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W J Novick

Publications and source records attributed to W J Novick.

At least 19 recordsLinked to original sources
PubMed1992

General guidelines for clinical bacteriology. Infectious Diseases Society of America and the Food and Drug Administration.

This guideline summarizes recommendations for (1) developing cogent procedures for diagnosis and antimicrobial susceptibility testing; (2) developing quality-control parameters for the microbiological components of clinical trials; (3) continually updating U.S. Food and Drug Administration (FDA) guidelines; (4) reviewing microbiological recommendations from other groups, such as Microbiology Subcommittees of the National Committee for Clinical Laboratory Standards; and (5) improving the microbiological aspects of FDA package inserts for antimicrobial drugs. Sensitive and specific methods for isolation and identification of pathogens are essential to the proper conduct of clinical trials. Susceptibility tests should be performed in an accurate and reproducible fashion. Verification of results in a reference laboratory is encouraged to monitor quality control.

Anti-Bacterial Agents↗
PubMed1992

Cytokine release from microglia: differential inhibition by pentoxifylline and dexamethasone.

Cytokines have been implicated in the pathogenesis of gram-negative bacterial meningitis. The effects of pentoxifylline and dexamethasone on the release of tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6 from primary murine microglial cell cultures were explored using bioassays. When added concomitantly with lipopolysaccharide, pentoxifylline blocked the release of TNF and IL-1 but not IL-6, while dexamethasone inhibited the release of TNF and IL-6. After a 2-h exposure of microglia to lipopolysaccharide, pentoxifylline but not dexamethasone still inhibited the release of TNF. Release of TNF was enhanced 20-fold by priming of the microglia with interferon-gamma; only pentoxifylline blocked the priming effect of interferon-gamma on TNF release. These results demonstrate that pentoxifylline and dexamethasone differentially regulate the release of cytokines in microglial cell cultures and provide potential insight into their role in the treatment of gram-negative bacterial meningitis.

Animals↗
PubMed1990

New pharmacological studies with pentoxifylline.

Polymorphonuclear (PMN) overactivation plays a critical role in microcirculation as well as in conditions such as multiorgan failure (MOF). Pentoxifylline has been shown to prevent PMN activation by endotoxin and cytokines such as TNF alpha and IL-1. In addition, MOF induced by IL-2 in animals can be prevented by pentoxifylline. The present studies evaluated two aspects of PMN activation and pentoxifylline interaction. The first was the time sequence for pentoxifylline prevention of TNF alpha activation and the second was the activity of pentoxifylline on amphotericin B activation of PMNs. TNF alpha activation of PMNs is blocked by pentoxifylline when cells are exposed to pentoxifylline prior to TNF alpha or after TNF alpha. Amphotericin B activation of PMNs was demonstrated by a decreased chemotaxis, increased chemiluminescence, and increased PMN spreading. In all conditions, pentoxifylline decreased amphotericin B activation of PMNs. These results suggest that pentoxifylline can reverse cytokine activation of PMNs and that pentoxifylline may alter some of the toxic effects of amphotericin.

Amphotericin B↗
PubMed1988

Inhibition of the inflammatory action of interleukin-1 and tumor necrosis factor (alpha) on neutrophil function by pentoxifylline.

Inflammatory cytokines, including interleukin-1 and tumor necrosis factor, are produced by monocytes and macrophages in response to microorganisms and microbial products such as endotoxins. The cytokines stimulate neutrophil adherence, degranulation, and superoxide production but inhibit neutrophil migration. We studied the modulation of cytokine-induced neutrophil activation by pentoxifylline and its principle metabolites. Lipopolysaccharide-stimulated mononuclear-leukocyte-conditioned medium containing inflammatory cytokines, purified human interleukin-1, or recombinant human tumor necrosis factor increased neutrophil adherence to nylon fiber, primed neutrophils for increased superoxide production in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP), increased neutrophil lysozyme release stimulated by FMLP, and decreased directed migration of neutrophils to FMLP. Pentoxifylline and its principle metabolites at or near therapeutically achievable levels were able to counteract these effects. Pentoxifylline inhibited the increase in free intracellular calcium in polymorphonuclear leukocytes stimulated by FMLP and increased binding of FMLP to neutrophils at 37 degrees C but not at 4 degrees C. By blocking the inflammatory action of interleukin-1 and tumor necrosis factor on neutrophils, pentoxifylline may diminish the tissue damage caused by neutrophils in such conditions as septic shock, adult respiratory distress syndrome, cardiopulmonary bypass lung damage, and myocardial reperfusion injury.

