Myeloperoxidase (MPO) is a highly oxidative, pro-inflammatory enzyme involved in post-myocardial infarction (MI) injury and is a potential therapeutic target. While multiple MPO inhibitors have been ...developed, the lack of an imaging reporter to select appropriate patients and assess therapeutic efficacy has hampered clinical development. Thus, a translational imaging method to detect MPO activity non-invasively would help to better understand the role MPO plays in MI and facilitate novel therapy development and clinical validation. Interestingly, many MPO inhibitors affect both intracellular and extracellular MPO, but previous MPO imaging methods can only report extracellular MPO activity. In this study, we found that an MPO-specific PET imaging agent (
F-MAPP) can cross cell membranes to report intracellular MPO activity. We showed that
F-MAPP can track the treatment effect of an MPO inhibitor (PF-2999) at different doses in experimental MI. The imaging results were corroborated by ex vivo autoradiography and gamma counting data. Furthermore, extracellular and intracellular MPO activity assays revealed that
F-MAPP imaging can report the changes induced by PF-2999 on both intracellular and extracellular MPO activities. These findings support
F-MAPP as a translational candidate to noninvasively report MPO activity and accelerate drug development against MPO and other related inflammatory targets.
West Nile (WN) virus is a mosquito-transmitted flavivirus. It is widely distributed in Africa, the Middle East, Asia, and southern Europe and was recently introduced to North America. Birds are ...involved in the cycle of transmission as amplifying hosts. Humans and horses are considered accidental dead-end hosts. WN fever was initially considered a minor arbovirosis, usually inducing a nonsymptomatic or a mild flu-like illness in humans, but some cases of encephalitis associated with fatalities were reported in Israel in the 1950s. After two silent decades, several human and equine outbreaks of fatal encephalitis occurred from 1996 to 2000 in Romania, Morocco, Tunisia, Italy, Russia, Israel, and France. In Romania, a few cases of WN encephalitis in humans are noticed every year, and in France, recent WN infections have been detected in monitored sentinel birds in 2001 and 2002. Phylogenetic studies have shown two main lineages of WN strains. Strains from lineage I are present in Africa, India, and Australia and are responsible for the outbreaks in Europe and in the Mediterranean basin, and strains from lineage II have been reported only in sub-Saharan Africa. In 1998, a virulent WN strain from lineage I was identified in dying migrating storks and domestic geese showing clinical symptoms of encephalitis and paralysis in Israel. A nearly identical WN strain suddenly emerged in New York in 1999, killing thousands of native birds and causing fatal cases in humans. The virus is now well established in the New World, and it disseminates rapidly. New modes of transmission through blood donations, organ transplants, and the intrauterine route have been reported. In Europe, an enhanced surveillance of WN infection in humans, horses, birds, and vectors may reveal the presence of the virus in different locations. Nevertheless, outbreaks of WN virus remain unpredictable. Further coordinated studies are needed for a better understanding of the ecology and the pathogenicity of the WN virus.
West Nile virus in Morocco, 2003 Schuffenecker, Isabelle; Peyrefitte, Christophe N; el Harrak, Mohammed ...
Emerging infectious diseases,
02/2005, Letnik:
11, Številka:
2
Journal Article
Recenzirano
Odprti dostop
West Nile virus (WNV) reemerged in Morocco in September 2003, causing an equine outbreak. A WNV strain isolated from a brain biopsy was completely sequenced. On the basis of phylogenetic analyses, ...Moroccan WNV strains isolated during the 1996 and 2003 outbreaks were closely related to other strains responsible for equine outbreaks in the western Mediterranean basin.
In May 2012, cariologists, dentists, representatives of dental organizations, manufacturers, and third party payers from several countries, met in Philadelphia, Pennsylvania, to define a common ...mission; goals and strategic approaches for caries management in the 21th century. The workshop started with an address by Mr. Stanley Bergman, CEO of Henry Schein Inc. which focused on the imperative for change in academia, clinical practice, and public health. For decades, new scientific evidence on caries and how it should be managed have been discussed among experts in the field. However, there has been some limited change, except in some Scandinavian countries, in the models of caries management and reimbursement which have been heavily skewed toward ‘drilling and filling’. There is no overall agreement on a caries' case definition or on when to surgically intervene. The participants in the workshop defined a new mission for all caries management approaches, both conventional and new. The mission of each system should be to preserve the tooth structure, and restore only when necessary. This mission marks a pivotal line for judging when to surgically intervene and when to arrest or remineralize early noncavitated lesions. Even when restorative care is necessary, the removal of hard tissues should be lesion‐focused and aim to preserve, as much as possible, sound tooth structure. Continuing management of the etiological factors of caries and the use of science‐based preventive regimens also will be required to prevent recurrence and re‐restoration. These changes have been debated for over a decade. The Caries Management Pathways includes all systems and philosophies, conventional and new, of caries management that can be used or modified to achieve the new mission. The choice of which system to use to achieve the mission of caries management is left to the users and should be based on the science supporting each approach or philosophy, experience, utility, and ease of use. This document also presents a new ‘Caries Management Cycle’ that should be followed regardless of which approach is adopted for caries prevention, detection, diagnosis, and treatment. To aid success in the adoption of the new mission, a new reimbursement system that third party payers may utilize is proposed (for use by countries other than Scandinavian countries or other countries where such systems already exist). The new reimbursement/incentive model focuses on the mission of preservation of tooth structure and outcomes of caries management. Also described, is a research agenda to revitalize research on the most important and prevalent world‐wide human disease. The alliance of major dental organizations and experts that started in Philadelphia will hopefully propel over the next months and years, a change in how caries is managed by dentists all over the world. A new mission has been defined and it is time for all oral health professionals to focus on the promotion of oral health and preservation of sound teeth rather than counting the number of surgical restorative procedures provided.
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