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Biomedical subjects

P C Srivastava

Publications and source records attributed to P C Srivastava.

At least 19 recordsLinked to original sources

Effect of farmyard manure application on boron adsorption-desorption characteristics of some soils.

Boron (B) availability to crop plants depends on soil properties as well as management practices like liming, fertilization and use of organic manures. To assess the effect of farmyard manure (FYM) application on availability of added B, adsorption-desorption of B was investigated in five different soils receiving varying doses of FYM (0, 5 and 10 g FYM kg(-1) soil). Two surfaces Freundlich model was found best to account for B adsorption-desorption data of all soils. Application of FYM increased B adsorption capacities pertaining to low (K1) and high (K2) concentration ranges in all soils, except Soil C (Alfisol) having a pH of 9.8, in which the higher rate of FYM decreased the value of K2. Application of FYM did not change B desorption capacities of soils corresponding to low B concentration range (K(1)(1)) significantly, however, it increased B desorption capacity pertaining to high B concentration (K(1)(2)) in all soils, except Soils C (Alfisol) and E (Entisol) having pH of 9.8 and 5.1, respectively. Application of FYM increased the desorption slope factor applicable to low concentration range (1/n(1)(1)) in Soil A (Inceptisol), but decreased it in Soil E (Entisol). The 1/n(1)(2) (desorption slope factor applicable to high concentration range) decreased with FYM application in all soils except Soil E (Entisol), where it was increased. Boron desorption index (slope(ads)/slope(des)) decreased with FYM application in low B concentration range, but increased in high concentration range for all soils except soil E (Entisol, pH 5.1), in which a reverse trend was observed. Application of FYM increased the retention of added B in soils and may help reducing the leaching losses.

Adsorption↗

Effect of metal spiking on different chemical pools and chemically extractable fractions of heavy metals in sewage sludge.

A laboratory experiment was conducted to study the effect of metal spiking and incubation on some properties and sequentially extractable chemical pools of some heavy metals (F1, two extractions with 0.1 M Sr(NO3)2; F2, one extraction with 1 M NaOAc (pH 5.0); F3, three extractions with 5% NaOCl (pH 8.5) at 90-95 degrees C; F4, three extractions with 0.2 M oxalic acid + 0.2 M ammonium oxalate + 0.1 M ascorbic acid (pH 3.0); and F5, dissolution of sample residue in HF-HClO4 (residual fraction,) and also 1 M CaCl2 and 0.005 M DTPA extractable heavy metals in sewage sludge. Metal spiking and incubation decreased pH and easily oxidizable organic C content of sludge but increased electrical conductivity. Metal spiking and incubation increased F1 fraction of all heavy metals, F2 fraction of Ni, Pb, Cu, and Cd, F3 fraction of Pb, Cu, and Cd, F4 or reducible fraction of Ni, Cu, and Cd and residual fraction of Zn and Pb, but decreased F2 fraction of Zn, F3 of Zn and Ni, F4 fraction of Zn and F5 fraction of Ni, Cu, and Cd. Metal spiking and incubation increased 1 M CaCl2 and 0.005 M DTPA extractable amounts of all heavy metals in sludge except for 0.005 M DTPA extractable Zn, which registered only very marginal decrease.

Biological Availability↗

Association between sarcoidosis and lymphoma revisited.

AIMS: To investigate the relation between sarcoidosis and lymphoma. METHODS: The hospital notes of five patients with sarcoidosis and a lymphoproliferative disorder were reviewed. Histological material on which the diagnoses of sarcoidosis and lymphoma were made was re-analysed. RESULTS: Four of the five patients had well documented sarcoidosis preceding the development of lymphoma by 18 months to 28 years; the fifth patient had lymphoplasmacytic lymphoma with a reactive granuloma reaction. Two patients had chronic sarcoidosis and three were treated with prednisolone. The types of lymphoma were: Hodgkin's disease (n = 1), B cell lymphoma (n = 2) (mantle cell and lymphoplasmacytic/local plasmacytoma) and large granular lymphocyte leukaemia (T cell) (n = 1). CONCLUSIONS: The association between sarcoidosis and lymphoma is confirmed, suggesting that sarcoidosis may be a predisposing factor for the development of a lymphoid malignancy due to disturbance of the immune system. All types of lymphoma may develop. The first case of T cell granular lymphocytic leukaemia in a patient with sarcoidosis has been documented.

