Search

18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) has been widely used for preoperative staging of lung adenocarcinomas. The aim of this study was to determine whether a high maximum standardized uptake value (SUVmax) could correlate with pathological characteristics in those patients. We retrospectively reviewed patients with clinical stage 0-IA lung adenocarcinoma who underwent preoperative 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography followed by curative anatomical resection. To identify more advanced disease and high-risk features, representing visceral pleural involvement, pulmonary metastasis, lymph node involvement, and lymphovascular involvement in resected surgical specimens, univariate and multivariate logistic regression analyses were performed. The optimal cutoff point for the SUVmax was determined by receiver operating characteristic analysis. In 2 groups divided according to the cutoff point, the disease-free survivals were calculated and compared using the Kaplan-Meier method and the log-rank test. More advanced disease and high-risk features were identified in 55 (18.9%) of the 291 patients. SUVmax was significantly correlated with more advanced disease and high-risk features, as did the consolidation/tumor ratio on computed tomography. Only 2 (1.2%) of the 169 patients with a SUVmax <3.20 showed more advanced disease and high-risk features, compared with 43.4% of patients with a SUVmax ≥3.20. The disease-free survival was significantly higher in patients with a SUVmax <3.20 than in those with a SUVmax ≥3.20 (P = 0.002). A high SUVmax correlates with more advanced disease and high-risk features in patients with clinical stage 0-IA lung adenocarcinoma. The SUVmax should be considered when deciding treatment strategy in early-stage lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Abstract Everolimus is an inhibitor of mammalian target of rapamycin (mTOR) and reduces the risk of cytomegalovirus (CMV) infection in transplant recipients. Everolimus inhibits mTOR complex 1, which regulates factors involved in several crucial cellular functions and is required for CMV replication. However, it is not clear how everolimus regulates CMV replication and prevents and alleviates CMV infection. Effects of everolimus on CMV infection, spread, and DNA synthesis and release from infected cells were assessed by plaque formation, infectious centre assay, real-time PCR of infected cells, and culture supernatant in CMV-infected cultures with and without everolimus. Everolimus enhanced plaque formation by 3.6 times, but the size of the plaques was reduced to 36.4% of untreated cultures in the absence of a pretreatment period. Everolimus reduced viral adsorption but enhanced the replication efficiency of inoculated virus, resulting in an increase in plaque number in the early phase of infection. Preinfection treatment of cells with everolimus efficiently exhibited its antiviral efficacy, and everolimus delayed and suppressed viral DNA synthesis and release from infected cells. Everolimus had suppressed the spread of infection and reduced the number of total infected cells to 40% of untreated cells on day 9, indicating reduction of the size of CMV lesions to one-sixth in 2–3 replication cycles. Preinfection treatment of the cells with everolimus augmented its suppressive effect on CMV infection and replication. Everolimus reduced the total number of infected cells and limited the CMV lesions, and this reduction in the spread of CMV infection would alleviate CMV infection in transplant recipients. Highlights • Everolimus is an inhibitor of mammalian target of rapamycin (mTOR). • Everolimus reduces the risk of cytomegalovirus infection in transplant recipients. • Everolimus suppressed viral adsorption and delayed and suppressed DNA synthesis and release. • Everolimus suppressed the spread of infection and reduced the number of infected cells to 40% of untreated cells on day 9. • Reduction in the spread of CMV infection would alleviate CMV infection in transplant recipients. [ABSTRACT FROM AUTHOR]

Favipiravir, a broad-spectrum RNA-dependent RNA polymerase inhibitor, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at significantly lower concentrations than the plasma trough levels achieved by the dosage adopted for influenza treatment and exhibits efficacy against coronavirus disease 2019 (COVID-19) pneumonia. Although high doses of favipiravir are required due to the molecule being a purine analog, its conversion into the active form in infected cells with active viral RNA synthesis enhances the antiviral specificity and selectivity as a chain terminator with lethal mutagenesis. Another characteristic feature is the lack of generation of favipiravir-resistant virus. COVID-19 pneumonia is caused by strong cell-mediated immunity against virus-infected cells, and the inflammatory response induced by adaptive immunity continues to peak for 3 to 5 days despite antiviral treatment. This has also been observed in herpes zoster (HZ) and cytomegalovirus (CMV) pneumonia. Inflammation due to an immune response may mask the effectiveness of favipiravir against COVID-19 pneumonia. Favipiravir significantly shortened the recovery time in patients with mild COVID-19 pneumonia by 3 days with the start of treatment by the 5th day of symptom onset. Since both CMV and COVID-19 pneumonia are caused by adaptive immunity and prevention of cytomegalovirus pneumonia is the standard treatment due to difficulties in treating refractory CMV pneumonia, COVID-19 pneumonia should be prevented with early treatment as well. In the present study, we have comprehensively reviewed the optimal antiviral therapy for COVID-19 based on clinical trials of favipiravir for the treatment of COVID-19 pneumonia and the concurrently established therapies for other viral infections, particularly HZ and CMV pneumonia. Optimally, antivirals should be administered immediately after COVID-19 diagnosis, similar to that after influenza diagnosis, to prevent COVID-19 pneumonia and complications resulting from microangiopathy. [ABSTRACT FROM AUTHOR]

