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An unusual case of systemic sclerosis occurring in a patient exposed to the vinyl chloride monomer (VCM) is presented. The dermatological aspects of vinyl chloride disease (VCD) are outlined and the mechanisms of pathogenesis discussed.
The opercular epithelium of Fundulus heteroclitus contains typical gill chloride-secreting cells at the high density of 4 X 10(5) cells per square centimeter. When isolated, mounted as a membrane, and short-circuited, it actively transports chloride ions from the blood side to the seawater side of the preparation. This preparation offers a useful approach to the study of osmoregulation in bony fishes.
An in vivo study of rats given a dominant lethal dose of methylmercury chloride (MMC) or mercuric chloride (HgCl2) was conducted to elucidate the rapid biotransformation of essential elements. The elements were measured by inductively coupled plasma atomic emission spectrometry. For the rat brain Zn concentrations were higher in the MMC group than in the HgCl2 and control groups. The highest Cu concentration was found in HgCl2 dosed rat liver. For the rat kidney the highest Zn concentration was seen in the MMC group. From principal component analysis on the time dependent behaviour of each element in rat organs, characteristics specific to Cu in the liver and kidney and Mn in the brain were found after exposure to HgCl2 and Ca and Zn in the brain after exposure to MMC.
Based on results from two previous studies where an excess of melanomas was found in a cohort of workers exposed to vinyl chloride (VCM), a follow up of the incidence of cancer in the same cohort of 428 workers was carried out to scrutinize whether or not the excess could be confirmed by new cases. The total number of deaths in the study group from 1953 to the end of 1993 was 132 v 141 expected, and the total number of incident cancer cases was 56 v 57 expected. There were 11 cases of lung cancer v eight expected, seven cases of melanomas v 2.07 expected, and two cases of thyroid cancer v 0.34 expected. Five of the seven melanoma cases had occurred in the group that had been most heavily exposed to VCM v 0.7 expected. In the present follow up we also found five cases of the spinocellular cancer of the skin v 1.7 expected. Out of these five cases four were diagnosed after 1984. Two of the five cases v 0.7 expected had occurred in the most heavily exposed group. The total number of skin cancers (melanomas and spinocellular cancers) were 12 v 3.7 expected. There was one new case of melanoma between 1985 and 1993 v 0.7 expected. Hence, the strength of the relation between the observed and expected number of cases was reduced compared with the last follow up, and does not strengthen the previously indicated causal relation between exposure to VCM and development of malignant melanoma. There was no excess of testicular cancers in this study. The present results may indicate that occurrence of spinocellular skin cancer could bear some relation to work in the manufacture of polyvinyl chloride (PVC). Confirmation is needed from studies on other cohorts exposed to VCM.
Exposure of mice to 1000 ppm of vinyl chloride (VC), 6 hr/day, 5 days/week, caused some acute deaths with toxic hepatitis and marked tubular necrosis of the renal cortex. Starting the sixth month, mice exposed to 1000, 250, or 50 ppm of VC became lethargic, lost weight quickly, and died. Only a few mice exposed to 50 ppm survived for 12 months. Pulmonary macrophage count was elevated in some mice. There was a high incidence of bronchiolo-alveolar adenoma, mammary gland tumors including ductular adenocarcinoma, squamous and anaplastic cell carcinomas with metastasis to the lung, and hemangiosarcoma in the liver, and, to a lesser extent, in some other organs. The incidence of these tumors quickly increased, and the severity was in direct proportion to the levels of VC and the length of exposure. Malignant lymphoma involving various organs was observed in a few mice. Rats were more resistant to the toxic effects of VC. Exposure to 1000 ppm slightly depressed the body weight of the females. Exposures of 250 or 1000 ppm caused a number of deaths and hemangiosarcoma in the liver starting the ninth month. Most rats with hepatic hemangiosarcoma also developed hemangiosarcoma in the lung. Hemangiosarcoma occasionally occurred in other tissues of one or two rats exposed to 50 ppm or higher level of VC. Exposure of mice to 55 ppm of vinylidene chloride (VDC) also caused a few acute deaths and a few hepatic hemangiosarcomas. Inflammatory, degenerative, and mitotic changes occurred in the liver. No mouse exposed to VDC developed any mammary gland tumors. Several mice had bronchioloalveolar adenoma. Exposure of rats to 55 ppm of VDC slightly depressed the body weight. Hemangiosarcoma occurred in the mesenteric lymph node or subcutaneous tissue in two rats.