Adult↗

Edaphological characteristics of unweathered and weathered fly ashes from Gondwana and lignite coal.

Naturally weathered and unweathered samples of fly ashes produced from Gondwana and lignite coals were characterized for their edaphological properties. The particle size distribution in these fly ashes varied widely, and the percentage of [Formula: see text] size particles governed their water holding capacity. All fly ashes were noncoherent in the dry state and had lower particle density than quartz and mulite. The fly ashes were low in available N, but were sufficient in available P, K, Ca, Mg, S, Cu, Fe, Mn, Zn and B. Among the fly ashes, unweathered lignite fly ash was the richest source of K, Ca, Mg, S and Fe, while weathered lignite fly ash had the highest amounts of Mn, Zn and B. The pH of the fly ashes was closely related to the ratio of exchangeable Ca to exchangeable Al. The fly ashes were high in soluble salt, but were poor in cation exchange capacity. As an amendment to correct soil pH, the fly ashes had a poor buffering capacity. Weathering decreased the total Fe, available S and exchangeable Na percentages, but increased the organic C content of the fly ashes. Invariably, an excess of soluble salts and exchangeable Na could limit plant growth on fly ash dumps. Toxic levels of B and Al existed in only some fly ashes.

Journal Article↗

Synthesis and biological studies of unsaturated acyclonucleoside analogues of S-adenosyl-L-homocysteine hydrolase inhibitors.

The design, synthesis, and biological evaluation of several unsaturated acyclonucleosides related to augustmycin A are described. The (propargyloxy)methyl acyclonucleoside analogues of 6-chloropurine, adenine, 6-methoxypurine, hypoxanthine, 6-mercaptopurine, and azathioprine have been prepared. The 9-[(propargyloxy)methyl]adenine (5) and 9-[(propargyloxy)methyl]hypoxanthine (12) analogues were converted to the corresponding 5'-tributylstannyl intermediates (9 and 13), respectively, which gave 9-[[[(Z)-5-iodo-5-propenyl]oxy]methyl]adenine (10) and 9-[[[(Z)-5-iodo-5-propenyl]oxy]methyl]hypoxanthine (14), respectively, after iododestannylation. The [125I]-radiolabeled congeners of 10 and 14 were prepared as potential metabolic markers. Among the unsaturated acyclonucleosides tested, 9-[(propargyloxy)methyl]-6-chloropurine (3), 9-[(propargyloxy)methyl]-6-mercaptopurine (15), 9-[(propargyloxy)methyl]azathioprine (17), and angustmycin A analogue 10 showed inhibition of cancer cell growth, but only at a minimal level, and 17 also showed 14% cancer cell death in vitro. Compound 10 provided approximately 50% protection against HIV at 10(-4) M concentrations. Biodistribution results of [125I]-10 in mice indicate that compound 10 is readily metabolized via deiodination in vivo, possibly by serving as a substrate for the enzyme S-adenosyl-L-homocysteine hydrolase.

Adenine↗

Adsorption-desorption behaviour of zinc(II) at iron(III) hydroxide-aqueous solution interface as influenced by pH and temperature.

Batch studies were carried out to investigate the adsorption of zinc(II) from fresh waters on an iron(III) hydroxide surface maintained at the pH of zero point of charge of hydroxide (ZPC, 6.85) and also on both the acidic (5.5) and alkaline (8.2) sides of pH of ZPC, at 15 and 35 degrees C. Zinc(II) adsorption on iron(III) hydroxide increased with an increase in pH. The rise in temperature from 15 to 35 degrees C increased zinc(II) adsorption at pH 5.5 and 6.85, but decreased it at alkaline pH (8.2). In none of the cases did adsorption attain a maximum adsorption density. The results indicate the presence of heterogeneous sites of varying affinity on the adsorbent. Zinc(II) adsorption followed Langmuir behaviour only at small adsorption densities (less than 10(-2.95) M Zn/kg at pH 5.5) and at higher adsorption densities, the availability of strongest binding sites decreased. Nonspecifically adsorbed zinc(II) (reversible to Ba(II)) decreased with the increase in pH and temperature. Sequential desorption experiments also revealed that desorption of adsorbed zinc(II) decreased with an increase in pH.

Journal Article↗

A new conjugating agent for radioiodination of proteins: low in vivo deiodination of a radiolabeled antibody in a tumor model.

