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Variable-Temperature NMR Analysis of the Thermodynamics of Plastic Dividing involving Aqueous and also Drug-Rich Levels and its particular Importance to Amorphous Preparations.
Intestinal ischemia-reperfusion (I/R) is a life-threatening condition associated with high morbidity and mortality. Dexmedetomidine (DEX), an agonist of α2-adrenoceptor with sedation and analgesia effect, has recently been identified with protective function against I/R injury in multiple organs. However, the mechanism underlying the beneficial effect of DEX on intestine after I/R injury remained poorly understood. In the present study, using in both in vitro and in vivo models, we found that intestinal I/R injury was associated with the activation of p38 MAPK cascade, while DEX was capable of deactivating p38 MAPK and thus protect intestinal cells from apoptosis by inhibiting p38 MAPK-mediated mitochondrial depolarization and cytochrome c (Cyto C) release. Moreover, through inhibiting p38 MAPK activity, the downstream production of pro-inflammatory cytokines-regulated by NF-κB was also suppressed by DEX treatment, leading to the resolution of I/R-induced inflammation in intestine. In general, our study provided evidence that DEX protected intestine from I/R injury by inhibiting p38 MAPK-mediated mitochondrial apoptosis and inflammatory response. A novel sampler device for flowing powders was tested to quantify drug concentrations as low as 0.76% w/w in pharmaceutical powder blends. The sampler device was developed based on the powder flow behavior within a tablet press feed frame, following the principles laid down in the Theory of Sampling. Two Near-Infrared (NIR) spectroscopic calibration models were developed with powder blends that varied from 0.52 to 2.52% w/w and 1.51-4.52% w/w. The calibration models were able to determine caffeine concentration in test set blends with root mean square error of predictions and bias below 0.1% w/w. Samples were collected from the sampler device and analyzed by ultraviolet-visible (UV-Vis) to determine the caffeine concentration. A high agreement between the in-line NIR predictions and the sampled UV-Vis results was found. The paddle wheel speed in the sampler can be varied up to ±10% without affecting NIR predictions; however, the models did not respond adequately to a 25% increase in this speed. Variographic analysis showed that the sampler device may quantify low drug concentrations with nugget effects below 0.0050 (%w/w)2. This study demonstrate that the sampler device may handle throughputs up to 45 kg/h, without significantly affecting the physical properties of powder blends. Extruded 3D printing is emerging as an attractive fabrication technology in the field of personalized oral medicines. The objective of this study was to develop a tunable extruded 3D printing platform based on thermo-sensitive gelatin pastes to meet the needs of achieving different drug release characteristics with flexible dosing and design. The printability and mechanisms of extrusion and deposition of the gelatin pastes were systematically studied. Ibuprofen and diclofenac sodium were used as model drugs for immediate- and sustained-release formulations, respectively. Following the optimization of formulation and process parameters, ibuprofen immediate-release formulations with different designs, and reservoir-type diclofenac sodium sustained-release formulations were printed. Target drug release patterns were successfully obtained for both model drugs. Rheological studies revealed that additives such as microcrystalline cellulose and hydroxypropyl methylcellulose can act as both thickeners and proppants of gelatin matrix. Furthermore, computational fluid dynamics simulation was used to visualize the printing process, and quantitatively analyze the influence of material viscosity, inlet velocity and nozzle diameter on the pressure and velocity of extrusion flow field. The present study demonstrated the great potential of extruded 3D printing technology using the thermo-sensitive gelatin paste platform for personalized oral medicines. In recent years, the number of cases with severe Plasmodium vivax malaria has shown an increasing trend. It is, therefore, important to identify routine laboratory markers that best characterize the acute disease phase and can serve as a tool for clinical follow-up of patients. In a cohort study, we followed 87 patients with acute P. vivax monoinfection acquired in an endemic region of the Brazilian Amazon. Forty-two different biochemical and hematological parameters frequently tested in clinical routine were evaluated at the acute phase and the convalescent phase. A total of 42 laboratory tests were performed biochemical parameters measured were serum lipids levels, aminotransferases, bilirubin, amylase, glucose, urea, creatinine, albumin, globulin, uric acid, C-reactive protein, and alpha-1-acid glycoprotein. Hematological parameters included total and differential white blood cell and platelet counts, hemoglobin concentration, mean platelet volume, platelet width distribution, and plateletcrit. Our results show that several biochemical and hematological parameters were associated with acute phase P. vivax malaria and these parameters reverted to normal values in the convalescent phase. The use of these parameters during diagnosis and follow-up of the infection is a useful clinical tool to evaluate the clinical course and therapeutic response of patients with uncomplicated