24-hour intraocular pressure in glaucoma patients randomized to receive dorzolamide or brinzolamide in combination with latanoprost

Yoshimi Nakamura, Shusaku Ishikawa, Yuko Nakamura, Hiroshi Sakai, Ichiko Henzan, Shoichi SawaguchiDepartment of Ophthalmology, University of the Ryukyus Faculty of Medicine, Okinawa, JapanPurpose: To investigate the efficacy of dorzolamide 1% (bid or tid) or brinzolamide 1% bid on 24-hour intraocular pressure (IOP) control as well as patients’ preference for either drug when added in combination with latanoprost against glaucoma (IOP, ≥18 mmHg).Methods: In this randomized crossover study patients were assigned to receive latanoprost plus either dorzolamide or brinzolamide for four weeks. Thereafter, patients underwent 24-hour IOP monitoring while continuing to receive dorzolamide (for two successive days/nights: at first bid then tid) or brinzolamide bid (once overnight). They were then switched over to receive the other test medication for a further four weeks and subsequently reexamined for 24-hour IOP. A questionnaire survey on treatment satisfaction was performed.Results: In 20 patients dorzolamide bid or tid or brinzolamide bid exerted significant (p < 0.001) reductions of IOP from baseline at all time-points over 24 hours; no difference was detected among the treatment regimens. Significantly (p < 0.05) more patients preferred dorzolamide (n = 9) over brinzolamide (n = 2), whereas nine patients gave a neutral answer. Conclusion: Dorzolamide bid or tid and brinzolamide bid when combined with latanoprost therapy elicited significant IOP reduction for 24 hours. It is rational to consider patients’ preference of therapeutic regimen especially long-term users such as those with glaucoma.Keywords: glaucoma, brinzolamide, dorzolamide, latanoprost combination therapy, 24-hour intraocular pressure (IOP), questionnaire surve

BCR-ABL1 tyrosine kinase sustained MECOM expression in chronic myeloid leukaemia

MECOM oncogene expression correlates with chronic myeloid leukaemia (CML) progression. Here we show that the knockdown of MECOM (E) and MECOM (ME) isoforms reduces cell division at low cell density, inhibits colony-forming cells by 34% and moderately reduces BCR-ABL1 mRNA and protein expression but not tyrosine kinase catalytic activity in K562 cells. We also show that both E and ME are expressed in CD34<sup>+</sup> selected cells of both CML chronic phase (CML-CP), and non-CML (normal) origin. Furthermore, MECOM mRNA and protein expression were repressed by imatinib mesylate treatment of CML-CP CD34<sup>+</sup> cells, K562 and KY01 cell lines whereas imatinib had no effect in non-CML BCR-ABL1 −ve CD34<sup>+</sup> cells. Together these results suggest that BCR-ABL1 tyrosine kinase catalytic activity regulates MECOM gene expression in CML-CP progenitor cells and that the BCR-ABL1 oncoprotein partially mediates its biological activity through MECOM. MECOM gene expression in CML-CP progenitor cells would provide an in vivo selective advantage, contributing to CML pathogenesis

Risk factors for CAR-T cell manufacturing failure among DLBCL patients: A nationwide survey in Japan

CAR-T細胞製造を成功させるためのレシピ --アフェレーシス前の下ごしらえでの工夫--. 京都大学プレスリリース. 2023-04-27.For successful chimeric antigen receptor T (CAR-T) cell therapy, CAR-T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for CAR-T cell manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B-cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical factors between 30 cases that failed (7.4%) with those that succeeded (n = 378). Among the failures, the proportion of patients previously treated with bendamustine (43.3% vs. 14.8%; p < 0.001) was significantly higher, and their platelet counts (12.0 vs. 17.0 × 10⁴/μL; p = 0.01) and CD4/CD8 T-cell ratio (0.30 vs. 0.56; p < 0.01) in peripheral blood at apheresis were significantly lower than in the successful group. Multivariate analysis revealed that repeated bendamustine use with short washout periods prior to apheresis (odds ratio [OR], 5.52; p = 0.013 for ≥6 cycles with washout period of 3–24 months; OR, 57.09; p = 0.005 for ≥3 cycles with washout period of <3 months), low platelet counts (OR, 0.495 per 105/μL; p = 0.022) or low CD4/CD8 ratios (<one third) (OR, 3.249; p = 0.011) in peripheral blood at apheresis increased the risk of manufacturing failure. Manufacturing failure remains an obstacle to CAR-T cell therapy for DLBCL patients. Avoiding risk factors, such as repeated bendamustine administration without sufficient washout, and risk-adapted strategies may help to optimize CAR-T cell therapy for DLBCL patients

Drying the leaves of Perilla frutescens

A regular intake of plant‐derived bioactive agents has gained popularity because of the health benefits. Fresh leafy greens, however, normally have a low concentration of such bioactive agents. In this study, we found that drying markedly affected the accumulation of secondary metabolites and that dried leaves of Perilla frutescens L. (perilla) contained more anticancer flavonoids than fresh leaves. Drying is a major method of food preparation, particularly for plant‐based foods, but the quality of the bioactive agents contained in the fresh and dried leaves of perilla has received only scant attention. Quantitative analysis of the concentrations of perillaldehyde, rosmarinic acid, apigenin, luteolin, 4‐hydroxyphenyllactic acid, and 4‐coumaric acid, some of which are known as nutraceuticals, revealed that the effect of drying significantly increased apigenin (28‐fold) and luteolin (86‐fold), but decreased rosmarinic acid in all leaf stages. We examined the positive effect on flavonoid levels on perilla leaves and confirmed that, by comparison with fresh perilla leaves, the dried leaves contained greater concentrations of anticancer flavonoids regardless of variety, form, or manner of cultivation. This indicates that drying can significantly increase the level of flavonoids in perilla leaves without a loss of flavor. Therefore, drying is a simple and effective method to improve the concentrations of bioactive agents, which increases the intake of beneficial substances derived from herbs and edible plants. This finding serves as a method for the supply of raw plant materials rich in bioactive agents that are suitable for labeling as edible nutraceuticals

Drying the leaves of Perilla frutescens increases their content of anticancer nutraceuticals

A regular intake of plant‐derived bioactive agents has gained popularity because of the health benefits. Fresh leafy greens, however, normally have a low concentration of such bioactive agents. In this study, we found that drying markedly affected the accumulation of secondary metabolites and that dried leaves of Perilla frutescens L. (perilla) contained more anticancer flavonoids than fresh leaves. Drying is a major method of food preparation, particularly for plant‐based foods, but the quality of the bioactive agents contained in the fresh and dried leaves of perilla has received only scant attention. Quantitative analysis of the concentrations of perillaldehyde, rosmarinic acid, apigenin, luteolin, 4‐hydroxyphenyllactic acid, and 4‐coumaric acid, some of which are known as nutraceuticals, revealed that the effect of drying significantly increased apigenin (28‐fold) and luteolin (86‐fold), but decreased rosmarinic acid in all leaf stages. We examined the positive effect on flavonoid levels on perilla leaves and confirmed that, by comparison with fresh perilla leaves, the dried leaves contained greater concentrations of anticancer flavonoids regardless of variety, form, or manner of cultivation. This indicates that drying can significantly increase the level of flavonoids in perilla leaves without a loss of flavor. Therefore, drying is a simple and effective method to improve the concentrations of bioactive agents, which increases the intake of beneficial substances derived from herbs and edible plants. This finding serves as a method for the supply of raw plant materials rich in bioactive agents that are suitable for labeling as edible nutraceuticals