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Chemotherapeutic agents with an imidazole moiety. II. Synthesis and biological activities of new 1,4-diarylimidazoles.

The synthesis, antifungal and pharmacological activities of new 1,4-diarylimidazoles are reported. Antimicrobial data in comparison with antifungal antibiotic pyrrolnitrin pointed out that the 1,4-diaryl-2-mercaptoimidazole derivatives were inactive and all 1,4-diarylimidazoles exhibited a weak antifungal activity. Some compounds showed a selective activity against strains of Candida sp. Instead pharmacological data did not evidence any significant antiinflammatory activity. The tested compounds were prepared by reacting appropriate phenacylanilines with potassium thiocyanate in acidic medium to afford 1,4-diaryl-2-mercapto imidazoles which were then transformed into title compounds by treatment with nitric acid.

Animals↗

Dissolved and acid available particulate beryllium in eastern UK surface waters.

The concentrations of beryllium (Be) in surface waters are presented for major water quality surveys of eastern UK rivers, based on extensive work within a major environmental programme, the Land Ocean Interaction Study (LOIS). Two measurements were made, one for dissolved Be (i.e. the fraction that can pass through 0.45-microm membrane filters) the other for acid available total Be (dissolved Be plus the fraction of particulate Be that can be leached by a 1% v/v concentrated nitric acid solution). Dissolved Be concentrations are generally less than 1 microg l(-1) with a mean of approximately 0.02 microg l(-1), but higher values occur across the eastern UK rivers between 16th October and 7th November 1995 under neutral to alkaline conditions where Be would not be expected to be mobile. The higher values vary from river to river and there is a marked increase from north to south with particularly high concentrations (up to 29 microg l(-1)) for the industrial and urban impacted rivers of the southern Humber basin. The results show a major increase in dissolved Be at a time of exceptional drought conditions and climate instability, which seems to be linked to industrial/urban catchment systems. The average dissolved Be flux is 0.22 gha(-1) year(-1) with a range in mean across the sites of 0.08-0.45 gha(-1) year(-1). Without the period of enhanced Be concentrations, the Be flux through the period would have been approximately 40% less. There is no clear distinction between the dissolved Be flux for the rural and urban/industrial catchment systems. Acid available particulate Be (AAPBe) concentrations are low across the eastern UK rivers, they range between 0 and 1.33 microg l(-1) with a mean of 0.02 microg l(-1) and the highest concentrations occur for the industrial/urban rivers (approximately twice the levels occurring within the rural rivers). The AAPBe concentrations are linearly correlated with the concentrations of suspended sediment, particulate organic carbon, particulate nitrogen, particulate phosphorus, and the AAP for several transition metals (Al, Co, Cr, Fe, Mn, Ni and Y), and the lanthanides. This reflects the nature of the catchment sources of particulate material (soil erosion and pollutant sources) and the hydrogeochemistry of Be with the high potential for hydrolysis and hydrogen bonding due to its small atomic size and high surface charge density. The acid available particulate flux averages approximately 0.42 gha(-1) year(-1) with a range in mean across the sites of 0.14-1.2 gha(-1) year(-1). The highest flux occurs for a river with a flood plain contaminated by spoil from historic mining of lead-zinc deposits, but there is no clear separation between the rural and the industrial/urban impacted catchments. The results indicate a potential and most unexpected dissolved Be stress to lowland aquatic environments, a stress that might well increase over time for the UK given the increasing climate instability within the country. The findings are linked to other information on Be in surface waters for other UK surface waters, including previously unpublished data, to allow a broader perspective for UK riverine environments. Information is provided on Be levels in acidic upland streams in mid Wales (upper River Severn), other eastern UK rivers (collected towards the end of the LOIS initiative) and drainage waters from a disused tin wine in Cornwall (Wheal Jane Mine).

Journal Article↗

Effect of fertilizer on the growth of radish plants exposed to simulated acidic rain containing different sulfate to nitrate ratios.

