Background: Despite the high success rate of ICSI, total fertilization failure still occurs in 1-3% of all ICSI cycles and can recur in subsequent cycles, even when a sufficient number of oocytes and motile spermatozoa are available. Several reports show that the majority of couples suffering from ICSI failure benefit from the application of ICSI combined with assisted oocyte activation. A variety of artificial activating methods is used in human assisted reproduction treatment, including physical, mechanical or chemical stimuli, which provoke one or more calcium rises in the oocyte cytoplasm. Study Design: Randomized controlled trial. Setting: A university fertility center. Methods: 150 infertile patients who underwent ICSI and all had history of recurrent fertilization failure. The patients were randomly allocated into 2 equal groups. Group1=75 patients who underwent ICSI without oocyte activation. Group2 patients =75 and underwent ICSI Patient underwent ICSI with oocyte activation. Reproductive outcomes were compared between both groups. Results: there were significant differences between groups regarding number of oocytes retrieved, number of mature oocyte, fertilization rate and pregnancy rate. Conclusion: Assisted oocyte activation with calcium ionophore results in significant improvement in the fertilization, cleavage and pregnancy rates after ICSI.

开始日期2017-07-15

申办/合作机构

Al-Azhar University

NCT02992665 / Unknown status临床2/3期IIT

Can Calcium Ionophore Application Enhance the ICSI Outcomes in Severe Male Factor Infertility?

The purpose of this study is to determine the impact of the use of calcium ionophore on the ICSI outcomes in couples with severe male factor infertility. Investigators conduct a randomized controlled trial on the sibling oocyte to justify the use of calcium ionophore in these cases.

开始日期2016-12-01

申办/合作机构

Assiut University

100 项与卡西霉素相关的临床结果

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100 项与卡西霉素相关的转化医学

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100 项与卡西霉素相关的专利（医药）

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12,371

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2024-12-01·Cytotechnology

Isolation of holostane-type saponins from the black sea cucumber Holothuria atra and evaluating their anti-allergic activity: in vitro and in silico study

Article

作者: Zaki, Ahmed Awad ; Ashour, Ahmed ; Hamed, El-Sayed A. E. ; Nagata, Maki ; Mittraphab, Yanisa ; Hamed, El-Sayed A E ; Shimizu, Kuniyoshi ; Wahab, Gehad Abdel ; Elkattan, Amira ; Matsumoto, Masako

Sea cucumbers are both versatile marine organisms and an Asian marine food known to have several medicinal effects. We evaluated the anti-allergic potential of some major purified holostane-type saponins from the body wall of the black sea cucumber, Holothuria atra. Six saponin compounds were isolated, holothurin B (1), holothurin A (2), 24-dehydro echinoside A (3), desholothurin A1 (4), desholothurin A (5), and des 24-dehydro echinoside A (6). The structures were identified based on spectroscopic methods and by comparison with the literature. Each compound's inhibitory activity toward the release of β-hexosaminidase was evaluated. Among the six compounds, holothurin B (1) showed the strongest inhibition of the degranulation at all tested concentrations in a dose-dependent manner, compared to the positive control, quercetin. We also observed that holothurin B (1) was able to alleviate the inflammatory mediators interleukin (IL)-6, IL-13, and tumor necrosis factor-alpha (TNF-α). Holothurin B (1) also inhibited the Ca²⁺ influx stimulated by the calcium ionophore A23187, by suppressing the expression of inositol-1,4,5-triphosphate receptor (IP3R) mRNA. These results suggest that (i) holothurin B (1) has good anti-allergy activity without cytotoxicity at effective concentrations, and (ii) this compound could be a lead compound for the treatment of allergic diseases and associated inflammation. We also performed a molecular docking study for the tested compounds to correlate their binding modes and affinity for the IP3R with the in vitro results. The results concluded that the holostane-type saponins could be used as anti-allergy agents, which may be attributed to their holostane group.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10616-024-00649-8.

