Spatial and seasonal variability of the mass concentration and chemical composition of PM2.5 in Poland

The seasonal changes in ambient mass concentrations and chemical composition of fine particulate matter (PM_2.5) were investigated in three locations in Poland. The analyses included PM_2.5-bound hazardous benzo(a)pyrene (BaP), As, Ni, Cd, and Pb. The samples of PM_2.5 were collected daily in Katowice (southern Poland, urban background site), Gdańsk, and Diabla Góra (northern Poland, urban and regional background sites, respectively) during 1-year-long campaign in 2010. Based on monthly ambient concentrations of PM_2.5-bound carbon (organic and elemental), water-soluble ions (Na⁺, NH₄ ⁺, K⁺, Mg²⁺, Ca²⁺, Cl^?, NO₃ ^?, SO₄ ^2?), and elements As, Ni, Cd, Pb, Ti, Al, Fe, the chemical mass closure of PM_2.5 was checked for each of the four seasons of the year and for the heating and non-heating periods at each site. Also, the annual concentrations of PM_2.5 were determined and the annual PM_2.5 mass closure checked. At each measuring point, the PM_2.5 concentrations were high compared to its Polish yearly permissible value, 25 μg/m³, and its concentrations elsewhere in Europe. The highest annual PM_2.5 concentration, 43 μg/m³, occurred in Katowice; it was twice the annual PM_2.5 concentration in Gdańsk, and thrice the one in Diabla Góra. The high annual averages were due to very high monthly concentrations in the heating period, which were highest in the winter. PM_2.5 consisted mainly of carbonaceous matter (elemental carbon (EC) + organic matter (OM), the sum of elemental carbon, EC, and organic matter, OM; its annual mass contributions to PM_2.5 were 43, 31, and 33 % in Katowice, Gdansk, and Diabla Góra, respectively), secondary inorganic aerosol (SIA), the Na_Cl group, and crustal matter (CM)—in the decreasing order of their yearly mass contributions to PM_2.5. OM, EC, SIA, Na_Cl, and CM accounted for almost 81 % of the PM_2.5 mass in Katowice, 74 % in Gdańsk, and 90 % in Diabla Góra. The annual average toxic metal contribution to the PM_2.5 mass was not greater than 0.2 % at each site. In Katowice and Gdańsk, the yearly ambient BaP concentrations were high (15.4 and 3.2 ng/m³, respectively); in rural Diabla Góra, the concentrations of BaP were almost equal to 1 ng/m³, the Polish BaP annual limit. The great seasonal fluctuations of the shares of the component groups in PM_2.5 and of the concentrations of PM_2.5 and its components are due to the seasonal fluctuations of the emissions of PM and its precursors from hard and brown coal combustion for energy production, growing in a heating season, reaching maximum in winter, and decreasing in a non-heating period. In Gdańsk, northern Poland, especially in the spring and autumn, sea spray might have affected the chemical composition of PM_2.5. The greatest hazard from PM_2.5 occurs in Katowice, southern Poland, in winter, when very high concentrations of PM_2.5 and PM_2.5-related carbonaceous matter, including BaP, are maintained by poor natural ventilation in cities, weather conditions, and the highest level of industrialization in Poland. In less industrialized northern Poland, where the aeration in cities is better and rather gaseous than solid fuels are used, the health hazard from ambient PM_2.5 is much lower.     

Metabolism of [U‐13C]glucose in human brain tumors in vivo

Glioblastomas and brain metastases demonstrate avid uptake of 2‐[¹⁸F]fluoro‐2‐deoxyglucose by positron emission tomography and display perturbations of intracellular metabolite pools by ¹H MRS. These observations suggest that metabolic reprogramming contributes to brain tumor growth in vivo. The Warburg effect, excess metabolism of glucose to lactate in the presence of oxygen, is a hallmark of cancer cells in culture. 2‐[¹⁸F]Fluoro‐2‐deoxyglucose‐positive tumors are assumed to metabolize glucose in a similar manner, with high rates of lactate formation relative to mitochondrial glucose oxidation, but few studies have specifically examined the metabolic fates of glucose in vivo. In particular, the capacity of human brain cancers to oxidize glucose in the tricarboxylic acid cycle is unknown. Here, we studied the metabolism of human brain tumors in situ. [U‐¹³ C]Glucose (uniformly labeled glucose, i.e. d ‐glucose labeled with ¹³ C in all six carbons) was infused during surgical resection, and tumor samples were subsequently subjected to ¹³C NMR spectroscopy. The analysis of tumor metabolites revealed lactate production, as expected. We also determined that pyruvate dehydrogenase, turnover of the tricarboxylic acid cycle, anaplerosis and de novo glutamine and glycine synthesis contributed significantly to the ultimate disposition of glucose carbon. Surprisingly, less than 50% of the acetyl‐coenzyme A pool was derived from blood‐borne glucose, suggesting that additional substrates contribute to tumor bioenergetics. This study illustrates a convenient approach that capitalizes on the high information content of ¹³C NMR spectroscopy and enables the analysis of intermediary metabolism in diverse cancers growing in their native microenvironment. Copyright © 2012 John Wiley & Sons, Ltd.     

