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PubMed1999

The effect of blood on the antiviral activity of sodium hypochlorite, a phenolic, and a quaternary ammonium compound.

OBJECTIVE: To assess the virucidal activity of three disinfectants (sodium hypochlorite, a phenolic, and a quaternary ammonium compound) in the presence and absence of blood. METHODS: Disinfectants at varying concentrations (hypochlorite: 5,000, 500, or 50 ppm; phenolic: 1:10 or 1:128 dilution; quaternary ammonium compound: 1:10 or 1:128 dilution) were added to either saline or whole blood (final concentration, 80% or 20% blood) and mixed. Test organisms included an attenuated vaccine strain of poliovirus type 1 (prototype for relatively resistant hydrophilic viruses) and herpes simplex virus (HSV) type 1 (prototype for relatively susceptible lipophilic viruses). Virus was added to create a viral-blood suspension. Viral survival was tested at room temperature at the following times: 0, 15 seconds, 30 seconds, 1 minute, 2 minutes, 5 minutes, and 10 minutes. A neutralizer stopped the reaction, and virus was assayed using a plaque technique. RESULTS: In the absence of blood, complete inactivation of HSV was achieved within 30 seconds with 5,000 (1:10 dilution of bleach) and 500 (1:100 dilution of bleach) ppm chlorine, 1:10 and 1:128 diluted phenolic (use dilution), and 1:10 and 1:128 diluted quaternary ammonium compound (use dilution). In the presence of 80% blood, only 5,000 ppm hypochlorite, 1:10 phenolic, and 1:10 or 1:128 quaternary ammonium compound were effective. In the absence of blood, complete inactivation of polio was achieved within 30 seconds by 5,000 and 500 ppm chlorine and 1:10 quaternary ammonium compound. In the presence of 80% blood, no solution tested was capable of completely inactivating poliovirus within 10 minutes. CONCLUSIONS: Our data suggest that, in the absence of visible blood, environmental surfaces may be disinfected with a diluted hypochlorite solution (1:10 or 1:100), a phenolic, or a quaternary ammonium compound. Based on our studies using HSV, which has similar susceptibilities to disinfectants as human immunodeficiency virus (HIV), phenolics at their use dilution and 1:100 diluted hypochlorite are unlikely to inactivate HIV or hepatitis B virus reliably in the presence of blood. Hypochlorite at a final concentration of 5,000 ppm (1:10 dilution) should be used to decontaminate blood spills, but, even after decontamination, care should be used to avoid sharps injuries.

Blood↗
PubMed1977

Toxicity and mutagenicity of hexavalent chromium on Salmonella typhimurium.

Four hexavalent and two trivalent chromium compounds were tested for toxicity and mutagenicity by means of the Salmonella typhimurium/mammalian-microsome test. All hexavalent compounds yielded a complete inhibition of bacterial growth at doses of 400 to 800 mug/plate, a significant increase of his(+) revertant colonies at doses ranging from 10 to 200 mug, and no effect at doses of less than 10 mug. The distinctive sensitivity of the four Salmonella strains tested (TA1535, TA1537, TA98, and TA100) suggested that hexavalent chromium directly interacts with bacterial deoxyribonucleic acid by causing both frameshift mutations and basepair substitutions. The latter mutations, which are prevalent, are amplified by an error-prone recombinational repair of the damaged deoxyribonucleic acid. On the average, 1 mumol of hexavalent chromium yielded approximately 500 revertants of the TA100 strain, irrespective of the compound tested (sodium dichromate, calcium chromate, potassium chromate, or chromic acid). The mutagenic potency of the hexavalent metal was not enhanced by adding the microsomal fraction of rat hepatocytes, induced either with sodium barbital or with Aroclor 1254. The two trivalent compounds (chromium potassium sulfate and chromic chloride), with or without the microsomal fraction, were neither toxic nor mutagenic for the bacterial tester strains.

Chromates↗
PubMed1977

Assessment of spermicides by a stripping technique against human spermatozoa.

