Showing papers by "Eli Lilly and Company published in 1972"
TL;DR: This chapter emphasizes the current concepts and observations hypothalamic control of prolactin secretion, and suggests a useful approach for controlling the secretion and functions of Prolactin in the organism.
Abstract: Publisher Summary This chapter emphasizes the current concepts and observations hypothalamic control of prolactin secretion. The regulation of prolactin secretion is exerted by the hypothalamus, and involves the action of a prolactin-inhibiting factor (PIF), a possible prolactin-releasing factor (PRF), catecholamines, serotonin, and other biogenic amines—all produced in the hypothalamus. Some other agents that stimulate or inhibit prolactin secretion including estrogen, the suckling stimulus, stresses, several drugs, and prolactin, act through hypothalamic mechanism. However, there are some hormones and drugs that can directly influence the anterior pituitary to increase or decrease prolactin secretion, although several of these also can act through the hypothalamus. The interference with hypothalamic pathways to the anterior pituitary by appropriate hypothalamic lesions, stalk section, pituitary transplantation or by administration of certain drugs, results in augmented prolactin release. PIF release from the median eminence is at least partially under the regulation of biogenic amines. The physiological importance of circulating prolactin in controlling secretion of pituitary prolactin remains to be elucidated. The ability of many drugs to either increase or depress prolactin release suggests a useful approach for controlling the secretion and functions of prolactin in the organism.
199 citations
TL;DR: Increase of stillbirths and adverse maternal effects in rats after administration of aspirin and indomethacin in the final days of pregnancy warns against their use in the late stages of human pregnancy.
Abstract: Aspirin and Indomethacin Prolong Parturition in Rats: Evidence that Prostaglandins Contribute to Expulsion of Foetus
193 citations
TL;DR: Experience leads us to believe that their use as visualizing systems in bioautographic procedures could be profitably increased, and use of one or more of these reagents would resolve the problem.
167 citations
TL;DR: Three new cephalosporin antibiotics, prepared by substitution of heterocyclic groups on 7-aminocephalosporanic acid, possess certain desirable chemical or biological properties and are active in vitro against a variety of gram-positive and gram-negative bacteria.
Abstract: Three new cephalosporin antibiotics, prepared by substitution of heterocyclic groups on 7-aminocephalosporanic acid, possess certain desirable chemical or biological properties. All three compounds are active in vitro against a variety of gram-positive and gram-negative bacteria. Minimal inhibitory concentrations (MIC) of these bactericidal antibiotics were not significantly affected by changes in pH or NaCl content of nutrient broth, or by the use of different inoculum sizes. However, agar-dilution MIC values were generally two- to fourfold lower than the MIC values in comparable broth-dilution tests. Stability to cephalosporinase by two of the compounds extended their antibacterial spectra over cephalothin and cephaloridine to include strains of Enterobacter sp. and indole-positive Proteus sp. Binding to serum proteins of the new cephalosporins was intermediate between cephalothin and cephaloridine. Excellent concentrations of the antibiotics were attained in mouse blood, after subcutaneous administration of 20 mg per kg. In vitro biological characteristics of the antibiotics were verified by successful therapy of experimental mouse infections. Regression lines were calculated to show the correlation of agar-dilution MIC values with zones of inhibition by the disc testing procedure. Because each of the three new cephalosporins has certain advantageous properties over cephalothin and cephaloridine, additional toxicological and pharmacological data should be obtained for all three compounds.
109 citations
TL;DR: Serum prolactin levels as measured by radioimmunoassay were depressed significantly as a result of treatment with each ergot alkaloid when compared with corn oil treated control rats, which significantly depressed lactation as assessed by litter weight gain.