Anti-Inflammatory Agents↗
PubMed1986

Production of hypoprothrombinaemia by cefazolin and 2-methyl-1,3,4-thiadiazole-5-thiol in the rat.

Recent findings have suggested that the 1-methyltetrazole-5-thiol (MTT) group contained in several beta-lactam antibiotics may be responsible for the hypoprothrombinaemia associated with these drugs. In order to determine if the hypoprothrombinaemia associated with cefazolin is due to the presence of the structurally related 2-methyl-1,3,4,-thiadiazole-5-thiol (MTD) group which it possesses, the ability of MTD and cefazolin to produce hypoprothrombinaemia in rats was examined. Female rats maintained on a vitamin K-deficient diet for ten days developed hypoprothrombinaemia after the intravenous administration of cefazolin for two subsequent days. Hypoprothrombinaemia was also produced by the oral administration to vitamin K-deficient rats of either cefazolin or MTD, while the oral administration of cefotaxime, which does not contain a thiol group, had no effect. In a rat liver microsomal system, MTD was found to be a much more potent inhibitor than cefazolin of the vitamin K-dependent step in clotting factor synthesis, the gamma-carboxylation of glutamic acid. These results suggest that the hypoprothrombinaemia associated with cefazolin may be due to the MTD group.

Administration, Oral↗
PubMed1984

Production of hypoprothrombinemia by moxalactam and 1-methyl-5-thiotetrazole in rats.

To determine whether the hypoprothrombinemia associated with antibiotics containing a 1-methyl-5-thiotetrazole (MTT) group is a result of the presence of the MTT group, rats were maintained on a vitamin K-deficient diet for 10 days and then received either intravenous moxalactam or cefotaxime or oral MTT for two additional days. MTT and moxalactam, which contains the MTT group, prolonged prothrombin time. Cefotaxime, which lacks the MTT group, had no effect.

Administration, Oral↗
PubMed1984

The in vitro antimicrobial activity of desacetylcefotaxime compared to other related beta-lactams.

Like all other cephalosporins that contain an acetyl side chain in the 3' position, cefotaxime (CTX) is partially desacetylated in vivo. Desacetylcefotaxime (des-CTX) possesses a broad antimicrobial spectrum and high beta-lactamase stability. With the exception of Pseudomonas aeruginosa, Morganella morganii, Bacteroides fragilis, and Staphylococcus aureus, most strains of other species tested usually had mean MICs of des-CTX lower than 1 microgram/ml. Its activity is generally lower than that of the parent compound. It was only against some strains of P. cepacia that des-CTX surpassed the activity of CTX. The activity of des-CTX markedly exceeds the activity of many therapeutically used cephalosporins. This is especially true for Haemophilus influenzae, Neisseria meningitidis, most species of Enterobacteriaceae, and streptococci other than Streptococcus faecalis.

Anti-Bacterial Agents↗
PubMed1982

[(3-aryl-1,2-benzisoxazol-6-yl)oxy]acetic acids. A new diuretic series.

A series of [(3-aryl-1,2-benzisoxazol-6-yl)oxy]acetic acids was synthesized and tested for diuretic activity in saline-loaded mice and in conscious, water-loaded dogs. The structural requirements for good diuretic activity in both mice and dogs were found to be very specific. In summary, the compounds with the best diuretic activity (13i, 13q, and 13ff) were substituted with a 2-fluorophenyl group at the 3 position and chlorine or bromine at the 7 position. Compound 13ff, [(7-bromo-3-(2-fluorophenyl)-1,2-benzisoxazol-6-yl]oxy]acetic acid (HP 522), was found to be moderately uricosuric in chimpanzees and was selected for further development.

Animals↗
PubMed1982

In vitro evaluation of pyridine-2-azo-p-dimethylaniline cephalosporin, a new diagnostic chromogenic reagent, and comparison with nitrocefin, cephacetrile, and other beta-lactam compounds.

