl(4-mercaptobenzoato-S)mercury) or other sulfhydryl specific reagents improved the soluble phase antiserum avidity for all ADH isozymes, thereby increasing the sensitivity. Thimerosal is an absolute requirement for chi-ADH antigen-antibody binding. The polyclonal rabbit antisera elicited by the individual isozymes of the three classes of ADH exhibit a high degree of isozyme class specificity. Cross-reactivity of the antibodies with the beta 1 beta 1, alpha gamma 1, alpha gamma 2, alpha beta 1, beta 1 gamma 1, beta 1 gamma 2, pi and chi isozymes were evaluated. Antisera against the class I isozymes beta 1 beta 1 and beta 1 gamma 1 cross-react with all class I isozymes and with pi-ADH. Antibodies against pi and chi-ADH are selective and specific only for their respective antigens. Neither one cross-reacts with any class I isozyme. Conformational effects resulting from subunit interactions likely account for differences in cross-immunoreactivity between the closely homologous class I isozymes.

Alcohol Dehydrogenase↗
PubMed1993

Porcine aortic endothelial cell membranes contain a LPAF: CoA-independent transacylase.

Membranes isolated from porcine aortic endothelial cells (PAEC) contain a CoA-independent transacylase enzyme (CoA-IT). CoA-IT, an integral membrane protein, transfers an acyl moiety to added [3H]alkylhydroxyglycerophosphocholine (LPAF) to generate [3H]alkylacylglycerophosphocholine (alkylacyl-GPC). This enzyme exhibits an apparent Km of 0.7 microM and a Vmax of 0.8 nmol/min per mg for the transfer of an acyl group to added [3H]LPAF. The addition of the nonionic detergent Triton X-100 (TX-100) (0.5 mg/ml), the sulfhydryl reagents N-ethylmaleimide (NEM) (200 microM) or thimerosal (200 microM), or pre-incubating the membranes at 95 degrees C for 10 min all decreased LPAF: CoA-IT activity by more than 95%. The inhibitory action of NEM or thimerosal suggests that sulfhydryl group(s) are involved in or are close to the catalytic site of LPAF: CoA-IT.

Acyltransferases↗
PubMed1985

Identification and synthesis of [1-asparagine, 5-valine, 9-glycine] angiotensin I produced from plasma of American eel Anguilla rostrata.

The major peptide produced by incubation of American eel (Anguilla rostrata) plasma with the eel kidney extract was identified as [1-asparagine, 5-valine, 9-glycine] angiotensin I (I). Two minor peptides were also identified as [1-aspartic acid, 5-valine, 9-glycine] angiotensin I (II) and [5-valine, 9-glycine] angiotensin I-(3-10)-octapeptide (III). These structures were further confirmed by comparison of these peptides on high-pressure liquid chromatography (HPLC) and high-performance thin-layer chromatography (HPTLC) with the synthetic peptides and the tryptic and chymotryptic digests of the synthetic and natural angiotensins. In the rat pressor bioassays, the synthetic decapeptides I and II possessed 45.4 and 52.2%, respectively, of the pressor activity of [1-aspartic acid, 5-isoleucine] angiotensin II. The pressor activity of I and II was blocked with the converting enzyme inhibitor captopril. Study of the conversion of asparaginyl decapeptide into aspartyl decapeptide in eel plasma indicated that the presence of thimerosal (sodium ethylmercurithiosalicylate) in the incubation mixture inhibited the conversion of I into II. These results suggest that (a) I is the natural form of angiotensin inherent in the American eel while II may be formed during incubation with plasma; (b) eel plasma contains an enzyme which is capable of converting asparaginyl angiotensins into aspartyl angiotensins; and (c) pressor activity of I and II is due to their conversion into the corresponding octapeptides. In a previous work when thimerosal was not included in the incubation mixture, the major peptide produced by incubation of Japanese eel (Anguilla japonica) plasma with its kidney extract was identified as II. (Y. Hasegawa, T. Nakajima, and H. Sokabe, 1983, Biomed. Res. 4, 417-420).

Angiotensin I↗
PubMed1985

Methods for reducing non-specific antibody binding in enzyme-linked immunosorbent assays.

