The effect of the deacetylated (amine) metabolite of diamphenethide (DAMD, 10 micrograms ml-1) on the uptake and incorporation by adult Fasciola hepatica of radioactively labelled precursors of DNA, RNA and protein synthesis ([3H]thymidine, [3H]uridine and [3H]leucine, respectively) was measured by liquid scintillation counting. Comparison was made between the effects of DAMD and those of specific inhibitors of DNA, RNA and protein synthesis, namely, 5-fluorouracil, cordycepin and cycloheximide, respectively. DAMD caused a significant decrease in the overall uptake and incorporation of [3H]uridine by F. hepatica, decreased the incorporation of [3H]leucine and also caused a significant decrease in the overall protein content of the flukes. The effect of DAMD was similar to that of cycloheximide (1 x 10(-3) M), a potent inhibitor of protein synthesis, which also caused a significant decrease in the incorporation of [3H]leucine by the fluke and a decrease in the overall protein content of the fluke. Cordycepin (100 micrograms ml-1) caused a significant decrease in the protein content of the fluke, but had no effect on the uptake or incorporation of [3H]uridine. 5-Fluorouracil (1 x 10(-4) M) did not affect the uptake or incorporation of [3H]thymidine, nor did it decrease the protein content of the fluke. The results indicate that DAMD inhibits protein synthesis by F. hepatica, possibly by inhibiting RNA synthesis. The results are also consistent with previous morphological investigations involving DAMD.

1988-12-01·International journal for parasitology2区 · 医学

Fasciola hepatica: Morphological changes in vitelline cells following treatment in vitro with the deacetylated (amine) metabolite of diamphenethide (DAMD)

2区 · 医学

Article

作者: L.T. Threadgold ; Heather Anderson ; Ian Fairweather

The effect of the deacetylated (amine) metabolite of diamphenethide (DAMD, 10 μg mL^-1) on the vitelline cells of F. hepatica over an 18 h period in vitro has been determined by transmission electron microscopy.DAMD acts preferentially on the undifferentiated stem cells and the intermediate cells in the early stage of protein synthesis; it appears to prevent their continued development.In the stem cell the nucleolus is absent after 6 h.During the rest of the drug treatment period considerable clumping of heterochromatin takes place, the cells round up and become electron-dense.Signs of autophagy are also evident, and the mitochondria become swollen and disorganized.From 6 h onwards there are progressive changes in the It1 (intermediate type 1) cells, including clumping of the heterochromatin in the nucleus, a decrease in the number of egg-shell globules (and consequently a reduction in the number and size of the shell globule clusters), and a decrease in the number of ribosomes on the GER cisternae, although the GER system remains well-developed.By 18 h the nucleolus is absent, and the cells are very rounded and electron-dense; the mitochondria are swollen and disorganized.Similar changes are evident in the It2 (intermediate type 2) cells, so that by 18 h it is difficult to distinguish between the It1 and It2 cells.In the mature cells there is a progressive decrease in the number and size of the shell globule clusters from 9 h onwards.Glycogen synthesis and yolk formation may also be impaired and lipid droplets are present.Spaces begin to appear between the nurse cell cytoplasm and the vitelline cells after 9 h, and disruption of the nurse cell cytoplasm is evident after 12 h, becoming very severe by 18 h.By this time the follicle is very disorganized and empty-looking.In more severely affected follicles the mature cells are seen to be breaking down.Over the 18 h drug treatment period, a change in the cell population of the follicle takes place, with relatively more stem, early Ig1 and mature cells being present, while few if any characteristic It1 and It2 cells remain.The results are interpreted as being due to an inhibition of protein synthesis in the vitelline cells by DAMD.

1988-01-01·Parasitology research

Diamphenethide ? a reassessment of its pharmacological action

Article

作者: S.D. Holmes ; Ian Fairweather ; P.J. Skuce

At a concentration of 1 x 10(-4) M (28.84 micrograms/ml), with a solvent concentration of 1.0% (v/v) ethanol, the deacetylated (amine) metabolite of diamphenethide (DAMD) causes an initial stimulation of activity, followed by suppression, leading to a paralysis within 3 h. These changes are accompanied by an increase in muscle tone of more than 200 mg. However, ethanol alone at a concentration of 1.0% (v/v) causes an initial stimulation of activity and increase in muscle tone (approximately 550 mg). If the concentration of DAMD is kept at 1 x 10(-4) M (28.84 micrograms/ml) but the solvent concentration reduced [e.g., 0.05% (v/v) dimethyl sulphoxide], then only a suppression of motility and flaccid paralysis are observed. This response is also seen at the lower concentration of 10 micrograms/ml, which corresponds to the maximum blood levels of DAMD in vivo. The sodium ionophore monensin induces a suppression of motility, leading to a rapid flaccid paralysis (in approximately 1.5 h at 1 x 10(-7) M, and within a few minutes at higher concentrations). Ouabain, an inhibitor of Na+/K+-ATPase activity, also causes a suppression of motility, but this is accompanied by an increase in muscle tone, leading to a spastic paralysis (in approximately 2.5 h at 1 x 10(-3) M, and 3.5 h at 1 x 10(-4) M). Pretreatment with ouabain (1 x 10(-3) M for 15 min) followed by monensin (1 x 10(-5) M) reverses the original effect of monensin by inducing a rapid spastic paralysis (in approximately 50 min).(ABSTRACT TRUNCATED AT 250 WORDS)

