11-keto-alpha-boswellic acid, a novel triterpenoid from Boswellia spp. with chemotaxonomic potential and antitumor activity against triple-negative breast cancer cells

Boswellic acids, and particularly 11-keto-boswellic acids, triterpenoids derived from the genus Boswellia (Burseraceae), are known for their anti-inflammatory and potential antitumor efficacy. Although boswellic acids generally occur as α-isomers (oleanane type) and β-isomers (ursane type), 11-keto-boswellic acid (KBA) was found only as the β-isomer, β-KBA. Here, the existence and natural occurrence of the respective α-isomer, 11-keto-α-boswellic acid (α-KBA), is demonstrated for the first time. Initially, α-KBA was synthesized and characterized by high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopy, and a highly selective, sensitive, and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) method was developed by Design of Experiments (DoE) using a pentafluorophenyl stationary phase. This method allowed the selective quantification of individual 11-keto-boswellic acids and provided evidence for α-KBA in Boswellia spp. oleogum resins. The contents of α-KBA as well as further boswellic acids and the composition of essential oils were used to chemotaxonomically classify 41 Boswellia oleogum resins from 9 different species. Moreover, α-KBA exhibited cytotoxicity against three treatment-resistant triple-negative breast cancer (TNBC) cell lines in vitro and also induced apoptosis in MDA-MB-231 xenografts in vivo. The respective β-isomer and the acetylated form demonstrate higher cytotoxic efficacies against TNBC cells. This provides further insights into the structure-activity relationship of boswellic acids and could support future developments of potential anti-inflammatory and antitumor drugs

Airborne observations of the Eyjafjalla volcano ash cloud over Europe during air space closure in April and May 2010

© Author(s) 2011. This work is distributed under the Creative Commons Attribution 3.0 LicenseAirborne lidar and in-situ measurements of aerosols and trace gases were performed in volcanic ash plumes over Europe between Southern Germany and Iceland with the Falcon aircraft during the eruption period of the Eyjafjalla1 volcano between 19 April and 18 May 2010. Flight planning and measurement analyses were supported by a refined Meteosat ash product and trajectory model analysis. The volcanic ash plume was observed with lidar directly over the volcano and up to a distance of 2700 km downwind, and up to 120 h plume ages. Aged ash layers were between a few 100 m to 3 km deep, occurred between 1 and 7 km altitude, and were typically 100 to 300 km wide. Particles collected by impactors had diameters up to 20 μm diameter, with size and age dependent composition. Ash mass concentrations were derived from optical particle spectrometers for a particle density of 2.6 g cm-3 and various values of the refractive index (RI, real part: 1.59; 3 values for the imaginary part: 0, 0.004 and 0.008). The mass concentrations, effective diameters and related optical properties were compared with ground-based lidar observations. Theoretical considerations of particle sedimentation constrain the particle diameters to those obtained for the lower RI values. The ash mass concentration results have an uncertainty of a factor of two. The maximum ash mass concentration encountered during the 17 flights with 34 ash plume penetrations was below 1 mg m-3. The Falcon flew in ash clouds up to about 0.8 mg m-3 for a few minutes and in an ash cloud with approximately 0.2 mg -3 mean-concentration for about one hour without engine damage. The ash plumes were rather dry and correlated with considerable CO and SO2 increases and O3 decreases. To first order, ash concentration and SO2 mixing ratio in the plumes decreased by a factor of two within less than a day. In fresh plumes, the SO2 and CO concentration increases were correlated with the ash mass concentration. The ash plumes were often visible slantwise as faint dark layers, even for concentrations below 0.1 mg m-3. The large abundance of volatile Aitken mode particles suggests previous nucleation of sulfuric acid droplets. The effective diameters range between 0.2 and 3 μm with considerable surface and volume contributions from the Aitken and coarse mode aerosol, respectively. The distal ash mass flux on 2 May was of the order of 500 (240-1600) kgs -1. The volcano induced about 10 (2.5-50) Tg of distal ash mass and about 3 (0.6-23) Tg of SO2 during the whole eruption period. The results of the Falcon flights were used to support the responsible agencies in their decisions concerning air traffic in the presence of volcanic ash.Peer reviewe

The role of endothelin-1 in hyperoxia-induced lung injury in mice

BACKGROUND: As prolonged hyperoxia induces extensive lung tissue damage, we set out to investigate the involvement of endothelin-1 (ET-1) receptors in these adverse changes. METHODS: Experiments were performed on four groups of mice: control animals kept in room air and a group of mice exposed to hyperoxia for 60 h were not subjected to ET-1 receptor blockade, whereas the dual ETA/ETB-receptor blocker tezosantan (TEZ) was administered via an intraperitoneal pump (10 mg/kg/day for 6 days) to other groups of normal and hyperoxic mice. The respiratory system impedance (Zrs) was measured by means of forced oscillations in the anesthetized, paralyzed and mechanically ventilated mice before and after the iv injection of ET-1 (2 μg). Changes in the airway resistance (Raw) and in the tissue damping (G) and elastance (H) of a constant-phase tissue compartment were identified from Zrs by model fitting. RESULTS: The plasma ET-1 level increased in the mice exposed to hyperoxia (3.3 ± 1.6 pg/ml) relative to those exposed to room air (1.6 ± 0.3 pg/ml, p < 0.05). TEZ administration prevented the hyperoxia-induced increases in G (13.1 ± 1.7 vs. 9.6 ± 0.3 cmH(2)O/l, p < 0.05) and H (59 ± 9 vs. 41 ± 5 cmH(2)O/l, p < 0.05) and inhibited the lung responses to ET-1. Hyperoxia decreased the reactivity of the airways to ET-1, whereas it elevated the reactivity of the tissues. CONCLUSION: These findings substantiate the involvement of the ET-1 receptors in the physiopathogenesis of hyperoxia-induced lung damage. Dual ET-1 receptor antagonism may well be of value in the prevention of hyperoxia-induced parenchymal damage

A qualitative investigation of lived experiences of long-term health condition management with people who are food insecure.

Background: As more people are living with one or more chronic health conditions, supporting patients to become activated, self-managers of their conditions has become a key health policy focus both in the UK and internationally. There is also growing evidence in the UK that those with long term health conditions have an increased risk of being food insecure. While international evidence indicates that food insecurity adversely affects individual's health condition management capability, little is known about how those so affected manage their condition(s) in this context. An investigation of lived experience of health condition management was undertaken with food insecure people living in north east Scotland. The study aimed to explore the challenges facing food insecure people in terms of, i. their self-care condition management practices, and ii. disclosing and discussing the experience of managing their condition with a health care professional, and iii. Notions of the support they might wish to receive from them. Methods: Twenty in-depth interviews were conducted with individuals attending a food bank and food pantry in north east Scotland. Interview audio recordings were fully transcribed and thematically analysed. Results: Individuals reporting multiple physical and mental health conditions, took part in the study. Four main themes were identified i.e.: 1. food practices, trade-offs and compromises, that relate to economic constraints and lack of choice; 2. illness experiences and food as they relate to physical and mental ill-health; 3. (in) visibility of participants' economic vulnerability within health care consultations; and 4. perceptions and expectations of the health care system. Conclusions: This study, the first of its kind in the UK, indicated that participants' health condition management aspirations were undermined by the experience of food insecurity, and that their health care consultations in were, on the whole, devoid of discussions of those challenges. As such, the study indicated practical and ethical implications for health care policy, practice and research associated with the risk of intervention-generated health inequalities that were suggested by this study. Better understanding is needed about the impact of household food insecurity on existing ill health, wellbeing and health care use across the UK