Enzyme-linked immunosorbent assays were used to study (i) binding of rabbit antibodies (raised against litter mate liver plasma membrane fraction) to the immunizing membrane fraction, and (ii) binding of human antibodies to liver membrane fractions and to liver-specific lipoprotein (a liver membrane-derived antigen complex). When assays were conducted using the non-ionic detergent Tween 20 as blocking agent, high non-specific binding was encountered. With the low titre rabbit antisera high binding of non-immune test antibody and of second antibody (anti-rabbit IgG) to the immunogen, and also directly to the solid phase, was found. This was abolished by replacement of Tween 20 in the antibody diluent buffers by a non-reactive protein, casein proving to be a more effective blocking agent than either bovine serum albumin or gelatin. With human sera, high binding of human IgG to the solid phase was noted. This too was blocked by casein, but only when the anti-microbial agent Thimerosal was included in the casein buffer, and when Tween 20 in the wash buffer was replaced by casein-Thimerosal so that the solid phase was exposed to casein before incubation with the test serum. The casein buffers described may prove of general value in solid-phase assays where high non-specific binding is encountered.

Antibody Specificity↗
PubMed1987

Glutaraldehyde inactivated pertussis vaccine: a less histamine sensitizing vaccine.

The effects of different inactivating agents on the biological activity of the histamine sensitization factor of Bordetella pertussis toxin were examined. The agents were used for inactivation in the preparation of whole cell pertussis suspension. The histamine sensitizing activity was reduced to 36.9-13.3% by treatment with glutaraldehyde, to about 50% by treatment with formaldehyde and by the acetone-II treatment, relative to the reduction by heat treatment. Treatment with thimerosal and the acetone-I treatment did not reduce the histamine sensitizing activity as the 50% histamine sensitizing doses of the heat inactivated pertussis preparation, the thimerosal inactivated pertussis preparation and the acetone-I treated pertussis preparation were very similar. Glutaraldehyde has thus been found to be a better inactivating agent for the preparation of a safe pertussis suspension as it considerably reduced the histamine sensitizing activity of pertussis toxin.

Acetone↗
PubMed1984

Octanol/water partition coefficients as a model system for assessing antidotes for methylmercury(II) poisoning, and for studying mercurials with medicinal applications.

1-Octanol/water partition coefficients, [HgII]octanol/[HgII]water, provide a simple but limited model system for aspects of the biological behavior of methylmercury(II) and commonly used organomercury(II) medicinal compounds. In an octanol/water system some widely studied antidotes for mercury poisoning at least partly displace the biological thiols L-cysteine and glutathione from binding to MeHgII at pH 6.9. Addition of the antidote meso-dimercaptosuccinic acid to MeHgII in the presence of glutathione results in formation of metallic mercury. For RHgII derivatives of L-cysteine and glutathione, octanol/water partition coefficients follow the order Ph greater than Et greater than Me. An exceptionally high value for diphenylmercury, compared with PhHgII derivatives of L-cysteine and glutathione, is consistent with reported results of the distribution of mercury compounds in rats. Ethylmercury(II) is partly displaced from thimerosal by L-cysteine and glutathione in the octanol/water system, indicating that the active form of thimerosal in vivo may involve binding of EtHgII to biological ligands.

Animals↗
PubMed2004

Effect of hydrogen peroxide on Ca2+ mobilisation in human platelets through sulphydryl oxidation dependent and independent mechanisms.

