Extending INR testing intervals in warfarin patients at a multi-center anticoagulation clinic.

Warfarin has been used as an anticoagulant by millions of patients due to its effectiveness, availability, and low cost. Evidence on the safe extension of international normalized ratio (INR) testing frequency remains an area of interest, especially during the recent COVID-19 pandemic. The purpose of this study is to safely extend INR testing intervals in patients throughout a multisite, system-wide anticoagulation clinic.

CD40/anti-CD40 antibody complexes which illustrate agonist and antagonist structural switches.

Background: CD40 is a 48 kDa type I transmembrane protein that is constitutively expressed on hematopoietic cells such as dendritic cells, macrophages, and B cells. Engagement of CD40 by CD40L expressed on T cells results in the production of proinflammatory cytokines, induces T helper cell function, and promotes macrophage activation. The involvement of CD40 in chronic immune activation has resulted in CD40 being proposed as a therapeutic target for a range of chronic inflammatory diseases.

Influence of gestational age and body weight on the pharmacokinetics of labetalol in pregnancy.

Background And Objectives: Labetalol is frequently prescribed for the treatment of hypertension during pregnancy; however, the influence of pregnancy on labetalol pharmacokinetics is uncertain, with inconsistent findings reported by previous studies. This study examined the population pharmacokinetics of oral labetalol during and after pregnancy in women receiving labetalol for hypertension.

Methods: Data were collected from 57 women receiving the drug for hypertension from the 12th week of pregnancy through 12 weeks postpartum using a prospective, longitudinal design.

2,4-Diaminopyrimidine MK2 inhibitors. Part I: Observation of an unexpected inhibitor binding mode.

MK2 is a Ser/Thr kinase of significant interest as an anti-inflammatory drug discovery target. Here we describe the development of in vitro tools for the identification and characterization of MK2 inhibitors, including validation of inhibitor interactions with the crystallography construct and determination of the unique binding mode of 2,4-diaminopyrimidine inhibitors in the MK2 active site. Use of these tools in the optimization of a potent and selective inhibitor lead series is described in the accompanying Letter.

Rational mutagenesis to support structure-based drug design: MAPKAP kinase 2 as a case study.

Background: Structure-based drug design (SBDD) can provide valuable guidance to drug discovery programs. Robust construct design and expression, protein purification and characterization, protein crystallization, and high-resolution diffraction are all needed for rapid, iterative inhibitor design. We describe here robust methods to support SBDD on an oral anti-cytokine drug target, human MAPKAP kinase 2 (MK2).

Outcomes of oral anticoagulant therapy managed by telephone vs in-office visits in an anticoagulation clinic setting.

Background: Anticoagulation management by a dedicated anticoagulation clinic improves patient outcomes compared to routine medical care. Telephone-based anticoagulation management has been described but has not been compared to management with traditional office-based visits. The objective of this study was to compare warfarin-related monitoring outcomes, clinical end points, and the use of health-care resources as a result of warfarin-related complications in anticoagulation clinic patients whose management was conducted by telephone or in-office-based visits.

Survival of partially differentiated mouse embryonic stem cells in the scala media of the guinea pig cochlea.

The low regenerative capacity of the hair cells of the mammalian inner ear is a major obstacle for functional recovery following sensorineural hearing loss. A potential treatment is to replace damaged tissue by transplantation of stem cells. To test this approach, undifferentiated and partially differentiated mouse embryonic stem (ES) cells were delivered into the scala media of the deafened guinea pig cochlea.

Purification and kinetic characterization of recombinant human mitogen-activated protein kinase kinase kinase COT and the complexes with its cellular partner NF-kappa B1 p105.

Cancer osaka thyroid (COT), a human MAP 3 K, is essential for lipopolysaccharide activation of the Erk MAPK cascade in macrophages. COT 30--467 is insoluble, whereas low levels of COT 30--397 can be expressed, but this protein is unstable. However, both COT 30--467 and COT 30--397 are expressed in a soluble and stable form when produced in complex with the C-terminal half of p105.

A single dose of neurotrophin-3 to the cochlea surrounds spiral ganglion neurons and provides trophic support.

Degeneration of spiral ganglion neurons (SGNs) in the cochlea following sensorineural hearing loss is preventable by the infusion of neurotrophins into the scala tympani. This study investigates the trophic effects and distribution of a single bolus infusion of neurotrophin-3 (NT3) into the scala tympani of the cochlea. The left cochleae of 28-day deafened guinea pigs were infused with 0, 100 or 140 ng 125I NT3 via a cochleostomy in the scala tympani of the basal turn.

Delivery of neurotrophin-3 to the cochlea using alginate beads.

Objective: The aim of this study was to design a novel cochlear neurotrophin (NT) delivery system for the rescue of auditory neurons after ototoxicity-induced deafening.

Background: NT-3 is a trophic growth factor that promotes the survival of the auditory nerve and may have a potential therapeutic role in slowing neuron loss in progressive deafness, especially as an adjunct to the current cochlear implant. Beads made from alginate are biodegradable, slow release substances that can be placed at the round window or inside the cochlea.

Resprouting and survival of guinea pig cochlear neurons in response to the administration of the neurotrophins brain-derived neurotrophic factor and neurotrophin-3.

Degeneration of auditory neurons occurs after deafening and is associated with damage to the organ of Corti. The administration of neurotrophins can protect auditory neurons against degeneration if given shortly after deafening. However, it is not known whether the delayed administration of neurotrophins, when significant degeneration has already occurred, will provide similar protection.

Tracing neurotrophin-3 diffusion and uptake in the guinea pig cochlea.

Neurotrophin therapy in the cochlea can potentially slow or reverse the degeneration of the auditory nerve that occurs during progressive deafness. Studies were performed to trace the diffusion and uptake of neurotrophin-3 (NT-3) following infusion into the cochlea. NT-3 labeled with (125)I or coated onto fluorescent microspheres was introduced into the basal turn of normal hearing and deafened guinea pig cochleae via a single slow-rate injection.

Postmenopausal hormone therapy: a concise guide to therapeutic uses, formulations, risks, and alternatives.

Postmenopausal hormone replacement therapy is helpful in relieving menopausal vasomotor symptoms and vaginal atrophy and can prevent osteoporosis; however, attendant risks include breast cancer, thromboembolism, gallbladder disease, stroke, CHD, dementia, and hypertriglyceridemia. Decision making must weigh these risks and benefits and also include potential benefits on mood, colorectal cancer prevention, and hip fracture reduction. Some areas, such as ovarian cancer risk and the impact of combination estrogen-progestin versus unopposed estrogen on risk, remain unclear.