Showing papers by "Eli Lilly and Company published in 1980"

Long-lasting depletion of striatal dopamine by a single injection of amphetamine in iprindole-treated rats

Abstract: A single injection of amphetamine given to rats treated concurrently with iprindole so that they could not metabolize the amphetamine by para-hydroxylation resulted in a decrease in the concentration of striatal dopamine 1 week later. The decrease was antagonized by amfonelic acid, an inhibitor of uptake into dopamine neurons. The long-lasting depletion of cerebral dopamine by amphetamine may be analogous to the depletion of cerebral serotonin by halogenated derivatives of amphetamine.

Controlled release formulations and method of treatment

Abstract: Controlled release formulations useful in the prolonged treatment and control of microbial infections in animals are comprised of a microbial agent intimately dispersed throughout a copolymer derived from lactic acid and glycolic acid. A method for providing protection to animals for extended periods of time following a single administration is provided.

Fibrinogen–fibrin conversion. The mechanism of fibrin-polymer formation in solution

Abstract: The fibrin polymers formed in solution during the earliest phase of the fibrinogen-fibrin conversion are shown to be stable soluble molecules at pH7.4 and 0.15m- or 0.3m-NaCl. The various sequential soluble fibrin polymers produced from the fibrinogen-thrombin reaction can be observed by gel chromatography and can be isolated for characterization. The mechanism of fibrin polymerization proposed from the present studies suggests that the initial event is the thrombin activation at only one of the Aalpha-chains in fibrinogen. The resulting highly reactive intermediate is the true fibrin monomer and it rapidly, and irreversibly, self-associates to form the stable fibrin dimer (s(20.w)=12S). Fibrin dimer possesses the N-terminal pattern alanine/glycine/tyrosine (1:1:2) per 340000 molecular weight, and possesses the chain structure [(alpha)Aalpha)(Bbeta)(2)(gamma)(2)](2). The fibrin dimer is a soluble inert molecule, but additional thrombin activation of its remaining intact Aalpha-chains leads to new associations into larger inert soluble fibrin polymers. In this manner progressively larger fibrin oligomers are constructed with thrombin continually in control of the process because of the necessity to repeatedly re-activate the various fibrin polymers in solution. The inert character of the soluble fibrin polymers can be explained by the reciprocal alignment of the associating molecules, which mutually consumes their active surfaces and leaves an intact Aalpha-chain at either end of each fibrin oligomer. The soluble fibrin polymers will proceed to further association only if thrombin activates these remaining Aalpha-chains, otherwise the fibrin molecules are stable indefinitely. The intermolecular associations within the soluble fibrin polymers are essentially irreversible under these nearly physiological conditions. However, the bonding is not covalent. This mechanism accounts for the clinical observations of stable fibrinogen-derived polymers in the plasma from patients undergoing thrombotic processes. Since it is shown that the intermediate fibrin polymers, themselves, are stable soluble molecules, it is no longer necessary, nor warranted, to invoke hypothetical ;fibrinogen-fibrin complexes' to explain observations of fibrin solubility.

Macrophage factor that induces neutral protease secretion by normal rabbit chondrocytes. Studies of some properties and effects on metabolism of chondrocytes.

Abstract: Normal rabbit-articular chondrocytes secrete very small amounts of degradative enzymes in culture Rabbit peritoneal macrophages, when activated with lipopolysaccharides, release a factor in the medium which stimulates the chondrocytes to produce significantly high levels of collagenase and other neutral protease for 2-3 days The soluble mediator from macrophages appears to be a polypeptide with a molecular weight of 13000-15000 and can be inactivated by short-term treatment with trypsin or pronase The enzyme-synthesis by chondrocytes can be stimulated to the same extent by repeated addition of the macrophage-medium The metabolism of chondrocytes is altered due to the presence of this mediator The cellular proliferation is diminished, while the rates of degradation as well as biosynthesis of the matrix are increased These studies suggest the possibility that in the conditions such as osteoarthritis, where the synovial cells may not play an active role in cartilage degradation, the proteases can be produced by the cartilage cells themselves after the stimulation by macrophage-derived mediators These intrinsic enzymes may be responsible for the slow, but progressive degeneration of cartilage tissue

Effect of diabetes upon penile sympathetic nerves in impotent patients.

Abstract: Samples of erectile tissue taken from the corpora cavernosa of 16 male diabetic patients suffering from impotence were studied. The content of norepinephrine, which reflects sympathetic nerve activity of that tissue, was significantly lower in insulin-dependent patients 104.2 +/- 24.8 (SE) pg/mg wet weight (P less than .001) and diet-controlled patients 483.7 +/- 103.7 (P less than .01) than the normal men (881.7 +/- 62.0). Myelinated and unmyelinated nerve fibers were observed intact and unaltered in each group of patients. The results indicated that normally a dense adrenergic innervation of human erectile tissue is present, but that a reduction occurs in norepinephrine content in diabetic patients with impotence. It appears, however, that the anatomic integrity of the sympathetic nerves is intact. The presence of intact nerve fibers along with a diminished content of neurotransmitter suggests the possibility of pharmacologic treatment of impotence.