Abstract: Ergocornine hydrogenmalienate, 0.5 mg and 1.0 mg; ergonovine maleate, 4.0 mg; dihydroergocornine, 1.0 mg; ergotamine tartrate, 4.0 mg; and ergocryptine mesylate, 0.5 mg; were administered subcutaneously once a day to lactating postpartum female rats from day 4 postpartum (delivery = day 0) to day 8 postpartum. Serum prolactin levels as measured by radioimmunoassay were depressed significantly as a result of treatment with each ergot alkaloid when compared with corn oil treated control rats. These compounds significantly depressed lactation as assessed by litter weight gain. The total mammary tissue weight determined in each animal of an ergocornine hydrogenmalienate treated group showed a reduction compared to those animals in a control group receiving corn oil. Hypophysial homografts equivalent to 2 pituitary glands from donor litter mates were transplanted beneath the kidney capsules of mature hypophysectomized female rats 3 days after hypophysectomy. The rats were treated for 2 days with 0.5 mg ergocor...
58 citations
TL;DR: The relative percentage of incorporation of 3H and 14C from doubly labeled cystine suggests the improbability of the C-7 methoxyl group arising from an intermediate containing a double bond between C-6 and C- 7.
Abstract: acid, byStreptomyces clavuligerus isreported. Aswithcephalosporin C biosynthesis by themoldCephalosporiwn acremoniwn, labels fromcysteine, valine, anda-aminoadipic acidwereincorporated. Unlike cephalosporin C,inA16886Blabel from lysine was incorporated into thea-aminoadipic acidside chain. Labelfrommethionine-'4C-methyl was incorporated into themethoxyl group.Therelative percentage ofincorporation of3Hand14Cfromdoubly labeled cystine suggests theimprobability oftheC-7methoxyl grouparising froman intermediate containing a double bondbetween C-6andC-7.
53 citations
TL;DR: The interaction of cycloheptaamylose with some barbiturates was examined by solubility analysis and by circular dichroism to yield formation constants for the 1:1 interactions.
46 citations
TL;DR: Preferential broadening of the angular methyl signals in the NMR spectra suggests that glycocholate micelles are formed by back-to-back hydrophobic association of the steroid nuclei.
43 citations
Patent•
15 Dec 1972TL;DR: For example, animals having a developed rumen function and animals which ferment fibrous vegetable matter in the cecum convert their feed more efficiently to energy when orally treated with an antibiotic chosen from among A477, A-4696, vancomycin, and ristocetin and their physiologically acceptable salts and esters.
Abstract: Ruminant animals having a developed rumen function and animals which ferment fibrous vegetable matter in the cecum convert their feed more efficiently to energy when orally treated with an antibiotic chosen from among A477, A-4696, vancomycin, and ristocetin and their physiologically-acceptable salts and esters.
43 citations
TL;DR: Single oral doses of aspirin, indomethacin, and fenoprofen (dl‐2‐[3‐phenoxyphenyl] propionic acid) have been evaluated and it is suggested that the method may be useful in evaluating anti‐inflammatory drugs.
Abstract: Nonsteroidal, anti‐inflammatory, antipyretic analgesics have been demonstrated to delay the onset of the erythemic response to high‐intensity ultraviolet irradiation in albino guinea pigs. A similar phenomenon has been demonstrated in male Caucasian sub;ects and is used as a clinical screen for anti‐inflammatory activity. Single oral doses of aspirin, indomethacin, and fenoprofen (dl‐2‐[3‐phenoxyphenyl] propionic acid) have been evaluated. A sequential experimental design demonstrated activity for all three drugs. It is suggested that the method may be useful in evaluating anti‐inflammatory drugs.
37 citations
TL;DR: The lack of response to guanethidine and tyramine indicate that the heart cells are not innervated by adrenergic nerves, and positive inotropic and chronotropic responses were observed following glucagon administration.
TL;DR: Examination of physical data and identification of hydrolysis products permitted the identification of this new metabolite as fumarylcarboxyamido-L-2,3-diaminopropionyl- L-alanine (I), a new antibiotic isolated from a new strain of Streptomyces collinus against Salmonella gallinarum.
