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.

Prevalence of rheumatoid arthritis in the United States adult population in healthcare claims databases, 2004–2014

Abstract: This study aimed to determine the prevalence of rheumatoid arthritis in the United States (US) adult insured population from 2004 to 2014. This was an observational, retrospective, cross-sectional study based on US administrative health insurance claims databases (Truven Health MarketScan® Research database and IMS PharMetrics Plus database). Trends in RA prevalence focusing on the 10-year period covering January 1, 2004–December 31, 2014 were analyzed using a validated algorithm for the identification of RA. Prevalence rates in the databases were determined and age- and gender-adjusted rates were projected to the US population in 2014. Analysis of data from the two databases indicated that the RA prevalence rate in commercially insured adult US population ranged from 0.41 to 0.54% from 2004 to 2014. The prevalence varied substantially by gender and age in each year and increased gradually across the years for most subgroups. In 2014, out of 31,316,902 adult patients with continuous enrollment in the Truven Health MarketScan® Research database, 157,634 (0.50%) patients met our criteria for RA. Similarly, out of 35,083,356 adult patients in the IMS PharMetrics Plus database, 139,300 (0.50%) patients met our criteria for RA. In 2014, the overall age-adjusted prevalence of RA ranged from 0.53 to 0.55% (0.29–0.31% for males and 0.73–0.78% for females). The prevalence of RA in the US appeared to increase during the period from 2004 to 2014, affecting a conservative estimate of 1.28–1.36 million adults in 2014.

Detection of methicillin-resistant staphylococci by using the polymerase chain reaction.

Abstract: A polymerase chain reaction (PCR)-based test was developed for the detection of mecA in staphylococci. To facilitate this process, a rapid cell lysis procedure was established for the release of DNA from staphylococcal strains. Primers based on the DNA sequence of the mecA gene from Staphylococcus aureus were used in PCRs to screen for the presence of this gene in a total of 98 staphylococcal isolates. Fifty-one isolates were mecA positive (17 S. aureus strains and 34 coagulase-negative staphylococci including S. epidermidis, S. haemolyticus, and S. simulans). Results obtained with PCRs were generally consistent with those of standard microbiological assays. PCRs designed to detect the femA gene (factor essential for methicillin resistance) revealed the presence of the gene in all S. aureus strains examined regardless of the susceptibility profiles of the strains to methicillin. In contrast, femA could not be detected in coagulase-negative staphylococci by PCR with the same primers. Low-stringency hybridization suggested the presence of a gene structurally related to femA in S. epidermidis and other coagulase-negative staphylococci examined. Images

Mechanisms of Dopamine Activation of Fast-Spiking Interneurons That Exert Inhibition in Rat Prefrontal Cortex

Abstract: Prefrontal cortical dopamine (DA) modulates pyramidal cell excitability directly and indirectly by way of its actions on local circuit GABAergic interneurons. DA modulation of interneuronal functions is implicated in the computational properties of prefrontal networks during cognitive processes and in schizophrenia. Morphologically and electrophysiologically distinct classes of putative GABAergic interneurons are found in layers II-V of rat prefrontal cortex. Our whole cell patch-clamp study shows that DA induced a direct, TTX-insensitive, reversible membrane depolarization, and increased the excitability of fast-spiking (FS) interneurons. The DA-induced membrane depolarization was reduced significantly by D1/D5 receptor antagonist SCH 23390, but not by the D2 receptor antagonist (-)sulpiride, D4 receptor antagonists U101958 or L-745870, alpha1-adrenoreceptor antagonist prazosin, or serotoninergic receptor antagonist mianserin. The D1/5 agonists SKF81297 or dihydrexidine, but not D2 agonist quinpirole, also induced a prolonged membrane depolarization. Voltage-clamp analyses of the voltage-dependence of DA-sensitive currents, and the effects of changing [K(+)](O) on reversal potentials of DA responses, revealed that DA suppressed a Cs(+)-sensitive inward rectifier K(+) current and a resting leak K(+) current. D1/D5, but not D2 agonists mimicked the suppressive effects of DA on the leak current, but the DA effects on the inward rectifier K(+) current were not mimicked by either agonist. In a subgroup of FS interneurons, the slowly inactivating membrane outward rectification evoked by depolarizing voltage steps was also attenuated by DA. Collectively, these data showed that DA depolarizes FS interneurons by suppressing a voltage-independent 'leak' K(+) current (via D1/D5 receptor mechanism) and an inwardly rectifying K(+) current (via unknown DA mechanisms). Additional suppression of a slowly inactivating K(+) current led to increase in repetitive firing in response to depolarizing inputs. This D1-induced increase in interneuron excitability enhances GABAergic transmission to PFC pyramidal neurons and could represent a mechanism via which DA suppresses persistent firing of pyramidal neurons in vivo.

Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group

Abstract: In contrast to studies on class I histone deacetylase (HDAC) inhibitors, the elucidation of the molecular mechanisms and therapeutic potential of class IIa HDACs (HDAC4, HDAC5, HDAC7 and HDAC9) is impaired by the lack of potent and selective chemical probes. Here we report the discovery of inhibitors that fill this void with an unprecedented metal-binding group, trifluoromethyloxadiazole (TFMO), which circumvents the selectivity and pharmacologic liabilities of hydroxamates. We confirm direct metal binding of the TFMO through crystallographic approaches and use chemoproteomics to demonstrate the superior selectivity of the TFMO series relative to a hydroxamate-substituted analog. We further apply these tool compounds to reveal gene regulation dependent on the catalytic active site of class IIa HDACs. The discovery of these inhibitors challenges the design process for targeting metalloenzymes through a chelating metal-binding group and suggests therapeutic potential for class IIa HDAC enzyme blockers distinct in mechanism and application compared to current HDAC inhibitors.