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Hepatic cholesterol biosynthesis from acetate-1-14C, hepatic cholesterol level and accumulation of mercury into various tissues were examined following oral administration of methyl- or ethyl-mercury to mice (or rat) at next dosage levels, 80 ppm for 10-19 days, 50 ppm for 30 days and 100 ppm for 15 days. The results obtained were as follows. 1. Hepatic cholesterol biosynthesis was elevated at a dose of 80 ppm and decreased at a dose of 50 and 100 ppm. The change of hepatic cholesterol biosynthesis showed the negative correlation with that of cholesterol level. 2. In comparison between methyl-and ethylmercury, the latter accumulated more than the former in liver and spleen, while the former accumulated more than the latter in kidney, cerebum and skeletal muscle. The administration of ethylmercury caused more decrease of body weight, increase of hepatic cholesterol biosynthesis and hepatic cholesterol level than the administration of methylmercury.

The report deals with the postoperative results of homologous cialit-preserved tendons and ligaments in 237 patients with 281 homologous cialit-preserved transplants. This material proved to be equally effective to the autologous and even superior to it when grafting flexor tendons of the finger.4.7% disturbed woundhealing, 5.2% infections, 5.5% mechanical insufficiency.

Strains of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus harbouring plasmids that confer mercury resistance grew in nutrient broth containing concentrations of phenylmercuric nitrate (PMN) that were inhibitory to isogenic plasmid-less strains. Decimal reduction times of P. aeruginosa and S. aureus in aqueous PMN solution were also increased by the presence of plasmids. The viable count of a plasmid-containing P. aeruginosa strain in Davis and Mingioli's minimal medium (DM) containing 10 μg ml−1 PMN fell by approximately 99% after 5 h. The count then remained constant for two weeks, when growth recommenced. This pattern of death followed by growth was also observed with the P. aeruginosa strain in DM + 10 μg ml−1 thiomersal.

The effect of the administration by methoxyethyl-mercuric chloride (Ceresan) on the activity of phosphatases and esterases of the rat brain was studied. From the observations made in this study it appears that ingestion of Ceresan, a fungicide of wide agricultural application, leads to a considerable increase of activity of many hydrolytic enzymes in the brains of rats treated with this compound. The changes of the histoenzymatic pattern resulting from the administration of this fungicide reveal a significant topographical differentiation.

Treatment of hog gastric microsomes with the sulfhydryl reagent, thimerosal (ethylmercurithiosalicylate), produced differential effects on the K+-ATPase and the K+-stimulated p-nitrophenylphosphatase activities. For example, exposure to 2 mM thimerosal for 3 min severely reduced the activity of K+-stimulated ATPase, while K+-p-nitrophenylphosphatase activity was enhanced 2- to 3-fold. Higher concentration of thimerosal, or longer incubation times, also led to inhibition of K+-p-nitrophenylphosphatase. The activated state of p-nitrophenylphosphatase could be sustained by a 20-fold, or greater, dilution of treated membranes, and could be reversed by reduction of membrane SH groups by exogenous thiols. Significant activation of K+-p-nitrophenylphosphatase was not produced by p-chloromercuribenzene sulfonate, p-chloromercuribenzoate or mersalyl; however, ethyl mercuric chloride had qualitatively similar activity effects as thimerosal. Kinetics of K+-p-nitrophenylphosphatase for thimerosal-treated membranes were altered as follows: V increased; Km for p-nitrophenylphosphate unchanged for Ka for K+ increased. ATP, which is a potent inhibitor of K+-p-nitrophenylphosphatase activity in native membranes (KI approximately 200 microM). These data suggest that there are multiple SH groups which differentially influence the gastric K+-stimulated ATPase activity. Defined treatments with thimerosal are interpreted as an uncoupling of the K+-stimulated phosphatase component of the enzyme (for which p-nitrophenylphosphatase is a presumed model reaction). Such differential modifications can be usefully applied to the study of partial reactions of the enzyme and their specific role in the related H+-transport reaction.