Eleven people accidentally inhaled a significant amount of a gaseous mixture of hydrogen chloride, phosphorus oxychloride, phosphorus pentachloride, oxalyl chloride, and oxalic acid. Clinical observations and laboratory tests were recorded from the time of admission throughout hospitalization. The main abnormalities were found in the respiratory tract and consisted of clinical and physiologic evidence of obstruction of the airways, mild interstitial and alveolar edema, a defect in diffusion, and inequalities of ventilation and perfusion that produced hypoxemia. All of these cleared within a short time.
The quantitative behaviour of Streptococcus mutans, Streptococcus sanguis and Streptococcus salivarius has been examined in initial findings and after application of 0.4% zinc chloride solution. After a 7 day rinsing the number of colony developing units of the species Streptococcus mutans and Streptococcus sanguis in the plaque decreased to about 30% of the determined initial values. The proportions of the species Streptococcus mutans and Streptococcus sanguis in the total streptococcus flora of the dental plaque were not changed by zinc chloride solution. The percentage of the Streptococcus salivarius increased significantly from 1% to 4% of the total number of streptococci.
The chemical form of mercury reactive by the histochemical technique was studied by using rats and mice treated with mercuric chloride (HgCl2) and methyl mercury chloride (MeHgCl). Mercury granules were demonstrated histochemically in the brain of HgCl2-treated rats with higher levels of inorganic mercury. However, mercury granules were not demonstrated in the brain of MeHgCl-treated rats in spite of a considerably high organic mercury level. In rats and mice with significant biotransformation of injected MeHg to inorganic mercury, the appearance of the peak inorganic mercury level and mercury granules in the brain seemed to occur on the same day. These results suggested that mercury granules in the brain represent inorganic mercury, but not organic mercury. In the brains showing mercury granules, the lowest level of inorganic mercury was 0.12 micrograms/g in HgCl2-treated rats, 0.14 micrograms/g in MeHgCl-treated rats, and 0.12 micrograms/g in MeHgCl-treated mice. These values were similar to the level of inorganic mercury in the brain from human autopsy cases. Mercury granules were demonstrated histochemically in nerve cells, choroid plexus and phagocytes in the brain of both HgCl2-and MeHgCl-treated rats, and in ependyma of MeHgCl-treated rats. The level of inorganic mercury of the brains showing mercury granules in phagocytes was lower in MeHgCl-treated rats than in HgCl2-treated rats. The numbers of mercury granules in nerve cells increased with the rising level of inorganic mercury in the brain of MeHgCl-treated rats.
The stability of milrinone in 0.45% and 0.9% sodium chloride injections and in 5% dextrose injection in glass and plastic containers was studied. Admixtures containing milrinone 0.2 mg/mL were prepared in three 500-mL glass containers, three 500-mL polyethylpolypropyl copolymer plastic containers, and three 1-L flexible plastic containers of each solution. Milrinone content was determined by high-performance liquid chromatography at intervals during 72 hours of storage at room temperature; one sample of each solution and container type was protected from light. Duplicate assays of each sample were performed, and samples were observed for visual and pH changes. In all samples milrinone concentrations were more than 97% of the initial concentration. No changes in pH or appearance occurred. Milrinone at a concentration of 0.2 mg/mL is stable for 72 hours at room temperature in 0.45% and 0.9% sodium chloride injections and in 5% dextrose injection in glass or plastic containers.
