a b s t r a c tA three-dimensional twenty-seven (D3Q27) discrete velocity multiple-relaxation-time lattice Boltzmann method is developed. The proposed scheme is validated in fully developed turbulent channel, pipe and porous medium flows through direct and large eddy simulations. The direct numerical simulation of the turbulent channel flow confirms that the present scheme is as reliable as the spectrum method for simulating turbulence. Through the large eddy simulations of the pipe and porous medium flows, the present scheme shows its satisfactory accuracy for simulating turbulent flows bounded by circular walls that is failed by the three-dimensional nineteen (D3Q19) model.

The production and role of tumor necrosis factor alpha (TNF-␣) in pneumococcal pneumonia were investigated in a mouse pneumonia model. When approximately 10 6 CFU of Streptococcus pneumoniae TUM19 were used to inoculate CBA/J mice intranasally, TNF-␣ levels in the lungs and serum began to increase from 1 and 3 days after infection, respectively, concomitantly with the increase in bacterial counts in the lungs. Anti-TNF-␣ antibody accelerated bacterial proliferation in the blood and the death of the mice. Although serum levels of immunoglobulin G antibody against the infecting bacteria were not affected by the anti-TNF-␣ antibody treatment, neutrophil counts in the blood were decreased by the treatment. These results suggest that TNF-␣ produced in the course of pneumococcal pneumonia prevents bacteremia by increasing the number of neutrophils in the blood.

BackgroundAcute respiratory distress syndrome (ARDS) can result in a life-threatening form of respiratory failure, and established, effective pharmacotherapies are therefore urgently required. Quercetin is one of the most common flavonoids found in fruits and vegetables, and has potent anti-inflammatory and anti-oxidant activities. Quercetin has been demonstrated to exhibit cytoprotective effects through the induction of heme oxygenase (HO)-1. Here, we investigated whether the intratracheal administration of quercetin could suppress lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice as well as the involvement of HO-1 in quercetin’s suppressive effects.MethodsMouse model of ALI were established by challenging intratracheally LPS. The wet lung-to-body weight ratio, matrix metalloproteinase (MMP)-9 activities, and pro-inflammatory cytokine productions, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in bronchoalveolar lavage fluid (BALF) were examined in ALI mice with or without quercetin pretreatment. We also examined the effects of quercetin on LPS stimulation in the mouse alveolar macrophage cell line, AMJ2-C11 cells.ResultsIntratracheal administration of quercetin decreased the wet lung-to-body weight ratio. Moreover, quercetin decreased MMP-9 activity and the production of pro-inflammatory cytokines in BALF cells activated by LPS in advance. We determined the expression of quercetin-induced HO-1 in mouse lung, e.g., alveolar macrophages (AMs), alveolar and bronchial epithelial cells. When AMJ2-C11 cells were cultured with quercetin, a marked suppression of LPS-induced pro-inflammatory cytokine production was observed. The cytoprotective effects were attenuated by the addition of the HO-1 inhibitor SnPP. These results indicated that quercetin suppressed LPS-induced lung inflammation, and that an HO-1-dependent pathway mediated these cytoprotective effects.ConclusionsOur findings indicated that quercetin suppressed LPS-induced lung inflammation, and that an HO-1-dependent pathway mediated these cytoprotective effects. Intratracheal administration of quercetin will lead to new supportive strategies for cytoprotection in these serious lung conditions.