A histochemical study concerning the activity of phosphatases and esterases of the brain has been undertaken in rats experimentally intoxicated by the fungicide ethyl-mercury-p-toluenesulfanilide (EMTS). The results have shown that compared with other mercury compounds, both organic and inorganic ones, such as corrosive sublimate and calomel, EMTS proved to be a less induced of alterations in the activity of cerebral hydrolases. The brains of animals intoxicated by EMTS revealed a notable decrease of ATP-ase and acid phosphatase activity as well as a moderate drop of AChE activity. Instead, the neuronal TPPase activity was distinctly elevated. Degenerative changes of neurons were observed in various regions of the experimental brains, the pyramidal cells of the Ammon's horn being affected most severely.

The establishment of neuronal cell lines from the central nervous system is greatly facilitated by the use of the ethyl mercurial compound, thimerosal. When used as a selecting agent in primary cultures this drug eliminates fibroblasts and other non-neuronal cells. The selectivity of the drug was established using several well-characterized clonal cell lines of different origin. Two idependently-derived clones selected by this method were characterized by several criteria, including morphology and electrical excitability.

The aim of our study was to evaluate the prevalence of thimerosal allergy in subjects free of dermatitis. 256 recruits, selected by the Military Health Authorities as healthy subjects, without dermatitis or ocular defects, underwent allergological examination. The percentage of sensitization observed (6.25%) was compared to that found among 2150 patients, consecutively admitted to the Allergological Service of our Department, with suspected allergic dermatitis. Here we found 76 positivities (3.53%). Contact sensitization to ammoniated-mercury is lower among thimerosal-negative subjects (1.88%) than among both the healthy group of thimerosal-positive subjects (12.5%) and thimerosal-positive patients (11.84%). In the group of 76 positive patients it was not possible to relate the sensitization to thimerosal to either a particular clinical dermatological picture or to a specific exposure.

Intragastrically administered thimerosal protects against ethanol induced ulceration with an ID50 of 1.6 mg/kg body weight. In contrast, intravenously administered thimerosal exhibits an ID50 of greater than 30 mg/kg. The antiulcerogenic effect of thimerosal persists for at least 20 hours before allowing gastric ulcers to be induced by ethanol. Intragastric application of thimerosal protects against acetyl salicylic acid induced with an ID50 of 6.8 mg/kg. Stress ulceration is inhibited by thimerosal with an ID50 of 9.2 mg/kg body weight. Investigations on the structure-activity relationship show that it is the mercury moiety and not the thiosalicylic acid moiety which is responsible for the inhibition by thimerosal.

Effects of a mercurial fungicide Agallol 3 widely used for treating sugarcane setts and seed potatoes was studied on Drosophila melanogaster by using parameters such as viability, rate of development, fecundity, hatchability, fertility, and reproductive performance. The chemical was administered by larval feeding. Concentrations of 20, 30, 40, 50 and 60 mg in every 100 ml of food medium were used. In all the concentrations, a significant effect on viability and rate of development was observed. Fecundity was significantly reduced in all the concentrations tested, while hatchability and fertility were not significantly affected. Reproductive performance (mean No. of offspring/pair for a specific period) was highly reduced. Such an effect of an alkoxyalkylmercury fungicide is discussed in the light of the effects caused by other organomercurials.

Mercuric chloride, phenylmercuric chloride, ethylmercuric chloride /0,23 mg Hg/kg/ and methylmercurycyan guanidine /0,46 mg Hg/kg/ were orally administered to rats every second day for 14 weeks. The same doses of the above mentioned mercury compounds were administered alternately with sodium selenite /0,18 mg Se/kg/ to parallel groups of rats at the same time. The level of total and inorganic mercury and of metallothionein was determined. All mercury compounds increased the level of metallothionein in rat kidneys. In rats which received only selenium the level of metallothionein was twice lower in the kidneys in relation to the physiological level of this protein. Selenium eliminated the stimulation of biosynthesis of metallothionein by mercury.

A patient treated his slight score-throat with a thiomersal first aid spray. The next day, because of continued discomfort, he repeated its use. Laryngeal obstruction followed within hours. Emergency tracheostomy produced prompt improvement. Patch testing revealed an extreme spreading reaction to thiomersal. It is our interpretation that the acute laryngeal obstruction was delayed hypersensitivity to this first aid spray.