Two successive experiments were performed in the greenhouse to test the hypothesis that plant response to the amounts and ratios of sulfuric and nitric acids in rain is affected by the amount of fertilizer added to the growing medium. Radish plants, grown with different levels of N?P?K fertilizer, were given ten 1-h exposures over a 3-week period to simulate acidic rain at pH values from 2.6 to 5.0 and sulfate to nitrate mass ratios from 0.3 to 7.5. Increased acidity of simulated rain reduced plant growth, with a greater depression of hypocotyl mass than shoot mass. The reverse growth response occurred with increased supply of fertilizer: plant biomass rose with a larger increase in shoot mass than hypocotyl mass. In one experiment, plants that received a greater supply of fertilizer exhibited more obvious reductions in growth of hoots at the higher levels of acidity of simulated rain. There were no significant effects of sulfate to nitrate ratios in simulated rain on plant growth, nor any effect of this ratio on the response of shoots and hypocotyls to acidity of simulated rain. Addition of fertilizer had no effect on plant response to sulfate to nitrate ratios. These results do not support the hypothesis that nutrient-deficient plants are either more or less responsive to sulfate and nitrate in rain than plants grown with optimal supplies of nutrients. They support previous results indicating no effects of sulfate to nitrate ratio in simulated acidic rain on plant growth. The results also suggest that the greatest risk of harmful effects on vegetation may come from the combination of high sulfate and high acidity in rainfall.

Journal Article↗

Nutritional factors in the pathobiology of human essential hypertension.

Endothelial cells produce vasodilator and vasoconstrictor substances. Dietary factors such as sodium, potassium, calcium, magnesium, zinc, selenium, vitamins A, C, and E, and essential fatty acids and their products such as eicosanoids can influence blood pressure, cardio- and cerebrovascular diseases, and concentrations of blood lipids and atherosclerosis. There might be a close interaction between these dietary factors, sympathetic and parasympathetic nervous systems, the metabolism of essential fatty acids, nitric oxide, prostacyclin, and endothelium in human essential hypertension. A deficiency in any one factor, dietary or endogenous, or alterations in their interactions with each other, can lead to endothelial dysfunction and development of hypertension. Therefore, alterations in the metabolism of essential fatty acids might be a predisposing factor to the development of essential hypertension and insulin resistance.

Diet↗

Chemotherapeutic agents with an imidazole moiety. I. Synthesis and antifungal activities of 1-aryl-4-p-nitrophenylimidazoles.

The synthesis and antifungal activities of 1-aryl-4-p-nitrophenylimidazoles and their 2-mercaptoderivatives is reported. Antimicrobial data in comparison with antifungal antibiotic pyrrolnitrin attributed the best activity to 1-p-methoxyphenyl-4-p-nitrophenylimidazole. The tested compounds were prepared by reacting p-nitrophenacylanilines with potassium thiocyanate in acidic medium to afford 1-aryl-2-mercapto-4-p-nitrophenylimidazoles, which were then transformed into the title compound by treatment with nitric acid.

Antifungal Agents↗

Nitrogen deposition in California forests: a review.

Atmospheric concentrations and deposition of the major nitrogenous (N) compounds and their biological effects in California forests are reviewed. Climatic characteristics of California are summarized in light of their effects on pollutant accumulation and transport. Over large areas of the state dry deposition is of greater magnitude than wet deposition due to the arid climate. However, fog deposition can also be significant in areas where seasonal fogs and N pollution sources coincide. The dominance of dry deposition is magnified in airsheds with frequent temperature inversions such as occur in the Los Angeles Air Basin. Most of the deposition in such areas occurs in summer as a result of surface deposition of nitric acid vapor (HNO3) as well as particulate nitrate (NO3-) and ammonium (NH4+). Internal uptake of gaseous N pollutants such as nitrogen dioxide (NO2), nitric oxide (NO), HNO3, peroxyacetyl nitrate (PAN), ammonia (NH3), and others provides additional N to forests. However, summer drought and subsequent lower stomatal conductance of plants tend to limit plant utilization of gaseous N. Nitrogen deposition is much greater than S deposition in California. In locations close to photochemical smog source areas, concentrations of oxidized forms of N (NO2, HNO3, PAN) dominate, while in areas near agricultural activities the importance of reduced N forms (NH3, NH4+) significantly increases. Little data from California forests are available for most of the gaseous N pollutants. Total inorganic N deposition in the most highly-exposed forests in the Los Angeles Air Basin may be as high as 25-45 kg ha(-1) year(-1). Nitrogen deposition in these highly-exposed areas has led to N saturation of chaparral and mixed conifer stands. In N saturated forests high concentrations of NO3- are found in streamwater, soil solution, and in foliage. Nitric oxide emissions from soil and foliar N:P ratios are also high in N saturated sites. Further research is needed to determine the ecological effects of chronic N deposition, and to develop appropriate management options for protecting water quality and managing plant nutrient resources in ecosystems which no longer retain excess N.

Journal Article↗

Single vessel procedure for acid-vapour partial digestion in a focused microwave: Fe and Co determination in biological samples by ETAAS.

