Drug‐induced liver injury (DILI) is the most frequent reason cited for the withdrawal of approved drugs from the market and accounts for up to 15% of the cases of acute liver failure. Investigators ...around the globe have begun to identify and study patients with DILI; several large registries and tissue banks are being established. In order to gain the maximum scientific benefit from these efforts, the definitions and terminology related to the clinical phenotypes of DILI must be harmonized. For this purpose, an international DILI Expert Working Group of clinicians and scientists reviewed current DILI terminology and diagnostic criteria so as to develop more uniform criteria that would define and characterize the spectrum of clinical syndromes that constitute DILI. Consensus was established with respect to the threshold criteria for definition of a case as being DILI, the pattern of liver injury, causality assessment, severity, and chronicity. Consensus was also reached on approaches to characterizing DILI in the setting of chronic liver diseases, including autoimmune hepatitis (AIH).
Clinical Pharmacology & Therapeutics (2011) 89 6, 806–815. doi:10.1038/clpt.2011.58
Cathodic arc plasma is one of the potential ion plating physical vapor deposition methods to prepare protective coatings on cutting tools, metal mold, etc. In particular, TiN, CrN, and TiAlN films ...are coated on industrial cutting tools using cathodic arc plasma. However, the cathode spot of the vacuum arc generates macrodroplets as coproducts of cathodic arc plasma containing high-energy ions. These macrodroplets may pose problems with smooth-surface films that are used for advanced high-precision applications. This paper reviews cathode phenomena particularly for a graphite cathode, the techniques for reduction of macrodroplet generation, and the techniques for macrodroplet removal from the processing plasma. The reduction technique includes steered arc, pulsed arcs, etc. The removal technique includes shielded arcs and filtered arcs. Recent filtered arc deposition systems are referred.
Thin films of titanium dioxide have been deposited on glass substrates and conducting (100) silicon wafers by filtered arc deposition (FAD). The influence of the depositing Ti
− energy, substrate ...types and substrate temperature on the structure, density, mechanical and optical properties have been investigated. The results of X-ray diffraction (XRD) showed that with increasing substrate bias, the film structure on silicon substrates changes from anatase to amorphous and then to rutile phase without auxiliary heating, the transition to rutile occurring at a depositing particle energy of about 100 eV. However, in the case of the glass substrate, no changes in the structure and optical properties were observed with increasing substrate bias. The optical properties over the range of 300–800 nm were measured using spectroscopic elliosometery, and found to be strongly dependent on the substrate bias, film density and substrate type. The refractive index values of the amorphous, anatase and rutile films on Si were found to be 2.56, 2.62 and 2.72 at a wavelength of 550 nm, respectively. The hardness and elastic modulus of the films were found to be strongly dependent on the film density. Measurements of the mechanical properties and stress also confirmed the structural transitions. The hardness and elastic modulus range of TiO
2 films were found to be between 10–18 and 140–225 GPa, respectively. The compressive stress was found to vary from 0.7 to 2.6 GPa over the substrate bias range studied. The composition of the film was measured to be stoichiometric and no change was observed with increasing substrate bias. The density of the film varied with change in the substrate bias, and the density ranged between 3.62 and 4.09 g/cm
3.
Multidrug resistance-associated protein 3 (MRP3) was initially cloned as a hepatic transporter induced under cholestatic/ hyperbilirubinemic conditions. In the present study, transport property of ...human MRP3 (hMRP3) was compared with that of rat MRP3 (rMRP3).
Adenosine 5' triphosphate (ATP)-dependent uptake of several organic anions into the membrane vesicles isolated from the Sf9 cells expressing hMRP3 and rMRP3 was measured by rapid filtration technique.
ATP-dependent uptake of glucuronide conjugates, glutathione conjugates. and 3Hmethotrexate (MTX) was stimulated by infection of cDNAs for hMRP3 and rMRP3. The mean (+/- SE) Km values for the uptake of 17beta estradiol 17beta-D-glucuronide (3HE(2)17 betaG) by hMRP3 and rMRP3 were 42.9 +/- 4.3 microM and 33.4 +/- 2.2 microM, respectively. Although the Ki values of glucuronides on the uptake of E217betaG were similar in humans and rats, hMRP3 exhibited higher Ki values toward MTX. In addition, although glycocholate and taurolithocholate 3-sulfate (TLC-S) were transported by both hMRP3 and rMRP3, taurocholate was only transported to a significant degree by rMRP3. Moreover, the inhibitory effect of taurocholate and glycocholate on the transport of E(2)17beta3G was much more potent in rMRP3 compared to hMRP3.
Collectively, the substrate specificity of hMRP3 resembles that of rMRP3 although differences were observed, particularly in bile acid transport.
We analyzed 388 cases of primary sclerosing cholangitis (PSC) in Japan, according to a questionnaire sent to gastroenterologists. There was male predominance (59%), and interestingly there were two ...peaks in the age distribution as seen in the previous study. Jaundice and itching, major symptoms in PSC patients included in the diagnostic criteria, were observed only 28 and 16%, respectively. Alkaline phosphatase level was less than twofold of the upper limit of the normal range in 35%. In this regard, the diagnostic criteria in 2003 from Mayo Clinic, including cholestatic symptoms and two to three-fold increases in serum alkaline phosphatase, should be modified in Japan. Inflammatory bowel diseases were complicated in 37%, and autoimmune pancreatitis (AIP) in 7.2%. PSC cases with inflammatory bowel diseases were younger than the average, creating the first peak in the age distribution, and have similar characteristics compared to patients with PSC in foreign countries. By contrast, those with AIP, who were more than 50 years old, responded well to corticosteroid therapy. In addition, even after the exclusion of cases of sclerosing cholangitis complicated with AIP, the second peak in the age distribution was clearly evident. Therefore, we conclude that PSC patients without apparent involvement of the pancreas are present in the older patients and seem to be specific in Japan.
Dielectric barrier discharge (DBD) treatment is one of the methods used to make carbon nanofibers stand up on substrates. Upright carbon nanofibers are used as field emission materials. We have used ...twisted carbon nanofibers (CNTws) as field emission materials and treated printed CNTws on substrates using DBD. In this report, we examine the effects of DBD conditions on the uprightness of the CNTws. The DBD experimental parameters were as follows: 1) N 2 /He gas mixture ratio, 2) pulse frequency, and 3) Pt coating on the CNTw surface. The lengths of upright CNTws from the substrate surface and from the surface of a printed CNTw dot were measured using scanning electron microscopy. N 2 gas was shown to be crucial for generating streamer discharges and making the CNTw stand up on the substrate. As the pulse frequency increased, the lengths of the upright CNTws and their number density increased. This is explained by an increase in the number of streamers; the streamers move about over the substrate surface. Pt coating lowered the onset voltage for field emission from the CNTws although the number of upright CNTws was less than that without the Pt coating.
