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Toxic effect of various selenium compounds on the rat in the early postnatal period.

The toxic effect of selenium compounds (sodium selenate, D,L-selenomethionine, D,L-selenocystine, dimethyl selenide, and trimethylselenonium ion) was tested in 10-day old male rats. Increasing doses of the compounds were administered an s.c. injection and control animals were not injected. All compounds tested were lethal. Eye lens cataract was induced by the administration of selenate, D,L-selenomethionine, and D,L-selenocystine, while dimethyl selenide and trimethylselenonium ion failed to cause cataract. The cataractogenic effect of the above compounds may be attributed to their interference with glutathione metabolism.

Animals↗

Contact allergens modulate the expression of MHC class II molecules on murine epidermal Langerhans cells by endocytotic mechanisms.

MHC class II molecules play an important role during the sensitization phase of allergic contact dermatitis. To study the influence of contact allergens on the expression of these molecules by murine epidermal Langerhans cells (LC), we performed a flow-cytofluorometric analysis of the Ia-antigen expression after in vivo application of contact allergens. A distinct decrease in the Ia-antigen expression of the entire LC population was noticed 3 h after in vivo application of the contact allergen 2,4-dinitrofluorobenzene (DNFB). This decrease was transient and balanced 24 h after in vivo application of DNFB. A downregulation was also detectable after in vivo application of the contact allergens 1-chloro-2,4-dinitrobenzene (DNCB), oxazolone, K2Cr2O7, 2,4,6-trinitrochlorobenzene (TNCB), and toxic concentrations of the irritant compound sodium dodecyl sulfate (SDS). In vitro studies showed that freshly prepared as well as 3-d cultured LC downregulated their Ia-antigen expression in the presence of DNFB, which was used as a model compound. This decrease was not inhibited by the MHC class II molecule transport-inhibitor brefeldin A nor by the ionophore monensin. The inhibition of receptor-mediated endocytosis with hypertonic media (0.45 M sucrose) abolished the DNFB-mediated downregulation of Ia-antigen expression. An accelerated clearance of cell-surface-expressed antibody-labeled IA molecules was detectable in the presence of DNFB. Internalization studies carried out with peroxidase-labeled anti-IA-antibody complexes showed remarkable alterations in the intracellular distribution of endocytosed material under the influence of subtoxic concentrations of DNFB, DNCB, K2Cr2O7, and TNCB. The irritant substance sodium dodecyl sulfate (SDS) influenced the intracellular distribution pattern of internalized material only when used in toxic concentrations. An augmented participation of MHC class II molecules in endocytotic processes is mediated by reactive substances like contact allergens and might contribute to the processing and presentation of these compounds.

Allergens↗

Effects of sodium butyrate on proliferation-dependent insulin gene expression and insulin release in glucose-sensitive RIN-5AH cells.

A rat islet tumor subclone, RIN-5AH-T2-B, was cultured with 2 mmol/liter of the proliferation-arresting compound sodium butyrate (NaB). Insulin gene expression and glucose-stimulated insulin release were analyzed and compared with logarithmically proliferating and confluent control cells cultured without NaB. Logarithmically proliferating control cells revealed high insulin gene expression. In the presence of amino acids, these cells showed a dose-dependent insulin response to glucose with a half-maximal and maximal 6.5-fold stimulation by 0.8 and 5.6 mmol/liter D-glucose, respectively. However, as the control cells approached growth arrest, insulin gene expression subsided to below detectability, an occurrence that is associated with decreased insulin release and accumulation of cells in the G1 phase of the cell cycle. In contrast, NaB-arrested cells showed continuous insulin gene expression throughout the experiment. Despite this, insulin release in response to glucose was lost. NaB revealed a biphasic effect on the cell-cycle: after an initial leaky G1 arrest during the first 24 h, the 5AH-B cells were arrested in G2 during the following 3 days. These data suggest that insulin gene expression and glucose-stimulated insulin release are affected by the cell cycle. These glucose-sensitive RIN-5AH-T2-B cells may be useful in studies of insulin secretion and gene regulation.

Animals↗

Ultrastructure of gastric epithelium after exposure to mild environmental agents (sodium nitrate, saprol).

Environmental chemical agents usually affect the human organism in combination rather than alone. The objective of this study was to determine the effect on the gastric mucosa of the herbicide Saprol alone or in combination with the nitroso compound sodium nitrate. We examined the cells of the gastric endocrine system by electronmicroscopy, and recorded the ultrastructural nuclear and cytoplasmic changes. The herbicide Saprol did not significantly change the ultrastructure of the gastric epithelial cells. Marked changes were noted in nuclei, mitochondria, and secretory granules of the gastric endocrine cells after exposure to both Saprol and sodium nitrate. These changes were significantly more severe after the combined exposure than after sodium nitrate exposure alone. The most affected were the vasointestinal polypeptide-producing D1 cells.