Fifty-two (52) compounds were tested for spermicidal activity by titration against human spermatozoa. The gradual decrease in mean sperm size was measured against increasing concentration of spermicide and the end-point was taken as the point at which all the peripheral cytoplasm had been removed and only the sperm core of nucleus and tail fibres remained. There were 14 compounds that produced this total effect. All were detergents, of various types, and the effect was purely physical. The most potent compounds caused complete stripping at 0.5-50 pmol/cell and most are already used in spermicidal preparations. A further 11 compounds, including sodium hypochlorite and some phenols, caused partial stripping, while 4 compounds caused sperm swelling. The test was not suitable for assessment of metabolic cell poisons.

Benzalkonium Compounds↗
PubMed1999

Therapeutic effects of LK 423, a phthalimido-desmuramyl-dipeptide compound, on dextran sulfate sodium-induced colitis in rodents through restoring their interleukin-10 producing capacity.

A new phthalimido compound, N-[2-(2-phthalimidoethoxy)acetyl]-L-alanyl-D-glutamic acid (CAS 142489-47-2, LK 423), was examined for its possible activity to modulate levels and species of cytokines in mice carrying a specific inflamed organ. Colonic inflammation was induced in mice by giving 5% dextran sulfate sodium (DSS) solution as drinking water. The capacity of spleen cells obtained from the DSS-inflamed mice to produce interleukin-10 (IL-10) in response to mitogen was significantly reduced when compared with the capacity of spleen cells from intact mice. Treatment of the mice administered DSS by subcutaneous multiple injections with a low dose of LK423 resulted in delaying the progression to full-blown inflammation in the colon. The mitogen-stimulated spleen cells obtained from the LK423-treated mice yielded significantly greater amounts of IL-10 and IL-6 than the untreated DSS group, and the peritoneal cells from the LK423-treated mice produced significantly lower levels of tumor necrosis factor alpha (TNF alpha). Based on this prophylactic effect of LK423 in the murine colitis model, its therapeutic effect was examined in rats in which colitis had been induced by feeding 3% DSS for 12 days. Intracolonic administration of LK423 to these rats for 7 days resulted in diminishing the ulcerative area in the colon. The immunological characteristics of this new compound are discussed from the point of view of its possible application as a therapeutic agent for inflammatory bowel diseases (IBD) and other inflammatory diseases.

Adjuvants, Immunologic↗
PubMed1988

Inhibition of the electrogenic Na,K pump and Na,K-ATPase activity by tetraethylammonium, tetrabutylammonium, and apamin.

The K+-induced hyperpolarization of Na-loaded mouse diaphragm muscle, enzymatic activity of Na,K-ATPase and 3H-ouabain binding to rat brain microsomes was measured in the presence of K+ channel blockers tetraethylammonium (TEA), tetrabutylammonium (TBA) and apamin. TBA, and to a lesser extent TEA in millimolar concentrations, inhibited the electrogenic effect of the Na,K pump, Na,K-ATPase activity, and 3H-ouabain binding. The inhibition of 3H-ouabain binding by TEA or TBA was more evident in the presence of ATP and Na+ ions. Apamin in nanomolar concentrations inhibited the electrogenic effect of Na,K pump and Na,K-ATPase but not the 3H-ouabain binding. The hyperpolarizing effects of insulin and NADH, but not that of noradrenaline, were also prevented by apamin. The inhibition of Na,K pump by TEA and TBA is apparently due to both competition with K+ for a binding site on the Na,K-ATPase and a reduction in the number of transporting sites. The site of action of apamin on Na,K-ATPase is different from that of tetra-alkylammonium compounds; it apparently decreases the turnover rate of the enzyme.

Animals↗
PubMed2000

Expression of zinc-positive cells and terminals in fetal neocortical homografts to adult rat depends on lesion type and rearing conditions.

