Showing papers by "Eli Lilly and Company published in 1975"

Aryloxyphenylpropylamines in treating depression

Abstract: 3-Aryloxy-3-phenylpropylamines and acid additions salts thereof, useful as psychotropic agents, particularly as anti-depressants.

Rapid Detection of Ampicillin-Resistant Haemophilus influenzae and Their Susceptibility to Sixteen Antibiotics

Abstract: Ampicillin-resistant and -susceptible strains of Haemophilus influenzae were tested for susceptibility to 16 antibiotics. Chloramphenicol and a new cephalosporin, cefamandole, were most active with minimal inhibitory concentrations (MICs) for all bacteria tested between 0.5 to 2.0 μg/ml. All but two organisms were susceptible to tetracycline. Ampicillin-resistant strains of H. influenzae were less susceptible (MIC, 4 to 32 μg/ml) to carbenicillin and ticarcillin than ampicillin-susceptible organisms (MIC, 0.25 to 1.0 μg/ml). A rapid assay for β-lactamase, utilizing a chromogenic cephalosporin substrate, detected enzyme production in all 17 ampicillin-resistant strains of H. influenzae . Images

Structure of althiomycin.

Abstract: The structure of the antibiotic althiomycin has been determined by a combination of chemical and physical methods.

Biosynthesis of Mycophenolic Acid: Purification and Characterization of S-Adenosyl-l-Methionine:Demethylmycophenolic Acid O-Methyltransferase

Abstract: The final step in the biosynthesis of mycophenolic acid involves the transfer of a methyl group from S -adenosylmethionine to demethylmycophenolic acid. The enzyme, S -adenosylmethionine:demethylmycophenolic acid O -methyltransferase, was isolated from Penicillium stoloniferum and purified 2,700-fold by ammonium sulfate fractionation and diethylaminoethyl-cellulose and Sephadex G-200 chromatography. Maximum enzyme activity was achieved at pH 7.5 and a temperature of 27 to 28 C. The apparent K m for demethylmycophenolic acid was 3.1 × 10 −6 M. The enzyme preparation was 50% inactivated when exposed to 33 C for 15 min. Mycophenolic acid, homocystine, S -adenosyl-homocysteine, ethanol, and Mg 2+ inhibited the methyltransferase. This enzyme appears to be subject to end product inhibition which may regulate the synthesis of mycophenolic acid. The methyltransferase activity was highest during the early phases of the fermentation.

Papillary cystadenoma lymphomatosum (Warthin's tumor) in patients in a general hospital over a 24-year period.

Abstract: One hundred thirty-seven Warthin's tumors from 120 patients seen during a 23 1/2 year period were studied as two groups. The first group consisted of 32 tumors removed by the otolaryngology department. Material from these cases was re-examined microscopically for evidence of tumor occurrence within lymph nodes located inside and outside the parotid gland. This group of 32 tumors was also studied as part of the second group, 105 additional lesions removed by the surgery department. Data on patient age, sex, and race, as well as tumor multiplicity, location, and size were incorporated into a single statistical analysis. Seventy-two percent of the tumors in the first group were intranodal in location. Second primary Warthin's tumors occurred in 13 (11%) of the patients. Eight occult tumors were identified, and their importance is discussed. A single Negro, a man, was found among 118 patients. The observed frequency of the tumor was twentyfold less than expected among the Negro population.

Physical properties and kinetic behavior of a cephalosporin acetylesterase produced by Bacillus subtilis.

Abstract: An esterase that deacetylates cephalosporins was recovered from the supernatant of a Bacillus subtilis culture. It was partially purified by ammonium sulfate fractionation and ultrafiltration. The enzyme had a temperature optimum between 40 and 50 C and a pH optimum of 7.0. The molecular weight was estimated by gel filtration to be 190,000. The enzyme was very stable and retained greater than 80% of its activity after storage in solution at 25 C for 1 month. The esterase exhibited Michaelis-Menton kinetics with the substrates 7-aminocephalosporanic acid (7-ACA) and 7-(thiophene-2-acetamido)cephalosporanic acid (cephalothin); the Km values were 2.8 × 10-3 and 8.3 × 10-3 M, respectively. The products of 7-ACA deacetylation were weak competitive inhibitors, and a Ki value of 5.0 × 10-2 M was determined for acetate and of 3.6 × 10-2 M for deacetyl-7-ACA. Weak product inhibition did not prevent the deacetylation reaction from going to completion. A 5-mg/ml solution of partially purified esterase completely hydrolyzed (>99.5%) a 24-mg/ml solution of 7-ACA in 3 h. Because of the kinetic properties and excellent stability, this enzyme may be useful in an immobilized form to prepare large quantities of deacetylated cephalosporin derivatives.