Pharmacologically active peptides

Abstract: of the Disclosure Compounds of the formula (I) and pharmaceutically acceptable non-toxic acid addition salts thereof, in which L and D define the chirality; R1 is hydrogen or C1-C3 primary alkyl; R2 is C1-C4 primary or secondary alkyl, allyl, cyclopropylmethyl, C1-C2 hydroxyalkyl, or -(CH2)m-U-CH3 in which U is -S- or and m is 1 or 2; R3 is hydrogen, C1-C4 primary or secondary alkyl, cyclopropylmethyl, or allyl; X is hydrogen, halo, hydroxy, C1-C3 alkoxy, nitro, C1l-C3 alkyl, or trifluoromethyl; and Z is -CH2OR4, -?-NHR4, or -?-OR5, in which R4 is hydrogen or C1-C3 alkyl and R5 is C1-C3 alkyl; are useful analgesic agents. These compounds of formula I are prepared by deblockiny the corresponding blocked compound of formula I by conventional methods.

Mechanism by which uptake inhibitors antagonizep-chloroamphetamine-induced depletion of brain serotonin

Abstract: The mechanism by which uptake inhibitors antagonizep-chloroamphetamine (PCA)-induced depletion of brain serotonin has been suggested to involve: (1) blockade of PCA uptake into the serotonin neuron by means of the membrane carrier, or (2) blockade of the efflux of released serotonin from the neuron, this efflux also requiring the membrane carrier. According to either mechanism, antagonism of serotonin depletion by PCA would provide a valid index of inhibition of the amine uptake system on serotonin neurons in vivo.

Effect of dietary monensin on ovarian response following gonadotropin treatment in prepuberal heifers.

Abstract: Twenty prepuberal Charolais X Brahman-Hereford heifers were randomly assigned to be fed a concentrate containing either 0 mg (C) or 200 mg (M) monensin sodium/head/day. Coastal bermudagrass hay was fed ad libitum. Average daily gain was similar for the two groups. Each heifer received 1 mg of porcine follicle stimulating hormone (FSH-P) (Armour) at 0800 and 2000 hr on days 22 through 26 (10 mg total) and 2,500 IU human chorionic gonadotropin (HCG) on day 27. Flank laparotomy was performed on day 30, for examination of ovaries, and ovariectomy was performed on day 37. The average ovarian size +/- standard error at day 15 ws 3,730 +/- 66 mm3 and 1,848 +/- 55 mm3 for groups M and C, respectively (P < .025), as measured by rectal palpation. Numbers of ovulation sites measured on day 30 were 9.1 +/- 2.2 and 4.9 +/- 1.8 per heifer for groups M and C, respectively (P < .01). After ovariectomy on day 37, heifers fed M were found to have greater ovarian weight (P < .05), more corpora lutea (CL) (P < .05), greater total luteal weight (P < .05), more follicles (P < .01) and greater weight of follicular fluid (P < .05) and stroma (P < .025) than controls. CL were analyzed for progesterone content by spectrophotometric procedures. Heifers fed M had slightly larger CL (P < .10) with progesterone concentrations similar to those in CL from controls. This resulted in more luteal progesterone per CL and more luteal progesterone per heifer in the M heifers than in the controls. Prepuberal heifers fed M, which caused the expected shifts in rumen fermentation and volatile fatty acid production, exhibited an enhanced ovarian response to gonadotropins compared to that exhibited by controls.

Cosmetic cleanser formulation

Abstract: A skin cleanser formulation, which is one of four components used in a cosmetic regime, is disclosed. Applying the regime to the skin increases epidermal cell turnover without skin irritation. The other three components used in the regime are a cream, a lotion, and a tonic.

Skin cell renewal regime

Abstract: A novel cell renewal cosmetic regime is disclosed, which increases epidermal cell turnover without skin irritation. The regime consists of the use of four components: a cleanser, a cream, a lotion, and a tonic.

Implantate package, system and method

Abstract: Implantates are packaged in means capable of aseptic treatment and forming a closed cell having a portion adapted for engagement, rupture, and entry by a tool that permits removal of the implantate for use without handling of the implantate by the user. In such a package, the closed cell is formed by a film which includes portions shaped to assist rupture and entry of the cell by the tool and to assist in encompassing the implantate within the tool for its removal from the cell. The tool used in this system can be the means used to implant the implantate subcutaneously in the body of an animal. Thus, using the system of this invention, an implantate can be provided within a closed cell which is capable of aseptic treatment and transported to a remote site for use. At such a site, the closed cell can be ruptured with an implanter and the implantate can be encompassed within the implanter and removed from the cell for implantation.

Growth promotant controlled release formulations and method of treatment

Abstract: Controlled release formulations comprised of a growth promoting agent admixed with a copolymer derived from lactic acid and glycolic acid and which is substantially free of polymerization catalyst are effective in the prolonged growth promotion of ruminants. A method for continuous dosing of active ingredients to a ruminant is provided.

