44 research outputs found
Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists
PURPOSE: The ferret cisplatin emesis model has been used for ~30ย years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT(3) receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (nย =ย 53) used a 10ย mgย kg(โ1) dose to induce acute emesis, which peaked after 2ย h. More recent studies (nย =ย 11) also used 5ย mgย kg(โ1), which induced a biphasic response peaking at 12ย h and 48ย h. Overall, 5-HT(3) receptor antagonists reduced cisplatin (5ย mgย kg(โ1)) emesis by 68% (45โ91%) during the acute phase (day 1) and by 67% (48โ86%) and 53% (38โ68%, all Pย <ย 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT(3) receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret
Laser-Shock Compression and Hugoniot Measurements of Liquid Hydrogen to 55 GPa
The principal Hugoniot for liquid hydrogen was obtained up to 55 GPa under
laser-driven shock loading. Pressure and density of compressed hydrogen were
determined by impedance-matching to a quartz standard. The shock temperature
was independently measured from the brightness of the shock front. Hugoniot
data of hydrogen provide a good benchmark to modern theories of condensed
matter. The initial number density of liquid hydrogen is lower than that for
liquid deuterium, and this results in shock compressed hydrogen having a higher
compression and higher temperature than deuterium at the same shock pressure.Comment: 8 pages, 7 figures, 2 tables, accepted for publication in Physical
Review
Irregular rhythm and atrial metabolism are key for the evolution of proarrhythmic atrial remodeling in atrial fibrillation
A neurokinin-1 receptor antagonist reduced hypersalivation and gastric contractility related to emesis in dogs
Supplementary Material for: Overexpression of VSNL1 enhances cell proliferation in colorectal carcinogenesis
Introduction: We have previously reported that overexpression of VSNL1 (Visinin-like protein 1) is frequently observed in advanced colorectal adenocarcinomas and correlates with poorer prognosis. In this study, we determined the levels of VSNL1 expression in the earlier stages of colorectal tumors including adenomas and adenocarcinomas, and attempted to clarify the functional significance of VSNL1 overexpression in colorectal carcinogenesis.
Methods: Levels of VSNL expression in colorectal tumor tissues were analyzed using immunohistochemistry. The effects of VSNL1 downregulation and overexpression on cell proliferation, resistance to apoptosis and invasiveness were determined using two VSNL1-overexpressing colorectal cancer cell lines, CW-2 and HCT116 and VSNL1 inducibly expressing SNU-C5, respectively. Gene expression signatures in VSNL1-downregulated CW-2 and HCT116 were identified using transcriptome and gene set enrichment analyses.
Results: VSNL1 expression was restricted to only a few crypt cells in the non-tumorous epithelium, whereas it became enhanced in adenomas and adenocarcinomas with the progression of tumorigenesis. Downregulation of VSNL1 in CW-2 and HCT116 cells suppressed their proliferation through induction of apoptosis. Conversely, overexpression of VSNL1 in SNU-C5 cells enhanced resistance to anoikis. Transcriptome and gene set enrichment analyses revealed that downregulation of VSNL1 altered the expression level of the apoptosis-related gene set in CW-2 and HCT116 cells.
Conclusion: VSNL1 plays a role in both the development and progression of colorectal tumors by enhancing cell viability
Supplementary Material for: Overexpression of VSNL1 enhances cell proliferation in colorectal carcinogenesis
Introduction: We have previously reported that overexpression of VSNL1 (Visinin-like protein 1) is frequently observed in advanced colorectal adenocarcinomas and correlates with poorer prognosis. In this study, we determined the levels of VSNL1 expression in the earlier stages of colorectal tumors including adenomas and adenocarcinomas, and attempted to clarify the functional significance of VSNL1 overexpression in colorectal carcinogenesis.
Methods: Levels of VSNL expression in colorectal tumor tissues were analyzed using immunohistochemistry. The effects of VSNL1 downregulation and overexpression on cell proliferation, resistance to apoptosis and invasiveness were determined using two VSNL1-overexpressing colorectal cancer cell lines, CW-2 and HCT116 and VSNL1 inducibly expressing SNU-C5, respectively. Gene expression signatures in VSNL1-downregulated CW-2 and HCT116 were identified using transcriptome and gene set enrichment analyses.
Results: VSNL1 expression was restricted to only a few crypt cells in the non-tumorous epithelium, whereas it became enhanced in adenomas and adenocarcinomas with the progression of tumorigenesis. Downregulation of VSNL1 in CW-2 and HCT116 cells suppressed their proliferation through induction of apoptosis. Conversely, overexpression of VSNL1 in SNU-C5 cells enhanced resistance to anoikis. Transcriptome and gene set enrichment analyses revealed that downregulation of VSNL1 altered the expression level of the apoptosis-related gene set in CW-2 and HCT116 cells.
Conclusion: VSNL1 plays a role in both the development and progression of colorectal tumors by enhancing cell viability
Phenotypes of SMA patients retaining SMN1 with intragenic mutation
Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous deletion or intragenic mutation of the SMN1 gene. It is well-known that high copy number of its homologous gene, SMN2, modifies the phenotype of SMN1-deleted patients. However, in the patients with intragenic SMN1 mutation, the relationship between phenotype and SMN2 copy number remains unclear. Methods: We have analyzed a total of 515 Japanese patients with SMA-like symptoms (delayed developmental milestones, respiratory failures, muscle weakness etc.) from 1996 to 2019. SMN1 and SMN2 copy numbers were determined by quantitative polymerase chain reaction (PCR) method and/or multiplex ligation-dependent probe amplification (MLPA) method. Intragenic SMN1 mutations were identified through DNA and RNA analysis of the fresh blood samples. Results: A total of 241 patients were diagnosed as having SMA. The majority of SMA patients showed complete loss of SMN1 (n = 228, 95), but some patients retained SMN1 and carried an intragenic mutation in the retaining SMN1 (n = 13, 5). Ten different mutations were identified in these 13 patients, consisting of missense, nonsense, frameshift and splicing defect-causing mutations. The ten mutations were c.275G > C (p.Trp92Ser), c.819820insT (p.Thr274Tyrfs*32), c.830A > G (p.Tyr277Cys), c.5C > T (p.Ala2Val), c.826 T > C (p.Tyr276His), c.79C > T (p.Gln27*), c.188C > A (p.Ser63*), c.422 T > C (p.Leu141Pro), c.835-2A > G (exon 7 skipping) and c.835-3C > A (exon 7 skipping). It should be noted here that some patients with milder phenotype carried only a single SMN2 copy (n = 3), while other patients with severe phenotype carried 3 SMN2 copies (n = 4). Conclusion: Intragenic mutations in SMN1 may contribute more significantly to clinical severity than SMN2 copy numbers. รยฉ 2021 The Japanese Society of Child Neurolog