Zinc-positive neurons and terminals, known to be associated with the glutamatergic projections in the brain, can be demonstrated by the histochemical Timm method and later modifications thereof. The adult rat neocortex contain a uniform lamination of zinc-positive cells with specific projections to, e.g., the striatum. We have previously reported that fetal neocortical grafts implanted in the adult rat neocortex combined with rearing in an enriched environment can improve behavioral functions and reduce the secondary atrophy of thalamus after cortex infarction in adult rats. In order to examine whether the expression of zinc positivity is ontogenetically inherent to neocortical neurons we grafted fetal neocortical tissue to aspiration or ischemic lesions of the frontoparietal neocortex of adult rats, followed by histochemical visualization of the vesicular zinc pool by selenite or sulfide. One further aim of the study was to elucidate to what extent the distribution of zinc-containing neurons and terminals in the grafts depended on rearing under different environmental conditions. The foremost finding of the present study was that the overall density of zinc-containing terminals in fetal cortical transplants placed in brain infarcts of adult spontaneously hypertensive rats is higher when the rats are reared in an enriched environment. Moreover, the presence and expression of zinc-positive neurons and terminals do not seem to be ontogenetically inherent to the cortical neurons as the fetal neocortical grafts placed in aspiration lesions contained no zinc-selenide-positive neurons and few or no zinc-selenide-positive terminals. The presence or expression of zinc-positive cells may thus be induced by ingrowth of fibers and terminals from the host brain as transplants placed in the ischemic lesions expressed both zinc-positive neurons and terminals.

Animals↗
PubMed1993

A possible role for cell proliferation in potassium bromate (KBrO3) carcinogenesis.

Accumulation of alpha 2u-globulin and induction of cell proliferation were examined in kidneys of rats exposed to KBrO3, KBr or NaBrO3 in their drinking water. Hyaline droplets observed after KBrO3 or NaBrO3 administration to male rats were specifically immunostained for alpha 2u-globulin. Increases in cell proliferation were found in the proximal tubules of male rats given KBrO3 or NaBrO3 but not KBr for 2, 4, and 8 weeks. No such change was evident in KBrO3-treated female rats or the distal tubules of any treated animal. The concordance between hyaline droplet accumulation and increased cell turnover suggests that KBrO3- and NaBrO3-induced cell replication in kidneys of male rats may result from alpha 2u-globulin nephropathy. Considering the fact that KBrO3 has genotoxic potential involving oxidative stress, we hypothesize that the induced cell proliferation might predominantly play an additive role in its carcinogenesis. Furthermore, the present data, showing similar effects of NaBrO3 on the rat kidney, are of direct significance to its risk assessment.

Alpha-Globulins↗
PubMed1992

Synthesis, characterization and biodistribution of a new hexadentate aminethiol ligand labeled with Tc-99m.

A new hexadentate aminethiol ligand (TACNS) derived from triazacyclononane was synthesized and characterized for the development of technetium radiopharmaceuticals. The ligand formed a neutral, lipophilic and stable complex with [99mTc]pertechnetate in the presence of tin(II)tartarate as a reducing agent. The biodistribution of [99mTc]TACNS indicates slight uptake in brain (0.23% ID/organ at 5 min) with a washout at 30 min to 0.14% ID/organ. A small uptake in heart (0.48% ID at 5 min) was also observed. The characterization of [99mTc]TACNS complex using single crystal x-ray analysis and mass spectroscopy has shown that an Sn-N3S3 complex was formed in which tin is oxidized from Sn(II) to Sn(IV). Pertechnetate was incorporated into the complex as counter anion. The nature of the species formed with Tc-99 and "no-carrier-added" [99mTc]pertechnetate is different as confirmed by ratio TLC. From these results, it is demonstrated that sometimes it may be difficult to predict the structure of new technetium radiopharmaceuticals, especially when stannous ion is used as a reducing agent. Moreover, the nature of the chemical species may not be the same at millimolar and at nanomolar levels.

Animals↗
PubMed2000

Foreign metallothionein-I expression by transient transfection in MT-I and MT-II null astrocytes confers increased protection against acute methylmercury cytotoxicity.