Clinical implications of warfarin interactions with five sedatives.

Abstract: The intensity, uniformity and time course of anticoagulant interference by phenobarbital, secobarbital, glutethimide, chloral hydrate and methaqualone were systematically investigated in 16 patients receiving coumarin therapy. Each subject received an individualized fixed daily dose of warfarin and served as his own pre- and postsedative treatment control. Prothrombin times were measured four times weekly during five long-term experiments. Anticoagulant inhibition was observed during the administration of phenobarbital, secobarbital and glutethimide; there was no significant change in prothrombin test results during the trials of chloral hydrate and methaqualone. Barbiturates and glutethimide should not be administered to patients receiving coumarin drugs. The concurrent use of drugs from these groups is decreasing according to a survey of 200 hospital medical records. Chloral hydrate and methaqualone interact pharmacologically with orally administered anticoagulant agents, but the effect is not clinically significant. It is concluded that chloral hydrate and methaqualone may be administered safely without additional caution in prothrombin test monitoring during oral anticoagulant therapy.

Seasonal fluctuations in cannabinoid content of Kansas Marijuana

Abstract: Marijuana (Cannabis sativa L.) was sampled at nine progressive growth stages in Riley County, Kansas, and analyzed for four major cannabinoids: cannabidiol (CBD), della-8-tetrahydrocannabinol (delta-8-THC), delta-9-tetrahydrocannabinol (delta-9-THC), and cannabinol (CBN). Seasonal fluctuation in cannabinoids were related to stage of plant development. Cannabinoids were lowest in seedlings, highest prior to flowering and at an intermediate level thereafter until physiological maturity. Cannabinoids were highest in flowers and progressively lower in leaves, petioles, stems, seeds, and roots. Cannabinoid content of male and female flowers was not significantly different.

13C-NMR. Spectroscopy of naturally occurring substances. XXXII. Vincaleucoblastine and related alkaloids.

Abstract: The total assignment of the 13C-shifts of the complex Vinica rosea L. alkaloids vincaleucoblastine, leurosidine and leurosine and of a synthetic isomer of the latter is presented. The structure of leurosidine is corrected and a tentative structure for the acid-catalyzed product of isomerization of leurosine is proposed.

2,4-Diaminoquinazolines as antithrombotic agents

Abstract: 2,4-Diaminoquinazolines are employed as antithrombotic agents and have the following general formula: ##STR1## wherein R 1 and R 2 are monovalent groups independently selected from the group consisting of A. ##STR2## wherein R 4 and R 5 independently are selected from the group consisting of hydrogen, alkyl, and cycloalkyl, with the proviso that both R 4 and R 5 cannot be cycloalkyl, B. ##STR3## wherein R 6 , R 7 , and R 8 independently are selected from the group consisting of hydrogen and alkyl, and A is a divalent organic group having from two to about six carbon atoms such that the two nitrogen atoms are separated by at least two carbon atoms, and C. heterocyclic-amino, and R 3 is a monovalent group selected from the group consisting of hydrogen, halogen, and alkyl.

New azasteroidal antifungal antibiotics from geotrichu flavo-brunneum

Abstract: Although Geotrichum species occur ubiquitously, antibiotic production by members of this genus has not previously been reported. The antibiotic complex designated A25822, consisting of one major and six minor structurally-related components active primarily against Candida and Trichophyton, represents a new family of naturally-occurring compounds. Approximately 90% of the antibiotic activity synthesized remained associated with the fungal cell mass, from which it was recovered by multiple methanolic extractions for quantitation. Antibiotic production was enhanced by tryptophan, iron, zinc, and high levels of dextrin.

New azasteroidal antifungal antibiotics from Geotrichum flavo-brunneum. II. Isolation and characterization.

