University of Pittsburgh

Other

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Yoram Vodovotz

Qi Mi

Maxim Mikheev

Gregory M Constantine

David L Steed

David Okonkwo

Katherine Verdolini Abbott

Patricia A Hebda

Yee Key Li

Jorg Gerlach

Joshua Thomas Sullivan

Gilles Clermont

Ivan Petrov Yotov

Gary An

Alexey Solovyev

Timothy R Billiar

Edward G Lakatta

Kari Nejak-Bowen

Alejandro Soto-Gutierrez

Frederick A Gage

Ira Jacob Fox

Victor Maltsev

Liang-I Kang

Ihor Zahanich

Syevda Sirenko

Aaron W Bell

Taichiro N Nishikawa

Joyeeta Dutta-Moscato

Lukas Schimunek

Rami Namas

Provided herein are methods for segregating trauma, e.g., blunt trauma, patients into different cohorts based on risk of multiple organ dysfunction syndrome using patient data obtained within a short time window following injury. The methods are useful in providing treatment to trauma patients, and for separating trauma patients into cohorts.

Time window-based platform for the rapid stratification of blunt trauma patients into distinct outcome cohorts

A bioreactor is provided which contains cells capable of producing cytokine inhibitors in response to cytokines, in a manner regulated by the local or systemic milieu of an individual patient and predicted by mechanistic computational simulations. The bioreactor transfers the cytokine inhibitors to a patient in need of control of the inflammation process as part of a disease or condition in the patient, such as sepsis, trauma, traumatic brain injury, or wound healing. Related methods also are provided.

Self-regulating device for modulating inflammation

Provided herein are in silico methods of modeling hepatic inflammation, fibrosis/cirrhosis, and cancer. The models are computer-implemented agent-based models and are useful in determining patient prognoses in hepatic conditions, including viral infections, damage, inflammation, and cancer. The modeling system also is useful in modeling the effects of active agents on normal hepatic tissue or hepatic tissue perturbed by inflammation, infection, damage, fibrosis/cirrhosis, and cancer.

Methods for modeling hepatic inflammation

The presently disclosed invention is directed to the discovery that hepatocyte nuclear factor 4 alpha (HNF4&#x3b1;; also known as NR2A1), a transcription factor, reverses hepatocyte dysfunction in an animal model of cirrhosis, resulting in improvement in hepatic function, treatment of cirrhosis, and prolonged survival.

Methods for the treatment and prevention of liver disease

Biological pacemakers engineered to intrinsically generate rhythmic excitations are disclosed. In addition, methods of producing the biological pacemakers are disclosed. Methods of treating or preventing arrhythmia and heart disease associated with a defective pacemakers are also disclosed.

Engineered biological pacemakers

Provided are methods of simulating tissue healing. The methods comprise using a mechanistic computer model of the interrelated effects of inflammation, tissue damage or dysfunction and tissue healing to predict an outcome of healing of damaged tissue in vivo, thereby predicting the outcome of healing of damaged tissue in vivo. Implementations of these methods on a computing device also are provided. Non-limiting examples of diseases and/or conditions that are amenable to simulation according to the methods described herein include: a diabetes, diabetic foot ulcers, necrotizing enterocolitis, ulcerative colitis, Crohn's disease, inflammatory bowel disease, restenosis (post-angioplasty or stent implantation), incisional wounding, excisional wounding, surgery, accidental trauma, pressure ulcer, stasis ulcer, tendon rupture, vocal fold phonotrauma, otitis media and pancreatitis.

Modeling wound healing

A kidney perfusion solution which includes at least one gluconate salt; glutathione; a nitric oxide donor chemical and a chemical inhibitor selective for the inducible isoform of the enzyme nitric oxide synthase; optionally further containing a reagent that causes the reduction of oxidized glutathione. A process for preserving a kidney for transplantation is also disclosed, which includes perfusing the kidney with an amount of a nitric oxide donor chemical in an amount sufficient to mimic enzymatic production of NO by NOS3 or NOS1, while preventing generation of an excessive amount of nitric oxide by the NOS2 isoform of nitric oxide synthase, with or without a reagent that causes the reduction of oxidized glutathione. The invention also includes a process wherein a deceased donor's body is perfused with a solution containing an NO donor, with or without a reagent that causes the reduction of oxidized glutathione, prior to removal of the organs for transplantation.

Kidney perfusion solution containing nitric oxide donor, inhibitor of NOS2, glutathione, gluconate and methods of use

Growing community of inventors

Sewickley, PA, United States of America

Yoram Vodovotz