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Aging and menopause reprogram osteoclast precursors for aggressive bone resorption

Bone Research 2020年第3期8卷 333-342页

作者： Anais Marie Julie Moller Jean-Marie Delaisse jacob bastholm olesen Jonna Skov Madsen Luisa Matos Canto Troels Bechmann Silvia Regina Rogatto Kent Soe Clinical Cell Biology Lillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark Department of Regional Health Research University of Southern Denmark5230 Odense MDenmark Department of Clinical Biochemistry and Immunology Lillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark Clinical Cell Biology Department of PathologyOdense University Hospital5000 Odense CDenmark Department of Clinical Research University of Southern Denmark5230 Odense MDenmark Department of Molecular Medicine University of Southern Denmark5230 Odense MDenmark Department of Clinical Genetics Lillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark Department of Oncology Lillebaelt HospitalUniversity Hospital of Southern Denmark7100 VejleDenmark OPEN Odense Patient data Explorative NetworkOdense University Hospital5000 Odense CDenmark

Women gradually lose bone from the age of〜35 years,but around menopause,the rate of bone loss escalates due to increasing bone resorption and decreasing bone formation levels,rendering these individuals more prone to developing *** increased osteoclast activity has been linked to a reduced estrogen level and other hormonal ***,it is unclear whether intrinsic changes in osteoclast precursors around menopause can also explain the increased osteoclast ***,we set up a protocol in which CD14f blood monocytes were isolated from 49 female donors(40-66 years old).Cells were differentiated into osteoclasts,and data on differentiation and resorption activity were *** multiple linear regression analyses combining in vitro and in vivo data,we found the following:(1)age and menopausal status correlate with aggressive osteoclastic bone resorption in vitro;(2)the type I procollagen N-terminal propeptide level in vivo inversely correlates with osteoclast resorption activity in vitro;(3)the protein level of mature cathepsin K in osteoclasts in vitro increases with age and menopause;and(4)the promoter of the gene encoding the dendritic cell-specific transmembrane protein is less methylated with *** conclude that monocytes are"reprogrammed"in vivo,allowing them to"remember"age,the menopausal status,and the bone formation status in vitro,resulting in more aggressive *** discovery suggests that this may be mediated through DNA *** suggest that this may have clinical implications and could contribute to understanding individual differences in age-and menopause-induced bone loss.

关键词： osteoclast menopause osteoporosis

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Pharmacological pain management in chronic pancreatitis

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World Journal of Gastroenterology 2013年第42期19卷 7292-7301页

作者： Sφren S olesen jacob Juel Carina Graversen Yuri Kolesnikov Oliver HG Wilder-Smith Asbjφrn M Drewes MechSense Department of Gastroenterology and HepatologyAalborg University Hospital9000 AalborgDenmark Mech-Sense Department of RadiologyAalborg University Hospital9000 AalborgDenmark Department of Neurorehabilitation Engineering Bernstein Center for Computational NeuroscienceUniversity Medical Center G ttingenGeorg-August UniversityD-37077 GttingenGermany Pain Service Department of OncologyEast Tallinn Central Hospital19086 TallinnEstonia Pain and Nociception Neuroscience Research Group Department of AnaesthesiologyPain and Palliative CareRadboud University Nijmegen Medical Centre6525 NijmegenThe Netherlands Center for Sensory-Motor Interaction Department of Health Science and TechnologyAalborg University9000 AalborgDenmark

Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical *** studies of pancreatic nerves and experimental human pain research have provided evidence that pain processing is abnormal in these patients and in many cases resembles that seen in neuropathic and chronic pain *** important ultimate outcome of such aberrant pain processing is that once the disease has advanced and the pathophysiological processes are firmly established,the generation of pain can become self-perpetuating and independent of the initial peripheral nociceptive ***,the management of pain by traditional methods based on nociceptive deafferentation(e.g.,surgery and visceral nerve blockade)becomes difficult and often *** novel and improved understanding of pain aetiology requires a paradigm shift in pain management of chronic *** mechanism based pain treatments taking into account altered pain processing are likely to increasingly replace invasive therapies targeting the nociceptive source,which should be reserved for special and carefully selected *** this review,we offer an overview of the current available pharmacological options for pain management in chronic *** addition,future options for pain management are discussed with special emphasis on personalized pain medicine and multidisciplinarity.

关键词： Chronic pancreatitis Pain Treatment Pharmacology Analgesics Adjuvant analgesics

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