STUDY OBJECTIVE To employ systems biology-based machine learning to identify biologic processes over-represented with genetic variants (gene enrichment) implicated in post-surgical pain. DESIGN Informed systems biology based integrative computational analyses. SETTING Pediatric research and teaching institution. INTERVENTIONS Pubmed search (01/01/2001-10/31/2017) was performed to identify "training" genes associated with postoperative pain in humans. Candidate genes were identified and prioritized using Toppgene suite, based on functional enrichment using several gene ontology annotations, and curated gene sets associated with mouse phenotype-knockout studies. MEASUREMENTS Computationally top-ranked candidate genes and literature-curated genes were included in pathway enrichment analyses. Hierarchical clustering was used to visualize select functional enrichment results between the two phenotypes. MAIN RESULTS Literature review identified 38 training genes associated with postoperative pain and 31 with CPSP. l annotation - based prioritization and enrichment approaches and identifies novel genes and unique/shared biological processes involved in acute and chronic postoperative pain. Results provide framework for future targeted genetic profiling of CPSP risk, to enable preventive and therapeutic approaches. Recently, non-covalent protein complexes and folds with extreme mechanical stabilities have been discovered. Various extracellular adhesin proteins of gram-positive bacteria exhibit complex rupture forces ranging from 800pN in the case of cellulolytic bacteria to over 2000pN withstood by pathogens adhering to their hosts. Here, we review and assess the mechanics of such systems, and discuss progress, as well as open questions regarding their biological function, and underlying molecular mechanisms - in particular the role of increased interaction lifetimes under mechanical load. These unexpected extreme strengths open an unchartered range of protein mechanics that can now be routinely probed by atomic force microscopy-based single-molecule force spectroscopy. The purpose of this study was to evaluate the efficacy of imiquimod-containing nanovesicles prepared with lipids extracted from the hyperhalophile archaebacterium Halorubrum tebenquichense (nanoARC-IMQ) to induce protection against Trypanosoma cruzi infection. The therapeutic efficacy of archaeolipid nanovesicles was assessed in an experimental murine model of acute infection with T. cruzi. The administration of nanoARQ-IMQ prevented mortality as compared to infected untreated animals, reduced parasitemia levels and diminished myocardial and musculoskeletal lesions in **** infected with a lethal strain of T. cruzi. Our findings suggest that the immunotherapy with nanoARC-IMQ has potential to limit the progression of Chagas disease. Bioactive glass (BAG) is a synthetic bone substitute with intrinsic antimicrobial properties, used for bone defect filling. We evaluated the antimicrobial activity of two formulations of BAG S53P4 against representative pathogens of osteomyelitis Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli and Candida albicans. Antimicrobial activity of BAG S53P4 was assessed by isothermal microcalorimetry, a highly sensitive assay measuring metabolic-related microbial heat production in real-time. Standard CFUs-counting was performed in parallel. BAG granules (diameter 500-800 μm) and powder ( less then 45 μm) were evaluated in two concentrations (400 and 800 mg/ml). Isothermal microcalorimetry was performed in glass ampoules containing growth medium, BAG and test microorganism, heat production was measured for 24 h. BAG S53P4 inhibited heat production of most-tested microorganisms with heat reduction of 60%-98% compared to positive control after 24 h of exposure to the highest-tested concentration (800 mg/ml). BAG S53P4 in powder formulation ( less then 45 μm) inhibited more microbial growth than in granule formulation (500-800 μm), with the exception of C. albicans for which both formulations presented similar inhibition rates ranging between 87 % and 97 %. The BAG inhibitory ratios estimated from the variation in the growth rate constants of each microorganism compared to the growth control ranged between 2.55 % and 100 %. Comparable results were obtained by CFUs-counting, with complete reduction in cell viability of most microorganisms after ≤ 24 h of microbial exposure to BAG S53P4 powder. In summary, BAG S53P4 demonstrated efficient inhibition of microbial growth, especially in powder formulation. Some additives had provided the expansion capacity to the polymethylmethacrylate (PMMA) bone cement and also reduced its maximum reaction temperature. However, the corresponding modified bone cement displayed inferior simulated body fluid (SBF) absorption capacity and expansion behavior, the mechanism of SBF absorption and the trend of expansion stress were ignored additionally. In this study, a homogeneous distribution of poly (methyl methacrylate-co-acrylic acid) [P(MMA-AA)] microspheres led to the formation of microchannels that favored the delivery of SBF to the interior, causing an increased absorption capacity and enhanced expansion behavior before solidification of the bone cement, with the maximum equilibrium absorption ratio and the expansion ratio reaching 27.3 % and 26.3 %, respectively, at an AA content of 50 %. In addition, the expansion stress induced by the expansion behavior experienced a gradual increase from the 0 s to 2590s, followed by a sharp climbed in a short period ranging from 2590s to 2900s, finally reaching maximum stress of 82.1 MPa. Furthermore, the expansion stress within the maximum value could be obtained by controlling the AA content in the P(MMA-AA) bone cement. With the above characteristics, the prepared P(MMA-AA) bone cement has potential applications as a filling and adhesive material in arthroplasties, vertebroplasties, joint replacements, bone screws, and dentistry. The implimentation of newer technologies in drug delivery system have always been the focus of pharmaceutical scientists with advancement of technologies. In this investigation, a novel controlled-release drug-resin combination device (DRC) was designed using dental resin to control the release of dextromethorphan hydrobromide (DH). The influence of different factors on in-vitro drug release were investigated. A Box-Behnken design was used to select the optimized DRC formulation. The optimized DH loaded DRC (DH-DRC) was prepared using 59.88% of PEG400, 16 mg of dental resin and 6.64 mg of sodium chloride (NaCl). https://www.selleckchem.com/products/canagliflozin.html The DH releases at 2 h, 4 h and 8 h of the optimized formulation were significantly close to the predicted responses. The pharmacokinetic study in rabbits showed DH-DRC had prolonged tmax and apparently reduced Cmax compared with commercial tablets and the AUC0-24h of DH-DRC was slightly higher than commercial tablets. This study confirmed the novel DRC could control the release of drug. It concluded that DRC would be a promising and alternative approach for the development of controlled release dosage form.
STUDY OBJECTIVE To employ systems biology-based machine learning to identify biologic processes over-represented with genetic variants (gene enrichment) implicated in post-surgical pain. DESIGN Informed systems biology based integrative computational analyses. SETTING Pediatric research and teaching institution. INTERVENTIONS Pubmed search (01/01/2001-10/31/2017) was performed to identify "training" genes associated with postoperative pain in humans. Candidate genes were identified and prioritized using Toppgene suite, based on functional enrichment using several gene ontology annotations, and curated gene sets associated with mouse phenotype-knockout studies. MEASUREMENTS Computationally top-ranked candidate genes and literature-curated genes were included in pathway enrichment analyses. Hierarchical clustering was used to visualize select functional enrichment results between the two phenotypes. MAIN RESULTS Literature review identified 38 training genes associated with postoperative pain and 31 with CPSP. l annotation - based prioritization and enrichment approaches and identifies novel genes and unique/shared biological processes involved in acute and chronic postoperative pain. Results provide framework for future targeted genetic profiling of CPSP risk, to enable preventive and therapeutic approaches. Recently, non-covalent protein complexes and folds with extreme mechanical stabilities have been discovered. Various extracellular adhesin proteins of gram-positive bacteria exhibit complex rupture forces ranging from 800pN in the case of cellulolytic bacteria to over 2000pN withstood by pathogens adhering to their hosts. Here, we review and assess the mechanics of such systems, and discuss progress, as well as open questions regarding their biological function, and underlying molecular mechanisms - in particular the role of increased interaction lifetimes under mechanical load. These unexpected extreme strengths open an unchartered range of protein mechanics that can now be routinely probed by atomic force microscopy-based single-molecule force spectroscopy. The purpose of this study was to evaluate the efficacy of imiquimod-containing nanovesicles prepared with lipids extracted from the hyperhalophile archaebacterium Halorubrum tebenquichense (nanoARC-IMQ) to induce protection against Trypanosoma cruzi infection. The therapeutic efficacy of archaeolipid nanovesicles was assessed in an