Eli Lilly and Company

About: Eli Lilly and Company is a company organization based out in Indianapolis, Indiana, United States. It is known for research contribution in the topics: Population & Receptor. The organization has 17826 authors who have published 22835 publications receiving 946714 citations. The organization is also known as: Eli Lily.

The Metabotropic Glutamate 2/3 Receptor Agonists LY354740 and LY379268 Selectively Attenuate Phencyclidine versus d-Amphetamine Motor Behaviors in Rats

Abstract: Previous animal studies have indicated that drugs targeted at metabotropic glutamate (mGlu) receptors may be useful for treatment of psychosis. In this article, the effects of the novel, potent, and selective mGlu2/3 receptor agonists LY354740 and LY379268, and the clinically effective agents clozapine and haloperidol, were investigated using phencyclidine (PCP; 5 mg/kg)- versus d-amphetamine (AMP; 3 mg/kg)-evoked motor activities. LY354740 (1-10 mg/kg s.c.), LY379268 (0.3-3 mg/kg s.c.), clozapine (1-10 mg/kg s.c.), and haloperidol (0.03-1 mg/kg s.c.) reversed the increases in ambulations, fine motor (nonambulatory) movements, and decreased time at rest evoked by PCP. Furthermore, the inhibitions of the PCP response by the mGlu2/3 agonist LY379268, but not by clozapine, were completely reversed by the selective mGlu2/3 receptor antagonist LY341495. Doses of LY354740 and LY379268 that blocked the effects on PCP had no effects on rotorod performance, and (with the exception of rearing behavior) had minimal effects on AMP-evoked motor activities. Clozapine blocked AMP-induced rearing but enhanced AMP-induced ambulations and fine movements at the lower doses (1 and 3 mg/kg). Unlike the mGlu2/3 agonists, the highest dose of clozapine tested (10 mg/kg) impaired animals on the rotorod. Haloperidol potently blocked all PCP and AMP effects, but only at doses associated with motor impairment. These data demonstrate that mGlu2/3 receptor agonists act via a unique mechanism to selectively block PCP-induced behaviors. Moreover, the marked mGlu2/3 receptor-mediated inhibitions of PCP-evoked behaviors by LY354740 and LY379268, with minimal effects on AMP, may indicate potential antipsychotic effects in humans in the absence of dopamine mediated extrapyramidal side effects.

Advances in the assessment and control of the effector functions of therapeutic antibodies.

Abstract: The Fc (crystallizable fragment) region of therapeutic antibodies can have an important role in their safety and efficacy. Although much is known about the structure-activity relationship of antibodies and the factors that influence Fc effector functions, a process has not yet been defined to clearly delineate how Fc functionality should be assessed and controlled during antibody development and manufacturing. In this article, we summarize the current knowledge of antibody Fc functionality, provide a strategy for assessing the effector functions of different classes of therapeutic antibodies (including Fc fusion proteins) and propose a path for routine testing and controls for manufacturers of antibody products.

Enhancement of Experimental Fracture-Healing by Systemic Administration of Recombinant Human Parathyroid Hormone (PTH 1-34)

Abstract: Background: Recombinant human parathyroid hormone (PTH [1-34]; teriparatide) is a new treatment for postmenopausal osteoporosis that can be systemically administered for the primary purpose of increasing bone formation Because several studies have described the enhancement of fracture-healing and o

Adaptive Designs in Clinical Drug Development—An Executive Summary of the PhRMA Working Group

Abstract: A PhRMA Working Group on adaptive clinical trial designs has been formed to investigate and facilitate opportunities for wider acceptance and usage of adaptive designs and related methodologies. A White Paper summarizing the findings of the group is in preparation; this article is an Executive Summary for that full White Paper, and summarizes the findings and recommendations of the group. Logistic, operational, procedural, and statistical challenges associated with adaptive designs are addressed. Three particular areas where it is felt that adaptive designs can be utilized beneficially are discussed: dose finding, seamless Phase II/III trials designs, and sample size reestimation.

An electroenzymatic glucose sensor fabricated on a flexible substrate

Abstract: A glucose-oxidase-based electroenzymatic glucose sensor has been developed using thin-/thick-film processing techniques. We believe that this processing scheme will overcome a major impediment to the successful movement of the devices from the research laboratory to the marketplace by removing the difficulty of fabricating large numbers of reproducible and economical sensors. Several hundred sensors have been fabricated and tested in vitro. The sensors respond linearly to glucose, are stable for 72 h, are oxygen independent and have a 90 s response time. The sensors have also responded appropriately during preliminary glucose tolerance tests performed in rabbits.