The proton pump inhibitor lansoprazole, but not rabeprazole, the increased blood concentrations of calcineurin inhibitors in Japanese patients with connective tissue diseases.

OBJECTIVE: Proton pump inhibitors (PPIs) are frequently coadministered with calcineurin inhibitors (CNIs) such as tacrolimus (TAC) and cyclosporin A (CSA), to treat or prevent upper gastrointestinal complications in Japanese patients with connective tissue diseases (CTDs). The coadministration of PPIs increases the blood concentration of TAC due to drug interaction. We retrospectively investigated the influence of the coadministration of PPIs and CNIs, as well as the influence of the cytochrome P450 (CYP) 2C19 gene polymorphism status, on the blood concentrations of TAC and CSA in patients with CTDs. METHODS: Patients treated with TAC (n=35) or CSA (n=30) were enrolled and divided into three groups according to the PPI they received: lansoprazole (LPZ)-combined, rabeprazole (RPZ)-combined, and non-PPI-combined groups. We compared the blood concentrations of TAC or CSA and the incidences of adverse events among the three groups. CYP2C19 gene polymorphisms were also assessed to investigate its influence on the blood concentration of TAC or CSA. RESULTS: LPZ significantly increased the blood concentration of TAC 12 hours after TAC administration (p=0.030 and p=0.003, respectively) and CSA (p=0.047 and p=0.014, respectively) in comparison with RPZ and non-PPI-combined treatment. There were no significant differences in the mean CSA blood concentration two hours after administration in patients with or without PPI treatment, in the incidence of adverse events, or in the CYP2C19 gene polymorphism status among the three groups. CONCLUSION: Combining agents that are mainly metabolized by CYP3A4 such as LPZ elevates the blood concentrations of TAC and CSA, which could leading to adverse events.

Low CTLA-4 expression in CD4+ helper T-cells in patients with fulminant type 1 diabetes.

Fulminant type 1 diabetes is a novel subtype of type 1 diabetes characterized by a remarkably abrupt onset of insulin-deficient hyperglycemia. An accelerated immune reaction has been suggested as the cause of markedly rapid beta cell loss in this disease, but the precise mechanism has not been clarified. We analyzed the expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) in CD4(+) helper T-cells in 16 patients with fulminant type 1 diabetes, 14 patients with type 1A diabetes, 10 patients with type 2 diabetes and 20 normal control subjects. There was a significant reduction in CTLA-4 expression in CD4(+) helper T-cells from patients with fulminant type 1 diabetes (P<0.05) compared with the other three groups. Low CTLA-4 expression was also observed in both CD4(+)CD25(high) T-cells and CD4(+)CD25(-) T-cells. There was a significant negative correlation between the proliferation of CD4(+)CD25(-) T-cells and the levels of CTLA-4. Intracellular expression of CTLA-4 in CD4(+) helper T-cells was not correlated with two CTLA-4 polymorphisms. In conclusion, the expression of CTLA-4 in CD4(+) helper T-cells was low in patients with fulminant type 1 diabetes.

Rapidly progressing aneurysm of infected thoracic aorta with pseudoaneurysm formation.

A 60-year-old man presented with chest discomfort with fever and high C-reactive protein (CRP). Chest computed tomography (CT) disclosed a mediastinal soft tissue swelling originating from the aortic arch, and gallium-67 single-photon emission CT revealed intense uptake in the same region. We initially suspected mediastinitis and/or a thoracic aortic infection. Antibiotics improved his symptoms and CRP levels. However, a follow-up CT scan 33 days later, revealed an aortic arch aneurysm and the patient was diagnosed with infective aortic aneurysm. Here, we report a rare case of a rapidly progressing aneurysm of infected aorta aortic infection with pseudoaneurysm formation.