Vortioxetine Exposure During Pregnancy and Lactation: A Japanese Case Study of Neonatal Implications and Quantitative Milk and Plasma Analyses.

Background: Information about influences of vortioxetine on pregnant women and neonates during perinatal period is almost unknown. Case Presentation: The case was a 28-year-old Japanese woman in her first pregnancy, treated for depression with vortioxetine (20 mg daily) among other medications. At 36 weeks of gestation, she was admitted for premature rupture of the membranes and delivered a girl with no apparent congenital anomalies. Immediately after birth, the neonate required brief respiratory support due to her dyspnea and poor muscle tone. Her respiratory condition improved in 6 days after delivery, and she demonstrated normal developmental progress afterward. Maternal plasma and breast milk samples, collected 4 days postpartum, revealed vortioxetine concentrations of 11.4 ng/mL and 9.3 ng/mL, respectively. The calculated relative infant dose (RID) was estimated at 0.32%. After discharge from hospital, the infant presented no detectable drug-related adverse effects, with over 50% of nutrition derived from breastfeeding. Conclusion: This case showed minimal transfer of vortioxetine into breast milk, reflected in a low RID. The findings suggest limited neonatal exposure to the drug, with no adverse developmental effects observed in the infant. However, the case also indicated the potential for vortioxetine use during pregnancy to contribute to the onset of severe neonatal asphyxia. Further research is needed for a comprehensive understanding of its impact on neonatal health.

A novel homozygous missense mutation in PNPLA2 in a patient manifesting primary triglyceride deposit cardiomyovasculopathy.

Primary triglyceride deposit cardiomyovasculopathy (P-TGCV), caused by a rare genetic mutation in PNPLA2 encoding adipose triglyceride lipase (ATGL), exhibits severe cardiomyocyte steatosis and heart failure. Here, we report the case of a 51-year-old man with P-TGCV homozygous for a novel PNPLA2 mutation (c.446C > G, P149R) in the catalytic domain of ATGL. Analyses of endomyocardial biopsy specimens and in vitro expression experiments showed mutant protein expression with conserved lipid binding, but reduced lipolytic activity, indicating mutation pathogenicity.

A stromal cell-derived membrane protein that supports hematopoietic stem cells.

Hematopoietic stem cells cannot be maintained in vitro without stromal cells, even if they are provided with growth factors, and it is likely that supportive cells in the bone marrow express membrane or secreted proteins that maintain hematopoiesis. Here we show that mKirre, a mammalian homolog of the gene kirre of Drosophila melanogaster, encodes a type Ia membrane protein that is involved in the hematopoietic supportive capacity of OP9 mouse stromal cells. Repressing mKirre expression with a short interfering RNA significantly reduced this supportive capacity. Our data suggest that mKirre is cleaved by metalloproteinases and that the extracellular domain of mKirre is responsible for supporting hematopoietic stem cells. These results contribute to our understanding of the mechanisms by which the hematopoietic microenvironment regulates hematopoiesis.