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Collaborations between Clinical Pharmacologists in Japan and in the United States - Report from the IQ CPLG and JPMA CPTF Meeting in Tokyo, Japan.

ABSTRACT: The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Clinical Pharmacology Leadership Group (CPLG) held its first meeting of Japan-based representatives at Astellas Pharma headquarters in Tokyo on October 1, 2019. The meeting was also attended by Japan Pharmaceutical Manufactures Association (JPMA) Clinical Pharmacology Task Force (CPTF) members. Overall, nearly 30 clinical pharmacologists representing 14 companies attended the event. The meeting met its goal of enhancing mutual understanding of each organization's activities. In a number of break-out sessions, participants identified scientific topics for potential future collaboration between JPMA CPTF and IQ CPLG.

SUBMITTER: Zhu T

PROVIDER: S-EPMC7877837 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Collaborations between Clinical Pharmacologists in Japan and in the United States - Report from the IQ CPLG and JPMA CPTF Meeting in Tokyo, Japan.

Zhu Tong T Kayama Makoto M Girish Sandhya S Sinha Vikram V Bello Akintunde A Kawaguchi Atsuhiro A Czerniak Richard R Nagao Lee L

Clinical and translational science 20200924 1

The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Clinical Pharmacology Leadership Group (CPLG) held its first meeting of Japan-based representatives at Astellas Pharma headquarters in Tokyo on October 1, 2019. The meeting was also attended by Japan Pharmaceutical Manufactures Association (JPMA) Clinical Pharmacology Task Force (CPTF) members. Overall, nearly 30 clinical pharmacologists representing 14 companies attended the event. The meeting met its goa ...[more]

PMID: 32969589

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Project description:BACKGROUND: An excessive immune-mediated inflammation is associated with cardiac dysfunction and poor clinical outcomes after myocardial infarction (MI). However, the precise regulatory mechanism to control the inflammatory response and subsequent tissue repair following MI is unclear. METHODS AND RESULTS: Bone-marrow (BM) cells from CD11c-diphtheria toxin receptor/GFP transgenic mice were transplanted into lethally irradiated wild-type (WT) recipient mice. After reconstitution of BM-derived cells, the recipient mice were treated with either diphtheria toxin (DC ablation) or vehicle (control), and MI was created by left coronary ligation. CD11c+ GFP+ DCs expressing CD11b and MHC class II were recruited into the heart, peaking on day 7 after MI in control group. Mice with DC ablation for 7 days showed deteriorated left ventricular (LV) function and remodeling. The DC-ablated group demonstrated enhanced and sustained expression of inflammatory cytokines, prolonged extracellular matrix degradation associated with a high level of matrix metalloproteinase-9 activity, and diminished expression level of interleukin (IL)-10 and endothelial cell proliferation post-MI compared with control group. In vivo and in vitro analyses revealed that DC-ablated infarcts had an enhanced capacity of monocyte/macrophage recruitment. Among these cells, augmented infiltration of proinflammatory Ly6Chigh monocytes and F4/80+ CD206 M1 macrophages and, conversely, impaired recruitment of anti-inflammatory Ly6Clow monocytes and F4/80+ CD206+ M2 macrophages in the infarcted myocardium were identified in DC-ablated group than in control group. Flow cytometric analysis for inflammatory cells extracted from infarcted tissue revealed that CD11c+ DC is one of the major sources of IL-10. Adoptive transfer of BM-derived DCs from WT, but not IL-10-deficient mice, abrogated the adverse effects of DC depletion on inflammatory response and LV remodeling after MI. CONCLUSION: DC could be a potent immunoprotective regulator during the postinfarction healing process, via controlling monocyte/macrophage homeostasis through IL-10 secretion.

Dataset Information

Collaborations between Clinical Pharmacologists in Japan and in the United States - Report from the IQ CPLG and JPMA CPTF Meeting in Tokyo, Japan.

Publications

Collaborations between Clinical Pharmacologists in Japan and in the United States - Report from the IQ CPLG and JPMA CPTF Meeting in Tokyo, Japan.

Similar Datasets

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