Review: peroxisome proliferator-activated receptor-gamma and its role in the development and treatment of diabetes

Since its identification as the receptor for antidiabetic thiazolidinedione drugs, peroxisome proliferator-activated receptor-gamma (PPARgamma) has been the focus of pharmaceutical drug discovery programs directed toward finding better drugs for the treatment of diabetes, as well as the object of basic research aimed at understanding its role in the regulation of metabolism. We now understand a great deal about the crucial role that PPARgamma plays in adipocyte differentiation and development, and are rapidly gaining knowledge about the role of the receptor in the regulation of metabolism. However, many crucial aspects of the molecular mechanism by which modulation of PPARgamma activity affects insulin resistance and glucose homeostasis are still not clearly understood. Here the authors review the current status of PPARgamma research, with an emphasis on its role in the causes and treatment of type 2 diabetes.     

Platelet glycoprotein IIb/IIIa inhibition using eptifibatide with primary coronary stenting for acute myocardial infarction: a 30-day follow-up study.

The results of primary coronary stenting for acute myocardial infarction (AMI) have been reported to improve significantly with the concomitant administration of platelet glycoprotein IIb/IIIa inhibitor abciximab. There are, however, no data available with the use of eptifibatide, a more cost-effective, small-molecule GP IIb/IIIa blocker with a shorter half-life. In a prospective multicenter feasibility and efficacy study, we assigned 55 consecutive patients with AMI being taken up for primary stenting to receive eptifibatide just before the procedure (two boluses of 180 microg/kg 10 min apart and a 24-hr infusion of 2 microg/kg/min). Clinical outcomes were evaluated at 30 days after the procedure. The angiographic patency of the vessel with TIMI flow rates, TIMI myocardial perfusion (TMP) grade, and corrected TIMI frame counts were assessed at the end of procedure and before hospital discharge. At 30 days, the primary endpoint, a composite of death, myocardial infarction, and urgent target vessel revascularization (TVR) was seen in 12.7% of patients. The TIMI 3 and TMP grade 3 flow, which was seen in 93% and 86% of patient, respectively, at the end of the procedure, declined to 86% and 78%, respectively (P < 0.05) before hospital discharge. Corrected TIMI frame counts also decreased from 25.7 +/- 7.2 to 22.9 +/- 6.8 (P < 0.05). There were five (9.1%) instances of subacute thrombosis (SAT) presenting as AMI, needing urgent TVR in all, within 3-5 days of the primary procedure. No excessive bleeding complication, directly attributable to the use of eptifibatide, was observed. The study was terminated prematurely because of an unacceptable SAT rate. Administration of eptifibatide along with primary stenting for AMI is associated with a high TIMI 3 and TMP grade 3 flow acutely. However, these flows decline significantly before hospital discharge and lead to a high rate of SAT. The dosage and duration of infusion of eptifibatide in this setting needs further evaluation.     

Enhanced green fluorescent protein targeted to the Sca-1 (Ly-6A) locus in transgenic mice results in efficient marking of hematopoietic stem cells in vivo

OBJECTIVE: Hematopoietic stem cells are important clinically, both as targets of disease and as reagents for cellular therapy. Studies in hematopoietic stem cell biology have been hampered by difficulties in purifying and manipulating these cells. To facilitate these studies, we sought to develop a system for targeting genes of interest to the hematopoietic stem cell compartment in transgenic mice. MATERIALS AND METHODS: We used Sca-1, a glycosyl phosphatidylinositol-anchored protein expressed on the surface of all hematopoietic stem cells in commonly used inbred mouse strains. We created a mutant Sca-1 allele in which the enhanced green fluorescent protein (EGFP) cDNA is integrated into the Sca-1 locus by homologous recombination in embryonic stem cells. RESULTS: EGFP protein is detectable in all hematopoietic tissues of mice heterozygous for the mutant Sca-1 allele. Growth and development of these mice are normal. No adverse effects of long-term, high-level EGFP expression were noted. Sca-1 positive cells coexpress EGFP in all tissues and lineages examined, as predicted by the targeting strategy. Sca-1 and EGFP expression are coordinately up-regulated in splenocytes from mutant mice. The Lin(-)EGFP(+) bone marrow population contains all progenitor activity in Sca-1(+)(/EGFP) mice. The Lin(-)EGFP(+) bone marrow cells are equivalent to Lin(-)Sca-1(+) cells in long-term repopulation and serial transplantation assays. CONCLUSION: The hematopoietic stem cell compartment appears to be targeted in Sca-1(+)(/EGFP) mutant mice. This system should be useful for studying the normal biology of hematopoietic stem cells and for targeting other genes to this cellular compartment.