Derivatives of A-30912A nucleus

Abstract: Compounds of the formula ##STR1## wherein R 1 is an N-alkanoyl amino acyl group of the formula ##STR2## wherein: W is a divalent aminoacyl radical of the formula: ##STR3## wherein A is C 1 -C 10 alkylene or C 5 -C 6 cycloalkylene; ##STR4## wherein R 3 is hydroxymethyl, hydroxyethyl, mercaptomethyl, mercaptoethyl, methylthioethyl, 2-thienyl, 3-indole-methyl, phenyl, benzyl, or substituted phenyl or substituted benzyl in which the benzene ring thereof is substituted with chloro, bromo, iodo, nitro, C 1 -C 3 alkyl, hydroxy, C 1 -C 3 alkylthio, carbamyl, or C 1 -C 3 alkylcarbamyl; ##STR5## wherein X is hydrogen, chloro, bromo, iodo, nitro, C 1 -C 3 alkyl, hydroxy, C 1 -C 3 alkoxy, mercapto, C 1 -C 3 alkylthio, carbamyl, or C 1 -C 3 alkylcarbamyl; ##STR6## wherein X 1 is chloro, bromo, or iodo; ##STR7## wherein B is a divalent radical of the formula: --(CH 2 ) n --, wherein n is an integer from 1 to 3; --CH═CH--; --CH═CH--CH 2 --; ##STR8## and R 2 is C 1 -C 17 alkyl or C 2 -C 17 alkenyl; have antifungal activity.

Comparison of three in vitro assays for carcinogen-induced DNA damage.

Abstract: DNA damage induced by five ultimate carcinogens and five procarcinogens was evaluated by three methods: (1) DNA strand breaks in Crandall feline kidney (CRFK) cells measured by alkaline sucrose gradient centrifugation; (2) unscheduled DNA synthesis (UDS) in CRFK, Syrian hamster embryo (SHE), and rat hepatocyte cultures measured by liquid scintillation counting; and (3) UDS in CRFK, SHE, and rat hepatocyte cultures measured by autoradiography. DNA strand breaks were observed with three procarcinogens and four ultimate carcinogens. Only two procarcinogens and two ultimate carcinogens could be identified by liquid scintillation counting. A positive autoradiographic response for UDS was observed in CRFK cells with four of five ultimate carcinogens and one procarcinogen. SHE cells showed a positive autoradiographic response for UDS with all ultimate carcinogens and three procarcinogens. The autoradiographic system with primary rat hepatocyte cultures was the only one in which a positive response for DNA damage was elicited for all 10 carcinogens.

Treatment of hypertension with fluoxetine and l-5-hydroxytryptophane

Abstract: Fluoxetine alone or a combination of fluoxetine and l-5-hydroxytryptophan, preferably also with a peripheral decarboxylase inhibitor, is administered to hypertensive mammals to lower blood pressure.

Contraceptive methods and compositions

Abstract: Introduction of a pharmaceutically acceptable non-toxic cation salt of a straight-chain or branched chain alkyl sulfonate having from 11 to 16 carbon atoms into the uterine lumen or vaginal cavity prevents conception. Sodium tetradecyl sulfonate is preferred.

The use of monensin in European pasture cattle

Abstract: Monensin increases propionic acid production in the rumen and improves the efficiency of feed conversion in fattening cattle. Trials carried out in the USA showed that 200 mg monensin/head per day was the optimum dose for increasing the rate of live-weight gain in beef cattle at pasture.Twelve pasture trials, involving a total of 434 beef cattle, were carried out during 1976 and 1977 to assess the efficacy of monensin for grazing cattle under European conditions. Each trial compared a group given 200 mg monensin/head per day in 0·5 to 10 kg of carrier supplement with a negative control group, fed blank supplement. The average initial live-weight was 260 kg and the average trial duration was 119 days. Daily live-weight gains of the control and monensin-treated cattle averaged 0·786 and 0·893 kg/head per day respectively, an advantage of 107g/head per day or 13·7 % in favour of the monensin treatment (P<0·001). The growth-promoting effect of monensin showed no tendency to diminish with time.

Controlled release parasitic formulations and method

Abstract: Controlled release formulations useful in controlling endoparasitic infestation in animals over a prolonged period of time are comprised of an anthelmintic agent intimately dispersed throughout a copolymeric matrix derived from the condensation of about 60 to about 95 weight percent of lactic acid and about 40 to about 5 weight percent of glycolic acid, said copolymeric matrix being substantially free of polymerization catalyst.

N-Methyl-N'-2-([(2-dimethylaminomethyl)-4-thiazolyl]methylthio)ethyl 2-nitro-1,1-ethenediamine

Abstract: N-Alkyl-N'-([2-(aminoalkyl)-4-thiazolylmethyl]thioalkyl) guanidines, thioureas, ethenediamines and related compounds, H 2 receptor antagonists, useful in inhibiting gastric acid secretion in mammals.