Usefulness of hexamethylenetetramine in combination with chemotherapy using free and pegylated liposomal doxorubicin in vivo, referring to the effect on quiescent cells

SCC VII tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all intratumor proliferating (P) cells. They received hexamethylenetetramine (HMTA) either once intraperitoneally or continuously subcutaneously together with chemotherapy using intraperitoneally administered free doxorubicin (DXR) or intravenously injected pegylated liposomal doxorubicin (PLD). One hour after the free DXR loading or 24 h after the PLD loading, the response of intratumor quiescent (Q) cells was assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The response of the total (P + Q) tumor cell population was determined from the tumors not treated with BrdU. Encapsulation of DXR into pegylated liposomes significantly enhanced cytotoxicity, especially in Q cells. HMTA, especially when administered continuously, efficiently increased the sensitivity to DXR, particularly in Q cells. The increase in sensitivity on the continuous rather than single administration of HMTA was a little clearer in the total cell population than in Q cells. DXR's encapsulation into pegylated liposomes and combination with HMTA, particularly when administered continuously, apparently reduced the difference in sensitivity to free DXR between the total and Q cell populations. In terms of the tumor cell-killing effect as a whole, including Q cells, the encapsulation of DXR into pegylated liposomes and combination with HMTA, particularly through continuous administration, are very promising, taking into account that HMTA has been used clinically

Heterometallic Benzenehexathiolato Coordination Nanosheets: Periodic Structure Improves Crystallinity and Electrical Conductivity.

Funder: White Rock FoundationFunder: Jardine FoundationFunder: Cambridge Commonwealth European and International TrustCoordination nanosheets are an emerging class of 2D, bottom-up materials having fully π-conjugated, planar, graphite-like structures with high electrical conductivities. Since their discovery, great effort has been devoted to expand the variety of coordination nanosheets; however, in most cases, their low crystallinity in thick films hampers practical device applications. In this study, mixtures of nickel and copper ions are employed to fabricate benzenehexathiolato (BHT)-based coordination nanosheet films, and serendipitously, it is found that this heterometallicity preferentially forms a structural phase with improved film crystallinity. Spectroscopic and scattering measurements provide evidence for a bilayer structure with in-plane periodic arrangement of copper and nickel ions with the NiCu2 BHT formula. Compared with homometallic films, heterometallic films exhibit more crystalline microstructures with larger and more oriented grains, achieving higher electrical conductivities reaching metallic behaviors. Low dependency of Seebeck coefficient on the mixing ratio of nickel and copper ions supports that the large variation in the conductivity data is not caused by change in the intrinsic properties of the films. The findings open new pathways to improve crystallinity and to tune functional properties of 2D coordination nanosheets.EPSRC-JSPS core-to-core program (EP/S030662/1, JPJSCCA20190005

Ischemic Stroke in Acute Decompensated Heart Failure: From the KCHF Registry

[Background] Heart failure (HF) is a known risk factor for ischemic stroke, but data regarding ischemic stroke during hospitalization for acute decompensated HF (ADHF) are limited. [Methods and Results] We analyzed the data from a multicenter registry (Kyoto Congestive Heart Failure [KCHF] Registry) that enrolled 4056 consecutive patients with ADHF in Japan (mean age, 78 years; men, 2238 patients [55%]; acute coronary syndrome [ACS], 239 patients [5.9%]). We investigated the incidence and predictors of ischemic stroke during hospitalization for ADHF. During the hospitalization, 63 patients (1.6%) developed ischemic stroke. The median interval from admission to the onset of ischemic stroke was 7 [interquartile range: 2–14] days, and the most common underlying cause was cardioembolism (64%). Men (OR, 1.87; 95%CI, 1.11–3.24), ACS (OR, 2.31; 95%CI, 1.01–4.93), absence of prior HF hospitalization (OR, 2.21; 95%CI, 1.24–4.21), and high B‐type natriuretic peptide (BNP)/N‐terminal proBNP (NT‐proBNP) levels (above the median) at admission (OR, 3.15; 95%CI, 1.84–5.60) were independently associated with ischemic stroke. In patients without ACS, the independent risk factors for ischemic stroke were fully consistent with those in the main analysis. Higher quartiles of BNP/NT‐proBNP levels were significantly associated with higher incidence of ischemic stroke (P for trend, <0.001). Patients with ischemic stroke showed higher in‐hospital mortality, longer length of hospital stay, and poorer functional status at discharge. [Conclusions] During hospitalization for ADHF, 1.6% of the patients developed ischemic stroke. Men, ACS, absence of prior HF hospitalization, and high BNP/NT‐proBNP levels at admission were independently associated with ischemic stroke

Reversible Visualization for Synchrotron Radiation Using Photochromic Dye and Photostimulable Phosphor Composite Film

The study reported herein is undertaken to visualize reversibly synchrotron radiation by using a composite film comprised of two components: a photochromic SP with the conversion characteristics of UV-to-visible color and PSP BaFCl:Eu2+ particles with the conversion characteristics of X-rays-to-UV emission