Abstract: A novel group of antibiotics, comprising microbiologically-active structurallyrelated factors A25822A, B, D, H, L, M and N, produced by culturing Geotrichum flavo-brunneum NRRL 3862 under submerged aerobic fermentation conditions was isolated by extraction. The individual factors were separated and purified by chromatography and crystallization. The major factor, A25822B, a 15-aza-24-methylene-D-homocholestadiene is a white crystalline compound, C28H45NO. The antibiotics are highly active against fungi and marginally active against bacteria.

Morphine withdrawal response and central cholinergic activity

Abstract: MOST of the different neurotransmitter systems have been implicated in opiate withdrawal. Frederickson and Pinsky1 suggested a primary role for acetylcholine (ACh) in both the development and the expression of dependence on morphine but the specific role of cholinergic mechanisms in opiate withdrawal is not yet clear and deserves further attention. The hypothesis of the role of ACh in the expression of withdrawal phenomena, on which most earlier experiments were based, was that of the ‘cholinergic excess’, first postulated by Paton2. Tests of this hypothesis in various laboratories have, however, produced conflicting results and thus confusion rather than clarification of the role of cholinergic mechanisms in the withdrawal syndrome3–9. Unfortunately, many such studies have neglected to differentiate between peripheral interference with expression and central interference with initiation of the signs of withdrawal by the various drugs studied. Our experiments were designed to eliminate this particular factor, which has contributed to much of the conflict. The results clearly illustrate the confounding effect of failure to separate peripheral from central cholinergic effects and suggest that the exact opposite of the cholinergic excess theory is the actual nature of the central cholinergic role in the morphine withdrawal syndrome.

Novel fluoroalkoxyphenyl-substituted nitrogen heterocycles

Abstract: There is disclosed a class of fluoroalkoxyphenyl-substituted nitrogen-containing heterocycles which are useful as herbicides, plant fungicides, and plant growth regulators. Internodal elongation of plants is inhibited by treatment with compounds of this invention.

Method for increasing cardiac contractility

Abstract: N-Mono or dihydroxyphenylalkyl dopamine derivatives and salts thereof are inotropic agents useful in a method for treatment of acutely depressed cardiac insufficiency.

Glutamate Dehydrogenase Specific Activity and Cephalosporin C Synthesis in the M8650 Series of Cephalosporium acremonium Mutants

Abstract: Conditions for the accurate measure of glutamic dehydrogenase (GDH) from Cephalosporium acremonium were determined. Km values for α-ketoglutarate and ammonium ion were 7 and 15 mM, respectively. The half-saturation for reduced nicotinamide adenine dinucleotide phosphate was 5 μM. Reduced nicotinamide adenine dinucleotide did not serve as a cofactor for the enzyme. The specific activity of GDH was measured in six mutants of C. acremonium which varied in their ability to synthesize cephalosporin C. The mutants represented two separately derived lines, A and B. The four mutants in line B were characterized by a derepression of the GDH upon entry into stationary phase. The two mutants in line A were characterized by repressed levels of GDH during the same period. Both lines exhibited high GDH activity early in their fermentations, but activity decreased during the period of active cell growth. Cytochrome c concentrations followed the same pattern as total soluble intracellular protein. Line A mutants were low in cephalosporin C productivity and line B encompassed low, intermediate, and high productivity mutants. The relative frequency of yield improvements in line A and B indicate that the altered regulation pattern for GDH in line B may have removed a nitrogen limitation for cephalosporin C synthesis.

Herbicidal use of 4-amino-3,3-dimethyl-1-phenyl-2-azetidinones

Abstract: A class of 4-amino-3,3-dimethyl-1-phenyl-2-azetidinones reduce the vigor of unwanted herbaceous plants to which the compounds are applied. The compounds are effective when applied either preemergence or postemergence at rates from about 2 to about 20 kg./ha.

Hexahydro-dibenzo[b,d,]pyran-9-ones as psychotropic, particularly anti-depressant drugs

Abstract: Use of 1-hydroxy-3-alkyl-6,6a,7,8,10,10a-hexahydro-9H-dibenzo[b,d]pyran-9-ones as psychotropic drugs, particularly as anti-depressant drugs, and pharmaceutical compositions containing same.