The ability to determine protein structures by X-ray crystallography is often thwarted by the difficulty of finding isomorphous heavy-atom derivatives. The crystal structure of the site-specific recombinase, resolvase, has been difficult to determine for this reason. We have overcome this problem by introducing 13 single cysteine substitutions into the resolvase catalytic domain using oligonucleotide mutagenesis. The mutant proteins were screened for their ability to crystallize into the orthorhombic form and bind mercury ions isomorphously. Two mutant proteins provided excellent heavy-atom derivatives. This approach should be of general use and particularly helpful in cases where traditional methods have failed to produce a derivative.

A conditioning procedure for chromatographic columns is described in which a benzene solution of mercuric chloride is repeatedly injected onto columns of diethylene glycol succinate; hitherto unparalleled column efficiency is demonstrated for the determination of methylmercuric and ethylmercuric compounds. More than 2700 theoretical plates are attainable, with an absolute detection limit of about 0.2 pg of methylmercuric chloride per injection. After treatment, peak areas are reasonably stable but do tend to decrease about 2–6% over a 4- to 5-h period. The beneficial effects of the treatment are only temporary, however, and it must be repeated daily; the cycle of improvement and subsequent decline in column efficiency and sensitivity seems to be repeatable indefinitely. Fundamental aspects of the chromatography involved and its practical application to the analysis of fish are discussed in detail.

1. 1. The (Na+ + K+) ATPase activity of a rat brain synaptic membrane preparation was inhibited by 10− M thimerosal. 2. 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. 3. All those kinetic characteristics were substantially altered by treatment with thimerosal.

The histological reactions to the implantation of allogenetic incus after conservation in Cialit or after controlled deepfreezing are described. After 5 months the incusses of both conservation technics show the same good tendency of revitalisation. Therefore the controlled deep-freezing technic does not offer an advantage compared to the Cialit conservation method at least for the present state of knowledge.

Suckling rats were exposed to methylmercury chloride or diethylmercury in order to induce chronic sublethal intoxication during the period of active myelination. Doses of 5 mg Hg/kg body weight were injected every second day from 5-25 days of age. The rats were killed at 27-28 days of age, and the brains contained about 1 microgram Hg/g wet weight. No changes in brain weight, myelin content of proteins or phospholipids were found, whereas the cholesterol and galactolipid levels were slightly reduced. The most significant change observed was a decrease in the ratio between alpha-hydroxy fatty acid and the nonsubstituted fatty acid in the myelin cerebrosides. The biochemical changes were less pronounced in the animals given diethylmercury than in animals receiving methylmercury.

The guppy ( Lebistes resticulatus ) and coontail ( Ceratophyllum demersum ) were exposed to water containing 203 Hg-labeled ethylmercuric chloride (EMC). The EMC uptake was related to the time of exposure and the concentration of EMC. Highest concentration of 203 Hg was found in the internal organs of the guppy and the body has the least concentration. The biological half-life of 203 Hg from EMC was approximately between 20 and 23 days. Both organisms are capable of converting the absorbed EMC to inorganic mercury with the coontail having a slightly higher rate (34%) of conversion as compared to the average of 29% for the guppy during a seven-day period. Both organisms accumulated slightly more MMC than EMC from a solution containing the same concentration of EMC or MMC. There was very little conversion of MMC to inorganic mercury by the guppy, indicating the stability of MMC in this organism. The absorbed MMC molecule was also more stable than the EMC in the coontail.

Conversion of human hexosaminidase A to a form having the electrophoretic, immunologic and heat stability characteristic of hexosaminidase B occurs upon incubation with commercial Vibrio cholerae culture filtrates. Purified neuraminidase preparations have no such conversion activity. The conversion factor of Vibrio cholerae culture filtrates is shown not to be neuraminidase by virtue of its heat stability, dialyzability and resistance to Pronase digestion. The conversion factor has been identified as merthiolate, a preservative added to these commercial Vibrio cholerae culture filtrates. Robinson and Stirling (Biochem. J. 107, 321–327, 1968) used a commercial Vibrio cholerae culture fluid (Burroughs Wellcome) containing merthiolate as a source of neuraminidase in their studies on the conversion of hexosaminidase A to a form resembling hexosaminidase B. In light of the results reported here on the effect of merthiolate, their conclusions that hexosaminidase A and hexosaminidase B are glycoproteins differing in the number of sialic acid residues must be reevaluated.

