No abstract

It is widely recognized that the phenotype of familial hyperkalemic hypertension is mainly a consequence of increased activity of the renal Na + -Cl 2 cotransporter (NCC) because of altered regulation by with no-lysine-kinase 1 (WNK1) or WNK4. either by low chloride hypotonic stress or coinjection of oocytes with the solute carrier family 26 (anion exchanger)-member 9 (SLC26A9) cRNA, promoted WNK4 autophosphorylation and increased NCC-dependent Na + transport in a WNK4-dependent manner. Substitution of the leucine with phenylalanine at residue 322 of WNK4, homologous to the chloride-binding pocket in L-WNK1, converted WNK4 into a constitutively autophosphorylated kinase that activated NCC, even without chloride depletion. Elimination of the catalytic activity (D321A or D321K-K186D) or the autophosphorylation site (S335A) in mutant WNK4-L322F abrogated the positive effect on NCC. These observations suggest that WNK4 can exert differential effects on NCC, depending on the intracellular chloride concentration.

The importance of functional right ventricular failure and resultant splanchnic venous congestion has long been under-appreciated and is difficult to assess by traditional physical examination and standard diagnostic imaging. The recent development of the venous excess ultrasound score (VExUS) and growth of point-of-care ultrasound in the last decade has made for a potentially very useful clinical tool. We review the rationale for its use in several pathologies and illustrate with several clinical cases where VExUS was pivotal in clinical management.

Background-The exposure of phosphatidylserine occurs during platelet activation and during in vitro storage. Phosphatidylserine exposure also occurs during apoptosis following the release of mitochondrial cytochrome c. We have examined the role of cytochrome c release, mitochondrial membrane potential (ΔΨm), and cyclophilin D (CypD) in phosphatidylserine exposure due to activation and storage.