Between the unstoppable and the feasible: the lucid pragmatism of transition processes for sustainable urban mobility: a literature review

This article presents a literature review of Transition Experiments applied to the Sustainable Urban Mobility context from a critical and operative point of view. The moment of transformation that we are living through determines concerns about the decarbonization and compliance with the 2050 Targets and imposes a paradigm shift towards sustainable urban mobility. In this regard, the necessary physical change will have to be accompanied by a socio–cultural transition, of which the challenge implies the construction of a collective ideal, shared by the population and the main stakeholders, leading to the opening of new political spaces and a change, also in terms of governance.This research was funded by Fundação para a Ciência and a Tecnologia, IP (FCT)/ Massachusetts Institute of Technology (MIT-Portugal), grant number SFRH/BD/151416/202

Subacute toxicology studies on the aqueous fraction of the ethanol extract of the leaves of Cissampelos sympodialis Eichl. (Menispermaceae) in dogs

Cissampelos sympodialis Eichl. (Menispermaceae) has been investigated about its botanical, chemical, pharmacological and toxicological aspects in our laboratory. Previous acute toxicology studies demonstrated that in dogs as well as in Wistar rats, 5 g/kg, p.o., and 2 g/kg, i.p. of the aqueous fraction of the ethanol extract of the leaves of Cissampelos sympodialis (AFL), induced a significant increase in the phosphatase alkaline and gama glutamil tranferase (GGT) levels, that were completely reversed in 15 days after interruption of AFL treatment. The aim of the present work was to investigate the subacute toxicology effects induced by AFL in dogs. We used the methods proposed by Portaria 116/96 of the Secretaria Nacional de Vigilância Sanitária, which regulates studies of toxicity for phytomedicines in Brazil. Daily administration (p.o.) of AFL, 45 mg/kg/day (5 times the dose used by human beings), during 4 weeks, was devoid of any effect on haematological (haemogram and platelets) and on blood biochemical parametes. In conclusion, the present study, using dogs, demonstrated that AFL, in a popularly used dose, by human beings, was devoid of any toxicological effect

Post-Transcriptional Regulation of 5-Lipoxygenase mRNA Expression via Alternative Splicing and Nonsense-Mediated mRNA Decay

5-Lipoxygenase (5-LO) catalyzes the two initial steps in the biosynthesis of leukotrienes (LT), a group of inflammatory lipid mediators derived from arachidonic acid. Here, we investigated the regulation of 5-LO mRNA expression by alternative splicing and nonsense-mediated mRNA decay (NMD). In the present study, we report the identification of 2 truncated transcripts and 4 novel 5-LO splice variants containing premature termination codons (PTC). The characterization of one of the splice variants, 5-LOΔ3, revealed that it is a target for NMD since knockdown of the NMD factors UPF1, UPF2 and UPF3b in the human monocytic cell line Mono Mac 6 (MM6) altered the expression of 5-LOΔ3 mRNA up to 2-fold in a cell differentiation-dependent manner suggesting that cell differentiation alters the composition or function of the NMD complex. In contrast, the mature 5-LO mRNA transcript was not affected by UPF knockdown. Thus, the data suggest that the coupling of alternative splicing and NMD is involved in the regulation of 5-LO gene expression

Oral tolerance inhibits pulmonary eosinophilia in a cockroach allergen induced model of asthma: a randomized laboratory study

<p>Abstract</p> <p>Background</p> <p>Antigen desensitization through oral tolerance is becoming an increasingly attractive treatment option for allergic diseases. However, the mechanism(s) by which tolerization is achieved remain poorly defined. In this study we endeavored to induce oral tolerance to cockroach allergen (CRA: a complex mixture of insect components) in order to ameliorate asthma-like, allergic pulmonary inflammation.</p> <p>Methods</p> <p>We compared the pulmonary inflammation of mice which had received four CRA feedings prior to intratracheal allergen sensitization and challenge to mice fed PBS on the same time course. Respiratory parameters were assessed by whole body unrestrained plethysmography and mechanical ventilation with forced oscillation. Bronchoalveolar lavage fluid (BAL) and lung homogenate (LH) were assessed for cytokines and chemokines by ELISA. BAL inflammatory cells were also collected and examined by light microscopy.</p> <p>Results</p> <p>CRA feeding prior to allergen sensitization and challenge led to a significant improvement in respiratory health. Airways hyperreactivity measured indirectly via enhanced pause (Penh) was meaningfully reduced in the CRA-fed mice compared to the PBS fed mice (2.3 ± 0.4 vs 3.9 ± 0.6; p = 0.03). Directly measured airways resistance confirmed this trend when comparing the CRA-fed to the PBS-fed animals (2.97 ± 0.98 vs 4.95 ± 1.41). This effect was not due to reduced traditional inflammatory cell chemotactic factors, Th2 or other cytokines and chemokines. The mechanism of improved respiratory health in the tolerized mice was due to significantly reduced eosinophil numbers in the bronchoalveolar lavage fluid (43300 ± 11445 vs 158786 ± 38908; p = 0.007) and eosinophil specific peroxidase activity in the lung homogenate (0.59 ± 0.13 vs 1.19 ± 0.19; p = 0.017). The decreased eosinophilia was likely the result of increased IL-10 in the lung homogenate of the tolerized mice (6320 ± 354 ng/mL vs 5190 ± 404 ng/mL, p = 0.02).</p> <p>Conclusion</p> <p>Our results show that oral tolerization to CRA can improve the respiratory health of experimental mice in a CRA-induced model of asthma-like pulmonary inflammation by reducing pulmonary eosinophilia.</p

Cysteinyl leukotrienes: multi-functional mediators in allergic rhinitis

Cysteinyl leukotrienes (CysLTs) are a family of inflammatory lipid mediators synthesized from arachidonic acid by a variety of cells, including mast cells, eosinophils, basophils, and macrophages. This article reviews the data for the role of CysLTs as multi-functional mediators in allergic rhinitis (AR). We review the evidence that: (1) CysLTs are released from inflammatory cells that participate in AR, (2) receptors for CysLTs are located in nasal tissue, (3) CysLTs are increased in patients with AR and are released following allergen exposure, (4) administration of CysLTs reproduces the symptoms of AR, (5) CysLTs play roles in the maturation, as well as tissue recruitment, of inflammatory cells, and (6) a complex inter-regulation between CysLTs and a variety of other inflammatory mediators exists.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75432/1/j.1365-2222.2006.02498.x.pd