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Wave-like propagation of [Ca2+]i increases is a remarkable intercellular communication characteristic in astrocyte networks, intercalating neural circuits and vasculature. Mechanically-induced [Ca2+]i increases and their subsequent propagation to neighboring astrocytes in culture is a classical model of astrocyte calcium wave and is known to be mediated by gap junction and extracellular ATP, but the role of each pathway remains unclear. Pharmacologic analysis of time-dependent distribution of [Ca2+]i revealed three distinct [Ca2+]i increases, the largest being in stimulated cells independent of extracellular Ca2+ and inositol 1,4,5-trisphosphate-induced Ca2+ release. In addition, persistent [Ca2+]i increases were found to propagate rapidly via gap junctions in the proximal region, and transient [Ca2+]i increases were found to propagate slowly via extracellular ATP in the distal region. Simultaneous imaging of astrocyte [Ca2+]i and extracellular ATP, the latter of which was measured by an ATP sniffing cell, revealed that ATP was released within the proximal region by volume-regulated anion channel in a [Ca2+]i independent manner. This detailed analysis of a classical model is the first to address the different contributions of two major pathways of calcium waves, gap junctions and extracellular ATP.

Despite improvements in medical care, the mortality of critically ill patients with acute kidney injury (AKI) who require renal replacement therapy (RRT) remains high. We describe a new approach, sustained hemodiafiltration, to treat patients who suffered from acute kidney injury and were admitted to intensive care units (ICUs). In our study, 60 critically ill patients with AKI who required RRT were treated with either continuous venovenous hemodiafiltration (CVVHDF) or sustained hemodiafiltration (S-HDF). The former was performed by administering a postfilter replacement fluid at an effluent rate of 35 mL/kg/h, and the latter was performed by administering a postfilter replacement fluid at a dialysate-flow rate of 300-500 mL/min. The S-HDF was delivered on a daily basis. The baseline characteristics of the patients in the two treatment groups were similar. The primary study outcome--survival until discharge from the ICU or survival for 30 days, whichever was earlier--did not significantly differ between the two groups: 70% after CVVHDF and 87% after S-HDF. The hospital-survival rate after CVVHDF was 63% and that after S-HDF was 83% (P < 0.05). The number of patients who showed renal recovery at the time of discharge from the ICU and the hospital and the duration of the ICU stay significantly differed between the two treatments (P < 0.05). Although there was no significant difference between the mean number of treatments performed per patient, the mean duration of daily treatment in the S-HDF group was 6.5 +/- 1.0 h, which was significantly shorter. Although the total convective volumes--the sum of the replacement-fluid and fluid-removal volumes--did not differ significantly, the dialysate-flow rate was higher in the S-HDF group. Our results suggest that in comparison with conventional continuous RRT, including high-dose CVVHDF, more intensive renal support in the form of postdilution S-HDF will decrease the mortality and accelerate renal recovery in critically ill patients with AKI.

The formation constant (KZnL), enthalpy and entropy changes (ΔH and ΔS), and deprotonation constant (Ka) of coordinated water for hydrated zinc(II)–triamine (1 : 1) complexes (N3–Zn-(OH2)n (N3 = diethylenetriamine (dien), N-(2-aminoethyl)-1,3-propanediamine (epd), dipropylenetriamine (dpt), cis,cis-1,3,5-triaminocyclohexane (tach), and 1,5,9-triazacyclododecane ([12]aneN3)) were determined by potentiometry. The pKa linearly increased along with an increase in -ΔH, and was explained in terms of a ligand–ligand interaction through the N3–Zn-O bond on the bases of a thermodynamic analysis and strain-energy calculation (MM2). The zinc(II) complex-promoted hydrolysis of 2,4-dinitrophenyl diethyl phosphate was investigated in 1% (v/v) methanol–water; the rate constants linearly increased along with decreases of pKa and −ΔH. This fact indicates that the hydrolysis proceeds via a concerted direct nucleophilic attacking mechanism of the coordinated hydroxide ion, in which the phosphate ester coordinates to the zinc(II) ion. X-ray structure analyses for synthesized model complexes, [Zn(OAc)(dien)](ClO4), [{Zn(dpt)}3(CO3)](ClO4)4·NaClO4, and [Zn(OAc)(tach)](ClO4), are also reported.

Dipeptides having a serine residue at the C-terminus, X-Ser, where X is an appropriate amino acid residue, were efficiently hydrolyzed in the presence of ZnCl2 at pH 7.0. The rapid hydrolysis of X-Ser is due to an autocatalysis of the hydroxy group in the serine residue, and is found to be accelerated by a metal ion, in particular by ZnCl2. Roles of the metal ion in the hydrolysis of peptides involving a serine residue, in relation to the recently reported protein cleavages, are discussed.

kTo determine the distribution and relationship of antimicrobial resistance determinants among extended-spectrum-cephalosporin (ESC)-resistant or carbapenem-resistant Escherichia coli isolates from the aquatic environment in India, water samples were collected from rivers or sewage treatment plants in five Indian states. A total of 446 E. coli isolates were randomly obtained. Resistance to ESC and/or carbapenem was observed in 169 (37.9%) E. coli isolates, which were further analyzed. These isolates showed resistance to numerous antimicrobials; more than half of the isolates exhibited resistance to eight or more antimicrobials. The bla NDM gene was detected in 14/21 carbapenem-resistant E. coli isolates: bla NDM-1 in 2 isolates, bla NDM-5 in 7 isolates, and bla NDM-7 in 5 isolates. The bla CTX-M gene was detected in 112 isolates (66.3%): bla CTX-M-15 in 108 isolates and bla CTX-M-55 in 4 isolates. We extracted 49 plasmids from selected isolates, and their whole-genome sequences were determined. Fifty resistance genes were detected, and 11 different combinations of replicon types were observed among the 49 plasmids. The network analysis results suggested that the plasmids sharing replicon types tended to form a community, which is based on the predicted gene similarity among the plasmids. Four communities each containing from 4 to 17 plasmids were observed. Three of the four communities contained plasmids detected in different Indian states, suggesting that the interstate dissemination of ancestor plasmids has already occurred. Comparison of the DNA sequences of the bla NDM -positive plasmids detected in this study with known sequences of related plasmids suggested that various mutation events facilitated the evolution of the plasmids and that plasmids with similar genetic backgrounds have widely disseminated in India.