Pyridine-2-azo-p-dimethylanaline cephalosporin (PADAC), a chromogenic reagent which is purple and changes to yellow upon cleavage of its beta-lactam ring, was evaluated in comparison with other chromogenic cephalosporins. PADAC exhibited little antimicrobial activity against gram-negative bacteria, but did have good activity (minimum inhibitory concentration, 0.12 to 0.5 microgram/ml) against Staphylococcus aureus, a quality comparable to nitrocefin. Nitrocefin, however, demonstrated an unexpected and uniquely potent activity against Streptococcus faecalis (minimum inhibitory concentration, less than or equal to 0.06 to 0.12 microgram/ml) The relative hydrolysis rate of PADAC when subjected to six different beta-lactamases was substantially greater than that of cephacetrile, but less than that of nitrocefin. The relative hydrolysis rates of PADAC and nitrocefin were comparable with type IIIa beta lactamase and the derived from Bacillus cereus. The inhibition of beta-lactamase hydrolysis of the chromogenic cephalosporin substrates by six enzyme-stable inhibitors was generally greater with PADAC than with nitrocefin. Unlike nitrocefin, PADAC mixed with 50% human serum or various broth culture media showed no evidence of color change or degradation over several hours. The subsequent enzyme hydrolysis rates of such mixtures were the same as in phosphate buffer. Beta-lactamase-containing bacterial suspensions and clinical specimens containing such bacteria produced positive visual and spectrophotometric color changes when mixed with PADAC or nitrocefin. Although color changes occurred more slowly with PADAC than with nitrocefin, PADAC was not adversely influenced (non-enzyme-related color change) by the protein content of specimens. PADAC appears to be a promising alternative for beta-lactamase diagnostic testing in the clinical and research microbiology laboratory.

Bacteria↗
PubMed1982

In vitro evaluation of CENTA, a new beta-lactamase-susceptible chromogenic cephalosporin reagent.

CENTA is a newly synthesized, beta-lactamase-labile, chromogenic cephalosporin reagent which changes color from light yellow (lambda maximum ca. 340 nm) to chrome yellow (lambda maximum ca. 405 nm) concomitant with hydrolysis of the beta-lactam ring. This compound offers promise as a diagnostic reagent comparable to other chromogens (PADAC and nitrocefin) for the early detection of beta-lactamase-producing clinical isolates, while retaining some antimicrobial effect against Escherichia coli, Klebsiella spp., Proteus mirabilis, Staphylococcus aureus, and non-enterococcal Streptococcus spp. CENTA is relatively unaffected by commonly used microbiological media and human serum.

Bacteriological Techniques↗
PubMed1981

Fendosal.

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Animals↗
PubMed1979

Plasma and tissue levels of furosemide in dogs and monkeys following single and multiple oral doses.

35S-Furosemide was administered to beagle dogs and rhesus monkeys as an oral solution on a single and a 20 repeated 5 mg/kg/day dosing regimen. In both species, furosemide is rapidly but incompletely absorbed with peak plasma levels being achieved within one hour after dosing. The plasma level versus time profiles do not appear to be significantly altered as a result of the repetitive dosing regimen employed, although the profiles themselves are quite different for the two species studied. Following single oral doses, the observed peak plasma levels achieved in dogs are approximately eight-fold higher than in monkeys. In dogs, oral administration of furosemide results in a biexponential disposition curve while in monkeys the profile appears monoexponential. The major disposition phase in dogs has a half-life or approximately 30 minutes and is followed by a slow elimination phase with a half-life of approximately 7 hours. Only a small percentage of the absorbed dose is affected by the slow disposition phase and consequently accumulation of furosemide on the once-daily dosing regimen is slight. In the monkey studies, the rapid disposition phase was not observed and the slow disposition phase had a half-life of approximately 11 hours. On the repetitive dosing regimen, the monkey appeared to accumulate furosemide to a slightly greater extnet than the dog and showed a lesser degree of fluctuation within a dosing interval. In both species, liver and kidney radioactivity levels were not detectable three days after a single dose although low levels of furosemide and/or metabolites were observed for six days following the last dose of the multiple dosing regimen. At the dosage level and regimen employed, no unusual or "typical" lesions associated with furosemide were found in the dog and monkey tissues examined histopathologically.

Administration, Oral↗
PubMed1978

Fendosal (HP 129): a potent anti-inflammatory and analgesic compound.

