Pharmacokinetic and pharmacodynamic study of 3 products of epoetin alfa as single subcutaneous dose in healthy volunteers

alexandrossfakianakis shared this article with you from Inoreader Pharmacokinetic and pharmacodynamic study of 3 products of epoetin alfa as single subcutaneous dose in healthy volunteers via Fundamental & Clinical Pharmacology Abstract Background Hemax® is an epoetin alfa product developed by Biosidus S.A. in Argentina at the end of the 1980's and has been present in that market since 1991. The initial presentation was a lyophilized powder containing albumin as stabilizer, to best adapt to environmental conditions in developing countries; more recently, a prefilled syringe, albumin-free presentation was developed, since this presentation has become the preferred standard in many markets. Objective The primary objective was to compare the pharmacokinetic profile of different formulations of epoetin alfa after a single subcutaneous administration to healthy volunteers of 40,000 IU of Eprex/Erypo® and Hemax® PFS. Methods This clinical trial was conceived following an open label, randomized, 3-way 3-period cross-over balanced, and sequential design. The study was conducted on 24 healthy volunteers. Results To analyze similarity between Hemax® PFS and the innovator product, Eprex®, AUC and Cmax of both products have been compared. The 90%CI lower limit for the geometric mean ratios was higher than 80% for any comparisons and the 90%CI upper limit for these geometric ratios was below 125% for all the comparisons made, thus demonstrating equivalence between both products. Conclusion The comparison between Hemax® PFS and Eprex® resulted in similar 90%CI for Cmax, AUC(0-120 h) and AUC(0-inf) ratios, all of them within the 80-125% interval, with a power above 95% for each ratio. These findings suggest biosimilar patterns for absorption velocity (with Tmax close to 15 h), absorption extent and elimination (with an elimination half-life close to 25-30 h for each formulation) View on Web

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Wnt3a promotes odonto/osteogenic differentiation in vitro and tertiary dentin formation in a rat model

alexandrossfakianakis shared this article with you from Inoreader Wnt3a promotes odonto/osteogenic differentiation in vitro and tertiary dentin formation in a rat model via International Endodontic Journal Abstract Aim To investigate the effect of Wnt3a on odonto/osteogenic differentiation of stem cells isolated from human exfoliated deciduous teeth (SHEDs) and reparative dentine formation in a rat model. Methodology SHEDs were cultured in media with Wnt3a (50-200 ng/mL). Wnt activation was confirmed by β-catenin immunocytochemistry. Colony-forming unit assay (normalised percentage area), osteogenic gene expression analysis by real-time polymerase chain reaction and mineralisation assays measured by the absorption at 540 nm were performed. Tertiary dentine formation in vivo was evaluated using 8-week-old, male Wistar rats. Cavities with pinpoint pulp exposure by a sharp instrument were prepared at the mesial surface of the first molars. Teeth were divided into (n=6): 1) distilled water (negative control), 2) phosphate-buffered saline (PBS), 3) lithium chloride in DI (20 μM), and 4) Wnt3a in PBS (200 ng/mL). Collagen sponge was used as a scaffold. The cavity was sealed with glass ionomer restoration. Four weeks later, animals were euthanised by sodium pentobarbital (120 mg/kg body weight). Hard tissue formation was evaluated using micro-computerised tomography. Sixty consecutive slides from the initial plane were analysed and calculated as bone/dentine volume per total tissue volume. Paraffin sections (2 μm) were stained with haematoxylin and eosin and Masson's trichrome for morphological evaluation. Data are presented as the mean ± standard error. Mann-Whitney U test was used for two-group comparison. Kruskal Wallis followed by pairwise comparison was employed for three or more group comparisons. Statistical analysis was performed using GraphPad Prism 7. Differences were considered significant at p < 0.05. Results Wnt3a decreased SHEDs colony formation and increased OSX, BMP2, and DMP1 expression, corresponding to an increase in mineralisation. Additionally, a significant increase in dentine/bone volume per total tissue volume was observed in Wnt3a treated defects. Dentine bridge formation at the exposure sites treated with Wnt3a demonstrated, while fibrous tissues were observed in the control. Conclusions Wnt3a suppressed proliferation, increased osteogenic differentiation of SHEDs and promotes tertiary dentine formation. Wnt3a could be utilised as biological molecule for vital pulp therapy. View on Web

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Pediatric inflammatory myofibroblastic tumor of the bladder with ALK–FN1 fusion successfully treated by alectinib

alexandrossfakianakis shared this article with you from Inoreader Pediatric inflammatory myofibroblastic tumor of the bladder with ALK–FN1 fusion successfully treated by alectinib via Pediatric Blood & Cancer Abstract An inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm characterized by the proliferation of myofibroblasts and inflammatory cell infiltration. Although radical resection is the only established treatment strategy for IMT, it can cause functional disorders when vital organs are affected. We describe a case of pediatric IMT of the bladder with FN1–ALK (fibronectin 1–anaplastic lymphoma kinase) fusion. Radical resection might lead to urinary disturbance due to the large tumor size at diagnosis. However, the tumor was successfully treated with alectinib, a second-generation ALK inhibitor, followed by transurethral resection of the bladder tumor without any complications. View on Web

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Automatic Dental Biofilm Detection Based on Deep Learning

alexandrossfakianakis shared this article with you from Inoreader Automatic Dental Biofilm Detection Based on Deep Learning via Journal of Clinical Periodontology Abstract Aim To estimate the automated biofilm detection capacity of the U-Net neural network on tooth images. Material and methods Two datasets of intraoral photographs taken in the frontal and lateral views of permanent and deciduous dentitions were employed. The first dataset consisted of 96 photographs taken before and after applying a disclosing agent and was used to validate the domain's expert biofilm annotation (intraclass correlation coefficient = 0.93). The second dataset comprised 480 photos, with or without orthodontic appliances, without disclosing agents, and was used to train the neural network to segment the biofilm. Dental biofilm labeled by the dentist (without disclosing agents) was considered the ground-truth. Segmentation performance was measured using accuracy, F1 score, sensitivity, and specificity. Results The U-Net model achieved an accuracy of 91.8%, F1 score of 60.6%, specificity of 94.4%, and sensitivity of 67.2%. The accuracy was higher in the presence of orthodontic appliances (92.6%). Conclusion Visually segmenting dental biofilm employing a U-Net is feasible and can assist professionals and patients in identifying dental biofilm, thus improving oral hygiene and health. This article is protected by copyright. All rights reserved. View on Web

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