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.

Prediction of future Alzheimer's disease dementia using plasma phospho-tau combined with other accessible measures.

Abstract: A combination of plasma phospho-tau (P-tau) and other accessible biomarkers might provide accurate prediction about the risk of developing Alzheimer’s disease (AD) dementia. We examined this in participants with subjective cognitive decline and mild cognitive impairment from the BioFINDER (n = 340) and Alzheimer’s Disease Neuroimaging Initiative (ADNI) (n = 543) studies. Plasma P-tau, plasma Aβ42/Aβ40, plasma neurofilament light, APOE genotype, brief cognitive tests and an AD-specific magnetic resonance imaging measure were examined using progression to AD as outcome. Within 4 years, plasma P-tau217 predicted AD accurately (area under the curve (AUC) = 0.83) in BioFINDER. Combining plasma P-tau217, memory, executive function and APOE produced higher accuracy (AUC = 0.91, P < 0.001). In ADNI, this model had similar AUC (0.90) using plasma P-tau181 instead of P-tau217. The model was implemented online for prediction of the individual probability of progressing to AD. Within 2 and 6 years, similar models had AUCs of 0.90–0.91 in both cohorts. Using cerebrospinal fluid P-tau, Aβ42/Aβ40 and neurofilament light instead of plasma biomarkers did not improve the accuracy significantly. The clinical predictions by memory clinic physicians had significantly lower accuracy (4-year AUC = 0.71). In summary, plasma P-tau, in combination with brief cognitive tests and APOE genotyping, might greatly improve the diagnostic prediction of AD and facilitate recruitment for AD trials. Plasma P-tau, in combination with clinical measures, predicts future Alzheimer’s disease dementia in two independent cohorts with high accuracy and is superior to the clinical diagnostic predictions of specialists.

Pharmacologically directed design of the dose rate and schedule of 2',2'-difluorodeoxycytidine (Gemcitabine) administration in leukemia.

Abstract: The objective of this study was to determine the dose rate of 2',2'-difluorodeoxycytidine (dFdC) that maximizes the accumulation of the active 5'-triphosphate (dFdCTP) in circulating leukemia cells during therapy. The investigational approach was to evaluate the relationship between plasma dFdC and the accumulation of dFdCTP by circulating leukemia cells during infusion of different dFdC dose rates in the same individuals. Four patients with relapsed leukemia were treated weekly with two or three consecutive infusions of 800 mg/m2, the first administered over 1 h, the second over 2 h, and the third over 3 h. Two patients, one with acute myelogenous leukemia and one with acute lymphocytic leukemia, received all three infusions, but thrombocytopenia prohibited infusion of the third dose to two patients with chronic lymphocytic leukemia. The average steady-state plasma dFdC levels, achieved within 15 min after the infusion began, were 43.8 microM during infusion of 800 mg/m2/h, 9.4 microM during infusion of 400 mg/m2/h, and 5.6 microM at 267 mg/m2/h. The median area under the concentration times time curve of dFdCTP in leukemia cells during infusion was increased 2.3- and 5.1-fold for the 2- and 3-h infusions, respectively. In vitro incubations of leukemia cells from the four patients with 2.5-100 microM dFdC for 1 h showed that the maximum cellular accumulation of dFdCTP was produced by 15-20 microM dFdC. We conclude that a dose rate of greater than 400 mg/m2/h was required to achieve plasma dFdC levels that supported the maximum rate of dFdCTP accumulation in leukemia cells.

The disposition of prasugrel, a novel thienopyridine, in humans.

Abstract: Prasugrel, a prodrug, is a novel and potent inhibitor of platelet aggregation in vivo. The metabolism of prasugrel and the elimination and pharmacokinetics of its active metabolite, 2-[1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-mercapto-3-piperidinylidene]acetic acid (R-138727), three inactive metabolites, and radioactivity were determined in five healthy male subjects after a single 15-mg (100 microCi) p.o. dose of [(14)C]prasugrel. Prasugrel was rapidly absorbed, and maximum plasma concentrations of radioactivity and R-138727 were achieved in 30 min, indicating rapid formation of R-138727. Prasugrel was extensively metabolized in humans, first by hydrolysis to a thiolactone, followed by ring opening to form R-138727, which was further metabolized by S-methylation and conjugation with cysteine. Total radioactivity was higher in plasma than in blood, suggesting limited penetration of prasugrel metabolites into red blood cells. Approximately 70% of the dose was excreted in the urine and 25% in the feces.

Leptin levels in patients with anorexia nervosa are reduced in the acute stage and elevated upon short-term weight restoration

Abstract: Circulating leptin concentrations are known to be low in acute anorexia nervosa (AN), which is characterized by low weight, amenorrhea and specific psychopathological features. In this study plasma leptin concentrations were determined during inpatient treatment of 23 adolescent females with AN using a sensitive radioimmunoassay (RIA) and set into relationship to leptin levels of females matched for age, body mass index (BMI; kg m-2) and/or percent body fat. At referral patients had leptin concentrations well below the female controls. Weight gains led to steep increases of leptin levels which peaked at values well in excess of those observed in controls matched for BMI. In patients who reached the final treatment stage and who were followed-up after discharge, levels subsequently fluctuated and finally dropped into or below the control range. The low leptin levels at referral are likely to be involved in the pathogenesis of amenorrhea and the reduced metabolic state of acutely ill patients. Peak leptin levels reached after weight gain are possibly the cause of increased energy expenditure during this stage of the disorder.