Fourteenth International Waste Management and Landfill Symposium

SUMMARY: The biopharmaceutical industry has been slow in carrying out LCA analyses. However, as the industry matures, the level of scrutiny placed on this industry by international governments will increase and hence, there is an urgent need for the industry to implement decision-support tools for the decision-making processes. Decision-support tools based on life cycle assessment (LCA) can be potentially used for application in the biopharmaceutical industry as an aid to decision making. This paper sets out the challenges associated with developing such decision-support LCA tools. This paper highlights that in order for the industry to overcome these challenges and successfully develop decision-support LCA tools, they require a broader understanding of the biopharmaceutical manufacturing processes and LCA methodology

Falls and Physical Activity in Persons with Multiple Sclerosis

Objectives. To examine the association between fall history and physical activity using an objective measure of physical activity (i.e., accelerometry) in persons with multiple sclerosis. Design. A community-based sample of 75 ambulatory persons with multiple sclerosis volunteered for the investigation. Participants self-reported fall history in the last year, underwent a neurological exam to determine Expanded Disability Status Scale (EDSS) score, and wore an accelerometer around the waist for 7 consecutive days to determine physical activity. Results. Overall, 37 persons (49.3% of the sample) reported falling in the last year with 28 of the 37 falling more than once. Persons who fell in the last year had a significantly lower number of steps/day than nonfallers (3510 versus 4940 steps/day; P \u3c .05). However, when controlling for disability status there was no statistically significant difference between fallers and nonfallers (4092 versus 4373 steps/day; P \u3e.05). Conclusions. Collectively, the findings suggest that fall history may have little impact on current physical activity levels in persons with multiple sclerosis

Citrus allergy from pollen to clinical symptoms

Allergy to citrus fruits is often associated with pollinosis and sensitization to other plants due to a phenomenon of cross-reactivity. The aims of the present study were to highlight the cross-reactivity among citrus and the major allergenic pollens/fruits, throughout clinical and molecular investigations, and to evaluate the sensitization frequency to citrus fruits in a population of children and adults with pollinosis. We found a relevant percentage of sensitisation (39%) to citrus fruits in the patients recruited and in all of them the IgE-mediated mechanism has been confirmed by the positive response to the prick-to-prick test. RT-PCR experiments showed the expression of Cit s 1, Cit s 3 and a profilin isoform, already described in apple, also in Citrus clementine pollen. Data of multiple sequence alignments demonstrated that Citrus allergens shared high percentage identity values with other clinically relevant species (i.e. Triticum aestivum, Malus domestica), confirming the possible cross-allergenicity citrus/grasses and citrus/apple. Finally, a novelty of the present work has been the expression of two phospholipaseA2 isoforms (PLA2 \u3b1 and \u3b2) in Citrus as well as in Triticum pollens; being PLA2 able to generate pro-inflammatory factors, this enzyme could participate in the activation of the allergenic inflammatory cascade

An unusual case of anti-neutrophilic cytoplasmic autoantibodies associated vasculitis with pauci-immune crescentic glomerulonephritis in young? Wegener’s? Churg Strauss

Anti-neutrophilic cytoplasmic autoantibodies-associated vasculitis (AAV) is very rare in India. It normally affects older population around 6th and 7th decade of life. The management of cases is also complicated. We present a case of 18 year old male patient who came with complaints of epistaxis and had hematuria and pain in the joints. He had sub conjunctival haemorrhage on presentation. On and off he had respiratory symptoms and epistaxis in the past for which he was treated as allergy and bronchial asthma. At admission he had high absolute eosinophil count and had blood 3+ positive in urine. Initially he was treated as post viral vasculitis. But patient had involvement of kidney, lung, skin, joints, eyes and on further evaluation he was found to have AAV. The case was unique due to the age of presentation and patient also had overlapping symptoms of both Wegner’s granulomatosis and Churg-Strauss syndrome

Direct activation of NADPH oxidase 2 by 2-deoxyribose-1-phosphate triggers nuclear factor kappa B-dependent angiogenesis.