Animals↗

Minerals and blood pressure.

The mineral elements sodium, potassium, calcium and magnesium play a central role in the normal regulation of blood pressure. In particular, these mineral elements have important interrelationships in the control of arterial resistance. These elements, especially sodium and potassium, also regulate the fluid balance of the body and, hence, influence the cardiac output. Evidence shows that the present levels of intake of mineral elements are not optimum for maintaining normal blood pressure but predispose to the development of arterial hypertension. Research results suggest that without sodium chloride (common salt) and other sodium compounds being added to the diet arterial hypertension would be virtually non existent. Moreover, blood pressure would not rise with age. In communities with a high consumption of added sodium, a high intake of potassium and, possibly, magnesium seem to protect against the development of arterial hypertension and the rise of blood pressure with age. A marked reduction of sodium intake is effective in treating even severe hypertension. A moderate restriction of sodium intake or an increase in potassium intake exert remarkable antihypertensive effects, at least in some hypertensive patients. Magnesium and possibly also calcium supplements may be effective in reducing blood pressure in some hypertensives. In hypertensive patients treated with drugs sodium restriction and potassium and magnesium supplementation enhance the therapeutic effect, reduce the number and dosage, and lessen the adverse effects of prescribed antihypertensive drugs. Hence, a fall in sodium consumption and increases in potassium and magnesium consumption are useful in preventing and treating arterial hypertension.

Animals↗

Stress associated with road transportation in desert sheep and goats, and the effect of pretreatment with xylazine or sodium betaine.

The present work investigates some clinical, endocrinological, biochemical and haematological variables in desert sheep and goats stressed in the course of individual road transportation, and the influence thereon of pretreatment with an established anti-stressor drug, xylazine HCl, and a test compound, sodium betaine (trimethylglycine). Road transportation for 2h resulted in variable and statistically insignificant increases in heart, pulse and respiratory rates in both control and experimental animals. Transportation stress significantly increased the concentrations of plasma cortisol, and glucose, and decreased that of magnesium. The endogenous thiocyanate concentration was unaffected. The stress also insignificantly decreased the haematocrit (PCV), and the number of lymphocytes, and increased the concentration of haemoglobin. Pretreatment of sheep and goats with xylazine at a single dose of 0.01 mg/kg by the intravenous route significantly ameliorated the effects induced by the stressful stimulus. The effects of pretreatment of the two species with sodium betaine (10 mg/kg) produced variable and insignificant effects.

Adrenergic alpha-Agonists↗

Cytogenetic damage induced in human lymphocytes by four vanadium compounds and micronucleus analysis by fluorescence in situ hybridization with a centromeric probe.

The genotoxicity of four vanadium compounds, sodium metavanadate (NaVO3), ammonium metavanadate (NH4VO3), sodium ortovanadate (Na3VO4) and vanadyl sulfate (SVO5), was evaluated in human lymphocyte cultures using structural and numerical chromosome aberrations, micronuclei, sister-chromatid exchanges and satellite chromosome associations as endpoints. These compounds were not found to increase the frequency of structural chromosome aberrations whereas a significant increase in numerical aberrations, micronuclei and satellite associations was found. Since these results could have been related to a possible mechanism of the action of vanadium as a mitotic spindle poison, the fluorescence in situ hybridization (FISH) technique was applied to the human lymphocyte micronucleus assay, by means of an alphoid centromere-specific DNA probe. The four vanadium salts showed a micronucleus percentage with positive signal (presence of centromere and thus of whole chromosome(s)) that was always higher than 68% at all doses tested. That confirmed the aneuploidogenic potentiality of vanadium.

Cells, Cultured↗

High sensitivity of Salmonella TA102 in detecting hexavalent chromium mutagenicity and its reversal by liver and lung preparations.

The recently developed strain TA102, particularly suited to the detection of oxidative mutagens (Levin et al., 1983), was the most sensitive out of 9 strains of S. typhimurium his- in revealing the mutagenicity of Cr(VI) compounds (sodium dichromate, calcium chromate and chromium trioxide). The rank of sensitivity was the following: TA102, TA100, TA97, TA92, TA1978, TA98, TA1538 and TA1537, TA1535 being the only insensitive strain. Cr(III) compounds (chromic acetate, chromic nitrate and chromic potassium sulfate) were totally inactive with all strains. The direct mutagenicity of Cr(VI) was markedly decreased, through NADPH-requiring mechanisms, by rat-liver S9 fractions and, to a lower extent, by human lung S12 fractions, which supports the hypothesis of a metabolically regulated threshold in chromium pulmonary carcinogenicity.

Animals↗

Sodium metasilicate hypersensitivity in BALB/c mice.

