Int J Med Sci
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Observational Study
Tacrolimus Concentration after Letermovir Initiation in Hematopoietic Stem Cell Transplantation Recipients Receiving Voriconazole: A Retrospective, Observational Study.
Letermovir (LMV) is a new antiviral drug used to prevent cytomegalovirus infection in hematopoietic stem cell transplantation (HSCT) recipients. It has been reported to increase tacrolimus (TAC) exposure and decrease voriconazole (VRCZ) exposure in healthy participants. However, VRCZ inhibits the metabolism of TAC. ⋯ In contrast, the VRCZ C/D ratio and concentration for the first and second 7-day periods after LMV initiation were significantly lower than those before initiating LMV administration (mean 1.11 ± 0.07, 0.12 ± 0.08, and 0.22 ± 0.12 [μg/mL]/[mg/kg] and 0.7 ± 0.5, 0.8 ± 0.5, and 1.3 ± 0.7 μg/mL, respectively; n = 12). This can be explained by the increase in TAC concentration caused by CYP3A4 inhibition due to LMV and by the decrease in TAC concentration ascribed to the decrease in VRCZ concentration by CYP2C19 induction due to LMV. These results suggest that it is unnecessary to adjust the dose of TAC based on LMV initiation; however, it is necessary to adjust the dose of TAC based on conventional TAC concentration measurements.
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Observational Study
Occult Hepatitis B Virus Infection in Maintenance Hemodialysis Patients: Prevalence and Mutations in "a" Determinant.
Background: Occult hepatitis B virus infection (OBI) is defined as undetectable serum hepatitis B surface antigen (HBsAg) with detectable HBV-DNA in the serum or liver. Patients with maintenance hemodialysis (MHD) are at a high risk of OBI. The prevalence of OBI in MHD patients in China is not well evaluated. ⋯ By sequencing analysis, we revealed mutations at the "a" determinant of HBsAg, including Q129R, T131N, M133S, F134L and D144E. The Q129R and M133S mutations were first reported. Conclusions: Our study clarifies the prevalence of OBI in MHD patients in Sichuan Province(4.2% in the test group, 2.1% in the overall dialysis cohort), and demonstrate the mutations of Q129R and M133S in the "a" determinant of HBsAg for the first time.
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Background: Endothelial dysfunction is one of the underlying causes for vascular diseases. tert-Butyl hydroperoxide (t-BHP), a short-chain lipid hydroperoxide analog, has been reported to cause adverse effects in different systems. However, the adverse actions of t-BHP on inducing endothelial dysfunction are unclear and remain under investigation. Aim of the present study was to identify the pathobiological mechanisms of t-BHP in rat aortic endothelial cells and thoracic aorta. ⋯ Increased injuries were observed by upregulating endothelial apoptosis- and senescence-positive staining, along with caspase-3 activity and down-regulating telomerase activity. Conclusion: These results confirmed that t-BHP impaired aortic endothelial cell survival at least partially by the activation of p53-mediated signaling pathways, inhibition of cell cycle regulatory proteins, and initiation of cellular senescence-related signaling pathways. In conclusion, t-BHP was found to be a major trigger for impairing aortic endothelial cell survival and deteriorating vascular dysfunction in experimental practice.
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Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks joint tissue. Interleukin (IL)-6 is a key proinflammatory cytokine in RA progression. Sphingosine-1-phosphate (S1P), a platelet-derived lysophospholipid mediator, reportedly regulates osteoimmunology. ⋯ PI3K, MEK, ERK and NF-κB inhibitors and their small interfering RNAs (siRNAs) reduced S1P-promoted IL-6 expression. S1P also facilitated PI3K, MEK/ERK and NF-κB signaling cascades. Our results indicate that S1P promotes the expression of IL-6 in osteoblasts via the PI3K, MEK/ERK and NF-κB signaling pathways.
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Aim: Tolvaptan, an oral vasopressin-2 antagonist, sometimes improves hepatic edema including ascites in patients with decompensated cirrhosis. In this study, we examined the effectiveness and survival advantage in patients with the long-term administration of tolvaptan. Methods: A total of 115 patients with refractory ascites who were treated with tolvaptan were retrospectively analyzed based on their clinical records. ⋯ Child-Pugh (classification C), HCC complication, and serum sodium levels (≥133 mEq/L) were determined as independent prognostic factors impacting overall survival (OS). Although there were no significant differences in OS between tolvaptan responders and non-responders, the responders without re-exacerbation within 3 months showed significantly longer OS than those with re-exacerbation within 3 months. Conclusion: A persistent therapeutic response, but not early response to tolvaptan, was associated with favorable survival of decompensated cirrhotic patients.