Two organomercurial fungicides, Ceresan containing phenyl mercury acetate and Agallol 3 containing methoxyethyl mercury chloride, were investigated for their mutagenicity in Drosophila melanogaster. The fungicides, administered by both larval and adult feeding techniques, were evaluated for their efficacy in inducing dominant lethals, sex-linked recessive lethals, and II-III translocations in the male germ cells. Both fungicides failed to induce significant dominant lethals, sex-linked recessive lethals, and II-III translocations when administered in the larval diet (P greater than 0.05). But Ceresan in the adult diet brought about a significant increase in the frequency of sex-linked recessive lethals (P less than 0.05). Broodwise analysis revealed that spermatids and spermatocytes were more sensitive than others to all the concentrations of Ceresan and Agallol 3 used. The mutagenic implications of such fungicides in the human environment are discussed.

Pathological manifestations causally related to pesticide poisoning have been described in both surficial and internal tissues of the fishes. Among the various organomercurials are phenyl mercuric acetate, methyl mercuric dicyanidiamide, methoxy ethyl mercuric chloride, methoxy ethyl mercuric silicate etc. Of these, the methoxy ethyl mercuric chloride (MEMC) is used in agriculture as an antifungal seed dressing, and its toxicity is primarily manifest in the Hg/sup 2 +/ ion. This report describes pathogenesis of branchial and renal lesions in the common freshwater fish, Puntius conchonius exposed chronically to sublethal levels of MEMC. Prior to this, alterations in the peripheral blood and metabolite levels in response to experimental MEMC poisoning have been demonstrated in this species.

52 persons who had been operated upon for large eventration by means of Cialit dermatoplasty were re-examined after an interval of 2 to 12 years. After a description of the operating technique, the immediate and then the long-term results are analysed. The quantity of mercury in the blood and the urine of 7 patients never shows an increase that reaches the critical threshold. The figures obtained go down to reference values found in the case of non-exposed persons after 9 months in the blood and 4 months in the urine. A fresh intervention in the case of 3 patients has permitted a histological examination of the cicatrix after Cialit skin transplantation. Analysis confirms the excellent tolerance of the material and its integration with the tissues of the recipient. The interest of this technique in an infected environment is to be emphasized.

Two cases of Morvan's chorea are reported. One of the patients presented the characteristic of having had two attacks, the first after organic mercury preparations, and the second after gold salts for inflammatory rheumatism. The second case had facial fibrillations only, and this was followed by a regressive polyradiculoneuritis one month later. This latter case raises certain diagnostic problems. The existence of a particular type of immuno-allergic tendency could be validly related to a triggering effect of various etiological agents (metals such as mercury or gold salts, or infective agents). The absence of hypotonia, and a regressive course appear to be the characteristics that distinguish fibrillary chorea from the continuous activity syndrome of the muscle fibers described by Isaacs.

The interaction of selenium with methyl mercury, methoxyethyl mercury and mercuric chloride was studied in a 37 days' experiment with rats. Liver, kidney, brain and faeces were analysed for mercury and seleneium at the end of the experimental period. Selenium supplementation increased the retention of mercury in liver, when mercuric chloride was given, in liver and brain when methyl mercury was given, and in all tissues examined when methoxyethyl mercury was given. The Hg/Se molar ratios in the tissues have been calculated and are found to vary considerably.

Sodium ethylmercurithiosalicylate (Merthiolate), used for preservation of buffer solutions, was found to inhibit the antigen-antibody binding reactions in radioimmunoassay systems in a noncompetitive manner. This effect is attributable to the mercury ion per se.

The mercury-tissue-concentrations of implants (structures of the middle ear, bones, cartilage, dura) after preservation in solutions of cialit are mostly independent on preservation conditions, low and seem to be physiological. A positive correlation exists between the weight of the implant and the mercury-tissue concentrations. An enrichment with mercury-ions cannot be stated. The statements do not concern the mercury which is bound on cialit in the implant.

Summary Results of animal experiments on the transplantability of cialite-preserved dura have been presented. Preserved human dura was grafted to the area of the forehead, orbit, upper and lower jaws of 18 rabbits. Specimens were taken for examination between the 8th and 241st day. The dura healed normally and was revitalised. Based on the results of these experiments and on those reported in the literature by other authors, the method of preserving connective tissue in cialite also appears to be suitable for clinical use in the maxillo-facial region.