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Latest Paper:Oxyfluoride glasses containing Ag species and rare earth (RE) ions (Dy<sup>3+</sup>, Sm<sup>3+</sup>, Tb<sup>3+</sup>) were prepared by melt-quenching technique. The type of luminescent species of novel excitation band (230-300 nm peaked at 255 nm) and emission band (300-600 nm peaked at 350 nm) were investigated by absorption, excitation, emission spectra, as well as decay lifetime measurements and can be ascribed to isolated Ag<sup>+</sup> ions. Owing to energy transfer from Ag<sup>+</sup> to RE ions, significant enhancements of RE ions emission (76 times for Sm<sup>3+</sup>, 41 times for Dy<sup>3+</sup>) were observed for non-resonant UV excitation (255 nm). Our research may extend the understanding of interactions between RE ions and Ag species.
J Infect Dis. 2012 Apr 3;:
22474037
Center for Tuberculosis Research, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA.
Individuals with latent tuberculosis infection (LTBI) live with a risk of reactivation, and several treatments for chronic inflammatory conditions are highly associated with such reactivation. A new Janus kinase inhibitor, tofacitinib (CP-690550), has shown promising results for treatment of inflammatory disorders, thus raising concerns of risk of active TB. Our goal was to characterize the impact of tofacitinib on LTBI using a mouse model of contained TB. Our data indicate that tofacitinib reduces host containment of M.tb. and promotes bacterial replication in the lungs, suggesting TB reactivation. Tofacitinib may carry a significant risk for LTBI reactivation in humans.
Department of Medical Biology, Hubei University of Medicine, Hubei, PRC.
Using the protein-protein docking program, this study investigates the relationship between TRAF2 and its related proteins and the diversity within the 3D structures of TRAF2s. TRAF2 exists in monomer, trimer, and hexamer forms and it can combine with a number of proteins. Through comparative analysis we found that TRAF2(122), TRAF2(22), TRAF2(21740), TRAF2(2), TRAF2( 22ABC), and TRAF2(Phyre) perform very close homoousia in docking with the same group of ligands, though these TRAF2s come from different sources. The TRAF2-related proteins of cluster 1 change docking values strongly from top to bottom. The TRAF2- related proteins of clusters 2 and 3 have acceptable variation of the docking values. In consideration of the amino acid percentage, TRAF2-related proteins of cluster 2 represent appropriate docking values.
Nat Commun. 2012 ;3 :753
22434196
Jong-Hee Lee,
Nicole C Ammerman,
Scott Nolan,
Deborah E Geiman,
Shichun Lun,
Haidan Guo,
William R Bishai
Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
The emergence of multi- and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) has intensified the critical public health implications of this global disease. The fitness of Mycobacterium tuberculosis (M.tb.) strains exhibiting MDR and XDR phenotypes is of fundamental importance in predicting whether the MDR-/XDR-TB epidemic will be sustained across the human population. Here we describe a potential mechanism of M.tb. resistance to the TB drug isoniazid (INH) conferred by loss of a sigma factor, SigI. We demonstrate that the gain of INH resistance in the M.tb. ΔsigI mutant might not diminish the organism's fitness for causing disease. These findings have significant implications when considering the ability of drug-resistant M.tb. strains to initiate untreatable TB epidemics, as it is possible that loss or alteration of SigI function could have a role in the generation of MDR and XDR M.tb. strains of suitable fitness to spread in a community setting.
J Int Med Res. 2012 ;40 (1):204-10
22429360
Department of Gastroenterology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
OBJECTIVE This study investigated the role of food intolerance in irritable bowel syndrome with diarrhoea (D-IBS). METHODS Specific immunoglobulin G (IgG) antibodies against 14 common food antigens in the serum were measured in 77 patients with D-IBS and 26 healthy controls. Food-specific IgG antibodies were identified in 39 (50.65%) patients with D-IBS patients compared with four (15.38%) controls. For 12 weeks following the serological testing, 35 patients with D-IBS and food intolerance consumed diets that excluded the identified food. Changes in the main symptoms of D-IBS were evaluated before treatment and regularly during treatment in these patients. RESULTS After 4 weeks' dietary therapy, most symptoms of D-IBS had improved. By 12 weeks, all symptom scores had decreased significantly compared with the baseline scores. CONCLUSIONS The 12-week specific-food exclusion diets resulted in significant improvements in abdominal pain (bloating level and frequency), diarrhoea frequency, abdominal distension, stool shape, general feelings of distress and total symptom score compared with baseline in patients with D-IBS.
Drug Metab Dispos. 2012 Mar 5;:
22393122
China Pharmaceutical University.
