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 & Agonist. The organization has 17826 authors who have published 22835 publications receiving 946714 citations. The organization is also known as: Eli Lily.

Efficacy and safety of subcutaneous tabalumab in patients with systemic lupus erythematosus: results from ILLUMINATE-1, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study

Abstract: Objectives Evaluate efficacy and safety of tabalumab, a human IgG4 monoclonal antibody that binds and neutralises membrane and soluble B-cell activating factor (BAFF) versus placebo plus standard of care (SoC) in patients with systemic lupus erythematosus (SLE). Methods This phase III, 52-week study randomised 1164 patients with moderate-to-severe SLE (Safety of Estrogens in Lupus Erythematosus National Assessment—SLE Disease Activity Index ≥6 at baseline). Patients received SoC plus subcutaneous injections of tabalumab or placebo, starting with a loading dose (240 mg) at week 0 and followed by 120 mg every two weeks (120 Q2W, n=387), 120 mg every four weeks (120 Q4W, n=389) or placebo Q2W (n=388). Primary endpoint: proportion of patients achieving SLE Responder Index 5 (SRI-5) response at week 52. Results Similar proportions of patients in each group achieved SRI-5 response at week 52 (120 Q2W: 31.8%; 120 Q4W: 35.2% and placebo: 29.3%). Key secondary endpoints were not met. In a sensitivity analysis not excluding patients who decreased antimalarials or immunosuppressants, SRI-5 response was achieved with 120 Q4W (37.0% vs 29.8% placebo; p=0.021), but not 120 Q2W (34.1%; p=0.171). Significant reductions in anti-dsDNA antibodies, increases in C3 and C4, and reductions in total B cells and immunoglobulins were observed with tabalumab. No differences were observed between treatment groups in percentage of deaths (120 Q2W: 0.8%; 120 Q4W: 0.5%; placebo: 0.5%), serious adverse events (AEs) (range 11.1–14.4%) or treatment-emergent AEs (range 81.1–82.3%). Conclusions Tabalumab had biological activity—changes in anti-dsDNA, complement, B cells and immunoglobulins—consistent with BAFF pathway inhibition. Key clinical efficacy endpoints did not achieve statistical significance. Safety profiles were similar with tabalumab and placebo. Trial registration number NCT01196091.

Olanzapine increases in vivo dopamine and norepinephrine release in rat prefrontal cortex, nucleus accumbens and striatum

Abstract: The in vivo effects of olanzapine on the extracellular monoamine levels in rat prefrontal cortex (Pfc), nucleus accumbens (Acb) and striatum (Cpu) were investigated by means of microdialysis Sequential doses of olanzapine at 05, 3 and 10 mg/kg (SC) dose-dependently increased the extracellular dopamine (DA) and norepinephrine (NE) levels in all three brain areas The increases appeared 30 min after olanzapine administration, reached peaks around 60–90 min and lasted for at least 2 h The highest DA increases in the Acb and Cpu were induced by olanzapine at 3 mg/kg but at 10 mg/kg in the Pfc The peak DA increase in the Pfc (421% ± 46 of the baseline) was significantly larger than those in the Acb (287% ± 24) and Cpu (278% ± 28) Similarly, the highest NE increase in the Pfc (414%±40) induced by 10 mg/kg olanzapine was larger than those in the Acb (233% ± 39) and Cpu (223% ± 24) The DA and NE increases in the Pfc induced by olanzapine at 3 and 10 mg/kg (SC) were slightly larger than those induced by clozapine at the same doses In contrast, haloperidol (05 and 2 mg/kg, SC) did not change Pfc DA and NE levels Extracellular levels of a DA metabolite, DOPAC, and tissue concentrations of a released DA metabolite, 3-methoxytyramine, were also increased by olanzapine, consistent with enhanced DA release However, olanzapine at the three sequential doses did not alter the extracellular levels of either 5-HT or its metabolite, 5-HIAA, in any of the three brain areas In conclusion, the present studies demonstrate that in the case of sequential dosing olanzapine more effectively enhances DA and NE release in the Pfc than in the subcortical areas, which may have an impact on its atypical antipsychotic actions

Serum Proprotein Convertase Subtilisin Kexin Type 9 Is Correlated Directly with Serum LDL Cholesterol

Abstract: Background: Proprotein convertase subtilisin kexin type 9 (PCSK9) is gaining attention as a key regulator of serum LDL-cholesterol (LDLC). This novel serine protease causes the degradation of hepatic LDL receptors by an unknown mechanism. In humans, gain-of-function mutations in the PCSK9 gene cause a form of familial hypercholesterolemia, whereas loss-of-function mutations result in significantly decreased LDLC and decreased cardiovascular risk. Relatively little is known about PCSK9 in human serum. Methods: We used recombinant human PCSK9 protein and 2 different anti-PCSK9 monoclonal antibodies to build a sandwich ELISA. We measured PCSK9 and lipids in 55 human serum samples and correlated the results. We used the anti-PCSK9 antibodies to assay lipoprotein particle fractions separated by sequential flotation ultracentrifugation. Results: Serum concentrations of PCSK9 ranged from 11 to 115 μg/L and were directly correlated with serum concentrations of LDLC ( r = 0.45, P = 0.001) and total cholesterol ( r = 0.50, P = 0.0003), but not with triglycerides ( r = 0.15, P = 0.28) or HDL cholesterol concentrations ( r = 0.13, P = 0.36). PCSK9 was not detectable in any lipoprotein particle fraction, including LDL. Conclusions: PCSK9 is present in human serum, likely not associated with specific lipoprotein particles. The circulating concentrations of human PCSK9 are directly correlated with LDL and total cholesterol concentrations.

Why Observational Studies Should Be Among The Tools Used In Comparative Effectiveness Research

Abstract: Doctors, patients, and other decision makers need access to the best available clinical evidence, which can come from systematic reviews, experimental trials, and observational research. Despite methodological challenges, high-quality observational studies have an important role in comparative effectiveness research because they can address issues that are otherwise difficult or impossible to study. In addition, many clinical and policy decisions do not require the very high levels of certainty provided by large, rigorous randomized trials. This paper provides insights and a framework to guide good decision making that involves the full range of high-quality comparative effectiveness research techniques, including observational research.

Aspirin and Indomethacin Prolong Parturition in Rats: Evidence that Prostaglandins Contribute to Expulsion of Foetus

Abstract: Aspirin and Indomethacin Prolong Parturition in Rats: Evidence that Prostaglandins Contribute to Expulsion of Foetus