Using Fura-2-loaded human platelets we studied the nature of the mechanisms involved in Ca2+ signalling mediated by H2O2. In a Ca2+-free medium, H2O2 (10 microM-100 mM) induced a concentration-dependent increase in [Ca2+]i. Depletion of either agonist-sensitive or mitochondrial Ca2+ pools reduced this effect while depletion of both stores abolished it. Xestospongin C, an inositol 1,3,5-trisphosphate (IP3) receptor inhibitor, reduced Ca2+ release evoked by 1 mM H2O2 by 45%, indicating that H2O2-induced Ca2+ release involves interaction with IP3 receptors. Blockade of the IP3 turnover by lithium or treatment with U-73122 did not modify H2O2-induced Ca2+ release from the agonist-sensitive pool, suggesting the involvement of a mechanism independent of IP3 generation. H2O2 inhibited Ca2+ reuptake into the agonist-sensitive stores mediated by the sarcoendoplasmic reticulum Ca2+ ATPase (SERCA). Thimerosal (5 microM), a sulphydryl reagent, induced Ca2+ release from the agonist-sensitive stores. This event was impaired by treatment with 2 mM DTT, which also inhibited H2O2-induced Ca2+ release from the agonist-sensitive pool but not from mitochondria. H2O2 reduced the ability of the plasma membrane Ca2+ ATPase (PMCA) to extrude Ca2+ by 75%, an effect that was unaffected by DTT. Consistent with this, thimerosal did not modify the PMCA activity. Finally, exposure to H2O2 triggered platelet aggregation, which was slower than that observed after agonist stimulation. We conclude that H2O2 induced Ca2+ release from agonist-sensitive stores by oxidation of sulphydryl groups in SERCA and the IP3 receptors independently of IP3 generation. In addition, H2O2 induced Ca2+ release from mitochondria and inhibited the PMCA activity by different mechanisms in human platelets.

Blood Platelets↗
PubMed2004

Evaluation of metal-conjugated compounds as inhibitors of 3CL protease of SARS-CoV.

3C-like (3CL) protease is essential for the life cycle of severe acute respiratory syndrome-coronavirus (SARS-CoV) and therefore represents a key anti-viral target. A compound library consisting of 960 commercially available drugs and biologically active substances was screened for inhibition of SARS-CoV 3CL protease. Potent inhibition was achieved using the mercury-containing compounds thimerosal and phenylmercuric acetate, as well as hexachlorophene. As well, 1-10 microM of each compound inhibited viral replication in Vero E6 cell culture. Detailed mechanism studies using a fluorescence-based protease assay demonstrated that the three compounds acted as competitive inhibitors (Ki=0.7, 2.4, and 13.7 microM for phenylmercuric acetate, thimerosal, and hexachlorophene, respectively). A panel of metal ions including Zn2+ and its conjugates were then evaluated for their anti-3CL protease activities. Inhibition was more pronounced using a zinc-conjugated compound (1-hydroxypyridine-2-thione zinc; Ki=0.17 microM) than using the ion alone (Ki=1.1 microM).

Amino Acid Sequence↗
PubMed2004

Prevalence and relevance of contact dermatitis allergens: a meta-analysis of 15 years of published T.R.U.E. test data.

BACKGROUND: The patch test procedure is frequently employed to help determine or confirm the cause of allergic contact dermatitis (ACD). The T.R.U.E. Test has become a global standard and is the commercially available patch test system currently used within the United States. Although many studies report T.R.U.E. Test data, none has measured the overall prevalence and relevance of reactions to the allergens tested by the T.R.U.E. Test. Our objective is to describe the prevalence and relevance of contact dermatitis allergens as tested by the T.R.U.E. Test. METHODS: We conducted a search of the MEDLINE database from 1966 to June 2000 for all publications on the use of the T.R.U.E. Test in the clinical evaluation of ACD in human subjects. Inclusion and exclusion criteria were applied. For each study, we identified and recorded the number of subjects tested, the number of patients with positive reactions, and the number with relevant reactions. Data were analyzed using the SAS system (Cary, NC). RESULTS: Ours is the first study to compile the entire corpus of published T.R.U.E. Test data and to examine these data using meta-analytic techniques. The meta-analysis shows that nickel (14.7% of tested patients), thimerosal (5.0%), cobalt (4.8%), fragrance mix (3.4%), and balsam of Peru (3.0%) are the most prevalent allergens. The 5 least prevalent allergens are paraben mix (0.5%), black rubber mix (0.6%), quaternium-15 (0.6%), quinoline mix (0.7%), and caine mix (0.7%). By contrast, North American Contact Dermatitis Data Group (NACDG) data show that the 5 most prevalent allergens are nickel (14.3%), fragrance mix (14%), neomycin (11.6%), balsam of Peru (10.4%), and thimerosal (10.4%). NACDG data indicate that the prevalence of allergy to cobalt is 9.2%. In order to assess the clinical importance of T.R.U.E. Test allergens, we employ the Significance-Prevalence Index Number (SPIN). Based on SPIN, the most clinically important allergens tested by the T.R.U.E. Test are nickel (SPIN=894), cobalt (266), fragrance mix (158), colophony (141), and thiuram mix (138). CONCLUSIONS: Our results identify the prevalence of common contact dermatitis allergens as tested by the T.R.U.E. Test and are in general agreement with previously published reports using other patch test methods. Over 3700 allergens have been identified as causing ACD, of which the T.R.U.E. Test tests only 23. Thus, the T.R.U.E. Test is a screening test at best. Comparison with NACDG data suggests that clinically important allergens may be missed by the T.R.U.E. Test.

