Validation of a method for the determination of Aderamastat (FP-025) in KEDTA human plasma by LC-MS/MS.

Aderamastat (FP-025) is a small molecule, selective matrix metalloproteinase (MMP)-12 inhibitor, under development for respiratory conditions which may include chronic inflammatory airway diseases and pulmonary fibrosis. To support evaluation of the pharmacokinetic parameters of Aderamastat in humans, we developed and validated a high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) analytical method for the quantification of Aderamastat in human plasma. This assay was validated in compliance with the Food and Drug Administration (FDA) Good Laboratory Practice Regulations (GLP) and European Medicines Agency (EMA) guidelines.

Trillions and Trillions: Herpes Simplex Virus-1 Hepatitis in an Immunocompetent Adult.

We describe a case of acute liver failure and myopericarditis due to herpes simplex virus-1 (HSV-1) in an immunocompetent adult. We estimate that, at the height of viremia, the patient contained a quantity of HSV-1 virions approaching that of human cells. The patient recovered with acyclovir that was dose-adjusted for neurotoxicity and developed a vigorous anti-HSV-1 T-cell response.

Irreversible Electroporation Can Effectively Ablate Hepatocellular Carcinoma to Complete Pathologic Necrosis.

Purpose: To describe full explant pathology and radiographic correlation in patients with hepatocellular carcinoma (HCC) treated with irreversible electroporation (IRE) who subsequently underwent liver transplant.

Materials And Methods: In a retrospective study, 6 patients who had undergone IRE for HCC and subsequent orthotopic liver transplant during the period 2011-2013 were evaluated. Of the 6 patients, 4 had Child-Pugh class A cirrhosis, and 2 had class B cirrhosis.

Cellular immune correlates analysis of an HIV-1 preexposure prophylaxis trial.

HIV-1-specific T-cell responses in exposed seronegative subjects suggest that a viral breach of the exposure site is more common than current transmission rates would suggest and that host immunity can extinguish subsequent infection foci. The Preexposure Prophylaxis Initiative (iPrEx) chemoprophylaxis trial provided an opportunity to rigorously investigate these responses in a case-control immunology study; 84 preinfection peripheral blood mononuclear cell samples from individuals enrolled in the iPrEx trial who later seroconverted were matched with 480 samples from enrolled subjects who remained seronegative from both the placebo and active treatment arms. T-cell responses to HIV-1 Gag, Protease, Integrase, Reverse Transcriptase, Vif, and Nef antigens were quantified for all subjects in an IFN-γ enzyme-linked immunospot (ELISpot) assay.

Increased expression of intrinsic antiviral genes in HLA-B*57-positive individuals.

The genetic background of HIV-1-infected subjects, particularly the HLA class I haplotype, appears to be critical in determining disease progression rates, thought to be a result of the role of HIV-1-specific CD8(+) T cell responses. The HLA-B*57 allele is strongly associated with viremic suppression and slower disease progression. However, there is considerable heterogeneity in HIV-1 disease progression rates among HLA-B*57-positive subjects, suggesting that additional factors may help to contain viral replication.