Abstract: Screening of a new strain of Streptomyces collinus, Lindenbein, A 19006, against Salmonella gallinarum led to the isolation of a new antibiotic. Examination of physical data and identification of hydrolysis products permitted the identification of this new metabolite as fumarylcarboxyamido-L-2,3-diaminopropionyl-L-alanine (I). The Gram-negative activity of the new antibiotic is inhibited by D-glucosamine and to a lesser extent by N-acetylglucosamine.
TL;DR: The results indicate that fenoprofen is rapidly and efficiently absorbed from the GI tract and extensively metabolized, and it and its metabolites are rapidly eliminated from the body by the kidneys.
TL;DR: Locomotor activity of mice was not affected by age up to 10 months, and before they became corpulent, none of the mice genetically destined to become obese were less active than normal mice.
Abstract: SummaryLocomotor activity of mice was not affected by age up to 10 months. Mice of the VY/Wf and YS/ChWf strains were more active than mice of the C57BL/6J and C57BL/KsJ strains. Locomotor activity of ob/ob and db/db mice decreased significantly after these mice became corpulent. This is not the case for Avy/a, Ay/a and NZO mice. Before they became corpulent, none of the mice genetically destined to become obese were less active than normal mice.The authors are indebted to Professor James Ashmore, Chairman, Department of Pharmacology, Indiana University, School of Medicine, for the use of the activity cages.
TL;DR: Exogenous penicillin in the range of 1 to 15 mg/ml of culture broth had no effect on utilization of acetate or glucose by Penicillium chrysogenum and the antibiotic-synthesizing capacity of the organism was not irreversibly inhibited by exogenous peniillin.
Abstract: aciddidnotlimit penicillin accretion. Incorporation ofradioactive precursors (cysteine, valine, andsodiumphenoxyacetate) intopenicillin inthepresence ofinhibitory concentrations oftheantibiotic indicated thatpenicillin synthesis continued despite thelackofaccretion oftheantibiotic inbroth. Therates ofpenicillin synthesis ina48-hr anda136-hr culture werecompared byshort-term exposure toNa2"5SO4, andnosignificant difference inthebiosynthetic ratewasobserved. Exogenous penicillin intherange of1to15mg/mlofculture broth hadnoeffect onutilization ofacetate orglucose byPenicillium chrysogenum. Theantibiotic-synth esizing capacity oftheorganism wasnotirreversibly inhibited byexogenous penicillin. Thedegradation ofpenicillin during thefermentation wasalso studied. Penicillin V wasstable inbroth filtrate. Catabolic enzymes suchaspenicillinase andpenicillin-acylase werenotdemonstrated inwholebroth, norwastheaccumulation of6-APA,penicilloic acid, orother degradation products detected. Anexamination oftheintracellular penicillin concentration andtheamountofpenicillin associated withthemycelium revealed thatcells contained significantly morepenicillin late inthefermentation thanearlier inthecycle. Thiscell-associated antibiotic maybearegulatory factor infurther penicillin synthesis. Thepenicillin fermentation, like thesynthesis ofmanyother antibiotics andsecondary metabolites, ischaracterized bytwophases. After a period ofrapid growth, strains ofPenicillium chrysogenum steadily synthesize penicillin. The cultures, nutrients, andphysical factors influencingpenicillin production havebeenreviewed extensively (1,4,7-9,13,14). Thecauseofthe termination ofpenicillin accumulation-in spite of themaintenance ofoptimal conditions during fermentation hasnotbeenfully determined. Thisinvestigation wasundertaken toascertain whether penicillin itself actsasaninhibitor or regulator ofpenicillin biosynthesis. MATERIALSAND METHODS Antibiotics. Potassium benzylpenicillin (penicillin G),potassium phenoxymethylpenicillin (penicillin
TL;DR: The systemic administration of a tertiary anticholinesterase agent (physostigmine) that readily penetrates to brain tissue suppressed the hyper-reactivity in a dose-related manner, consistent with the proposition thathyper-reactive, aggressive behavior is suppressed by a centrally acting cholinergic system.