Allergens↗
PubMed1996

Anandamide- and delta9-tetrahydrocannabinol-evoked arachidonic acid mobilization and blockade by SR141716A [N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4 -methyl-1H-pyrazole-3-carboximide hydrochloride].

The purpose of this study was to investigate whether anandamide induces cannabimimetic responses, mainly mobilization of arachidonic acid, in primary cultures of rat brain cortical astrocytes. Confluent monolayer cultures of astrocytes, prelabeled with [3H]arachidonic acid, were incubated with anandamide or delta9-tetrahydrocannabinol (delta9-THC) in the presence or absence of thimerosal, a fatty acid acyl CoA transferase inhibitor and phenylmethylsulfonyl fluoride, an amidohydrolase inhibitor. Anandamide and delta9-THC induced a time- and concentration-dependent release of arachidonic acid in the presence, but not in the absence, of thimerosal. Anandamide- and delta9-THC-stimulated arachidonic acid release was pertussis toxin-sensitive, indicating a receptor/G-protein involvement. A novel and selective cannabinoid receptor antagonist, SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carboximide hydrochloride], blocked the arachidonic acid release, suggesting a cannabinoid receptor-mediated pathway. In astrocytes, the magnitude of anandamide-induced arachidonic acid release was equal to that released by equimolar concentrations of delta9-THC. Furthermore, direct assay of amidohydrolase activity indicated that degradation of anandamide into arachidonic acid and ethanolamine was negligible in cortical astrocytes. Our results suggest that anandamide stimulates receptor-mediated release of arachidonic acid, and the receptor may be the cannabinoid receptor. Astrocytes, containing a cannabinoid receptor and lower or negligible amidohydrolase activity, may be an important brain cell model in which to study the cannabimimetic effects of anandamide at a cellular and molecular level.

Amidohydrolases↗
PubMed1991

Effect of contact lens preservatives on Acanthamoeba.

Single preservatives used in contact lens solutions were evaluated for their effectiveness in killing Acanthamoeba castellanii and Acanthamoeba polyphaga trophozoites and cysts. Preservatives were tested against amoebae at intervals varying from 30 minutes to 24 hours. The preservatives were tested with axenically and nonaxenically grown organisms. Chlorhexidine (0.001% and 0.005%), polyaminopropyl biguanide (0.0015%), benzalkonium chloride (0.001% and 0.004%), and hydrogen peroxide (3%) were very effective preservatives. Lower concentrations of these same preservatives were less effective. Thimerosal (0.001% and 0.004%), sorbic acid (0.1%), potassium sorbate (0.13%), EDTA (0.1%), polyaminopropyl biguanide (0.00005%), and polyquaternium-1 (0.001%) were not effective as tested. However, thimerosal 0.004% when combined in solution with EDTA was effective. Preservatives were more effective when tested against axenically prepared organisms than when tested against co-cultured organisms.

Acanthamoeba↗
PubMed1998

North American Contact Dermatitis Group patch test results for the detection of delayed-type hypersensitivity to topical allergens.