The purpose of the study was to evaluate the contribution of the impaired cytochrome P450s (CYP450s) and breast cancer resistance protein (Bcrp) activity and expression to drug pharmacokinetics under diabetic states. Diabetic rats were induced by intraperitoneal administration of streptozocin (STZ). Glibenclamide (GLB), a substrate of Bcrp, was served as a model drug. The pharmacokinetics of oral GLB (10 mg/kg) was studied. The results showed that diabetes mellitus significantly increased exposure (AUC and C(max)) of GLB following an oral administration. Data from hepatic microsomes suggested impairment of GLB metabolism in diabetic rats. GLB metabolism in hepatic microsomes was significantly inhibited by a selective inhibitor (sulfaphenazole, SUL) of CYP2C11 and CYP2C11 antibody. Western blot further showed the contribution of impaired CYP2C11 expression to the impairment of GLB metabolism. Data from excretion showed that approximately 72% of oral dose was excreted via feces of normal rats, indicating an important role of intestinal Bcrp. Diabetes significantly decreased recovery from feces, which was only 40% of oral dose. Results from in situ single-pass intestine perfusion revealed that diabetes significantly increased the apparent permeability coefficient (Peff) and decreased efflux of GLB via intestine, inferring impairment of intestinal Bcrp function, which may play a role in the increased exposure of oral GLB in diabetic rats. Insulin treatment partly or completely reversed the changes in diabetic rats. All results gave the conclusion that both the impaired hepatic CYP2C11 and intestinal Bcrp expression and activity induced by diabetes contributed to the increased exposure of oral GLB.
J Dent Res. 2012 Feb 29;:
22378694
Inflammation has been strongly related to metabolic syndrome (MetS). Periodontal disease is the most common chronic infection in adults. We investigated a cross-sectional (n = 925) and 3-year longitudinal (n = 685) relationship between the daily frequency of toothbrushing and MetS. In the cross-sectional analysis, the prevalence of MetS was 15.7%. After adjustment for potential confounding factors (including all lifestyle factors), the odds ratios (95% confidence interval [CI]) of having MetS in those who brushed 2 times/day and ≥ 3 times/day were 0.71 (0.48-1.05) and 0.47 (0.24-0.92), respectively, as compared with ratios in those with a toothbrushing frequency of ≤ 1 time/day. Increasing toothbrushing frequency tended to relate inversely to hypertriglyceridemia and high-sensitivity C-reactive protein. In the longitudinal analysis, 99 participants were newly diagnosed with MetS. The adjusted odds ratios (95% CI) of the MetS in participants who brushed 2 times/day and ≥ 3 times/day as compared with participants who brushed ≤ 1 time/day were 0.80 (0.49-1.31) and 0.43 (0.19-0.97), respectively. The frequency of toothbrushing was related inversely only to hypertriglyceridemia, consistent with the cross-sectional analysis. This study found that more frequent toothbrushing is related to a lower prevalence and incidence of MetS. These results suggest that more frequent toothbrushing may contribute to the prevention of MetS due to the inflammation/triglyceride pathway.
Org Biomol Chem. 2012 Feb 27;:
22366754
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543. chmwangj@nus.edu.sg.
3,4-Dihydrocoumarins, considered to be valuable building blocks, have attracted considerable attention due to their various biological activities. Herein, we have documented an efficient and convenient double decarboxylation process for the synthesis of 4-substituted 3,4-dihydrocoumarin in moderate to excellent yields under mild reaction conditions (up to 98%).
J Biol Chem. 2012 Feb 21;:
22354961
UNC-CH, United States;
p38 MAPK has been strongly implicated in the development of atherosclerosis but its role in cholesterol ester accumulation in macrophages and formation of foam cells, an early step in the development of atherosclerosis, has not been investigated. We addressed this issue and made some brand new observations. First, elevated intracellular cholesterol level induced by the exposure to LDL activated p38 MAPK and activation of p38 MAPK with anisomycin increased the ratio of cholesterol esters over free cholesterol while inhibition of p38 MAPK with SB203580 or siRNA reduced the LDL loading-induced intracellular accumulation of free cholesterol and cholesterol esters in macrophages. Second, exposure to LDL cholesterol inhibited autophagy in macrophages; and inhibition of autophagy with 3-methyladenine increased intracellular accumulation of cholesterol (free cholesterol and cholesterol esters) while activation of autophagy with rapamycin decreased intracellular accumulation of free cholesterol and cholesterol esters induced by the exposure to LDL cholesterol. Third, LDL cholesterol loading-induced inhibition of autophagy was prevented by blockade of p38 MAPK with SB203580 or siRNA. Cholesterol ester hydrolase (CEH) was co-localized with autophagosomes. Finally, LDL cholesterol loading and p38 activation suppressed expression of the key autophagy gene, Ulk1, in macrophages. Together, our results provide brand new insight about cholesterol ester accumulation in macrophages and foam cell formation.
Environ Pollut. 2012 Apr ;163 :8-13
22325425
Institute of Mineralogy and Geochemistry, Karlsruhe Institute of Technology, Adenauerring 20b, 76131 Karlsruhe, Germany. haraldneid@googlemail.com
Consequences of irrigation by arsenic (As) enriched groundwater were assigned in the Hetao Plain, part of Chinas' Inner Mongolia Autonomous Region. Examinations followed the As flow path from groundwater to soil and finally plants. A sunflower and a maize field were systematically sampled, each irrigated since three years with saline well water, characterized by elevated As concentrations (154 and 238μgL(-1)). The annual As input per m(2) was estimated as 120 and 186mg, respectively. Compared to the geogenic background, As concentrations increased toward the surface with observed enrichments in topsoil being relatively moderate (up to 21.1mgkg(-1)). Arsenic concentrations in plant parts decreased from roots toward leaves, stems and seeds. It is shown that the bioavailability of As is influenced by a complex interplay of partly counteracting processes. To prevent As enrichment and soil salinization, local farmers were recommended to switch to a less problematic water source.
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