Increasing data suggest that mitochondrial dysfunction may be an important early component of nephrotoxin-induced changes in renal cell function and viability. This study was designed to obtain more detailed information about the effects on several basic bioenergetic parameters of the direct interaction of Hg2+ with renal cortical mitochondria in vitro as a necessary prelude to studies of mitochondrial functional changes after treatment with mercuric chloride in vivo. Beginning at a threshold level of 2 nmol of Hg2+/mg of mitochondrial protein, Hg2+ induced marked stimulation of State 4 respiration, mild inhibition of State 3 respiration, and 2,4-dinitrophenol uncoupled respiration, a striking increase in atractyloside-insensitive ADP uptake and stimulation of both basal- and Mg2+-activated oligomycin-sensitive mitochondrial ATPase activity. These effects of Hg2+ could be prevented and reversed by the sulfhydryl reagent dithioerythritol and by albumin but were not affected by Mg2+. Detailed studies on the addition of HgCl2 to the preparation at different stages of the mitochondrial isolation procedure demonstrated that the presence of other proteins decreased mitochondrial Hg2+ binding, that the Hg2+ was not readily washed off the mitochondria by nonprotein-containing solutions, and that prolonged exposure of mitochondria to Hg2+ during the isolation procedure did not markedly alter its functional effects or their reversibility as assessed on the final mitochondrial preparation. These data provide an important basis for critically assessing the changes in function of mitochondria isolated after in vivo treatment with mercuric chloride.
A total of 125 sputum specimens, collected in the field, were homogenised, aliquoted in sterile universal containers and randomly allocated to the cetylpyridinium chloride - sodium chloride (CPC-NaCl) method and sodium hydroxide (NaOH) method for culture of tubercle bacilli. After storage for 8 days at ambient temperature in the field laboratory at Thiruvallur, the aliquots were transported to the main laboratory at Madras where they were processed for culture by the respective methods. The yield of positive cultures in the CPC-NaCl (31/125) method was only marginally better than that in the NaOH method (27/125) (95% CI being-3.4 to 9.8%), while the contamination of cultures was significantly less in the CPC-NaCl method (3/125) than in the NaOH method (12/125) (95% CI being 2.2 to 12.2%). As the CPC-NaCl method has advantages over the NaOH method in reducing contamination, in augmenting the yield of positive cultures and also in its simplicity, it can be applied in field studies.
Polyvinyl chloride, of all the plastic polymers, has been implicated primarily in causing the most serious problem in fire fighting today because it releases hydrogen chloride gas when burning. One hundred seventy fire fighters who experienced symptoms from its toxicity have been studied from 1970 to 1975. One died.
Urinary extracts (in methylene dichloride) of subjects on high sodium-chloride (NaCl) intake produce net Cl- efflux (active transport) in isolated short-circuited frog skin. Activity is not found in the urine of NaCl-deprived normal subjects or NaCl-loaded subjects with adrenal insufficiency. These findings suggest that presence of an adrenocortical steriod which participates in adaptation to high salt intake. We describe here a lipid-soluble factor extracted from urine of chronically salt-loaded subjects which stimulates active Cl- transport in isolated frog skin. Our findings indicate that the factor is of adrenal origin and that it induces active ion transport in the direction opposite to that stimulated by the adrenal hormone, aldosterone. Aldosterone produces NaCl conservation in states of salt deprivation. We expect this new factor to produce NaCl excretion in states of excess salt ingestion.
Four macrotricyclic cage hosts which feature four positive binding sites oriented toward the center of the intramolecular cavity are presented as promising candidates for anion receptors and they have been expected to play a important role in the selective encapsulation of the halide ion Cl- or Br . The complementarity between a macrotricyclic quaternary ammonium ion and Cl- was achieved by fine-tuning of the four ammonium nitrogen atoms and the endocyclic methylene groups. The cage hosts [R4N4(C5H10)4(C6H12)2]4+ (abbreviated as [556]) showed perfect encapsulation of all chloride ions in acetonitrile at 0 < r= ([Cl-]o/[[556]]o) < or = 1 within the sensitivity of the 1H NMR spectra in combination with a rather slow chemical exchange of the Cl- ion in an encapsulation/decapsulation equilibrium with [556]. Further, the selective encapsulation of all the chloride ions into [556] cage occurs unambiguously at r = 1 in the presence of equimolar amounts of Br-. The structural complementarity of the newly designed [556] host prevails over the Hofmeister-series restraints determined by differences in Gibbs free energy of halide anion solvation.