A new radioiodinating agent, N-(p-[125I]iodophenyl)maleimide, has been synthesized for its potential utility in the radioiodination of monoclonal antibodies and other proteins. The efficiency of incorporation of 125I in the B72.3 antibody by iodine monochloride iodination or by maleimide conjugation was 19% and 43%, respectively. The thyroid uptake following intraperitoneal administration of the two 125I-labeled antibody preparations was evaluated in nude mice implanted with LS174T colon carcinoma xenografts. The iodine monochloride preparation showed substantially greater uptake in the thyroid with values of 2.1% ID at 6 h after injection and reaching a maximum of 4.3% ID after 6 days. In contrast, the maleimide preparation showed a uniformly low uptake in thyroid of 0.1%-0.2% ID. The results of these preliminary studies demonstrate that the N-(p-[125I]iodophenyl)maleimide-labeled monoclonal antibodies showed markedly less (less than 10-fold) uptake of radioiodine in the thyroid, indicating significantly less in vivo deiodination than iodine monochloride-labeled monoclonal antibodies, while retaining some tumor localization in vivo. Studies are in progress to optimize N-(p-[125I]iodophenyl)maleimide radioiodination conditions and to improve the tumor localization.

Animals↗

Grey platelet syndrome: studies on platelet alpha-granules, lysosomes and defective response to thrombin.

The platelets of a young man with the grey platelet syndrome were severely depleted of all seven alpha-granule proteins assayed as well as partially deficient in alpha-mannosidase and alpha-fucosidase; four other lysosomal enzymes were present in normal concentrations. Total platelet 5-hydroxytryptamine (5HT) and adenine nucleotides were normal, and 14C-5HT uptake reached normal levels only slightly more slowly than a control. Aggregation and dense body secretion occurred normally in response to ADP, adrenaline, collagen, PAF-acether, sodium arachidonate, A23187, Ionomycin, TPA and U44069, but were very delayed in response to thrombin. The increase in cytosolic free calcium in response to thrombin was very slow and much reduced in amplitude, whether in the presence or absence of extracellular Ca2+. These defects in response to thrombin were not corrected by the separate addition of purified alpha-granule proteins or by a whole releasate from normal platelets. It is suggested that these platelets, in addition to their alpha-granule deficiency, may have a specific defect of thrombin receptor-mediated activation of phospholipase C.

Blood Platelet Disorders↗

Effects of alkyl and aryl substitution on the myocardial specificity of radioiodinated phosphonium, arsonium, and ammonium cations.

Several radioiodinated iodopentenyl-trisubstituted phosphonium, arsonium, and ammonium iodides have been prepared and evaluated in rats to determine the effects of structural variations of the cations on myocardial uptake and retention. The synthesis of (E)-(1-iodo-1-penten-5-yl)-trisubstituted phosphonium, arsonium, and ammonium iodides via the condensation of trisubstituted phosphine, arsine, and amine precursors, respectively, with (E)-1,5-diiodopentene is described. In some cases a second route involved condensation with (E)-1-borono-5-iodo-1-pentene followed by iodination. In the phosphonium series, the compounds triphenyl 1, dicyclohexylphenyl 5, tricyclohexyl 6, and dimethyl-n-octyl 8 were prepared. The triphenylarsonium 10 and triethylammonium 11 compounds were also prepared. The corresponding radioiodinated analogues were prepared and tissue distribution studies performed in rats. The results (percent dose/gram, 30 min) demonstrate that replacement of phosphorus with arsenic (1, 3.99%; 10, 3.17%) or the replacement of the phenyl ring with the cyclohexyl ring system (6, 2.67%) has no apparent effect on heart uptake. In the series of compounds studied, replacement of the cyclic ring system with alkyl groups, however, significantly decreased heart uptake with both the phosphorus (8, 1.95%) and nitrogen agents (11, 1.11%). Gamma camera imaging studies with [123I]-5 and [123I]-8 further substantiated the decreased heart uptake with alkyl substitution and the apparent hepatobiliary clearance of 8.

Alkylation↗

Evaluation of the brain-specific delivery of radioiodinated (iodophenyl)alkyl-substituted amines coupled to a dihydropyridine carrier.

