Age influence on mice lung tissue response to [i]Aspergillus fumigatus[/i] chronic exposure

INTRODUCTION AND OBJECTIVE: Exposure to conidia of Aspergillus fumigatus was described as a causative factor of a number of the respiratory system diseases, including asthma, chronic eosinophilic pneumonia, hypersensitivity pneumonitis and bronchopulmonary aspergillosis. The study investigates the effects of the repeated exposure to A. fumigatus in mice pulmonary compartment. Our work tackles two, so far insufficiently addressed, important aspects of interaction between affected organism and A. fumigatus: 1) recurrent character of exposure (characteristic for pathomechanism of the abovementioned disease states) and 2) impact of aging, potentially important for the differentiation response to an antigen. MATERIALS AND METHODS: In order to dissect alterations of the immune system involved with both aging and chronic exposure to A. fumigatus, we used 3- and 18-month-old C57BL/6J mice exposed to repeated A. fumigatus inhalations for 7 and 28 days. Changes in lung tissue were monitored by histological and biochemical evaluation. Concentration of pro- and anti-inflammatory cytokines in lung homogenates was assessed by ELISA tests. RESULTS AND CONCLUSIONS: Our study demonstrated that chronic inflammation in pulmonary compartment, characterized by the significant increase of proinflammatory cytokines (IL1, IL6, IL10) levels, was the dominant feature of mice response to repeated A. fumigatus inhalations. The pattern of cytokines' profile in the course of exposure was similar in both age groups, however in old mice the growth of the cytokines' levels was more pronounced (especially in case of IL1)

Age influence on hypersensitivity pneumonitis induced in mice by exposure to Pantoea agglomerans

Hypersensitivity pneumonitis (HP) represents the immunologically mediated lung disease induced by repeated inhalations of a wide variety of certain finely dispersed organic antigens. In susceptible subjects, these inhalations provoke a hypersensitivity reaction characterized by intense inflammation of the terminal bronchioles, the interstitium and the alveolar tree. The inflammation often organizes into granulomas and may progress to pulmonary fibrosis. Our previous work indicated that cell extract of gram-negative bacteria Pantoea agglomerans (SE-PA) causes, in young C57BL/6J mice, pulmonary changes that are very similar to the clinical manifestations of HP in men. The purpose of presented studies was to describe the response of mice immune system while exposed to SE-PA. Particular attention was paid to examine the age influence on SE-PA induced inflammation and fibrosis in lung tissue. We used 3- and 18-month-old C57BL/6J mice. Lung samples were collected from untreated mice and animals exposed to harmful agent for 7 and 28 days. HP development was monitored by histological and biochemical evaluation. Using ELISA tests, we examined concentration of pro-and anti-inflammatory cytokines in lung homogenates. Our study demonstrated again that SE-PA provokes in mice changes typical for the clinical picture of HP, and that successive stages of disease (acute, subacute and chronic) might be obtained by modulation of time exposure. Furthermore, we found that animals' age at the time of sensitization influences the nature of observed changes (cytokine expression pattern) and the final outcome (reaction intensity and scale of fibrosis)

The T=2 mirrors 36Ca and 36S : a test for isospin symmetry of shell gaps at the driplines

The first excited 2+ state of 36Ca has been identified by its gamma -decay, exploiting the two-step fragmentation technique at the FRS-RISING setup at GSI. This is the heaviest Tz=-2 nucleus in the Segre chart in which a gamma -decay of an excited state has been observed. A stable beam of 40Ca at 420A MeV impinged on a primary 9Be target. Out of the secondary beam of fragmentation products, 37Ca was separated by the FRS and struck on a second 9Be target at the final focus of the FRS. The energy for the 21+ decay of 36Ca was determined to be 3015(16) keV, which is 276 keV lower than in its T=2 mirror 36S. This mirror energy difference (MED) is discussed in the framework of shell model calculations using a 16O core, the sd shell isospin symmetric interaction USD and experimental single-particle energies from 17O and 17F. The results show that the MED within the sd shell provide a sensitive test for the evolution of the N, Z=14,16 subshell gaps towards the driplines. Especially the N, Z=16 gap is determined by Thomas-Ehrman shift in the A=17, T=1/2 isospin doublet, while Coulomb effects are found to have marginal influence

\u3b2-decay of102Y produced in projectile fission of238U

The population of Zr-102 following the beta decay of Y-102 produced in the projectile fission of U-238 at the GSI facility in Darmstadt, Germany has been studied. Y-102 is known to beta decay into Zr-102 via two states, one of high spin and the other low spin. These states preferentially populate different levels in the Zr-102 daughter. In this paper the intensities of transitions in Zr-102 observed are compared with those from the decay of the low-spin level studied at the TRISTAN facility at Brookhaven National Laboratory and of the high-spin level studied at the JOSEF separator at the Kernforschungsanlage Julich

Isomers in neutron-rich lead isotopes populated via the fragmentation of238U at 1 GeV A

eutron-rich nuclei beyond N = 126 in the lead region were populated by fragmenting a (238)U beam at 1 GeV A on a Be target and then separated by the Fragment Separator (FRS) at GSI. Their isomeric decays were observed, enabling study of the shell structure of neutron-rich nuclei around the Z=82 shell closure. Some preliminary results are reported in this paper

New Isomers in the Full Seniority Scheme of Neutron-Rich Lead Isotopes: The Role of Effective Three-Body Forces

The neutron-rich lead isotopes, up to 216Pb, have been studied for the first time, exploiting the fragmentation of a primary uranium beam at the FRS-RISING setup at GSI. The observed isomeric states exhibit electromagnetic transition strengths which deviate from state-of-the-art shell-model calculations. It is shown that their complete description demands the introduction of effective three-body interactions and two-body transition operators in the conventional neutron valence space beyond 208Pb

Hindered gamow-teller decay to the odd-odd N=Z Ga 62: Absence of proton-neutron T=0 condensate in A=62

Search for a new kind of superfluidity built on collective proton-neutron pairs with aligned spin is performed studying the Gamow-Teller decay of the T=1, Jπ=0+ ground state of Ge62 into excited states of the odd-odd N=Z nucleus Ga62. The experiment is performed at GSI Helmholtzzentrum für Schwerionenforschung with the Ge62 ions selected by the fragment separator and implanted in a stack of Si-strip detectors, surrounded by the RISING Ge array. A half-life of T1/2=82.9(14) ms is measured for the Ge62 ground state. Six excited states of Ga62, populated below 2.5 MeV through Gamow-Teller transitions, are identified. Individual Gamow-Teller transition strengths agree well with theoretical predictions of the interacting shell model and the quasiparticle random phase approximation. The absence of any sizable low-lying Gamow-Teller strength in the reported beta-decay experiment supports the hypothesis of a negligible role of coherent T=0 proton-neutron correlations in Ga62

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, 120.29 percentage points; 95% confidence interval [CI], 120.32 to 120.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P=0.98). There were no significant between-group differences in rates of acute pancreatitis (P=0.07) or pancreatic cancer (P=0.32). CONCLUSIONS Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events. (Funded by Merck Sharp & Dohme; TECOS ClinicalTrials.gov number, NCT00790205.