The mechanisms associated with metallothionein (MT) gene regulation are complex and poorly understood. Only a modest increase in brain MT expression levels is attained by exposure to metals, MT gene transfection, and MT gene knock-in techniques. Accordingly, in the present study, MT null astrocytes isolated from transgenic mice deficient in MT-I and MT-II genes were introduced as a zero background model of MT expression. MT protein levels were determined by western blot analysis. MT proteins in MT-I and MT-II null astrocytes were undetectable. Transient MT-I gene transfection increased the levels of foreign MT expression in MT-I and MT-II null astrocytes by 2.3-fold above basal levels in wild-type astrocytes. Intracellular Na(2)51CrO(4) efflux and D-[2,3-3H]aspartate uptake were studied as indices of acute methylmercury (MeHg) (5 microM) cytotoxicity. In MT-I and MT-II knockout astrocytes MeHg led to significant (p<0.01) increase in Na(2)51CrO(4) efflux and a significant (p<0.05) decrease in the initial rate (1 min) of D-[2, 3-3H]aspartate uptake compared to MT-I and MT-II knockout controls. Transfection of the MT-I gene in MT-I and MT-II null mice significantly (p<0.01) decreased the effect of MeHg on Na(2)51CrO(4) efflux in MT null, as well as wild-type astrocytes. MT-I gene transfection in MT-I and MT-II null astrocytes reversed the inhibitory effect of MeHg on D-[2,3-3H]aspartate uptake, such that initial rates of uptake in MT-I transfected cells in the presence and absence of MeHg (5 microM) were indistinguishable. These results demonstrate that: (1) astrocytes lacking MTs are more sensitive to MeHg than those with basal MT protein levels, (2) the MT-I gene can be overexpressed in MT-I and MT-II null astrocytes by transient MT-I gene transfection, and (3) that foreign MT expression endows astrocytes with increased resistance to MeHg.

Animals↗
PubMed1998

Inhibitory actions of various vasorelaxants on the myogenic contraction induced by quick stretch studied in canine cerebral artery.

Quick stretch at a rate of 10 cm/s with the amount of 30% of the initial muscle length (= 100%) produced a myogenic contraction in canine cerebral artery. The inhibitory actions of various vasorelaxants on the stretch-induced contraction were investigated. Ca2+ channel blockers (nicardipine, D-cis-diltiazem) inhibited the stretch-induced contraction by 50-60% at the concentrations which abolished high KCl-induced contraction. Inhibitions of the stretch-induced contraction by nitro-compounds (nitroglycerin, sodium nitroprusside) were about 50%. In contrast, inhibitions by the compounds which activate ATP-sensitive K+ channels (cromakalim, nicorandil, pinacidil) of the myogenic contraction in response to quick stretch were only 20%. Papaverine totally abolished the stretch-induced contraction. It is likely that all the vasorelaxant compounds tested in the present study except papaverine are beneficial in the sense that they do not suppress the intrinsic myogenic contraction, which may be related to the autoregulation of local blood flow.

Animals↗
PubMed1998

Retention behavior of D,L-dansyl-amino acids on a human serum albumin chiral stationary phase: effect of a mobile phase modifier.

The effect of perchlorate anion as a mobile phase modifier on the retention of dansyl norvaline and dansyl tryptophan enantiomers on a human serum albumin (HSA) column was studied by varying the chaotropic agent concentrations. The thermodynamic parameters for the transfer of a solute from the mobile to the HSA stationary phases were determined from linear van't Hoff plots. An enthalpy-entropy compensation study revealed that the type of interaction between the solute and HSA was independent of the molecular structure. The parabolic variations observed with the enthalpic and entropic terms of dansyl amino acid transfer in relation to the concentration of perchlorate anion were considered to be the result of the change from reversed to normal-phase conditions for this chromatographic system.

Amino Acids↗
PubMed1986

Comparison of three platelet markers for measurement of platelet survival time in healthy volunteers.