BACKGROUND: Sodium metasilicate (SMS) is a key ingredient for a number of industrial and consumer products. Although little is known about potential for this chemical to cause allergic reactions, a similar silicate compound, sodium silicate, was reported to elicit IgE-mediated contact urticaria. OBJECTIVE: The aim of this study was to evaluate the potential for sodium metasilicate to elicit an allergic response in female BALB/c mice after dermal exposure. METHODS: The primary irritancy assay (IA), local lymph node assay (LLNA), and a mouse ear swelling test (MEST) were used to evaluate the hypersensitivity response elicited by SMS exposure. An evaluation of lymph node subpopulations, cytokine mRNA expression, and serum IgE levels was also conducted. RESULTS: SMS caused significant dermal irritation at concentrations >or=6% and an allergic response after mice were sensitized with 4% SMS then challenged with 6% SMS in the MEST. Lymph node cell proliferation was not observed in the LLNA after treatment with SMS (2% to 6% SMS). Increases in lymph node cellularity, the percentage of B cells, and the expression of certain cytokine mRNAs were observed in mice treated with SMS. Changes in the concentration of serum IgE after SMS treatment, however, were not observed. CONCLUSIONS: SMS appears to elicit a chemical hypersensitivity response in mice, as indicated by the MEST, but not by the LLNA. Increases in auricular lymph node cellularity, the percentage of B cells, and certain cytokine mRNAs support classifying SMS as a weak chemical allergen.

Allergens↗

The effect of crystal imperfections on particle fracture behaviour.

Micronisation of active pharmaceutical ingredients is a process which is sometimes difficult to control. The main purpose of this study was to assess the effect of the pre-existing flaws in the material to be milled. The rate of breakage of four samples of a model compound (sodium chloride), originating from different sources, was determined in a jet mill. It appeared that each type of sodium chloride has a distinct particle rate of breakage and breakage pattern. The numbers of flaws in the different types of sodium chloride have been determined by immersing the sodium chloride particles in a liquid with the same refractive index. This makes the cracks better visible. Microphotographs were made and flaws were counted manually. The study shows that the flaw density has an impact on the fracture behaviour of particles. The degree of fracture tends to increase with increasing flaw density. The paper shows however that the mechanical properties of the material as well as the starting particle size dominate the significance of the impact of flaws on fracture behaviour.

Crystallization↗

Permeability enhancement in Caco-2 cell monolayers by sodium salicylate and sodium taurodihydrofusidate: assessment of effect-reversibility and imaging of transepithelial transport routes by confocal laser scanning microscopy.

The effects of sodium salicylate and sodium tauro-24,25-dihydrofusidate (STDHF) on the aqueous permeability of confluent monolayers of Caco-2 cells were studied. Measurements of transepithelial electrical resistance (TEER) showed a concentration-dependent effect of both compounds after apical incubation for 1 hr. Reductions in TEER resulting from EC50 concentrations (2.8 mM for STDHF; 173 mM for salicylate) were reversible within 5.75 hr. The transpithelial fluxes of two hydrophilic model compounds, sodium fluorescein F (molecular weight 376) and a fluorescein isothiocyanate-labeled dextran (mean molecular weight 4000) was significantly increased by STDHF (2.8 mM). Sodium salicylate (173 mM) only enhanced the transport of sodium fluorescein significantly. At the EC50 concentrations, confocal laser scanning microscopy (CLSM) visualized both fluorescent tracers mainly in the paracellular route. With higher enhancer concentrations (373 mM sodium salicylate and 8 mM STDHF), both transport markers appeared intracellularly as a result of cell death. STDHF rapidly extracted an exogenous lipophilic membrane probe, 5-(N-hexadecanoyl)aminofluorescein (HEDAF), from the apical part of Caco-2 plasma membranes, indicating qualitatively that STDHF interacts with the lipid portion of cell membranes. These results suggest that both sodium salicylate and STDHF can be used to reversibly increase paracellular permeability of Caco-2 cell monolayers, whereby STDHF appears to be advantageous compared to sodium salicylate. By adapting the Costar cell culture system to CLSM, we have shown that this technique is suitable to study membrane interactions qualitatively and for visualizing transport routes of hydrophilic tracers through nonfixed, filter-grown monolayers.

Adjuvants, Pharmaceutic↗

THE DEVELOPMENT IN THE LABORATORY OF RESISTANCE TO SODIUM PENTACHLOROPHENATE IN AUSTRALORBIS GLABRATUS.

Although reports-some of them conflicting-have been published on the development of resistance to molluscicides in species of Oncomelania, little or nothing is known of the potential of pulmonate snails to develop such resistance, in particular to the much-used compound, sodium pentachlorophenate. This paper describes efforts made between 1952 and 1961 to developed increased resistance in two laboratory-reared strains of Australorbis glabratus. Two lines were eventually established from 10 successive generations of survivors of a 24-hour exposure to LD(90) dosages of pure sodium pentachlorophenate. Each line showed an increase of 50% in the 24-hour LD(50) dosage of chemical over that of the parent strain (e.g., from 1.09 p.p.m. to 1.70 p.p.m. for one strain). While this increase seems low in comparison with dosages recommended for application in the field, it does indicate that colonies of A. glabratus with an increased level of resistance to NaPCP can be developed.

