Recently, researchers identified a distinct vessel subtype called type H vessels that couple angiogenesis and osteogenesis. We previously found that type H vessels are reduced in ovariectomy (OVX)-induced osteoporotic mice, and preosteoclasts are able to secrete platelet-derived growth factor-BB (PDGF-BB) to stimulate type H vessel formation and thereby to promote osteogenesis. This study aimed to explore whether harmine, a β-carboline alkaloid, is capable of preventing bone loss in OVX mice by promoting preosteoclast PDGF-BB-induced type H vessel formation.Methods: The impact of harmine on osteoclastogenesis of RANKL-stimulated RAW264.7 cells was verified by gene expression analysis and tartrate-resistant acid phosphatase (TRAP) staining. Enzyme-linked immunosorbent assay (ELISA) was conducted to test PDGF-BB production by preosteoclasts. A series of angiogenesis-related assays in vitro were performed to assess the pro-angiogenic effects of the conditioned media from RANKL-stimulated RAW264.7 cells treated with or without harmine. Meanwhile, the role of PDGF-BB in this process was determined. In vivo, OVX mice were intragastrically administrated with harmine emulsion or an equal volume of vehicle. 2 months later, bone samples were collected for µCT, histological, immunohistochemical and immunofluorescent analyses to evaluate bone mass, osteogenic and osteoclastic activities, as well as the numbers of type H vessels. Bone marrow PDGF-BB concentrations were assessed by ELISA.Results: Exposure of RANKL-stimulated RAW264.7 cells to harmine enhanced the formation of preosteoclasts and the production of PDGF-BB. Harmine augmented the ability of RANKL-stimulated RAW264.7 cells to promote angiogenesis of endothelial cells, whereas the effect was blocked by PDGF-BB inhibition. In vivo, the oral administration of harmine emulsion to OVX mice resulted in enhanced trabecular bone mass and osteogenic responses, increased numbers of preosteoclasts, as well as reduced numbers of osteoclasts and fat cells. Moreover, OVX mice treated with harmine exhibited higher levels of bone marrow PDGF-BB and much more type H vessels in bone.Conclusion: Harmine may exert bone-sparing effects by suppression of osteoclast formation and promotion of preosteoclast PDGF-BB-induced angiogenesis.
In January 2004, we investigated a cluster of acute hepatitis in Baripada, Orissa, India. Between January and March 2004, 538 cases (definition: fever with loss of appetite and jaundice) were reported (attack rate: 263 per 100 000, 5 deaths, case fatality rate: 0.93%). Forty-seven of 48 sera were positive for IgM antibodies to hepatitis E virus. Cases peaked in February 2004 and decreased rapidly, suggesting a common source outbreak. Five neighbourhoods supplied by a common water supply were most affected. Ninety-one percent of the 538 cases and 30% of 538 unaffected controls reported drinking water from one source (odds ratio 31, 95% CI 27-48). The neighbourhood's water was pumped directly from a river and had not been treated during a 10-day period in early January (1 month before the peak of the outbreak) because of a strike at the treatment plant. This large hepatitis E outbreak was associated with drinking untreated raw river water. Measures must be in place to check the quality of municipal water and to ensure essential services in case of strikes.
Unilateral hemispheric edema may occur with or without seizures. It is a rare entity, found more often in children, than in adults. As many of these patients develop pronounced unilateral complete cortical hemispheric (uni-hemispheric) edema on MRI, we have used the term "cortical unihemispheric brain edema" (CUBE) to describe this entity. We describe a case of CUBE occurring along with a post COVID multi-system inflammatory syndrome in adults (MIS-A). A 30-yearold man was admitted with status epilepticus. He was found to have CUBE and features of MIS-A. He had a history of mild COVID-19 illness one month earlier.He was noted to have persistently elevated inflammatory markers and multiorgan dysfunction compatible with MIS-A. We review the cases of CUBE in the literature and describe the features and etiology of this uncommon syndrome. Furthermore, we discuss the differences between two types of CUBE; cytotoxic CUBE (CUBE-C) and vasogenic CUBE (CUBE-V).
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