Abstract: The sequential glycosylation of a soybean isoflavone, daidzein, with cultured suspension cells of Eucalyptus perriniana and cyclodextrin glucanotransferase was studied. Daidzein was converted into two glycosylation products, daidzein 7-O-β-d-glucopyranoside (39%) and daidzein 7-O-[6-O-(β-d-glucopyranosyl)]-β-d-glucopyranoside (β-gentiobioside, 6%), by cultured E. perriniana cells. Further glycosylation of daidzein 7-O-β-glucoside with cyclodextrin glucanotransferase gave daidzein 7-O-[4-O-(α-d-glucopyranosyl)]-β-d-glucopyranoside (β-maltoside, 26%), daidzein 7-O-β-maltotrioside (15%), and daidzein 7-O-β-maltotetraoside (7%). [Copyright &y& Elsevier]

We review magnetic and superconducting properties of UT2Al3 (T = Pd, Ni) and UGe2 together with URu2Si2. For UPd2Al3, we have suggested that the superconducting attractive paring interaction is mediated by magnetic excitons. Knight shift measurements of UNi2Al3 show an odd parity pairing in contrast to an even parity formation in UPd2Al3. The ac magnetic susceptibility measurements of UGe2 indicate that the volume fraction of superconductivity grows with increasing pressure, suggesting inhomogeneous coexistence of superconductivity and ferromagnetism. Recent dc magnetization measurements on UGe2 exhibit a step like hysteresis loop at low temperatures. An analysis of the data suggests that a magnetic domain size is smaller than a superconducting coherence length. Finally, we report the observation of an anomaly appearing in the thermal expansion of URu2Si2 under high pressures, which can be ascribed to the phase transition between a hidden and antiferromagnetic order. [Copyright &y& Elsevier]

Amenamevir is a helicase-primase inhibitor of herpes simplex virus (HSV) and varicella-zoster virus (VZV) and is used for the treatment of herpes zoster in Japan. The half maximal effective concentrations (EC 50 s) of acyclovir and sorivudine for VZV increased as the time of treatment was delayed from 6 to 18 h after infection, while those of amenamevir and foscarnet were not affected. Susceptibility of infected cells at 0 and 18 h after infection was examined with four anti-herpes drugs, and the fold increases in EC 50 for acyclovir, sorivudine, amenamevir, and foscarnet were 13.1, 6.3, 1.3, and 1.0, respectively. The increase in the EC 50 s for acyclovir in the late phase of infection in VZV and HSV was abolished by hydroxyurea, a ribonucleotide reductase (RR) inhibitor. The common mechanism affecting antiviral activities of acyclovir to HSV and VZV was examined in HSV-infected cells. The amount of HSV DNA in cells treated with amenamevir at 10 x EC 50 was similar at 0 and 12 h but less than that in cells treated with acyclovir at 10 x EC 50. dGTP, produced through viral RR, peaked at 4 h and decreased thereafter as it was consumed by viral DNA synthesis. Because acyclovir and amenamevir inhibited viral DNA synthesis, thus making dGTP unnecessary, dGTP was significantly more abundant in the presence of acyclovir and amenamevir than in untreated, infected cells. Abundant dGTP supplied by RR may compete with acyclovir triphosphate and attenuate its antiviral activity. In contrast, abundant dGTP did not influence the inhibitory action of amenamevir on viral helicase-primase activity. ATP was significantly decreased at 12 h after infection and significantly more abundant in untreated infected cells compared to cells treated with acyclovir and amenamevir. The anti-herpetic activity of amenamevir was not affected by the replication cycle of VZV and HSV, indicating the suitability of amenamevir for the treatment of herpes zoster and suppressive therapy for genital herpes. • dGTP increased at 4h and thereafter decreased in HSV infected cells. • dGTP significantly increased in cells treated with acyclovir and amenamevir. • ATP decreased in HSV infected cells and furthermore in antiviral-treated cells at 12 h after infection. • Antiviral activity of acyclovir was attenuated by viral RR in the late phase of infection. • Antiviral activity of amenamevir was not affected by the replication cycle of VZV. [ABSTRACT FROM AUTHOR]