A single vessel procedure using a focused microwave oven is proposed for biological sample preparation with nitric acid vapour under atmospheric pressure. A laboratory-made PTFE support vessel equipped with four cups that received the samples was adapted to fit on the microwave glass vessel. Biological samples (30 mg) were directly weighed into these PTFE cups followed by the addition of 150 microliters of water or H2O2. The mixture was exposed to acid vapour stemming from 15 ml of concentrated HNO3 placed in the bottom of the glass vessel. The acid vapour was formed at 115 degrees C and brought about the Co and Fe extraction in 10 and 60 min, respectively. The resulting suspension was diluted with 0.14 mol l-1 HNO3 to a final volume of 1.0 ml, shaken and centrifuged. The supernatant was analysed by electrothermal atomic absorption spectrometry (ETAAS) by placing the cups directly in the autosampler of the spectrometer. This system minimised contamination, and reagent and time consumption and was suitable for Co and Fe determination in biological materials. The accuracy of the proposed method was assessed by using certified reference materials and by comparison with the closed vessel microwave as a comparative technique. Cobalt and Fe recovery was around 82-99%. As an additional advantage, up to 6 samples can be simultaneously prepared in each vessel, thereby improving the sample throughput from 6 to 24, when a 6-cavity focused microwave is used.

Animals↗

The effect of COX-2 inhibitors on periprosthetic osteolysis.

We aimed to test the hypothesis that COX(cyclooxygenase)-2 inhibitors suppress periprosthetic osteolysis in a rabbit model. Porous coated titanium bar was inserted into distal femur of 24 skeletally mature New Zealand white rabbits. The rabbits were randomized into 3 groups. Group I (8 rabbits) was the control group. In Group II (8 rabbits), 5mg of ultrahigh molecular weight polyethylene particles was inserted along with prosthesis. In Group III (8 rabbits), the same procedure as in Group II was done and a COX-2 inhibitor (celecoxib, Pharmacia: 10mg/day) was administered for 7 weeks. Rabbits were sacrificed after 8 weeks of implantation. Gross, radiological, histological, and immunohistochemical assessments were done. Gross examination showed that one implant in Group II was loose. In radiological evaluation, focal osteolysis was found in 2 rabbits of Group II and 1 rabbit of Group III. Linear osteolysis was found in 2 rabbits of Group II and 1 rabbit of Group III. On histological examination, focal area of granulation tissue laden with macrophages was observed in 6 rabbits of Group II and 6 rabbits of Group III. The mean number of osteoclasts as demonstrated by tartarate positive acid phosphatase staining was 0.5+/-0.5 in Group I, 6.5+/-2.7 in Group II, 3.6+/-2.6 in Group III (p<0.05). Immunohistochemical staining for inducible nitric acid synthase and COX-2 did not show significant difference between Groups II and III. The overall results of this study suggest that COX-2 inhibitors in the therapeutic dose may have a place in suppressing the process of periprosthetic osteolysis.

Animals↗

Biosorption of reactive dye using acid-treated rice husk: factorial design analysis.

A factorial experimental design technique was used to investigate the biosorption of reactive red RGB (lambda(max)=521 nm) from water solution on rice husk treated with nitric acid. Biosorption is favored because of abundance of biomass, low cost, reduced sludge compared to conventional treatment techniques and better decontamination efficiency from highly diluted solutions. Factorial design of experiments is employed to study the effect of four factors pH (2 and 7), temperature (20 and 40), adsorbent dosage (5 and 50mg/L) and initial concentration of the dye (50 and 250 mg/L) at two levels low and high. The efficiency of color removal was determined after 60 min of treatment. Main effects and interaction effects of the four factors were analyzed using statistical techniques. A regression model was suggested and it was found to fit the experimental data very well. The results were analyzed statistically using the Student's t-test, analysis of variance, F-test and lack of fit to define most important process variables affecting the percentage dye removal. The most significant variable was thus found to be pH.

Acids↗

Effect of surface treatment on unalloyed titanium implants: spectroscopic analyses.