AbstractAims: Deoxyribose-1-phosphate (dRP) is a proangiogenic paracrine stimulus released by cancer cells, platelets, and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells.Results: Live cell imaging, electron paramagnetic resonance, pull-down of dRP-interacting proteins, followed by immunoblotting, gene silencing of different NADPH oxidases (NOXs), and their regulatory cosubunits by small interfering RNA (siRNA) transfection, and experiments with inhibitors of the sugar transporter glucose transporter 1 (GLUT1) were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NOX2 complex, but not NOX4. Increased reactive oxygen species generation in response to NOX2 activity leads to redox-dependent activation of the transcription factor nuclear factor kappa B (NF-κB), which, in turn, induces vascular endothelial growth factor receptor 2 (VEGFR2) upregulation. Using endothelial tube formation assays, gene silencing by siRNA, and antibody-based receptor inhibition, we demonstrate that the activation of NF-κB and VEGFR2 is necessary for the angiogenic responses elicited by dRP. The upregulation of VEGFR2 and NOX2-dependent stimulation of angiogenesis by dRP were confirmed in excisional wound and Matrigel plug vascularization assays in vivo using NOX2−/− mice.Innovation: For the first time, we demonstrate that dRP acts intracellularly and stimulates superoxide anion generation by direct binding and activation of the NOX2 enzymatic complex.Conclusions: This study describes a novel molecular mechanism underlying the proangiogenic activity of dRP, which involves the sequential activation of NOX2 and NF-κB and upregulation of VEGFR2. Antioxid. Redox Signal. 28, 110–130

Expression of Protease-Activated Receptor 1 and 2 and Anti-Tubulogenic Activity of Protease-Activated Receptor 1 in Human Endothelial Colony-Forming Cells

Endothelial colony-forming cells (ECFCs) are obtained from the culture of human peripheral blood mononuclear cell (hPBMNC) fractions and are characterised by high proliferative and pro-vasculogenic potential, which makes them of great interest for cell therapy. Here, we describe the detection of protease-activated receptor (PAR) 1 and 2 amongst the surface proteins expressed in ECFCs. Both receptors are functionally coupled to extracellular signal-regulated kinase (ERK) 1 and 2, which become activated and phosphorylated in response to selective PAR1- or PAR2-activating peptides. Specific stimulation of PAR1, but not PAR2, significantly inhibits capillary-like tube formation by ECFCs in vitro, suggesting that tubulogenesis is negatively regulated by proteases able to stimulate PAR1 (e.g. thrombin). The activation of ERKs is not involved in the regulation of tubulogenesis in vitro, as suggested by use of the MEK inhibitor PD98059 and by the fact that PAR2 stimulation activates ERKs without affecting capillary tube formation. Both qPCR and immunoblotting showed a significant downregulation of vascular endothelial growth factor 2 (VEGFR2) in response to PAR1 stimulation. Moreover, the addition of VEGF (50–100 ng/ml) but not basic Fibroblast Growth Factor (FGF) (25–100 ng/ml) rescued tube formation by ECFCs treated with PAR1-activating peptide. Therefore, we propose that reduction of VEGF responsiveness resulting from down-regulation of VEGFR2 is underlying the anti-tubulogenic effect of PAR1 activation. Although the role of PAR2 remains elusive, this study sheds new light on the regulation of the vasculogenic activity of ECFCs and suggests a potential link between adult vasculogenesis and the coagulation cascade

Superconducting ground state study of valence skip compound AgSnSe2_2

The valence-skipped superconductors are natural candidates for unconventional superconductivity, as they can exhibit a negative effective, attractive interaction for electron-pairing. This work reports comprehensive XRD, magnetization, specific heat and muon spin rotation and relaxation measurements ($\mu$SR) on a valence-skipped compound: AgSnSe$_2$. The temperature dependence of the electronic specific heat ($C_{el}(T)$) and of the upper critical field ($H_{c2}(T)$) provide evidence of two-gap superconductivity, which is also confirmed by our transverse-field $\mu$SR measurements. Our zero-field $\mu$SR measurements suggest preserved time-reversal symmetry in the superconducting ground state of AgSnSe$_2$.Comment: 8 pages, 6 figure