项与干性老年黄斑变性 (本导基因) 相关的新闻（医药）

2022-12-15

·PRNewswire

Verana Health Study of Patients with Dry Age-Related Macular Degeneration Reveals Compelling New Insights Published in International Ophthalmology Journal

Study used curated real-world data from the IRIS Registry to report risk of progression by stage SAN FRANCISCO, Dec. 15, 2022 /PRNewswire/ -- Verana Health®—a digital health company elevating quality in real-world data—today announced that Ophthalmology and Therapy, an international, peer-reviewed medical journal, has published the results of a study Verana Health conducted to analyze American Academy of Ophthalmology (Academy) IRIS® Registry (Intelligent Research in Sight) data for insights into characterizing the most common form of vision loss in the elderly population, age-related macular degeneration (AMD). The study, "Dry Age-Related Macular Degeneration: Distribution of Visual Acuity and Progression Risk in a Large Registry," is a novel study to report on how the stage of disease, as determined by visual acuity (VA), can help predict the risk of progression in dry AMD (dAMD) by stage. Macular degeneration occurs when a person's retina becomes damaged over time, leading to different levels of vision loss. There are two types of AMD: dry and wet. Dry AMD occurs in 85% to 90% of all AMD patients. The most advanced form of dAMD is called geographic atrophy (GA), a condition in which regions of the macula cease to function. There are no available treatments for GA, which impacts roughly 1.5 million Americans and can lead to irreversible vision loss and even blindness. The study used curated real-world data (RWD) from the Academy IRIS Registry—managed by Verana Health's VeraQ® population health data engine—to better understand how patients progress through the stages of dAMD. After searching a database of de-identified patient records, researchers evaluated a cohort of approximately 645,000 patients with confirmed dAMD. Tracking these patients over a four-year period (2016-2019), the study determined that patients with a lower ability to see, or lower VA, at the beginning of the study period had more advanced dAMD. Researchers also concluded that as these patients' disease worsened, so did their vision. More specifically, the study concluded that: Patients with intermediate dAMD were four times more likely to progress to GA than patients with mild dAMD. There was a larger variation in VA among patients with GA compared to those with mild or intermediate dAMD. VA progression generally is faster with each progressive dAMD stage. Disease progression to GA and wet AMD occurred much faster once a patient reached the intermediate dAMD stage. Results speak to the urgent need for an effective therapy to avoid long-term effects of dAMD and GA. "The clinical recommendation we can draw from this study is that if you have a patient with intermediate AMD, you need to watch them more closely than someone with mild dry AMD," said Theodore Leng, M.D., director of research at the Byers Eye Institute at Stanford University School of Medicine and a Verana Health medical advisor. "These findings highlight the need for new medication options to reverse or delay the worsening of dry AMD and improve the quality of life for patients. We are hopeful that the results will guide novel therapies for dry AMD that are on the cusp of being approved." The IRIS Registry is one of the largest specialty society clinical data registries in all of medicine, containing ophthalmic records for more than 75 million patients stretching approximately 10 years. Verana Health is the end-to-end data and technology partner for the IRIS Registry, responsible for data curation, electronic health record (EHR) integration, analytics, practice support, and quality reporting for physicians contributing to the registry. To request a copy of the recently published study, conducted by Dr. Leng and a team of researchers from Verana Health, visit: veranahealth.com/amd-manuscript. About Verana Health Verana Health® is a digital health company elevating quality in real-world data. Verana Health operates an exclusive real-world data network of more than 20,000 healthcare providers (HCPs) and about 90 million de-identified patients, stemming from its strategic data partnerships with the American Academy of Ophthalmology®, American Academy of Neurology, and American Urological Association. Using its clinician-informed and artificial intelligence-enhanced VeraQ® population health data engine, Verana Health transforms structured and unstructured healthcare data into curated, disease-specific data modules, Qdata®. Verana Health's Qdata helps power analytics solutions and software-as-a-service products for real-world evidence generation, clinical trials enablement, HCP quality reporting, and medical registry data management. Verana Health's quality data and insights help drive progress in medicine to enhance the quality of care and quality of life for patients. For more information, visit . SOURCE Verana Health

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100 项与干性老年黄斑变性 (本导基因) 相关的药物交易

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