BACKGROUND: Allergic contact dermatitis is a significant cause of cutaneous disease affecting many individuals. Patch testing, when used properly, often provides support for the diagnosis of allergic contact dermatitis. OBJECTIVE: This article reports patch testing results from July 1, 1994, to June 30, 1996, by the North American Contact Dermatitis Group (NACDG). METHODS: Patients evaluated in our patch test clinics were tested with the same screening series of allergens by the use of a standardized patch testing technique. The data from these patients were recorded on a standard computer entry form and analyzed. RESULTS: Forty-nine allergens were tested on 3120 patients. Budesonide was added to the series in July 1995 and tested on 1678 patients. Of these patients, 66.5% had positive allergic patch test reactions, and 57% had at least one allergic reaction that was felt to be clinically relevant to the present or past dermatitis. The 20 screening allergens commercially available to United States dermatologists in the Allergen Patch Test Kit, accounted for only 54.1% of the patients with positive allergic reactions. The additional 30 allergens on the NACDG screening series accounted for 47% of patients with positive allergic reactions. Had the Allergen Patch Test Kit alone been used, 12.4% of all patients tested may have had their disease misclassified as a nonallergic disorder, and an additional 34.4% of all tested patients would not have had their allergies fully defined. Among those patients with positive responses to the supplemental allergens, 81% of the responses were of present or past relevance. The 12 most frequent contact allergens were nickel sulfate, fragrance mix, thimerosal, quaternium-15, neomycin sulfate, formaldehyde, bacitracin, thiuram mix, balsam of Peru, cobalt chloride, para-phenylenediamine, and carba mix. The present relevance varied with the specific allergen from 10.7% (thimerosal) to 85.7% (quaternium-15). Among newer allergens, methyldibromoglutaronitrile/phenoxyethanol (cosmetic preservative) caused positive allergic reactions in 2% of the patients; tixocortol-21-pivalate and budesonide (corticosteroids), in 2.0% and 1.1% of the patients, respectively; and ethylene urea/melamine formaldehyde mix (textile resin), in 5% of the patients. CONCLUSION: The usefulness of patch testing is enhanced with the number of allergens tested, because allergens not found on the commercially available screening series in the United States frequently give relevant allergic reactions.

Allergens↗
PubMed2001

Hormonal stimulation of proline synthesis in the fat body of the fruit beetle, Pachnoda sinuata, is calcium dependent.

The role of calcium in the transduction of the hyperprolinaemic signal of the endogenous neuropeptide Mem-CC was investigated in the cetoniid beetle Pachnoda sinuata using in vivo and in vitro methods to measure changes in the concentration of proline and its precursor alanine. Extracellular calcium is necessary for maximal stimulation of proline synthesis at saturating doses of Mem-CC (0.3 nM) in vitro. This effect depends on the dose of Ca(2+): maximal proline synthesis of 2.1 micromol mg(-1) protein h(-1) was stimulated by Mem-CC at calcium levels of 0.5 mM, and the EC(50) was 0.16 mM. Using the ionophore A 23187 in vivo and in vitro, we demonstrated that the extracellular calcium acts, via an influx into the cell, on the stimulation of proline production and alanine consumption. The release of calcium from intracellular sources is part of the signalling process: the agent thapsigargin, which inhibits the Ca(2+)-ATPase, is able to stimulate proline synthesis in vivo and in vitro. Thimerosal, however, which triggers the release of calcium from IP3-sensitive stores in the endoplasmic reticulum, had no influence on proline production nor alanine consumption, indicating that inositolphosphates are not part of the transduction of the hyperprolinaemic signal of Mem-CC. Both substances, thapsigargin and thimerosal, stimulate calcium entry in vitro from the medium (similar to Mem-CC), which indicates that a capacitative calcium entry takes place. Neither the entry of extracellular calcium nor the release from the endoplasmic reticulum, however, are alone sufficient for a full stimulation of proline synthesis in vitro. The results of the present study suggest that calcium from extra- as well as from intracellular sources is part of the second messenger system for the transduction of the hyperprolinaemic signal of Mem-CC in the fat body of P. sinuata. Calcium acts most likely via the elevation of cAMP levels: the concentration of this cyclic nucleotide in the fat body during in vitro incubation was elevated by 487% by Mem-CC in the presence of calcium, while the increase was only 122% when calcium was absent.

Animals↗
PubMed1995

Effect of oxidized glutathione and temperature on inositol 1,4,5-trisphosphate binding in permeabilized hepatocytes.

