Reduction of Proteinuria in a Patient With Primary Aldosteronism by Angiotensin II Receptor Blocker Administration.

The renin-angiotensin-aldosterone system (RAAS) is a major target for treating hypertension and preventing various complications. Mineralocorticoid receptor (MR) antagonists are recommended as specific drugs to ameliorate hyperactive MR signaling, especially for patients with idiopathic hyperaldosteronism. However, the clinical implications of an increased RAAS activity and angiotensin II level induced by MR antagonist administration remain unclear. A 72-year-old Japanese man was referred to our university hospital for refractory hypertension management. He has also had type 2 diabetes mellitus and nephropathy for 8 years. MR antagonists, initiated based on the diagnosis of primary aldosteronism, effectively improved his hypertension. However, proteinuria of 2.5 g/g creatinine, concomitant with an increase in both active renin concentration and plasma aldosterone concentration, occurred. Additional administration of an angiotensin II receptor blocker successfully reduced the plasma aldosterone concentration and proteinuria (<0.3 g/g creatinine). Preserved renal function was confirmed for 1 year thereafter. In conclusion, this case suggests that the angiotensin II receptor is a potential target to treat proteinuria concomitant with primary aldosteronism. RAAS reactivation should be considered when an MR antagonist is initiated for patients with primary aldosteronism, especially idiopathic hyperaldosteronism.

The Tom40 assembly process probed using the attachment of different intramitochondrial sorting signals.

The TOM40 complex is a protein translocator in the mitochondrial outer membrane and consists of several different subunits. Among them, Tom40 is a central subunit that constitutes a protein-conducting channel by forming a ß-barrel structure. To probe the nature of the assembly process of Tom40 in the outer membrane, we attached various mitochondrial presequences to Tom40 that possess sorting information for the intermembrane space (IMS), inner membrane, and matrix and would compete with the inherent Tom40 assembly process. We analyzed the mitochondrial import of those fusion proteins in vitro. Tom40 crossed the outer membrane and/or inner membrane even in the presence of various sorting signals. N-terminal anchorage of the attached presequence to the inner membrane did not prevent Tom40 from associating with the TOB/SAM complex, although it impaired its efficient release from the TOB complex in vitro but not in vivo. The IMS or matrix-targeting presequence attached to Tom40 was effective in substituting for the requirement for small Tim proteins in the IMS for the translocation of Tom40 across the outer membrane. These results provide insight into the mechanism responsible for the precise delivery of ß-barrel proteins to the outer mitochondrial membrane.

Significance of histopathologic examination in the diagnosis of dentin defects associated with type IV osteogenesis imperfecta: two case reports.

Two cases of type IV osteogenesis imperfecta, which is divided into subtypes A and B on the basis of the absence or the presence of dental alterations, respectively, are examined with respect to their dental features clinically, radiographically, and histopathologically. There were no characteristic dental abnormalities noted on the clinical and radiographic examination. However, the histopathologic examination with both light and electron microscopy disclosed characteristic dentin defects such as unevenly calcified matrixes, irregular tubular patterns, obliterated dentinal tubules, and cellular inclusions in the circumpulpal dentin of primary teeth. As a result, the patients were diagnosed as having osteogenesis imperfecta type IVB, although the clinical dental alterations were scarcely apparent. These findings indicate the importance of histopathologic examination with light and transmission electron microscopy for accurate diagnosis of osteogenesis imperfecta.