To evaluate the potential usefulness of radioiodinated phenylamines attached to dihydropyridine carriers as a means of brain-specific delivery of radiopharmaceuticals, 1-methyl-3-[N-[beta- (4-[125I]iodophenyl)ethyl]carbamoyl]-1,4-dihydropyridine ([125I]-9) and 1-methyl-3-[N-(4-[125I]iodophenyl)carbamoyl]-1,4-dihydropyridine ([125I]-13) have been prepared by dithionite reduction of the corresponding pyridinium precursors, [125I]-8 and [125I]-12, respectively. Formation of 8 involved coupling of (p-aminophenyl)ethylamine with N-succinimidyl (1-methyl-3-pyridinio)formate iodide (4) followed by transformation to the corresponding N-piperidinyl- (6) or (diethylamino)- (7) triazines that were converted to 8 by treatment with HI. Alternatively, 12 was prepared by initial conversion of (4-amino-phenyl)mercuric acetate (10) to 4-iodoaniline (11) by treatment with I2 and then coupling with 4. The radioiodinated quaternary products, 8 and 12, showed low brain uptake and low brain to blood ratios, whereas the dihydropyridine analogues, 9 and 13, showed comparatively good brain uptake and good brain to blood ratios in rats. These data demonstrate that dihydropyridine-coupled radiopharmaceuticals can cross the blood-brain barrier and the technique may be useful for the measurement of cerebral blood perfusion.

Animals↗

Myocardial imaging agents: synthesis, characterization, and evaluation of (Z)- and (Z,E)-18-[82Br]bromo-5-tellura-17-octadecenoic acids.

The effects of replacement of radioiodide with radiobromide on the biological properties of a model vinyl halide substituted tellurium fatty acid have been evaluated. The use of a facile radiobromination method involving the reaction of [82Br]Br2 with vinylmercuric bromide substrates has been investigated. Unexpectedly, both the cis- and trans-vinyl bromide products are formed as confirmed by chromatographic and spectral studies. With use of this technique, (E,Z)-1-[82Br]bromo-13-iodo-1-tridecene was prepared and used as the substrate to prepare (E,Z)-18-[82Br]bromo-5-tellura-17-octadecenoic acid (13-E,Z), which was evaluated in rats. Both [82Br]-13-E,Z and [82Br]-13-Z, prepared by an established procedure using N-chorosuccinimide-Br- reaction with the trans-boronovinyl substrates, showed tissue distribution properties similar to those of (E)-18-[125I]iodo-5-tellura-17-octadecenoic acid. These results demonstrate that replacement of I with Br and also the stereochemistry about the olefinic bond do not drastically affect heart uptake and retention.

Animals↗

Effect of tellurium position on the myocardial uptake of radioiodinated 18-iodotellura-17-octadecenoic acid analogues.

The effect of tellurium (Te) position on myocardial specificity and retention of fatty acids in which radioiodide is stabilized as a trans-(E)-vinyl iodide has been evaluated in rats. Five analogues of 18-iodo-17-octadecenoic acid (ICH = CH-R-Te-R'-COOH) with Te at positions 5, 7, 9, 11, and 13 were prepared by coupling of a trans-diiodoalkene (ICH = CH-R-I) with the requisite sodium [(alkoxycarbonyl)alkyl]telluride substrate (NaTe-R'-COOR"; R" = Me or Et), followed by basic hydrolysis. By varying R and R', a series of analogues with a chain length of 18 carbon atoms was prepared. The telluride substrates were generated in situ by NaBH4 reduction of the corresponding ditellurides, and the diiodoalkenes were prepared by sodium iodide-chloramine-T treatment of the corresponding vinylboronic acids [(HO)2BCH = CH-R-I)]. The vinylboronic acids were prepared by treatment of the terminal acetylenes (HC identical to C-R-I), synthesized from commercially available materials, with catecholborane. All new compounds were analyzed by TLC, NMR, MS, and elemental analyses. The 125I analogues [(E)-125ICH = CH-R-Te-R'-COOH] were prepared in the same manner and evaluated in rats (four per group). Heart uptake and retention were dependent upon the Te position. The analogue with Te at position 5 showed the most pronounced (5-min values) heart uptake (3.7-4.1 dose/g), myocardial retention, and heart/blood ratios (37:1) and is a candidate for radiolabeling with 123I and further evaluation as a myocardial imaging agent.

Animals↗

Synthesis and biological activity of nucleosides and nucleotides related to the antitumor agent 2-beta-D-ribofuranosylthiazole-4-carboxamide.

