Capability of Utilizing CYP3A5 Polymorphisms to Predict Therapeutic Dosage of Tacrolimus at Early Stage Post-Renal Transplantation

While CYP3A5 polymorphisms are used to predict the initial dosage of tacrolimus therapy, the predictive capability of genetic information for dosing at early stage post-renal transplantation is unknown. We investigated the influence of polymorphisms over time. An initial oral dose of modified-release once-daily tacrolimus formulation (0.20 mg/kg) was administered to 50 Japanese renal transplant patients every 24 h. Stepwise multiple linear regression analysis for tacrolimus dosing was performed each week to determine the effect of patient clinical characteristics. The dose-adjusted trough concentration was approximately 70% higher for patients with the CYP3A5*3/*3 than patients with the CYP3A5*1 allele before the second pre-transplantation tacrolimus dose (0.97 (0.78–1.17) vs. 0.59 (0.45–0.87) ng/mL/mg; p < 0.001). The contribution of genetic factors (CYP3A5*1 or *3) for tacrolimus dosing showed increased variation from Day 14 to Day 28 after transplantation: 7.2%, 18.4% and 19.5% on Days 14, 21 and 28, respectively. The influence of CYP3A5 polymorphisms on the tacrolimus maintenance dosage became evident after Day 14 post-transplantation, although the tacrolimus dosage was determined based only on patient body weight for the first three days after surgery. Tacrolimus dosage starting with the initial administration should be individualized using the CYP3A5 genotype information.     

Apoptosis Signaling Is Altered in CD4(+)CD25(+)FoxP3(+) T Regulatory Lymphocytes in Pre-Eclampsia

The aim of our study was to estimate the surface expressions of CD95 (APO-1/Fas) antigen and the intracellular expressions of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in CD4(+)CD25(+)FoxP3(+) T regulatory lymphocytes (Tregs) as well as the percentage of CD8(+)CD28(+) T cytotoxic cells in peripheral blood of patients with pre-eclampsia in comparison with healthy pregnant women in the third trimester of physiological pregnancy. Twenty-four women with pre-eclampsia and 20 normal third trimester pregnant women were included in the study. The lymphocytes were isolated from peripheral blood samples and labeled with monoclonal antibodies. The expressions of surface antigens and intracellular proteins were estimated using flow cytometry. The population of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly lower in peripheral blood of patients with pre-eclampsia when compared to normal third trimester pregnant women. The percentages of CD4(+)CD25(+)FoxP3(+) Treg cells that express Bcl-2 protein were significantly lower in peripheral blood of patients with pre-eclampsia when compared to healthy pregnant women, whereas the percentages of CD4(+)CD25(+)FoxP3(+) Treg cells with the expressions of Bax protein did not differ in both groups. Moreover, the mean fluorescence intensity (MFI) of Bcl-2 protein in CD4(+)CD25(+)FoxP3(+) Treg cells was significantly lower and MFI of Bax protein significantly higher in pre-eclampsia when compared to the control group. The percentage of CD8(+)CD28(+) T cells did not differ in both studied groups but MFI of CD28 antigen on T CD8(+) cells was significantly higher in pre-eclampsia when compared to the control group. The obtained results suggest that the deficit of CD4(+)CD25(+)FoxP3(+) Treg lymphocytes which is observed in pre-eclampsia may be associated with altered apoptosis signaling in Tregs.     

Oxidation of green rust suspensions containing different chromium ion species

The oxidation of hydrosulphate green rust (GR2(SO₄²⁻)) suspension containing different chromium ion species was investigated by X-ray diffraction, X-ray absorption spectroscopy and transmission electron microscopy. The pH, oxidation-reduction potential and amount of dissolved oxygen in aqueous solutions were measured during the reactions. The results show that the addition of Cr(III)₂(SO₄)₃ solution suppresses the transformation of GR2(SO₄²⁻) into iron oxyhydroxides and oxides in aqueous solution, while the addition of Na₂Cr(VI)O₄ solution promotes the transformation of GR2(SO₄²⁻) in which Cr(VI) is reduced to Cr(III); α-FeOOH particles were refined by the addition of the chromium ions.     

In situ X-ray diffraction of surface oxide on type 430 stainless steel in breakaway condition using synchrotron radiation

Changes in the crystal structure of type 430 stainless steel and the oxides on its surface were studied in situ at 1373 K using a high-intensity synchrotron X-ray source provided by SPring-8 in Japan. The surface of the steel was initially covered with Cr₂O₃, which was then converted to FeCr₂O₄, and finally Fe₃O₄ and Fe₂O₃ formed on it. These results indicated that the reason for the breakaway oxidation in type 430 stainless steel is Cr depletion beneath Cr₂O₃ layer and the subsequent ionisation of Fe, not the simple mechanical failure of Cr₂O₃.     