Animals↗

Removal of electrolytes from institutionally packaged foods.

Soaking and rinsing resulted in significant (p less than .01) reductions in sodium and potassium concentrations of peeled potatoes and hard-cooked eggs packed in brines containing sodium compounds and packaged for institutional use. In this study, no significant differences (p greater than .01) were found between soaking and rinsing in deionized water and in tap water; however, tap water can vary greatly in sodium and potassium content. Sodium and potassium levels of chopped lettuce dipped in sodium hypochlorite were not significantly (p greater than .01) affected by soaking and rinsing procedures. However, the sodium and potassium levels of the processed lettuce were not high relative to the levels of unprocessed lettuce before soaking and rinsing.

Eggs↗

Nitric oxide inhibits depolarization-induced release of endogenous dopamine in the rabbit retina.

The effect of nitric oxide donor compounds (sodium nitroprusside, hydroxylamine and S-nitroso-N-acetyl-D,L-penicillamine) on depolarization-induced release of endogenous dopamine in the light-adapted, isolated retina of the rabbit was studied by HPLC. All three compounds had the same effect, reducing the amount of dopamine released by up to 90%. The effect was concentration dependent, saturating at 300 microM; it was blocked by the nitric oxide scavenger, mannitol (50 mM), which by itself had no effect on the basal release of dopamine. GABAA receptors were not involved. Possible cellular mechanisms underlying the findings are discussed. It is suggested that the inhibitory interaction between dopamine and nitric oxide could represent a higher order function in the light adaptation process in the retina.

Animals↗

Optimal dithiocarbamate structure for immunomodulator action.

While the commercially available sodium diethyldithiocarbamate (DEDTC) has been used by several groups in the treatment of AIDS patients, chemical evidence suggests that other dithiocarbamates which are more stable at pH 7.4 might prove to be quite superior for this purpose. Of these other compounds, sodium pyrrolidinedithiocarbamate (PDTC) and sodium di-n-propyldithiocarbamate (DPDTC) which have much longer half lives at pH 7.4, are expected to exhibit similar lipophilicity to DEDTC but superior stability towards hydrolysis. They can be expected to be superior to DEDTC, especially for oral administration.

Acquired Immunodeficiency Syndrome↗

Acid and bile salts induce DNA damage in human oesophageal cell lines.

Barrett's oesophagus is an acquired precancerous condition that develops from mucosal injury incurred due to chronic gastro-oesophageal reflux. The aim of this study was to determine if bile and/or acid components of the refluxate can induce DNA damage in vitro. The oesophageal cell lines FLO-1 and HET1-A were exposed to primary bile salts, individually or as a mixture, and the secondary bile salt sodium deoxycholate, in neutral or acidified media. Cells were then examined in the comet assay to measure DNA strand breaks. Cell viability was also monitored. Acidified media induced DNA damage in a pH- and time-dependent manner. The primary bile compounds sodium glycocholate, glycocholic acid, sodium taurocholate and taurochenodeoxycholate, as an equimolar mixture (100 microM), caused a small but significant (P < 0.028) elevation in DNA damage, but only at neutral pH in FLO-1 cells. Sodium deoxycholate (100 microM) caused a significant (P < 0.008) elevation in DNA damage in both cell lines, but again only at neutral pH. These data suggest that specific components of gastro-oesophageal refluxate are capable of causing DNA damage and may participate in the genesis and progression of Barrett's oesophagus via this mechanism.

Barrett Esophagus↗

Ready biodegradability test in seawater: a new methodological approach.

To estimate the persistence of xenobiotic in the environment, a new ultimate mineralization approach for assessing ready biodegradability in seawater has been developed, based on the OECD 301 B guideline for freshwater. a few changes in the currently accepted procedure have been made to adapt the test to seawater. The assays, realized with seawater as test medium and inoculum, give high variability results of biodegradability. To lower this variability a synthetic marine medium joined to a highly concentrated inoculum from a marine aquarium filter have been used. The results reveal (i) a decrease of variability, together with an increase in degradation rate of the tested chemicals due to a better control of inoculum and test medium, and (ii) no difference in easy biodegradable compound (sodium benzoate) biodegradation rate when two marine aquarium inocula are tested. This study demonstrates that the ready biodegradability test developed on synthetic marine medium and inoculum from marine aquarium filter minimizes the effect of the sample location on the biodegradation results of compounds and allows classifying chemicals as a function of their biodegradability.

Aniline Compounds↗