TL;DR: The results suggest that the 3 compounds inhibited self-stimulation by a mechanism independent of brain serotonin, which raises the possibility that this behavioral effect of p -chlorophenylalanine occurs after it is converted to 3-chlorotyrosine.
TL;DR: 4-Chloroamphetamine and 3-chloroamphetamine, which lowered serotonin equally in DMI-pretreated rats, were both present mainly in the particulate fraction after high speed centrifugation of brain homogenates, whereas 2- chloroamphetamine was evenly distributed between the supernatant and particulate fractions and amphetamine was present main in thesupernatant fraction.
Patent•
22 Sep 1972TL;DR: In this article, a mirror is used to reflect light from a single lamp filament and reflected onto a capsule from a mirror in the form of a narrow band cut from an ellipsoid and positioned so that the filament is adjacent to one focus and the capsule adjacent to the other focus.
Abstract: Medicinal-capsule inspection apparatus. Successive capsules spun on their axis in an inspection position are illuminated by intense light originating at a single lamp filament and reflected onto the capsule from a mirror in the form of a narrow band cut from an ellipsoid and positioned so that the filament is adjacent to one focus and the capsule adjacent to the other focus. The mirror wraps around the capsule endwise and produces on the capsule, as seen by a side-viewing lens and two end-viewing lenses, a narrow well-defined and continuous glare line area which is unique in that it curves over the ends substantially to the axis. The lenses project images of the capsule in side and end elevation. Masks at the image planes block the glare light from acceptable capsules, but contain apertures in selected relation to the image glare light areas, which pass light specularly reflected from defects in selected observation areas on the spinning capsules. Such light acts on light sensors behind the apertures to generate electrical control signals which provide inspection output information.
Patent•
20 Nov 1972TL;DR: A test for condUCTing a PLURALITY of LABORATORY ANALYTICAL TEST is forMED from a file-paper bearing a large number of visible printings as mentioned in this paper.
Abstract: A TEST FOR CONDUCTING A PLURALITY OF LABORATORY ANALYTICAL TEST IS FORMED FROM FILTER PAPER BEARING A PLURALITY OF VISIBLE PRINTINGS WHICH CIRCUMSCRIBE PREDETERMINED AREAS ON THE FILTER PAPER FOR RECEIVING LIQUID TEST SAMPLES.
TL;DR: Of the three compounds tested, fenoprofen sodium appears to be the most active inhibitor of platelet function.
Abstract: SummaryFenoprofen sodium (a new antiinflammatory drug), aspirin, and phenylbutazone were compared with respect to their inhibitory activity on platelet function. These compounds inhibit collagen-induced platelet aggregation both in vitro (human, rabbit, and guinea pig) and in vivo (rabbit and guinea pig).In an extracorporeal shunt experiment in the rabbit, both fenoprofen sodium and aspirin inhibited thrombus formation.Of the three compounds tested, fenoprofen sodium appears to be the most active inhibitor of platelet function.
TL;DR: It has been shown that a modified, live panleucopenia virus is quite stable when stored in the medium in which it was produced.
Abstract: It has been shown that a modified, live panleucopenia virus is quite stable when stored in the medium in which it was produced.
TL;DR: Adsorption of Propoxyphene Hydrochloride by Activated Charcoal by Activator Charcoal is inhibited by the following substance: carbon dioxide, carbon monoxide, and carbon dioxide.
Abstract: (1972). Adsorption of Propoxyphene Hydrochloride by Activated Charcoal. Clinical Toxicology: Vol. 5, No. 3, pp. 317-329.
TL;DR: It is suggested that prolactin inhibitors may cause regression of breast cancer in its early stages and may prevent formation of tumors through prophylactic treatment.