Phosphorylation of 2-beta-D-ribofuranosylthiazole-4-carboxamide (1) provided the 5'-phosphate 2, which was converted to the corresponding 5'-triphosphate 4 and the cyclic 3',5'-phosphate 5. Treatment of 2-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)thiazole-4-carbonitrile (6) with NH3-NH4Cl provided 2-beta-D-ribofuranosylthiazole-4-carboxamidine hydrochloride (7), and treatment with H2S-pyridine provided the corresponding 4-thiocarboxamide 9. Compound 9 was treated with ethyl bromopyruvate, followed by treatment with methanolic ammonia, to yield 2'-(2-beta-D-ribofuranosylthiazol-4-yl)thiazole-4'-carboxamide (11). 5'-Phosphate 2 was cytotoxic to L1210 cells in culture and significantly effective against the intraperitoneally implanted murine leukemias in mice. Amidine 7 was slightly toxic to L1210 in culture and inhibitory to purine nucleoside phosphorolysis. The cyclic 3',5'-phosphate 5 was less effective than the corresponding 5'-phosphate 2 or the parent nucleoside 1 as an antitumor agent.

Animals↗

[(E)-1-[123I]Iodo-1-penten-5-yl]triphenylphosphonium iodide: convenient preparation of a potentially useful myocardial perfusion agent.

A rapid iodination method has been developed for the synthesis of the new 123I-labeled phosphonium cation [(E)-1-iodo-1-penten-5-yl]triphenylphosphonium iodide by I+ treatment of the corresponding trans-vinylboronic acid. This new model myocardial perfusion agent is obtained after purification in 25-50% yield in less than 1 h. High myocardial uptake (5 min, 2.38% dose/g) with prolonged retention (3 h, 2.21% dose/g) was observed in rats. In addition, heart/blood ratios were high and continued to increase over a 1-day period (5 min, 17:1; 60 min, 23:1; 3 h, 27:1; 1 day, 158:1). In rats, the liver uptake was moderate (5 min, 1.40% dose/g; 60 min; 0.25% dose/g). Excellent myocardial images were obtained in a dog.

Animals↗

2',5'-Oligoadenylates and related 2',5'-oligonucleotide analogues. 1. Substrate specificity of the interferon-induced murine 2',5'-oligoadenylate synthetase and enzymatic synthesis of oligomers.

The substrate specificity of the interferon-induced mouse L-cell enzyme, 2',5'-oligoadenylate synthetase, was determined with a number of nucleoside 5'-triphosphate analogues. Selected nucleoside 5'-triphosphates were converted to 2',5'-oligonucleotides with the following order of efficiency for the nucleoside: 8-azaadenosine greater than adenosine = 2-chloroadenosine greater than sangivamycin greater than toyocamycin greater than formycin greater than 3-ribosyladenine greater than ribavirin greater than tubercidin greater than adenosine 1-oxide greater than 2-beta-D-ribofuranosylthiazole-4-carboxamide greater than inosine = 1,N6-ethenoadenosine greater than guanosine greater than 8-bromoadenosine = uridine greater than cytidine. Adenosine 5'-((beta, gamma-imidotriphosphate) did not seem to be a recognizable substrate since no detectable product resulted. Either the 2',5'-oligoadenylate synthetase is not as specific as had been previously thought, or there may be more than one 2',5'-oligonucleotide synthetase. The 2',5'-oligonucleotide analogue products in which the adenosine of ppp(A2'P5')nA was replaced by the various nucleoside analogues were separated by DEAE-cellulose column chromatography and the chain length and number of 5'-phosphate residues analyzed by a rapid, efficient high-performance liquid chromatographic (HPLC) system involving ion-pairing C18 reversed-phase column chromatography. Separation of the 5'-mono-, 5'-di-, and 5'-triphosphorylated forms of the 2',5'-oligonucleotide analogue dimers, trimers, tetramers, and pentamers was readily achieved by this useful HPLC system. No 5'-nonphosphorylated forms were detected for any of the 2',5'-oligonucleotide analogue products.

2',5'-Oligoadenylate Synthetase↗

Synthesis and antitumor activity of 2-beta-D-ribofuranosylselenazole-4- carboxamide and related derivatives.

