Plasma and Breast Milk Pharmacokinetics of Tenofovir Disoproxil Fumarate in Nursing Mother with Chronic Hepatitis B-Infant Pairs.

Tenofovir use is associated with lower risk of mother-to-infant transmission of the virus, and discontinuation of the treatment is not safe. However, the safety of the drug during pregnancy and breastfeeding is not clear. In this study, we aimed to determine the tenofovir concentration in plasma of mother-infant pairs along with breast milk in chronic hepatitis B patients during the lactation period. A total of 11 mother-infant pairs were enrolled in the study. All the mothers received tenofovir disoproxil fumarate (TDF) 245 mg/day for at least 1 month because of chronic hepatitis B infection. Maternal blood, breast milk, and infant blood samples were obtained concomitantly. Tenofovir concentrations were determined by liquid chromatography-tandem mass spectrometry. The median concentrations of tenofovir in maternal plasma and breast milk samples were 88.44 (interquartile range [IQR], 62.47 to 116.17) ng/ml and 6.69 (IQR, 4.88 to 7.03) ng/ml, respectively. Tenofovir concentrations were undetectable (<4 ng/ml) in all of the infant plasma samples. The ratio of tenofovir concentration in breast milk to that in maternal plasma was 0.07. Tenofovir disoproxil fumarate passes through the breast milk in a small amount. Infants had no detectable tenofovir level in their plasma. Our study suggests that tenofovir disoproxil fumarate treatment is safe during the breastfeeding period in chronic hepatitis B patients.

Pancreatic islet derived stem cells can express co-stimulatory molecules of antigen-presenting cells.

BACKGROUND: Antigen-presenting cells (APCs) are crucial intermediates in the generation of both innate and specific immune responses. It has long been understood that some APCs are resident in islets in situ as well as after isolation. Our aim was to investigate the presence of molecules involved in antigen presentation in rat pancreatic islet-derived stem cells (PI-SCs). METHODS: We used immunocytochemistry and reverse transcription polymerization chain reaction to study immunophenotypic characteristics; pluripotent-related gene expressions; transcripts coding for antigen-presenting surface proteins CD40, CD80, CD86; and major histocompatibility complex class II in addition to genes with known antiapoptotic functions including mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2), tumor necrosis factor alpha-induced protein 3 (TNFAIP3) interacting protein 1 (TNIP1) and BCL3 of the PI-SCs. RESULTS: Rat PI-SCs were negative for CD45 as demonstrated by flow cytometry and for CD31, CD34, and CD71 as demonstrated by immunocytochemistry. Therefore, there was no evidence of hematopoietic precursors in the cultures. OCT4, SOX2, and REX1 were expressed by rat PI-SCs. We determined the expression of genes for antigen-presenting surface proteins CD40 and CD80, and genes with known antiapoptotic functions including MAPKAPK2, TNIP1 and BCL3, besides the surface protein, CD80, by flow cytometry. CONCLUSION: Expression of these genes by rat PI-SCs implied that they could be involved in the regulation of immunity in islets, highlighting the influence of protective role-playing antiapoptotic mechanisms on pancreatic islet cells. This study offers the potential to understand the molecular mechanisms of a devastating disease, type-1 diabetes mellitus.