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.

Effects of duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, on central neural control of lower urinary tract function in the chloralose-anesthetized female cat.

Abstract: Because all three components of lower urinary tract control (parasympathetic, sympathetic and somatic) are intimately associated with serotonin (5-hydroxytryptamine [5HT])- and norepinephrine (NE)- containing terminals and receptors, in the present study, we examined the effects of increasing extracellular levels of 5HT and NE with duloxetine, a 5HT and NE reuptake inhibitor, on lower urinary tract function under "normal" or nonirritated conditions (transvesical infusion of saline) and in a model of bladder irritation (i.e., transvesical infusion of 0.5% acetic acid) in chloralose-anesthetized cats. Irritation reduced bladder capacity (to 20% of control) and produced insignificant increases in periurethral electromyographic (EMG) activity compared with nonirritated control animals. Duloxetine produced insignificant increases in bladder capacity and sphincter EMG activity when administered under nonirritated bladder conditions. However, this duloxetine "pretreatment" did prevent the typical acetic acid-induced reductions in bladder capacity and unmasked a marked activation of sphincter EMG activity on acetic acid infusion (by 8-fold). Furthermore, when administered initially under irritated bladder conditions, duloxetine produced dose-dependent increases in bladder capacity (by 5-fold) and increased periurethral striated muscle EMG activity (by 8-fold). The effects on bladder activity were due to central mechanisms since bladder contractions evoked by direct electrical stimulation of efferent fibers in the pelvic nerve were not effected by duloxetine. The effects of duloxetine on bladder capacity were antagonized by methiothepin, a non-selective 5HT receptor antagonist, but not by the other 5HT and NE receptor antagonists examined: LY53857, a 5HT2 antagonist; prazosin, an alpha-1-adrenergic receptor antagonist; idazoxan, an alpha-2-adrenergic receptor antagonist; or propranolol, a beta-adrenergic receptor antagonist. The facilitatory effects of duloxetine on periurethral sphincter EMG were significantly antagonized to various degrees by methiothepin, LY53857 and prazosin but not by idazoxan or propranolol. These results indicate that duloxetine, through inhibition of 5HT and NE reuptake, has weak effects under normal conditions. However, under conditions of bladder irritation, duloxetine suppresses bladder activity through 5HT receptor mechanisms and enhances external urethral sphincter activity through 5HT2 and alpha-1-adrenergic mechanisms.

The Role of Angiogenesis in Hepatocellular Carcinoma.

Abstract: Hepatocellular carcinoma (HCC) accounts for about 90% of all primary liver cancers and is the second leading cause of cancer-related deaths worldwide. The hypervascular nature of most HCC tumors underlines the importance of angiogenesis in the pathobiology of these tumors. Several angiogenic pathways have been identified as being dysregulated in HCC, suggesting they may be involved in the development and pathogenesis of HCC. These data provide practical targets for systemic treatments such as those targeting the vascular endothelial growth factor receptor and its ligand. However, the clinical relevance of other more recently identified angiogenic pathways in HCC pathogenesis or treatment remains unclear. Research into molecular profiles and validation of prognostic or predictive biomarkers will be required to identify the patient subsets most likely to experience meaningful benefit from this important class of agents.

Osteoporosis Medication Use After Hip Fracture in U.S. Patients Between 2002 and 2011

Abstract: Hip fractures are common, morbid, costly, and associated with subsequent fractures Historically, postfracture osteoporosis medication use rates have been poor, but have not been recently examined in a large-scale study We conducted a retrospective, observational cohort study based on US administrative insurance claims data for beneficiaries with commercial or Medicare supplemental health insurance Eligible participants were hospitalized for hip fracture between January 1, 2002, and December 31, 2011, and aged 50 years or older at admission The outcome of interest was osteoporosis medication use within 12 months after discharge Patients were censored after 12 months, loss to follow-up, or a medical claim for cancer or Paget's disease, whichever event occurred first During the study period, 96,887 beneficiaries met the inclusion criteria; they had a mean age of 80 years and 70% were female A total of 34,389 (355%) patients were censored before reaching 12 months of follow-up The Kaplan-Meier estimated probability of osteoporosis medication use within 12 months after discharge was 285% The rates declined significantly from 402% in 2002, to 205% in 2011 (p for trend <0001) In multivariable Cox proportional hazards models, a number of patient characteristics were associated with reduced likelihood of osteoporosis medication use, including older age and male gender However, the predictor most strongly and most positively associated with osteoporosis medication use after fracture was osteoporosis medication use before the fracture (hazard ratio = 745; 95% confidence interval [CI], 723–769) Most patients suffering a hip fracture do not use osteoporosis medication in the subsequent year and treatment rates have worsened © 2014 Eli Lilly and Company Journal of Bone and Mineral Research published by Wiley Periodicals, Inc on behalf of the American Society for Bone and Mineral Research