We studied mean platelet survival times in healthy volunteers with use of [51Cr]disodium chromate, 111In-oxine (in a solution of acid-citrate-dextrose [ACD] and saline), and 111In-tropolone (in ACD-plasma) as markers. Differences found between the 51Cr and 111In labels probably can be attributed to a variation in localization of the label on the cell and of renal handling of the free label after release. The mean platelet survival time with 51Cr was slightly longer than the survival time with both indium labels and showed a sex difference not seen with 111In-oxine. Protein-bound plasma 51Cr was lower than plasma 111In and remained constant throughout the study. Plasma 111In increased with time. For survival time calculations, no correction for free 51Cr is necessary, but correction should routinely be performed when 111In markers are used. Both 111In markers gave similar results with respect to platelet survival time. The somewhat more elaborate plasma labeling procedure with tropolone shows no measurable advantage over the original 111In-oxine method. 111In-tropolone labeling takes less time and maintains platelets in the physiologic environment of plasma during incubation. Biodistribution studies show no difference between the two 111In markers.

Blood Platelets↗
PubMed2001

Investigation of thermal parameters and crytallisation in a ternary CaO-Na2O-P2O5-based glass system.

This paper presents the results of a study of the thermal properties of a range of phosphate-based glasses in the system CaO-Na2O-P2O5. The glasses had a fixed P2O5 content of 45 mol% and the CaO:Na2O ratio was varied. The glasses were produced and ground and their thermal properties measured using a Setaram differential thermal analyser (DTA). Initial data showed that for the high Na2O containing glass, NaPO3 forms and a second unidentified phase that is probably calcium rich. In the middle compositional region, multiple phases precipitated out and were identified as NaPO3 and Na4Ca(PO3)6. For the high CaO content glasses, Na4Ca(PO3)6 was the only phase formed. Further studies were carried out to examine whether the phases were bulk or surface nucleating, by grinding the samples to different particle sizes. From this data, it is evident that the NaPO3 forms via a bulk nucleation mechanism and that Na4Ca(PO3)6 forms via surface nucleation. The factors controlling this precipitation process are discussed and ionic radius as a controlling factor is hypothesised.

Calcium Compounds↗
PubMed2003

PBPK predictions of perchlorate distribution and its effect on thyroid uptake of radioiodide in the male rat.

Due to perchlorate's (ClO4-) ability to competitively inhibit thyroid iodide (I-) uptake through the sodium-iodide symporter (NIS), potential human health risks exist from chronic exposure via drinking water. Such risks may include hypothyroidism, goiter, and mental retardation (if exposure occurs during critical periods in neurodevelopment). To aid in predicting perchlorate's effect on normal I- kinetics, we developed a physiologically-based pharmacokinetic (PBPK) model for the adult male rat. The model structure describes simultaneous kinetics for both anions together with their interaction at the NIS, in particular, the inhibition of I- uptake by ClO4-. Subcompartments and Michaelis-Menten (M-M) kinetics were used to describe active uptake of both anions in the thyroid, stomach, and skin. Separate compartments for kidney, liver, plasma, and fat were described by passive diffusion. The model successfully predicts both 36ClO4- and 125I- kinetics after iv doses of 3.3 mg/kg and 33 mg/kg, respectively, as well as inhibition of thyroid 125I- uptake by ClO4- after iv doses of ClO4- (0.01 to 3.0 mg/kg). The model also predicts serum and thyroid ClO4- concentrations from 14-day drinking water exposures (0.01 to 30.0 mg ClO4-/kg/day) and compensation of perchlorate-induced inhibition of radioiodide uptake due to upregulation of the thyroid. The model can be used to extrapolate dose metrics and correlate observed effects in perchlorate toxicity studies to other species and life stages, such as rat gestation (Clewell et al., 2003). Because the model successfully predicts perchlorate's interaction with iodide, it provides a sound basis for future incorporation of the complex hypothalamic-pituitary-thyroid feedback system.

Animals↗