Surgical implant finishing and sterilization procedures were investigated to determine surface characteristics of unalloyed titanium (Ti). All specimens initially were cleaned with phosphoric acid and divided into five groups for comparisons of different surface treatments (C = cleaned as above, no further treatment; CP = C and passivated in nitric acid; CPS = CP and dry-heat sterilized; CPSS = CPS and resterilized; CS = C and dry-heat sterilized). Auger (AES), X-ray photoelectron (XPS), and Raman spectroscopic methods were used to examine surface compositions. The surface oxides formed by all treatments primarily were TiO2, with some Ti2O3 and possibly TiO. Significant concentrations of carbonaceous substances also were observed. The cleaning procedure alone resulted in residual phosphorus, primarily as phosphate groups along with some hydrogen phosphates. A higher percentage of physisorbed water appeared to be associated with the phosphorus. Passivation (with HNO3) alone removed phosphorus from the surface; specimens sterilized without prior passivation showed the thickest oxide and phosphorus profiles, suggesting that passivation alters the oxide characteristics either directly by altering the oxide structure or indirectly by removing moieties that alter the oxide. Raman spectroscopy showed no crystalline order in the oxide. Carbon, oxygen, phosphorus, and nitrogen presence were found to correlate with previously determined surface energy.

Electron Probe Microanalysis↗

Fluorimetric determination of arsanilic acid by flow-injection analysis using on-line photo-oxidation.

A flow-injection-fluorimetric method for the determination of arsanilic acid is proposed. The assay is based on the on-line decomposition of arsanilic acid in the presence of peroxydisulfate on irradiation with UV light. The arsenate generated in the photochemical reaction was reacted with molybdate in dilute nitric acid to form arsenomolybdic acid, which oxidised thiamine to thiochrome. The thiochrome was monitored fluorimetrically at 440 nm with excitation at 375 nm. The calibration graph was linear in the range 0.10-10.8 microg mL(-1) with a correlation coefficient of 0.999. The detection limit was 0.01 microg mL(-1) and the sample throughput was 55 samples h(-1). The applicability of the method was demonstrated by determining arsanilic acid in animal foodstuffs and water.

Animal Feed↗

Analysis of plutonium in soil samples

Procedures for analysis of plutonium in soil samples were developed using anion exchange as a purification technique. Special attention was paid to removing impurities of 228Th which interferes in 238Pu determination by alpha spectrometry. Two anion-exchange methods were compared. The determination of plutonium in soil involves the conversion of soil samples to acid-soluble form. Two methods for the extraction of plutonium from a natural reference soil were compared. The first method (a direct digestion in nitric acid) is suitable for the determination of plutonium in large amounts of sample. The second method involves microwave digestion of soil (5 g) with a mixture of HNO3, HCl and HF, and is suitable for saving time in routine determinations. Activities calculated with a reference soil matrix were in good agreement with the reference value. The microwave digestion method was applied in a study of different soil samples, and recoveries ranged between 20% and 50%.

Journal Article↗

Determination of cadmium, chromium, copper and lead in sediments and soil samples by electrothermal atomic absorption spectrometry using zirconium containing chemical modifiers.

A method for direct determination of cadmium, chromium, copper and lead in sediments and soil samples by electrothermal atomic absorption spectrometry using Zr, Ir, etylenediamine acetic acid (EDTA), Zr + EDTA, Ir + EDTA, Zr + Ir and Zr + Ir + EDTA as chemical modifiers in 0.5% (v/v) Triton X-100 plus 0.2% (v/v) nitric acid mixture used as diluent was developed. The effects of mass and mass ratio of modifiers on analytes in sample solutions were studied. The optimum masses and mass ratios of modifiers: 20 microg of Zr, 4 microg of Ir, 100 microg of EDTA and 20 microg of Zr + 4 microg of Ir + 100 microg of EDTA, were used to enhance the analyte signals. Pyrolysis and atomization temperatures, atomization and background absorption profiles, characteristic masses, and detection limits of analytes in samples were compared in the presence or absence of a modifier. The detection limits and characteristic masses of analytes in a 0.5% (m/v) dissolved sample (dilution factor of 200 ml g(-1)) obtained with Zr + Ir + EDTA are 8.0 ng g(-1) and 1.2 pg for Cd, 61 ng g(-1) and 4.3 pg for Cr, 32 ng g(-1) and 23 pg for Cu, and 3.4 ng g(-1) and 19 pg for Pb, respectively. The Zr + Ir + EDTA modifier mixture was found to be preferable for the determination of analytes in sediment and soil-certified and standard reference materials. Depending on the sample type, the percent recoveries of analytes were increased from 81 to 103% by using the proposed modifier mixture; the results obtained are in good agreement with the certified values.

Cadmium↗

[Exogenous iron and gamma-radiation induces synthesis of NO-synthetase in mouse liver].