Abstract: SummaryAdministration of ergocornine 11 days before, and 5 days after, treatment with DMBA significantly inhibited the induction of mammary tumors in rats. Ergocornine caused rapid and complete (to palpation) regression of 62% of established, DMBA-induced mammary tumors. Examination of sites where tumors had completely regressed to palpation, 2 months after ergocornine treatment was discontinued, revealed that 64% of the tumors did not recur. The effectiveness of ergocornine in regressing tumors was found to be related to initial tumor size. Tumors with volumes up to 1.8 cm3 regressed rapidly after ergocornine; whereas tumors approximately 14.1 cm3 and over did not respond to treatment. Tumors intermediate between these two sizes showed growth inhibition, and many showed regression in varying degrees. Therefore, mammary tumors start to lose their hormonal dependence as they become larger, and eventually may lose it completely. In view of these results, we suggest that prolactin inhibitors may cause regres...
TL;DR: Structural analysis of two new β-lactam antibiotics indicated that they, like cephalosporin C, were composed of modified valine and cysteine residues, and α-aminoadipic acid, however, acid hydrolysis of A16886B and A16884A produced three times as much glycine as did hydrolytic of cEPhalospora C under the same conditions.
Abstract: Structural analysis of two new beta-lactam antibiotics, A16884A and A16886B, indicated that they, like cephalosporin C, were composed of modified valine and cysteine residues, and alpha-aminoadipic acid. However, acid hydrolysis of A16886B and A16884A produced three times as much glycine as did hydrolysis of cephalosporin C under the same conditions. Samples of A16886B-(14)C-6 and A16886B-(14)C-8 were prepared by the addition of cysteine-(14)C-3 and cystine-(14)C-1 to fermentations of Streptomyces clavuligerus. The specific activity of glycine obtained from hydrolysis of A16886B-(14)C-6 was considerably higher than that from hydrolysis of A16886B-(14)C-8. An explanation for the difference in amounts of glycine obtained from hydrolysis of these antibiotics is discussed.
Patent•
13 Jun 1972TL;DR: In this article, a 2-chlorobenzimidazole with an anthranilic acid or ester was used in the presence of trifluoroacetic acid.
Abstract: Benzimidazo [2,1-b]quinazolin- 12(6H)ones, immunosuppressives and agents for treatment of auto-immune diseases, are prepared via (1) reacting a 2-chlorobenzimidazole with an anthranilic acid or ester; (2) reacting a 2-aminobenzimidazole with an anthranilic acid or ester in the presence of trifluoroacetic acid or (3) reacting a 2-methylmercaptobenzimidazole with an anthraniloyl halide hydrohalide.
Patent•
01 Aug 1972TL;DR: In this article, an N-SULFONYLATED O-AMINOPHENYL CARBONYL COMPOUND, SPECIFICally AN N-SUKFONY LONY OAMIN OPHENEL KETONE, with an A-HELOKETONE or ANA-HALOESTER TOPRODUCE AN N,N-DISUBSTITUTED SULFONAMIDE, RINGCLOSING and SEHYDRATING the RESULTing N-N-disubstitut
Abstract: AN INODE IS PRODUCED BY REACTING AN N-SULFONYLATED O-AMINOPHENYL CARBONYL COMPOUND, SPECIFICALLY AN N-SULFONYLATED O-AMINOPHENYL KETONE OR AN N-SUKFONYLATED OAMINOBENZALDEHYDE, WITH AN A-HELOKETONE OR AN A-HALOESTER TOPRODUCE AN N,N-DISUBSTITUTED SULFONAMIDE, RINGCLOSING AND SEHYDRATING THE RESULTING N,N-DISUBSTITUTED SULFONAMIDE TO PRODUCE AN N-SULFONYL INDOLE, AND CLEAVING THE N-SULFONYL GROUP OF N-SULFONYL INDOLE TO OBTAIN A 1-UNSUBSTITUTED INDOLE PRODUCT
Patent•
14 Aug 1972TL;DR: Psoriasis is treated orally and topically with mycophenolic acid or its β-D-glucuronide as discussed by the authors, which can be found in many countries.
Abstract: Psoriasis is treated orally .[.and topically.]. with mycophenolic acid or its β-D-glucuronide.