The Governance of Credit Rating Agencies in the European Regulation: the Right Way to Enhance Market Competition?

Since 2007 financial markets worldwide have been suffering from a confidence crisis which has emphasised the discussion about the Credit Rating Agencies (CRAs) and the opportunity to enhance the competition in such a highly concentrated sector. The reform process, carried out by European and American regulators, aims at reinforcing the external surveillance on CRAs and, at the same time, improving the governance of the agencies in terms of board composition, internal control systems and disclosure. After an in-depth and comparative analysis of the legal rules, the article shows and discusses the results of an investigation focalised on the contents and quality of the disclosure of 32 selected CRAs, with the purpose of foreseeing the future competitive conditions in the European rating market, since the new European Regulation should break the oligopoly of the largest American agencies by introducing minimal governance requirements

Alterations of brain eicosanoid synthetic pathway in multiple sclerosis and in animal models of demyelination: Role of cyclooxygenase-2

Inflammation is a physiological response to exogenous and endogenous stimuli and, together with demyelination and immune system activation, is one of the key features of multiple sclerosis (MS). Arachidonic acid (AA) metabolism by cyclooxygenase (COX) and lipoxygenase (LO) enzymes leads to the production of proinflammatory eicosanoids, and stimulates cytokine production and activation of microglia and astrocytes, thereby contributing to MS pathology. Current therapies target the immune system but do not specifically target AA-related inflammatory pathway. Corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently associated with immunomodulatory therapies to treat flu-like adverse effects. Few clinical and mounting preclinical data in MS show that AA metabolism contributes to immune system activation, demyelination and motor disabilities, and administration of NSAIDs reduces these symptoms. The beneficial effect of NSAIDs seems to be a prerogative of COX-2 selective inhibitors and suggests that NSAIDs selective for COX-2 may be more effective than mixed COX-1/2 inhibitors

Sustainability and Convergence: The Future of Corporate Governance Systems?

In today’s world, a sustainable approach to corporate governance can be a source of competitive advantage and a long-term success factor for any firm. Sustainable governance requires that the board of directors considers economic, social and environmental expectations in an integrated way, no matter what ownership structure and formal rules of corporate governance apply to the company: this mitigates the traditional differences between insider and outsider systems of corporate governance. Previous studies failed to consider the contribution of sustainability in the process of corporate governance convergence. Therefore, the aim of this article is to fill the gap in the existing literature by means of a qualitative analysis, supporting the international debate about convergence of corporate governance systems. The article describes the evolution of outsider and insider systems in the light of the increasing importance of sustainability in the board’s decision-making and firm’s operation to satisfy the needs of all the company’s stakeholders. According to this, a qualitative content analysis developed with a directed approach completes the theoretical discussion, demonstrating that sustainability can bring de facto convergence between outsider and insider corporate governance systems. The article aims to be a theoretical starting point for future research, the findings of which could also have practical implications: the study encourages the policy makers to translate the sustainable business best practices into laws and recommendations, strengthening the mutual influence between formal and substantial convergence

Neuroinflammatory response to lipopolysaccharide is exacerbated in mice genetically deficient in cyclooxygenase-2

<p>Abstract</p> <p>Background</p> <p>Cyclooxygenases (COX) -1 and -2 are key mediators of the inflammatory response in the central nervous system. Since COX-2 is inducible by inflammatory stimuli, it has been traditionally considered as the most appropriate target for anti-inflammatory drugs. However, the specific roles of COX-1 and COX-2 in modulating a neuroinflammatory response are unclear. Recently, we demonstrated that COX-1 deficient mice show decreased neuroinflammatory response and neuronal damage in response to lipopolysaccharide (LPS).</p> <p>Methods</p> <p>In this study, we investigated the role of COX-2 in the neuroinflammatory response to intracerebroventricular-injected LPS (5 μg), a model of direct activation of innate immunity, using COX-2 deficient (COX-2^-/-) and wild type (COX-2^+/+) mice, as well as COX-2^+/+mice pretreated for 6 weeks with celecoxib, a COX-2 selective inhibitor.</p> <p>Results</p> <p>Twenty-four hours after LPS injection, COX-2^-/-mice showed increased neuronal damage, glial cell activation, mRNA and protein expression of markers of inflammation and oxidative stress, such as cytokines, chemokines, iNOS and NADPH oxidase. Brain protein levels of IL-1β, NADPH oxidase subunit p67^phox, and phosphorylated-signal transducer and activator of transcription 3 (STAT3) were higher in COX-2^-/-and in celecoxib-treated mice, compared to COX-2^+/+mice. The increased neuroinflammatory response in COX-2^-/-mice was likely mediated by the upregulation of STAT3 and suppressor of cytokine signaling 3 (SOCS3).</p> <p>Conclusion</p> <p>These results show that inhibiting COX-2 activity can exacerbate the inflammatory response to LPS, possibly by increasing glial cells activation and upregulating the STAT3 and SOCS3 pathways in the brain.</p

Oral contraceptives and colorectal cancer risk: a systematic review and meta-analysis

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Differential gene expression patterns in cyclooxygenase-1 and cyclooxygenase-2 deficient mouse brain

BACKGROUND: Cyclooxygenase (COX)-1 and COX-2 produce prostanoids from arachidonic acid and are thought to have important yet distinct roles in normal brain function. Deletion of COX-1 or COX-2 results in profound differences both in brain levels of prostaglandin E(2 )and in activation of the transcription factor nuclear factor-κB, suggesting that COX-1 and COX-2 play distinct roles in brain arachidonic acid metabolism and regulation of gene expression. To further elucidate the role of COX isoforms in the regulation of the brain transcriptome, microarray analysis of gene expression in the cerebral cortex and hippocampus of mice deficient in COX-1 (COX-1(-/-)) or COX-2 (COX-2(-/-)) was performed. RESULTS: A majority (>93%) of the differentially expressed genes in both the cortex and hippocampus were altered in one COX isoform knockout mouse but not the other. The major gene function affected in all genotype comparisons was 'transcriptional regulation'. Distinct biologic and metabolic pathways that were altered in COX(-/- )mice included β oxidation, methionine metabolism, janus kinase signaling, and GABAergic neurotransmission. CONCLUSION: Our findings suggest that COX-1 and COX-2 differentially modulate brain gene expression. Because certain anti-inflammatory and analgesic treatments are based on inhibition of COX activity, the specific alterations observed in this study further our understanding of the relationship of COX-1 and COX-2 with signaling pathways in brain and of the therapeutic and toxicologic consequences of COX inhibition

The contribution of myelin to magnetic susceptibility-weighted contrasts in high-field MRI of the brain

T(2)*-weighted gradient-echo MRI images at high field (≥ 7T) have shown rich image contrast within and between brain regions. The source for these contrast variations has been primarily attributed to tissue magnetic susceptibility differences. In this study, the contribution of myelin to both T(2)* and frequency contrasts is investigated using a mouse model of demyelination based on a cuprizone diet. The demyelinated brains showed significantly increased T(2)* in white matter and a substantial reduction in gray-white matter frequency contrast, suggesting that myelin is a primary source for these contrasts. Comparison of in-vivo and in-vitro data showed that, although tissue T(2)* values were reduced by formalin fixation, gray-white matter frequency contrast was relatively unaffected and fixation had a negligible effect on cuprizone-induced changes in T(2)* and frequency contrasts