Fendosal (HP 129) is one of a series of potent non-steroidal anti-inflammatory agents. Fendosal was compared with aspirin in several anti-inflammatory and analgesic bioassay procedures. Results indicate that fendosal has an anti-inflammatory activity 1.4 times greater than does aspirin in carrageenan-induced rat paw edema. Fendosal is 6.9 to 9.5 times more active than aspirin in the prophylactic and therapeutic adjuvant-induced polyarthritis models of chronic inflammation. The analgesic activity of fendosal is considered to be superior to that of aspirin, with the advantage of a prolonged duration of action. The gastric-irritating properties of fendosal are very low in comparison with those of aspirin. Fendosal has a much wider separation of effective and gastric-irritating doses than does aspirin.

Animals↗
PubMed1978

A comparison of clonidine with morphine for antinociceptive and antiwithdrawal actions.

Clonidine was found to possess dose-dependent analgesic and antiwithdrawal activity. In mice, clonidine prolonged the tail flick latency and inhibited phenylquinone-induced writhing. In rats, it inhibited tail withdrawal from hot water and a pain response to pressure application on an inflamed paw. The effective doses of clonidine were different in the different tests employed, but they were always smaller than those of morphine. Naloxone failed to antagonize the analgesic actions of clonidine but effectively antagonized those of morphine. Phenoxybenzamine also did not alter the inhibition of tail flick-induced by clonidine. Clonidine suppressed morphine withdrawal body shakes in a dose-dependent manner as does morphine. This action of clonidine was not reversed by naloxone. In usual laboratory tests, clonidine appears to be an effective analgesic which antagonizes signs of morphine withdrawal.

Analgesics↗
PubMed1977

Pharmacology of a new non-steroidal, anti-inflammatory agent: 6,11-dihydro-11-oxodibenz [b, e] oxepin-2-acetic acid (HP 549).

HP 549 is an orally effective non-steroidal anti-inflammatory agent with moderate analgesic and antipyretic activity. It is active in adjuvant-induced polyarthritis when given prophylactically or therapeutically. HP 549 also inhibits carrageenan-induced paw edema in the rat, an activity which is not altered by adrenalectomy. The analgesic activity of HP 549 was demonstrated in phenylquinone writhing. However, HP 549 produced variable results in the Randall-Selitto analgesia test. The anti-pyretic activity of HP 549 appears to be weak. HP 549, unlike other pharmacologically active anti-inflammatory drugs, does not produce gastric irritation at effective doses and is 45 times less ulcerogenic than indomethacin. Also the acute therapeutic indices for HP 549 are more favorable than for indomethacin.

Acetates↗
PubMed1976

Absorption, distribution, metabolism, and excretion of furosemide in dogs and monkeys I: analytical methodology, metabolism, and urinary excretion.

35S-Furosemide was administered to beagle dogs and rhesus monkeys in an oral solution on a single and a 20 repeated 5-mg/kg/day dosing regimen. Following the single dose, 25.0% (dogs) and 24.0% (monkeys) of the dose were excreted in the urine in 24 hr. TLC analysis demonstrated that both species had similar excretory patterns; i.e., over 80% of the amount excreted in the urine was present as unchanged durosemide and the remainder was composed of a known metabolite, saluamine, and an as yet unidentified metabolite(s). The repetitive dosing regimen did not appear to alter significantly either the total amount recovered in the 24-hr urine or the excretion pattern. Studies in dogs showed that only 50-60% of furosemide was absorbed from oral solution. A significant biliary secretion elimination pathway for furosemide also was observed.

Animals↗
PubMed1976

Carboxyarylindoles as nonsteroidal antiinflammatory agents.

An extensive series of carboxyarylindoles has been evaluated for antiinflammatory activity in the carrageenin paw edema assay. The requirements for optimal antiinflammatory activity in this series are relatively specific: a central pyrrole nucleus with (a) a 3-carboxy-4-hydroxyphenyl moiety substituted directly on the nitrogen, (b) a 2-phenyl group (R2) with a substituent of low electronegativity, (c) absence of a substituent in the 3 position (R3), and (d) a system fused across the 4,5 positions (X), which is lipophilic, quasiplanar, and does not interact sterically with the N-phenyl group. One derivative, 3-(3-carboxy-4-hydroxyphenyl)-2-phenyl-4,5-dihydro-3H-benz[e]indole (42), has been selected for further study.

Animals↗