The effect of oxidized glutathione (GSSG) on inositol 1,4,5-trisphosphate (IP3) binding and the activity of IP3-gated Ca2+ channels was examined in permeabilized hepatocytes. The permeability properties of the channel were measured by using Mn2+ quenching of compartmentalized fura-2 at 37 degrees C and at 4 degrees C for comparison with IP3-binding measurements. GSSG (2 mM) increased the IP3-sensitivity of Mn2+ quenching, consistent with previous studies based on Ca(2+)-release measurements [Renard, Seitz and Thomas (1992) Biochem. J. 284, 507-512]. Measurements of [3H]IP3 binding were made at 4 degrees C after preincubation of permeabilized hepatocytes at 37 degrees C in the absence or presence of GSSG. Under these conditions GSSG stimulated IP3 binding by increasing the number of binding sites without changing the Kd. This effect was observed in the absence or presence of Ca2+, but was abolished when the preincubation with GSSG was carried out at 4 degrees C. Thimerosal also stimulated [3H]IP3 binding, but this effect was mediated both by an increase in the maximum number of binding sites and by a decrease in the Kd. The effects of thimerosal and GSSG were not additive. Further analysis of the effect of GSSG revealed that preincubation of permeabilized hepatocytes at 37 degrees C results in a progressive loss of [3H]IP3-binding sites that can be prevented and reversed by inclusion of GSSG. A parallel loss of IP3-sensitive Mn(2+)-quenchable stores was observed after incubation at 37 degrees C, and this could also be reversed by adding back GSSG. The loss of IP3 binding was not the result of IP3-receptor proteolysis, as judged by Western blotting of immunoreactive protein. The sensitivity of [3H]IP3 binding in permeabilized hepatocytes to varied ratios of GSSG and GSH suggests that the IP3 receptor responds to an oxidized redox environment such as that found in the lumen of the endoplasmic reticulum. GSSG had no direct effect on the ligand-binding activity of detergent-solubilized and partially purified IP3 receptors. We conclude that GSSG exerts an indirect effect on the IP3 receptors in permeabilized hepatocytes by preventing a temperature-dependent loss of IP3-binding sites. We suggest that the hepatic IP3 receptors may interact with a thiol-disulphide oxidoreductase that utilizes GSSG as a substrate and prevents inappropriate unfolding of the ligand-binding domain occurring after incubation of the receptor at 37 degrees C in vitro.

Animals↗
PubMed2003

Intrathecally applied flurbiprofen produces an endocannabinoid-dependent antinociception in the rat formalin test.

It is generally accepted that the phospholipase-A2-cyclooxygenase-prostanoids-cascade mediates spinal sensitization and hyperalgesia. However, some observations are not in line with this hypothesis. The aim of the present work was to investigate whether different components of this cascade exhibit nociceptive or antinociceptive effects in the rat formalin test. Intrathecal (i.th.) injection of prostaglandin E2 (PGE2) induced a dose-dependent antinociceptive effect on the formalin-induced nociception. Furthermore, thimerosal, which inhibits the reacylation of arachidonic acid thereby enhancing arachidonic acid levels, had an antinociceptive effect rather than the expected pronociceptive effect when given i.th. While the phospholipase A2 inhibitor methyl arachidonyl fluorophosphonate (MAFP; i.th.) had a significant antinociceptive effect, its analogue palmitoyl trifluoromethyl ketone (PTFMK; i.th.) had no significant effect on the formalin-induced nociception. However, MAFP, but not PTFMK, showed a cannabinoid CB1 agonistic effect as shown by the inhibition of electrically evoked contractions of the vas deferens isolated from CB1 wild-type mice but not of that from CB1 knockout mice. The antinociceptive effect of MAFP was completely reversed by the CB1 receptor antagonist AM-251 (i.th.), thus attributing such effect to its CB1 agonistic effect. Moreover, the antinociceptive effect of the cyclooxygenase inhibitor, flurbiprofen (i.th.) was reversed by the co-administration of AM-251, but not by PGE2. Finally. the combination of phenylmethylsulfonyl fluoride (PMSF; intraperitoneal), which inhibits the degradation of anandamide through the inhibition of fatty acid amidohydrolase, with thimerosal (i.th.) produced a profound CB1-dependent antinociception. The present results show that endocannabinoids play a major role in mediating flurbiprofen-induced antinociception at the spinal level.

Analgesics↗
PubMedDate not supplied

Patch testing in children, adults, and the elderly: influence of age and sex on sensitization patterns.