Treatment of 2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl-1-carbonitrile with hydrogen selenide provided 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonselenoamide (3). Compound 3 was treated with ethyl bromopyruvate to provide ethyl 2-(2,3,5-tri-O-benzoyl-D-ribofuranosyl)selenazole-4-carboxylates, which after ammonolysis were converted to 2-beta-D-ribofuranosylselenazole-4-carboxamide (6) and its alpha-analogue 7, respectively. Acetylation of nucleoside 6 provided 2-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)selenazole-4-carboxamide, and phosphorylation of 6 provided the corresponding 5'-phosphate 9. Compounds 6 and 9 were found to be cytotoxic toward P388 and L1210 cells in culture and effective against Lewis lung carcinoma in mice.

Animals↗

Potential cerebral perfusion agents: synthesis and evaluation of a radioiodinated vinylalkylbarbituric acid analogue.

A new iodinated barbiturate has been prepared. Treatment of 5-chloropentyne and propargyl bromide with diethyl 2-ethyl-2-sodiomalonate (DESM) provided diethyl 2-ethyl-2-(1-pentyn-5-yl)malonate (3) and diethyl 2-ethyl-2-propargylmalonate (4), respectively. Similar condensation of DESM with (E)-(5-iodo-1-penten-1-yl)boronic acid (9) or the reaction of catecholborane with 3 provided diethyl (E)-2-ethyl-2-(1-borono-1-penten-5-yl)malonate (8). The direct sodium iodide-chloramine-T iodination of 8 or the treatment of (E)-1,5-diiodo-1-pentene (10) with DESM provided diethyl (E)-2-ethyl-2-(1-iodo-1-penten-5-yl)malonate (11). The condensation of functionalized malonates 3, 4, and 11 with urea in the presence of a base provided the corresponding barbiturates, 5-ethyl-5-(1-pentyn-5-yl)-(5), 5-ethyl-5-propargyl- (6), and (E)-5-ethyl-5-(1-iodo-1-penten-5-yl)barbituric acid (12), respectively. (E)-6-(Ethoxycarbonyl)-1-iodo-1-octene-6-carboxylic acid (13) was isolated as the hydrolytic byproduct of 11. Compound 13 decarboxylated under vacuum to provide ethyl (E)-1-iodo-1-octene-6-carboxylate (14). The 125I-labeled congeners of 12 and 13 were synthesized in the same manner and evaluated in rats. The barbiturate 12 exhibited significant brain uptake (approximately 1% dose after 5 min), demonstrating that iodinated barbiturates freely cross the intact blood-brain barrier.

Animals↗

Broad-spectrum antiviral activity of 2-beta-D-ribofuranosylselenazole-4-carboxamide, a new antiviral agent.

The relative in vitro antiviral activities of three related nucleoside carboxamides, ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide), and selenazole (2-beta-D-ribofuranosylselenazole-4-carboxamide), were studied against selected DNA and RNA viruses. Although the activity of selenazole against different viruses varied, it was significantly more potent than ribavirin and tiazofurin against all tested representatives of the families Paramyxoviridae (parainfluenza virus type 3, mumps virus, measles virus), Reoviridae (reovirus type 3), Poxviridae (vaccinia virus), Herpes-viridae (herpes simplex virus types 1 and 2), Togaviridae (Venezuelan equine encephalomyelitis virus, yellow fever virus, Japanese encephalitis virus), Bunyaviridae (Rift Valley fever virus, sandfly fever virus [strain Sicilian], Korean hemorrhagic fever virus), Arenaviridae (Pichinde virus), Picornaviridae (coxsackieviruses B1 and B4, echovirus type 6, encephalomyocarditis virus), Adenoviridae (adenovirus type 2), and Rhabdoviridae (vesicular stomatitis virus). The antiviral activity of selenazole was also cell line dependent, being greatest in HeLa, Vero-76, and Vero E6 cells. Selenazole was relatively nontoxic for Vero, Vero-76, Vero E6, and HeLa cells at concentrations of up to 1,000 micrograms/ml. The relative plating efficiency at that concentration was over 90%. The effects of selenazole on viral replication were greatest when this agent was present at the time of viral infection. The removal of selenazole from the medium of infected cells did not reverse the antiviral effect against vaccinia virus, but there was a gradual resumption of viral replication in cells infected with parainfluenza type 3 or herpes simplex virus type 1 (strain KOS). However, the antiviral activity of ribavirin against the same viruses was reversible when the drug was removed.

Animals↗