Mechano-catalytic overall water splitting on some mixed oxides

Simple transition metal oxides such as NiO, Co₃O₄, Fe₃O₄ and Cu₂O were found to catalytically decompose water into H₂ and O₂ by mechanical energy. The reaction is regarded as “mechano-catalytic” overall water splitting” and is a quite novel catalytic reaction. In this paper, some general aspects on the mechano-catalytic overall water splitting are reviewed on simple oxides. In addition, recent results on the mechano-catalytic activity of a groups of mixed oxides, wolramite-type oxides with a formula of ABO₄ (A=Fe, Co, Ni and Cu, etc., B=W, Mo), are shown. AWO₄ (A=Fe, Co, Ni and Cu) decomposed water into H₂ and O₂ under the supply of mechanical energy, indicating that mechano-catalytic overall water splitting proceeded on wolframite-type compounds containing 3d-transition metals. AMoO₄ (A=Fe, Co, Ni) also decomposed water into H₂ and O₂ under supply of mechanical energy. The reaction properties on wolframite-type oxides are discussed.     

One-Step Oxidation of Benzene to Phenol over Cu/Ti/HZSM-5 Catalysts

The gas-phase catalytic oxidation of benzene over copper supported on HZSM-5 added with titanium (Cu/Ti/HZSM-5) was carried out by using molecular oxygen as an oxidant. Phenol was effectively produced by the titanium addition to Cu/HZSM-5. The titanium addition to Cu/HZSM-5 induces the easy reduction of Cu²⁺ species to Cu⁺ species in the catalysts, and the produced Cu⁺ species seems to produce the phenol effectively.     

Ethanol Conversion on MCM-41 and FSM-16, and on Ni-Doped MCM-41 and FSM-16 Prepared without Hydrothermal Conditions

MCM-41 and FSM-16 were both prepared using no hydrothermal conditions, and nickel was doped into these catalysts (Ni-MCM-41 and Ni-FSM-16) using a template ion exchange method. FSM-16 and Ni-FSM-16 had greater catalytic activity for the conversion of ethanol than MCM-41 and Ni-MCM-41, indicating that FSM-16 has potential as a catalyst for the conversion of ethanol to propylene.     

In utero exposure to a low concentration of diesel exhaust affects spontaneous locomotor activity and monoaminergic system in male mice

Background

Epidemiological studies suggest that inhalation of carbonaceous particulate matter from biomass combustion increases susceptibility to bacterial pneumonia. In vitro studies report that phagocytosis of carbon black by alveolar macrophages (AM) impairs killing of Streptococcus pneumoniae. We have previously reported high levels of black carbon in AM from biomass smoke-exposed children and adults. We therefore aimed to use a mouse model to test the hypothesis that high levels of carbon loading of AM in vivo increases susceptibility to pneumococcal pneumonia.

Methods

Female outbred mice were treated with either intranasal phosphate buffered saline (PBS) or ultrafine carbon black (UF-CB in PBS; 500 μg on day 1 and day 4), and then infected with S. pneumoniae strain D39 on day 5. Survival was assessed over 72 h. The effect of UF-CB on AM carbon loading, airway inflammation, and a urinary marker of pulmonary oxidative stress was assessed in uninfected animals.

Results

Instillation of UF-CB in mice resulted a pattern of AM carbon loading similar to that of biomass-smoke exposed humans. In uninfected animals, UF-CB treated animals had increased urinary 8-oxodG (P = 0.055), and an increased airway neutrophil differential count (P < 0.01). All PBS-treated mice died within 72 h after infection with S. pneumoniae, whereas morbidity and mortality after infection was reduced in UF-CB treated animals (median survival 48 h vs. 30 h, P < 0.001). At 24 hr post-infection, UF-CB treated mice had lower lung and the blood S. pneumoniae colony forming unit counts, and lower airway levels of keratinocyte-derived chemokine/growth-related oncogene (KC/GRO), and interferon gamma.

Conclusion

Acute high level loading of AM with ultrafine carbon black particles per se does not increase the susceptibility of mice to pneumococcal infection in vivo.     

Energy Transfer Enables 1.53 μm Photoluminescence from Erbium-Doped TiO2 Semiconductor Nanocrystals Synthesized by Ar/O2 Radio-Frequency Thermal Plasma

Highly crystalline, highly luminescent nanopowders of Er³⁺-doped TiO₂ have been successfully synthesized via one-step Ar/O₂ radio-frequency thermal plasma processing. Energy transfer from the TiO₂ host to Er³⁺ activators has been confirmed by combined means of UV-vis, excitation, and photoluminescence spectroscopies. As a consequence, bright photoluminescence at ∼1.53 μm was observed from the nanopowders either by directly exciting the Er³⁺ activator or by exciting the TiO₂ host lattice. A comparative study shows that the nanopowder of the same system made via coprecipitation lacks the energy transfer. The plasma-generated nanopowders may thus find applications in optoelectronic devices.