Cold ischemia/warm reperfusion (CI/WR) injury remains a problem in liver transplantation. The aim of the current study was to assess the utility of the pan-caspase inhibitor IDN-6556 on CI/WR injury during human liver transplantation. This report is a post hoc analysis of a Phase II, multi-center, randomized, placebo-controlled, double-blinded, parallel group study. Subjects were assigned to four treatment groups: Group 1 (Organ storage/flush: Placebo-Recipient: Placebo); Group 2 (Organ storage/flush: 15 microg/mL-Recipient: Placebo); Group 3 (Organ storage/flush: 5 microg/mL-Recipient: 0.5 mg/kg); and Group 4 (Organ storage/flush: 15 microg/mL-Recipient: 0.5 mg/kg). Liver cell apoptosis was assessed by serum concentrations of the apoptosis-associated CK18Asp396 ('M30') neo-epitope, TUNEL assay and caspase 3/7 immunohistochemistry. Liver injury was assessed by serum AST/ALT determinations. Serum markers of liver cell apoptosis were reduced in all groups receiving drug as compared to placebo. However, TUNEL, caspase 3/7 positive cells and serum AST/ALT levels were only consistently reduced in Group 2 (drug exposed to organ only). This reduction in serum transaminases was significant and observed across the study. In conclusion, IDN-6556 when administered in cold storage and flush solutions during liver transplantation offers local therapeutic protection against CI/WR-mediated apoptosis and injury. However, larger studies are required to confirm these observations.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1600-6143.2006.01595.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Characterization of Factors Associated With Death in Deceased Patients With Mitochondrial Disorders: A Multicenter Cross-Sectional Survey.
Neurology
February 2025
Department of Medicine and Geriatrics, Tuen Mun Hospital, Hong Kong, People's Republic of China.
Background And Objectives: Mitochondrial disorders are multiorgan disorders resulting in significant morbidity and mortality. We aimed to characterize death-associated factors in an international cohort of deceased individuals with mitochondrial disorders.
Methods: This cross-sectional multicenter observational study used data provided by 26 mitochondrial disease centers from 8 countries from January 2022 to March 2023.
Conformational dynamics of a multienzyme complex in anaerobic carbon fixation.
Science
January 2025
Redox and Metalloprotein Research Group, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
In the ancient microbial Wood-Ljungdahl pathway, carbon dioxide (CO) is fixed in a multistep process that ends with acetyl-coenzyme A (acetyl-CoA) synthesis at the bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase complex (CODH/ACS). In this work, we present structural snapshots of the CODH/ACS from the gas-converting acetogen , characterizing the molecular choreography of the overall reaction, including electron transfer to the CODH for CO reduction, methyl transfer from the corrinoid iron-sulfur protein (CoFeSP) partner to the ACS active site, and acetyl-CoA production. Unlike CODH, the multidomain ACS undergoes large conformational changes to form an internal connection to the CODH active site, accommodate the CoFeSP for methyl transfer, and protect the reaction intermediates.
View Article and Find Full Text PDFFood hardness preference reveals multisensory contributions of fly larval gustatory organs in behaviour and physiology.
PLoS Biol
January 2025
Department of Biology, University of Fribourg, Fribourg, Switzerland.
Article Synopsis
- Food is a multisensory experience, relying on visuals, taste, smell, and, surprisingly, texture to assess nutritional value and safety.
- Despite being overlooked, texture offers crucial information about food's physical properties, like hardness and liquidity.
- Recent findings show that some sensory neurons are not limited to specific stimuli; instead, they can respond broadly, indicating greater sensory complexity than previously thought.
"Minimal-Advice" on Salt Intake: Results of a Multicentre Pilot Randomised Controlled Trial on Hypertensive Patients.
High Blood Press Cardiovasc Prev
January 2025
Department of Clinical Medicine and Surgery, ESH Excellence Center of Hypertension, "Federico II" University of Naples Medical School, Via S. Pansini, 5, 80131, Naples, Italy.
Introduction: A strong and well-known association exists between salt consumption, potassium intake, and cardiovascular diseases. MINISAL-SIIA results showed high salt and low potassium consumption in Italian hypertensive patients. In addition, a recent Italian survey showed that the degree of knowledge and behaviour about salt was directly interrelated, suggesting a key role of the educational approach.
View Article and Find Full Text PDFRejection of the concept of hemiurid genus Pulmovermis (Digenea: Hemiuridae) and other taxonomic propositions: new morphological and molecular data regarding Lecithochirium cyanovitellosum (Coil and Kuntz, 1960) Urabe and Sokolov, comb. nov. (formerly Pulmovermis cyanovitellosus).
Syst Parasitol
January 2025
A.N. Severtsov Institute of Ecology and Evolution RAS, Moscow, Russia.
Pulmovermis cyanovitellosus Coil and Kuntz, 1960 is a species of hemiurid trematode that localizes in the lung of sea snakes, an unusual trait for this group of parasites. Recent molecular phylogenetic studies based on 28S rRNA gene sequences have shown that this species is closely related to members of the genus Lecithochirium Lühe, 1901. This finding is unexpected given that Pulmovermis Coil and Kuntz, 1960 and Lecithochirium are currently classified in different subfamilies of Hemiuridae (Pulmoverminae Sandars, 1961 vs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!