2024-12-01·Medicinal Chemistry

N,N-Disubstituted 4-Sulfamoylbenzoic Acid Derivatives as Inhibitors of Cytosolic Phospholipase A2α: Synthesis, Aqueous Solubility, and Activity in a Vesicle and a Whole Blood Assay

Article

作者: Lehr, Matthias ; Fabian, Jörg ; Vilsendorf, Imke Meyer zu ; Borecki, Daniel

Background:Cytosolic phospholipase A2α (cPLA2α) is the key enzyme that initiates the arachidonic acid cascade through which pro-inflammatory lipid mediators can be formed. Therefore, cPLA2α is considered an interesting target for the development of anti-inflammatory drugs. Although several effective inhibitors of the enzyme have been developed, none of them has yet reached clinical application.Objective:Recently, we have prepared new 4-sulfamoylbenzoic acid derivatives based on a cPLA2α inhibitor found in a ligand-based virtual screening. The most effective of these compounds were now subjected to further variations in which the substitution pattern on the sulfamoyl nitrogen atom was changed.Methods:The new compounds were tested in vitro in a vesicle assay for cPLA2α inhibition as well as for their water solubility, metabolic stability, and selectivity towards related enzymes. In addition, they were evaluated ex vivo in a whole blood assay in which metabolites of the arachidonic acid cascade formed after activation of cPLA2α were quantified using a combined online dilution/ online solid phase extraction HPLC-MS method.Results:Inhibitors with submicromolar inhibitory in vitro potency were found with favourable water solubility and selectivity. However, their efficacy did not match that of the highly effective, known, structurally related cPLA2α inhibitor giripladib, which was also tested as a reference. One advantage of some of the new compounds compared to giripladib was their significantly improved water solubility. When analyzing the substances in the ex vivo whole blood assay, it was found that the obtained inhibition data correlated better with the in vivo results when the phorbol ester 12-Otetradecanoylphorbol- 13-acetate was used for activation of the enzyme in the blood cells instead of the calcium ionophore A23187.Conclusion:New compounds with good activity towards cPLA2α and reasonable physicochemical properties were identified. Overall, the results obtained could be helpful in the development of clinically applicable inhibitors of this enzyme.

2024-12-01·Cellular Signalling

Gelsolin controls the release of phosphatidylserine (PS)-positive microvesicles (MVs) from platelets

Article

作者: Falet, Hervé ; Kim, Hugh ; Hong, Felix ; Paul, Manoj

Upon activation by vascular injury or extracellular agonists, platelets undergo rapid change shape, a process regulated by the actin cytoskeleton and accessory proteins. Platelet shape change is accompanied by the secretion of hemostatic factors and immunomodulatory cytokines from their intracellular granules, as well as the release of microvesicles (MVs) containing pro-inflammatory cytokines and procoagulant phosphatidylserine (PS). However, the role of actin dynamics in MV generation remains unclear. In this study, we found that blocking actin polymerization with cytochalasin D attenuated the release of PS-positive MVs in human platelets stimulated by thrombin or the calcium ionophore A23187. The actin-severing protein gelsolin (Gsn) facilitates normal actin filament turnover in activated platelets. Platelets from Gsn-deficient (Gsn^-/-) mice showed reduced MV release compared to platelets from control mice. These findings indicate that the proper dynamics of the actin cytoskeleton are essential for MV generation in platelets, which has implications for their pro-inflammatory and procoagulant functions.

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男性不育症	临床3期	-	Merck Serono SA	-

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NCT02424214 (Pubmed \| Hum Reprod)	N/A	-	343	ICSI with calcimycin AOA	(鏇醖遞構鏇積獵鏇築積) = 鏇選壓網範衊鹹顧範齋觸鹽觸鏇鏇網鹹艱蓋淵 (憲鏇築艱顧醖積窪憲膚 ) 更多	-	2018-09-01