Patch testing was done on 2776 consecutive patients (76.5% female) with a locally revised standard series of 34 contact allergens and the results analyzed for age- and gender-specific differences. At least one positive epicutaneous test reaction occurred in 48.9% of patients. Nickel (20.9%), ethylmercuric chloride (13.2%), thimerosal (11.8%), fragrance mix (9.3%), metallic mercury (8.9%), palladium (5.8%), balsam of Peru (3.8%), copper (3.7%), cobalt (3.3%), and chromium (2.3%) were the 10 most important sensitizers. The following tested allergens with sensitization rates of more than 1% were not part of the usual standard series: ethylmercuric chloride, metallic mercury, copper, propolis (1.3%), propylene glycol (1.0%). Reactions to nickel, cobalt, and palladium, but not to chromium, were significantly more abundant in females (p < 0.002, chi-squared test). The overall sensitization rate was highest in children less than 10 years old (62%) and decreased steadily, to be lowest among patients more than 70 years old (34.9%). The rate of positive reactions to nickel and thimerosal decreased with age, while fragrance mix and metallic mercury stayed at the same level through all age groups.

Adolescent↗
PubMed2001

Dental metal allergy in patients with oral, cutaneous, and genital lichenoid reactions.

BACKGROUND: The subject of lichen planus (LP) and dental metal allergy long has been debated. An overwhelming majority of the existing literature focuses on mercury and gold salts in relation to oral lichen planus. OBJECTIVE: Our objective was to expand current knowledge regarding LP and lichenoid lesions (LL) and dental metal allergy by investigating more metals and investigating cutaneous and genital disease in addition to oral disease. METHODS: Fifty-one patients with known LP or LL were patch tested to a series of dental metals. Patients chose to replace their dental metals or make no revision. A telephone survey was conducted after 1 year to determine disease state. RESULTS: Thirty-eight of 51 patients (74.5%) had at least 1 positive reaction. Twenty-five of 51 patients (49.0%) showed sensitivity to at least 1 mercurial allergen. Prevalence data for patients patch tested by the North American Contact Dermatitis Group (NACDG) from 1996 to 1998 was available for chromate, cobalt, gold, nickel, and thimerosal. The prevalence of positive reactions was higher in our group than in the NACDG group for all 5 of these allergens, and statistical significance was achieved for chromate (P = .028), gold (P = .041), and thimerosal (P = .005). Of patients who had a positive patch test reaction to 1 or more metals, 100% (9 of 9) reported improvement after metal replacement, whereas 62.5% (15 of 24) reported improvement without metal replacement. CONCLUSION: Sensitization to dental metals is more common among LP and LL patients than in routinely tested patients, and might be an etiologic or triggering factor in the disease.

Adolescent↗
PubMed1996

The role of ryanodine-sensitive Ca2+ stores in the Ca2+ oscillation machine of human oocytes.

This study was undertaken to localize ryanodine-sensitive Ca2+ stores in human oocytes and to evaluate their role in the Ca2+ oscillations responsible for oocyte activation at fertilization. The addition of ryanodine provoked a Ca2+ discharge from stores localized throughout the ooplasm with the exception of the cortical and subcortical peripheral regions. The ryanodine-induced discharge was typically followed by a short series of Ca2+ oscillations that only involved the cytoplasmic region populated by the ryanodine-sensitive stores. In contrast, the Ca2+ oscillations induced by the thiol reagent thimerosal or by spermatozoa at fertilization were of a much longer duration and also involved ryanodine-insensitive stores. Presumably, these ryanodine-insensitive stores are sensitive to inositol 1,4,5-trisphosphate (InsP3). The addition of ryanodine to oocytes during ongoing thimerosal- or sperm-induced Ca2+ oscillations inhibited the oscillations. These data suggest a co-operation between the ryanodine-sensitive and ryanodine-insensitive stores in maintaining the sperm-induced Ca2+ oscillations. In this two-store oscillation model, each periodic [Ca2+]i increase is triggered by a Ca2+ discharge from the peripheral, InsP3-sensitive stores inducing Ca(2+)-induced Ca2+ release from the ryanodine-sensitive stores. However, the pacemaker frequency of the Ca2+ discharges from the InsP3-sensitive stores is conditioned by the actual physiological state of the ryanodine-sensitive stores.

Calcium↗