An ab initio molecular dynamics method was used to compare the ionic dissolution of soluble sodium chloride (NaCl) in water clusters with the highly insoluble silver chloride (AgCl). The investigations focused on the solvation structures, dynamics, and energetics of the contact ion pair (CIP) and of the solvent-separated ion pair (SSIP) in NaCl(H(2)O)(n) and AgCl(H(2)O)(n) with cluster sizes of n = 6, 10 and 14. We found that the minimum cluster size required to stabilize the SSIP configuration in NaCl(H(2)O)(n) is temperature-dependent. For n = 6, both configurations are present as two distinct local minima on the free-energy profile at 100 K, whereas SSIP is unstable at 300 K. Both configurations, separated by a low barrier (<10 kJ mol(-1)), are identifiable on the free energy profiles of NaCl(H(2)O)(n) for n = 10 and 14 at 300 K, with the Na(+)/Cl(-) pairs being internally solvated in the water cluster and the SSIP configuration being slightly higher in energy (<5 kJ mol(-1)). In agreement with the low bulk solubility of AgCl, no SSIP minimum is observed on the free-energy profiles of finite AgCl(H(2)O)(n) clusters. The AgCl interaction is more covalent in nature, and is less affected by the water solvent. Unlike NaCl, AgCl is mainly solvated on the surface in finite water clusters, and ionic dissolution requires a significant reorganization of the solvent structure.
The photodegradation of 6-hydroxy-10-chlorobenzo[c]quinolizinium chloride (MPB-07), a new activator of the transmembrane conductance regulator chloride channel, was studied in aqueous solutions exposed to artificial daylight (2300 Lux intensity). Various conditions of pH, concentration, and temperature were used. MPB-07 concentration was determined at regular time intervals by reversed-phase HPLC. MPB-07 stability was also studied at pH 7.4 in the dark. Results showed that in all the conditions tested MPB-07 underwent rapid photodegradation, apparently following first-order kinetics. Rate constants were dependent on the initial MPB-07 concentration, temperature, and pH. At pH 7.4, and for concentrations from 1 to 125 microM, half-lives ranged from 0.681 +/- 0.047 to 4.54 +/- 0.28 h. The Arrhenius plot was linear and activation energy was calculated to be 20.7 kJ x mol(-1). Analysis by chemical ionization-mass spectrometry showed that the chlorine atom of the MPB-07 molecule might be replaced by an OH group during the photodegradation process. In the dark, MPB-07 in solutions at pH 7.4 was found to be stable over a 6-week period. In conclusion, MPB-07 is a highly photolabile molecule that should be carefully protected from light when used.
The intestinal transfer of two poorly absorbed quaternary ammonium drugs, hexamethonium chloride (I) and pralidoxime chloride (II), in the presence of various organic and inorganic anions was investigated in the rat using a modified in situ gut technique. The results were in agreement with those of the conventional in situ loop and plasms drug level techniques. Of the anions investigated, cholate, desoxycholate, taurocholate, phoscholate, dehydrocholate, and hyodesoxycholate had the greatest effect on increasing the amount and rate of disappearance of I. Similarly, the amount and rate of disappearance of II were enhanced markedly in the presence of phoscholate and trichloroacetate. The effect of cholate and phoscholate was investigated in detail. The membrane permeability and histological studies indicated that these anions may compromise the structural integrity of the membrane tissue, thus enhancing drug transfer.
Mixture toxicity studies in dual combinations for three metals, tributyltin chloride, dibutyltin dichloride, and tin chloride, and one experiment using all chemicals were performed using the bioluminescent marine bacterium Vibrio harveyi as the test organism in a direct toxicity test procedure. Combination toxicity was evaluated using an additive index equation method and two isopleth procedures, isobole plot and isobologram. Additive index values were determined at both estimated effective median concentration (EC50) and one-third EC50 values for each dual combination and all three chemicals for one-third EC50 values. Isopleths employed chemical combinations at 20% intervals of the EC50 concentrations. Additive index values for various mixtures were either additive or antagonistic (less than additive). Isobolograms for all mixtures were descriptively additive or synergistic (greater than additive). Isobole plots were also descriptively additive or synergistic, although a few measurements were statistically different for synergism. Statistical evaluation between mixtures and single values, using the z test, were in some cases different at the 5% level. Bioluminescent counts were determined to be normally distributed using a statistical test for small sample numbers at the 1% level. Evaluation for outliers, using the Dixon test, was also performed and found one mixture to have an outlier. This single outlier had no influence on the combined toxicity results. The use of low-cost and rapid bioluminescent microbial toxicity tests for mixture studies is discussed.