The incidence rate of bacterial meningitis caused by methicillin-resistant staphylococci is lower than that of bacterial meningitis caused by other gram-positive bacteria. However, considering the high mortality rate of staphylococcal infections, empirical vancomycin (VCM) therapy is often used. On the other hand, VCM is known to affect renal function. Therefore, it is necessary to understand the risks of empirical VCM therapy in patients with suspected bacterial meningitis. We aimed to investigate the risk of acute kidney injury (AKI) associated with empirical VCM therapy in patients with suspected bacterial meningitis. We reviewed the records of 35 suspected bacterial meningitis patients treated with empirical VCM therapy at Fukuoka University Hospital between 2011 and 2017. The incidence rate of AKI associated with empirical VCM therapy was evaluated based on Kidney Disease: Improving Global Outcome criteria. The patients were aged 65.0 (44.0-75.0) years, and had various underlying diseases such as subarachnoid hemorrhage, cerebral hemorrhage, other diseases of the head and community-acquired infection. Methicillin-resistant staphylococci were detected in only 3 patients. In 4 patients with negative culture results, empirical VCM therapy was continued for more than 1 week; this resulted in AKI. The incidence rate of AKI associated with empirical VCM therapy was 11.4%. For patients with suspected bacterial meningitis requiring empirical VCM therapy, it is important to check the necessity of VCM by bacterial culture tests and ensure the safety by monitoring blood concentrations in order to avoid the risk of AKI.
Background: Approved anticancer drug combinations are classified into the following groups: broader than (broad label), the same as (same label), or smaller than (narrow label) the series of combination regimens investigated in clinical studies. The present research attempted to elucidate the characteristics of the broad/narrow label to clarify what types of combination regimens are given these labels. Methods: All anticancer drugs approved in Japan between April 2006 and March 2020 and their review reports were selected from the Pharmaceuticals and Medical Devices Agency (PMDA) website. The differences in the number of regimens in clinical trials given each label were investigated using Tukey’s test. Multinomial logistic regression analysis was also conducted to examine the factors influencing each category. Results and Discussion: There were significant differences in the numbers of regimens among the labels. The factors that significantly contributed to labeling could not be identified. However, key features were identified. If there were multiple clinically comparable regimens and a clinical trial was conducted to evaluate the clinical benefit of adding new anticancer agents to one of the major regimens, there was a high probability of receiving a broad label. A narrow label may be granted if a regimen considered clinically comparable despite possessing a different mechanism of action does not exhibit clinical benefits in phase III studies. Conclusion: The present study revealed the PMDA stance for reviewing the clinical data of anticancer combination therapies submitted by sponsors in their totality to allow physicians to provide patient-centric, evidence-based, optimized cancer care to patients.
Metal responsive transcription factor-1 (MTF-1) is ubiquitously expressed in various tissues, and is thought to be an intracellular zinc sensor that regulates transcriptional activation of zinc responsive genes. We investigated the distribution of MTF-1 in the mouse testis, where zinc plays an essential role in spermatogenesis. By performing immunohistochemical analysis of the ddY mouse testis using the anti-MTF-1 antibody, we observed a donut-shaped staining pattern in the seminiferous tubules in the region proximal to the lumen, where spermatocytes primarily localize. A similar staining pattern was obtained using in situ hybridization to detect MTF-1 mRNA. Furthermore, we confirmed that MTF-1 could not be detected at both the protein and mRNA levels in the premature 20-d-old mouse testis, where spermatocytes are thought not to have been formed in the seminiferous tubules yet. These lines of evidence strongly indicated the selective expression of MTF-1 in mouse spermatocytes and suggested that MTF-1 played a role in a certain stage of spermatogenesis.
The performance of hexavalent chromium (Cr(VI)) adsorption by activated carbon (AC) prepared from coconut shell (AC1) and modified with silver nanoparticles (AC2), titanium oxide (AC3), and magnetic powder (AC4) was evaluated in this study. The interaction between AC surface properties and Cr(VI) was also assessed via elemental distribution and binding energy analyses. More Cr(VI) was adsorbed onto AC1 than onto any other AC, indicating that the specific surface area and surface functional groups are key factors for Cr(VI) adsorption from the aqueous phase (with correlation coefficients of 0.988 and 0.868–0.949, respectively). Activation of the coconut shell with silver nanoparticles, titanium oxide, and magnetic powder did not increase Cr(VI) adsorption. Cr atoms were detected on the AC1 surface by electron probe microanalysis only after adsorption. Moreover, the binding energies of Cr (2s, 2p, 3s, and 3p) and O (1s) were confirmed after absorption. These results indicate that AC surface properties were strongly related to adsorption performance. Finally, this study reveals the optimal pH conditions for the removal of Cr(VI) from the aqueous phase of approximately pH 2–3 (acidic conditions). In conclusion, this study elucidates the Cr(VI) adsorption mechanisms of coconut shell-derived AC.