The inhibitor of protein biosynthesis, cycloheximide (CHI) and the exogenous antioxidant, phenazan, attenuated the synthesis of nitric acid oxide (NO) in mouse liver in vivo induced by gamma-irradiation, bacterial lipopolysaccharide (LPS) or LPS+Fe(2+)-citrate treatment of experimental animals. The rate of NO synthesis was followed by accumulation of paramagnetic mononitrosyl iron complexes with the exogenous ligand--diethyldithiocarbamate (MNIC-DETC). The latter were formed as a result of NO binding to selective NO traps (DETC complexes with exogenous or endogenous Fe2+ ions) and measured by the EPR method. A conclusion is drawn that the activation of NO biosynthesis under the action of gamma-irradiation, LPS or LPS+Fe(2+)-citrate treatment was due to the induction of NO synthase synthesis inhibited by CHI. This process is initiated by active oxygen species, presumably due to the activation of the transcription factor, NFkB protein. The accumulation of active oxygen species was inhibited by the antioxidant, phenazan.

Amino Acid Oxidoreductases↗

[Effects of exogenous nitric oxide, salicylic acid and hydrogen peroxide on free amino acid and soluble protein contents in tobacco leaves].

The work focused on the effects of signal molecules of nitric oxide (NO), salicylic acid (SA) and hydrogen peroxide (H(2)O(2)) on compounds of nitric metabolites of free amino acid, soluble protein and proline in tobacco. The results indicated that NO, SA and H(2)O(2) were able to regulate the proline, free amino acid and soluble protein content in tobacco. Lower concentration of NO and H(2)O(2) raised the level of proline; while higher concentration of NO and H(2)O(2) lowered the proline, free amino acid content in tobacco. The above three signal molecules also showed similar effects on proline, free amino acid and soluble protein content in tobacco.

Amino Acids↗

Release of heavy metals from European and Asian porcelain dinnerware.

Samples of porcelain dinnerware manufactured in five European and three Asian countries before the mid-1970s and subsequently brought into the US were subjected to acid leaching tests to investigate the release of heavy metals. Forty-six dishes decorated with decals or hand painted designs applied over the glaze were examined. Included in the selection were dishes from major manufacturers of fine dinnerware (Haviland Limoges, Rosenthal, Noritake) as well as samples from lesser-known or unidentified factories. During 24-h tests with 4% acetic acid, half of the samples (23 dishes) released lead in concentrations exceeding the US Food and Drug Administration (FDA) allowable maximum of 3.0 micrograms/ml and another 17 dishes released lead in concentrations ranging from 0.1 to 2.9 micrograms/ml. Five dishes released cadmium, but only one value exceeded the FDA limit of 0.5 microgram/ml. Zinc, cobalt, copper and chromium were also released by some of the dishes. None of the acetic acid solutions contained measurable concentrations of nickel although this metal, as well as those named above, could be extracted from some samples with 6 M nitric acid. The FDA has not established dinnerware extraction limits for any metals except lead and cadmium. All overglaze-decorated dishes imported into the US before the mid-1970s should be tested for lead release before they are used in the preparation, serving, or storage of food.

Acetic Acid↗

Hemocompatibility of layer-by-layer hyaluronic acid/heparin nanostructure coating on stainless steel for cardiovascular stents and its use for drug delivery.

In order to develop drug-eluting cardiovascular stents, stainless steel (SUS316L) sheets were coated with hyaluronic acid (HA) and heparin (HEP), and their in vitro characteristics and drug release pattern were investigated. The surface of stainless steel (SS) was treated with nitric acid and followed by anchoring aminotrimethoxysilane (ATMS), then a nanolayer of HA was covalently immobilized onto the surface. Heparin was then covalently bonded to the HA-immobilized SS substrate. After repeating 1 to 5 cycles, 1 to 5 layers polyelectrolyte complex (PEC) nanobrush of HA/HEP were resulted with the thickness ranging from 280 to 630 nm (measured with ellipsometry). A model drug (sirolimus) was loaded in the HA/HEP layers at a density ranging from 1.02 to 3.12 microg/cm2. The SS-ATMS-HA-HEP substrates were evidenced by X-ray photoelectron spectroscope (XPS), contact angle, and AFM measurement. The effect of this surface modification on the coagulation time of the resulting SS substrates was investigated. The results show that the multilayer HA/HEP stainless steel would exhibit higher anticoagulant activity than pure SS substrates. In addition, the results of the in vitro drug delivery study showed that release of sirolimus from the 5-layer-HA-HEP stainless steel was able to maintain more than 30 days. Thus layer-by-layer HA/HEP PEC can improve the hemocompatibility of SS surface and control the drug released rate by multiple layers of HA/HEP PEC. These results indicate that the multi-layer HA/HEP PEC coated stainless steel would be suitable for drug eluting stents.

Adjuvants, Immunologic↗