The Redox Modulating Sonlicromanol Active Metabolite KH176m and the Antioxidant MPG Protect Against Short-Duration Cardiac Ischemia-Reperfusion Injury

Cardiovascular Drugs and Therapy - Sonlicromanol is a phase IIB clinical stage compound developed for treatment of mitochondrial diseases. Its active component, KH176m, functions as an antioxidant,...     

Oral prostaglandin (PGE2) therapy for chronic viral hepatitis B and C

The cytoprotective effects of prostaglandins have been utilized in the prevention of hepatitis B virus reactivation after liver transplantation. This pilot study evaluated the effects of oral prostaglandin E₂ (PGE₂) in chronic viral hepatitis B and C. Twenty patients with chronic hepatitis B and 20 patients with chronic hepatitis C received 4mgday^–1 PGE₂ for 6 months. The lymphocyte antiviral enzyme 2',5'-oligoadenylate synthetase (2',5'-OAS) and peripheral blood monocyte procoagulant activity (PCA) were measured before, during and after the treatment. Three of 20 hepatitis B and five of 20 hepatitis C patients withdrew from the study. Eight of 17 hepatitis B patients responded: in seven of these eight patients, serum alanine aminotransferase (ALT) levels normalized; loss of viral replication was sustained in all eight patients; and seroconversion from hepatitis Be antigen (HBeAg) to hepatitis Be antibody (HBeAb) positivity occurred in seven patients over the 48-week duration of this study. In 14 of the 15 hepatitis C patients, hepatitis C virus (HCV) RNA remained detectable and the serum ALT levels remained elevated. 2',5'-OAS levels and PCA values did not correlate with other markers of response to PGE₂ therapy in either chronic hepatitis B or C. In summary, PGE₂ was associated with sustained loss of viral replication in 47% of chronic hepatitis B patients; no beneficial effects were apparent in chronic hepatitis C.     

Evaluating the landscape of gene cooperativity with receptor tyrosine kinases in liver tumorigenesis using transposon-mediated mutagenesis

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Impact of a Low-Glucose Peritoneal Dialysis Regimen on Fibrosis and Inflammation Biomarkers

♦ Background: The impact of a low-glucose peritoneal dialysis (PD) regimen on biomarkers of peritoneal inflammation, fibrosis and membrane integrity remains to be investigated.♦ Methods: In a randomized, prospective study, 80 incident PD patients received either a low-glucose regimen comprising Physioneal (P), Extraneal (E) and Nutrineal (N) (Baxter Healthcare Corporation, Deerfield, IL, USA) (PEN group), or Dianeal (control group) for 12 months, after which both groups continued with Dianeal dialysis for 6 months. Serum and dialysate levels of vascular endothelial growth factor (VEGF), decorin, hepatocyte growth factor (HGF), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), hyaluronan (HA), adiponectin, soluble-intracellular adhesion molecule (s-ICAM), vascular cell adhesion molecule-1 (VCAM-1) and P-selectin, and dialysate cancer antigen 125 (CA125), were measured after 12 and 18 months. This paper focuses on results after 12 months, when patients in the PEN group changed to glucose-based PD fluid (PDF).♦ Results: At the end of 12 months, effluent dialysate levels of CA125, decorin, HGF, IL-6, adiponectin and adhesion molecules were significantly higher in the PEN group compared to controls, but all decreased after patients switched to glucose-based PDF. Macrophage migration inhibitory factor level was lower in the PEN group but increased after changing to glucose-based PDF and was similar to controls at 18 months. Serum adiponectin level was higher in the PEN group at 12 months, but was similar in the 2 groups at 18 months. Body weight, residual renal function, ultrafiltration volume and total Kt/V did not differ between both groups. Dialysate-to-plasma creatinine ratio at 4 h was higher in the PEN group at 12 months and remained so after switching to glucose-based PDF.♦ Conclusion: Changes in the biomarkers suggest that the PEN PD regimen may be associated with better preservation of peritoneal membrane integrity and reduced systemic vascular endothelial injury.