Application of Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions between Elexacaftor/Tezacaftor/Ivacaftor and Tacrolimus in Lung Transplant Recipients.

Elexacaftor/tezacaftor/ivacaftor (ETI) treatment has potential benefits in lung transplant recipients, including improvements in extrapulmonary manifestations, such as gastrointestinal and sinus disease; however, ivacaftor is an inhibitor of cytochrome P450 3A (CYP3A) and may, therefore, pose a risk for elevated systemic exposure to tacrolimus. The aim of this investigation is to determine the impact of ETI on tacrolimus exposure and devise an appropriate dosing regimen to manage the risk of this drug-drug interaction (DDI). The CYP3A-mediated DDI of ivacaftor-tacrolimus was evaluated using a physiologically based pharmacokinetic (PBPK) modeling approach, incorporating CYP3A4 inhibition parameters of ivacaftor and in vitro enzyme kinetic parameters of tacrolimus.

Comparison of Skin Cancer Incidence in Caucasian and Non-Caucasian Liver Vs. Lung Transplant Recipients: A Tale of Two Regimens.

Background: Organ transplantation is a significant risk factor for the development of skin cancer. The impact of skin type, immunosuppressive regimens, and photosensitizing agents requires further study.

Objective: The objective of this study was to compare skin cancer development between Caucasian and non-Caucasian transplant recipients at the University of Southern California.

Use of Foscarnet Therapy for EBV Infection following Control of PTLD with Enhancement of Cellular Immunity in a Lung-Transplant Recipient.

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication following solid organ transplantation with an annual incidence rate of 3-5% in lung-transplant recipients. Pathogenesis indicates a strong association with functional over-immunosuppression and EBV infection. Clinical improvement is generally observed with reduction in immunosuppression intensity alone.

Endothelial dysfunction and decreased vascular responsiveness in the anterior cruciate ligament-deficient model of osteoarthritis.

Chronic inflammation associated with osteoarthritis (OA) may alter normal vascular responses and contribute to joint degradation. Vascular responses to vasoactive mediators were evaluated in the medial collateral ligament (MCL) of the anterior cruciate ligament (ACL)-deficient knee. Chronic joint instability and progressive OA were induced in rabbit knees by surgical transection of the ACL.

A laser speckle imaging technique for measuring tissue perfusion.

Laser Doppler imaging (LDI) has become a standard method for optical measurement of tissue perfusion, but is limited by low resolution and long measurement times. We have developed an analysis technique based on a laser speckle imaging method that generates rapid, high-resolution perfusion images. We have called it laser speckle perfusion imaging (LSPI).

ACL deficiency impairs the vasoconstrictive efficacy of neuropeptide Y and phenylephrine in articular tissues: a laser speckle perfusion imaging study.

Sympathetic-derived neuropeptide Y (NPY) helps regulate inflammatory responses in injury and disease, is a vasoconstrictor, and stimulates angiogenesis. Rupture of the anterior cruciate ligament (ACL) is a common clinical presentation that results in tissue inflammation, hyperemia, and angiogenesis in the intact medial collateral ligament (MCL). This study is the first to examine the vasoregulatory role of NPY in ACL-deficient knee joints by using the newly developed technique of laser speckle perfusion imaging (LSPI).

Laser Doppler imaging of burn scars: a comparison of wavelength and scanning methods.

Unlabelled: Laser Doppler perfusion imaging (LDI) is a useful tool for the early clinical assessment of burn depth and prognostic evaluation of injuries that may require skin grafting. We have evaluated two commercially available laser Doppler imagers for the perfusion measurement of normal and burn scar tissue.

Methods: A single wavelength (635 nm), step-wise scanning LDI and a dual wavelength (633 and 780 nm), continuous scanning LDI were used.