experimental murine model of acute infection with T. cruzi. The administration of nanoARQ-IMQ prevented mortality as compared to infected untreated animals, reduced parasitemia levels and diminished myocardial and musculoskeletal lesions in mice infected with a lethal strain of T. cruzi. Our findings suggest that the immunotherapy with nanoARC-IMQ has potential to limit the progression of Chagas disease. Bioactive glass (BAG) is a synthetic bone substitute with intrinsic antimicrobial properties, used for bone defect filling. We evaluated the antimicrobial activity of two formulations of BAG S53P4 against representative pathogens of osteomyelitis Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli and Candida albicans. Antimicrobial activity of BAG S53P4 was assessed by isothermal microcalorimetry, a highly sensitive assay measuring metabolic-related microbial heat production in real-time. Standard CFUs-counting was performed in parallel. BAG granules (diameter 500-800 μm) and powder ( less then 45 μm) were evaluated in two concentrations (400 and 800 mg/ml). Isothermal microcalorimetry was performed in glass ampoules containing growth medium, BAG and test microorganism, heat production was measured for 24 h. BAG S53P4 inhibited heat production of most-tested microorganisms with heat reduction of 60%-98% compared to positive control after 24 h of exposure to the highest-tested concentration (800 mg/ml). BAG S53P4 in powder formulation ( less then 45 μm) inhibited more microbial growth than in granule formulation (500-800 μm), with the exception of C. albicans for which both formulations presented similar inhibition rates ranging between 87 % and 97 %. The BAG inhibitory ratios estimated from the variation in the growth rate constants of each microorganism compared to the growth control ranged between 2.55 % and 100 %. Comparable results were obtained by CFUs-counting, with complete reduction in cell viability of most microorganisms after ≤ 24 h of microbial exposure to BAG S53P4 powder. In summary, BAG S53P4 demonstrated efficient inhibition of microbial growth, especially in powder formulation. Some additives had provided the expansion capacity to the polymethylmethacrylate (PMMA) bone cement and also reduced its maximum reaction temperature. However, the corresponding modified bone cement displayed inferior simulated body fluid (SBF) absorption capacity and expansion behavior, the mechanism of SBF absorption and the trend of expansion stress were ignored additionally. In this study, a homogeneous distribution of poly (methyl methacrylate-co-acrylic acid) [P(MMA-AA)] microspheres led to the formation of microchannels that favored the delivery of SBF to the interior, causing an increased absorption capacity and enhanced expansion behavior before solidification of the bone cement, with the maximum equilibrium absorption ratio and the expansion ratio reaching 27.3 % and 26.3 %, respectively, at an AA content of 50 %. In addition, the expansion stress induced by the expansion behavior experienced a gradual increase from the 0 s to 2590s, followed by a sharp climbed in a short period ranging from 2590s to 2900s, finally reaching maximum stress of 82.1 MPa. Furthermore, the expansion stress within the maximum value could be obtained by controlling the AA content in the P(MMA-AA) bone cement. With the above characteristics, the prepared P(MMA-AA) bone cement has potential applications as a filling and adhesive material in arthroplasties, vertebroplasties, joint replacements, bone screws, and dentistry. The implimentation of newer technologies in drug delivery system have always been the focus of pharmaceutical scientists with advancement of technologies. In this investigation, a novel controlled-release drug-resin combination device (DRC) was designed using dental resin to control the release of dextromethorphan hydrobromide (DH). The influence of different factors on in-vitro drug release were investigated. A Box-Behnken design was used to select the optimized DRC formulation. The optimized DH loaded DRC (DH-DRC) was prepared using 59.88% of PEG400, 16 mg of dental resin and 6.64 mg of sodium chloride (NaCl). https://www.selleckchem.com/products/canagliflozin.html The DH releases at 2 h, 4 h and 8 h of the optimized formulation were significantly close to the predicted responses. The pharmacokinetic study in rabbits showed DH-DRC had prolonged tmax and apparently reduced Cmax compared with commercial tablets and the AUC0-24h of DH-DRC was slightly higher than commercial tablets. This study confirmed the novel DRC could control the release of drug. It concluded that DRC would be a promising and alternative approach for the development of controlled release dosage form.
0 Comentários
0 Compartilhamentos
12 Visualizações
0 Anterior