The present study confirms that CBA/J mice are susceptible to several clinical isolates of Streptococcus pneumoniae, including four of five penicillin-susceptible and all five penicillin-resistant strains tested, thus providing the first noncompromised animal model for penicillin-resistant S. pneumoniae pneumonia. In this model, doses of penicillin G of 0.6 mg/kg of body weight given six times at 1-h intervals produced effective pulmonary clearance of a penicillin-susceptible strain (penicillin G MIC, 0.015 microgram/ml), while doses of 40 mg/kg given six times at 1-h intervals were required to clear a penicillin-resistant strain (penicillin G MIC, 1 microgram/ml). Imipenem (MIC, 0.25 microgram/ml) was the most active antibiotic tested against the penicillin-resistant strain, with a calculated dose of 0.42 mg/kg given six times at 1-h intervals, resulting in a 2-log decrease in the number of pulmonary bacteria. Comparable effects were seen with vancomycin (MIC, 0.5 microgram/ml), cefotaxime (MIC, 0.5 microgram/ml), and penicillin G at doses of 3.3, 5.5, and 31.0 mg/kg given six times at 1-h intervals, respectively. The pharmacokinetic profile of vancomycin in infected lungs was superior to those of the other antibiotics, especially in regard to the elimination half-life (215.4 min for vancomycin versus 15.0, 14.5, and 14.5 min for penicillin G, cefotaxime, and imipenem, respectively). Both imipenem and vancomycin allowed 90% survival when 40-mg/kg doses were administered twice a day beginning 5 days after infection. Survival rates with penicillin G (160-mg/kg doses) and cefotaxime (40-mg/kg doses) were 40 and 30%, respectively, while no saline-treated mice survived. The present study shows that the CBA/J mouse pneumonia model may be useful for evaluating antibiotic efficacies against penicillin-resistant pneumococcal pneumonia in immunocompetent individuals. Our data suggest that imipenem and vancomycin may be the most active agents against penicillin-resistant S. pneumoniae pneumonia.

Examination of strain differences in the susceptibility of mice to experimental respiratory tract infection with penicillin-resistant Streptococcus pneumoniae TUM19 revealed that a fatal infection model could be induced in immunocompetent CBA/J mice, but not in C3H/HeN, C57BL/6 or ICR mice. After intranasal instillation of c.

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Amino acid oxidases are selective for amino acids, but not for particular amino acids. That is, they act on a considerable number of amino acids. In addition, amino acid oxidases have an optical specificity for D-or L-isomers; L-amino acid oxidase (L-AAO) is specific for L-amino acids and D-amino acid oxidase (D-AAO) is specific for D-amino acids. The general enzyme reaction is Amino acids + O2 + H2O AAO → 2-oxo acids + NH3 + H2O2.Many research groups have proposed the enzyme sensors for the specific detection of L-1-7 or D-3,8,9 isomers of amino acids. Most of the enzyme sensors proposed are based on the amperometric 1,2,4-6,8 and potentiometric 7 detections or chemiluminometric 3,9 detection of hydrogen peroxide or ammonia produced by the amino acid oxidases. In addition, the development of new biosensors which may enable the simultaneous determination of L-and D-isomers of amino acids is also important, but it had not been achieved except for the successive detection 3,10 of both isomers. In this note, a dual enzyme electrode suitable for the simultaneous amperometric detection of D-and L-amino acids is described. The proposed dual electrode consists of two platinum disks modified by an L-AAO or D-AAO membrane cross-linked by glutaraldehyde.Furthermore, the electropolymerization to coat with a thin film of poly(1,2-diaminobenzene) was subsequently carried out to protect the electrode from direct (nonenzymatic) oxidation of electroactive amino acids such as methionine and tyrosine or electroactive interferents such as L-ascorbate, urate, and cysteine, which may otherwise cause electrode fouling. The analytical performance of the dual enzyme electrode is assessed under flow-injection conditions, particularly on substrate selectivity within a group of amino acids and on optical specificity for D-and L-isomers of amino acids. ExperimentalReagents D-AAO (EC 1.4.3.3, 9.9 U mg -1 of solid from porcine kidney), L-AAO (EC 1.4.3.2, 4 U mg -1 of solid from Crotalus adamanteus), and the D-and L-forms of alanine, arginine, histidine, leucine, lysine, methionine, phenylalanine, proline, serine, tyrosine, and valine were obtained from Sigma. Bovine serum albumin (BSA, 96 -99 % albumin), glutaraldehyde (20% solution), ascorbic acid, uric acid, L-cysteine, and 1,2-diaminobenzene were obtained from Wako. They were used as received. The phosphate buffers were prepared from sodium dihydrogen phosphate. Distilled water purified with the use of a Millipore Milli-Q system was used throughout. Construction of the dual enzyme electrodeA BAS cross-flow electrochemical flow-cell was used for the surface modification of the electrode. The electrode assembly consisted of a dual electrode with two platinum disks (3 mm in diameter) as a working electrode, a silver-silver chloride reference electrode, and a stainless-steel as an auxiliary electrode. Prior to the enzyme coating, the surface of the platinum disks was polished with 6 µm diamond particles (BAS) and then with 0.05 µm alumina particles (BAS), then rinsed with distilled water an...

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