vivax malaria. BACKGROUND The spinal cord is composed of nine distinct cellular laminae that currently can only be visualized by histological methods. Developing imaging methods that can visualize laminar architecture in-vivo is of significant interest. Manganese enhanced magnetic resonance imaging (MEMRI) yields valuable architectural and functional information about the brain and has great potential in characterizing neural pathways in the spinal cord. Here we apply MEMRI to visualize laminae architecture in the thoracic region of the spinal cord with ultra-high resolution. NEW METHOD Manganese chloride (MnCl2) was delivered systemically and imaging of the lumbar and thoracic spinal cord levels was acquired in high field, 11.7 T MRI scanner, 48 h following MnCl2 administration. RESULTS Here we demonstrate laminar specific signal enhancement in the spinal cord of rats administered with MnCl2 with 69 μm in-plane resolution. We also report reduced T1 values over time in MnCl2 groups across laminae IIX. COMPARISONS WITH EXISTING METHODS This is the first study to demonstrate that MEMRI is capable of identifying spinal laminae at a high resolution of 69 μm in a living animal. This would enable the visualization of architecture and function of distinct regions with improved resolution, in healthy and diseased animal models. CONCLUSIONS The regions with the largest T1 enhancements were observed to correspond to laminae that contain either high cell density or large motor neurons, making MEMRI an excellent tool for studying spinal cord architecture, physiology and function in different animal models. OBJECTIVE Metabolic bone disease concerns a broad spectrum of conditions related to reduced bone density. Metabolic bone disease has been linked to chronic inflammatory diseases, such as ulcerative colitis. check details This study examines the prevalence of metabolic bone disease in ulcerative colitis patients and explores possible clinical predictors. METHOD The authors performed a retrospective study involving children and adolescents with confirmed ulcerative colitis between January 2013 and December 2018. Bone density was evaluated through a dual-energy X-ray absorptiometry scan of the spine and total body. Osteoporosis was defined as a bone mineral density Z-score of less then -2 and osteopenia as a Z-score of between -1.0 and -2. RESULTS A total of 37 patients were included in this analysis, with a mean age of 13.4±3.9 years and a mean duration of illness of 2.1±2.4 years. Using lumbar spine Z-scores and total body Z-scores, osteoporosis and osteopenia were identified by dual-energy X-ray absorptiometry scan measurements in 11 patients (29.7%) and 15 patients (40.5%), and in ten patients (27%) and 13 patients (35%), respectively. Lumbar spine Z-scores were significantly positively associated with male gender (B=2.02; p=0.0001), and negatively associated with the presence of extraintestinal manifestations (B=-1.51, p=0.009) and the use of biologics (B=-1.33, p=0.004). However, total body Z-scores were positively associated with body mass index Z-scores (B=0.26, p=0.004) and duration of illness in years (B=0.35, p=0.003). CONCLUSIONS Metabolic bone disease is very common in this cohort of Saudi Arabian children and adolescents with ulcerative colitis and its occurrence appears to increase in female patients who suffer from extraintestinal manifestations. BACKGROUND Chronic steroid treatment causes an increase in visceral adiposity and osteoporosis. It is believed that steroids may alter a balance between differentiation of mesenchymal stem cells (MSCs) into either adipocytes or osteoblasts; however, the detailed molecular mechanisms are unclear. We previously identified Dexras1 as a critical factor that potentiates adipogenesis in response to glucocorticoids. Thus, in this study, we investigated the role of Dexras1 in maintaining the balance between chronic steroid treatment-associated adipogenesis and osteoporosis. MATERIAL AND METHODS We treated wild type (WT) and Dexras1 knockout (KO) mice with dexamethasone for five weeks followed by 60% HFD for additional two weeks with dexamethasone. The changes of glucocorticoid-induced body weight gain and osteoporosis were analyzed. Bone marrow derived stromal cells (BMSCs) and mouse embryonic fibroblasts (MEFs) extracted from WT and Dexras1 KO mice, as well as MC3T3-E1 pre-osteoblasts and osteoclasts differentiated from RAW264.7 were analyzed to further define the role of Dexras1 in osteoblasts and osteoclasts. RESULTS Dual-energy X-ray absorptiometry and micro-computed tomography analyses in murine femurs revealed that Dexras1 deficiency was associated with increased osteogenesis, concurrent with reduced adipogenesis. Furthermore, Dexras1 deficiency promoted osteogenesis of BMSCs and MEFs in vitro, suggesting that Dexras1 deficiency prevents steroid-induced osteoporosis. We also observed that Dexras1 downregulated SMAD signaling pathways, which reduced the osteogenic differentiation capacity of pre-osteoblast MC3T3-E1 cells into mature osteoblasts. CONCLUSION We propose that Dexras1 is critical for maintaining the equilibrium between adipogenesis and osteogenesis upon steroid treatment. The horseshoe crab is a living fossil and a species of marine arthropod with unusual immune system properties which are also exploited commercially. Given its ancient status dating to the Ordovician period (450 million years ago), its standing in phylogeny and unusual immunological characteristics, the horseshoe crab may hold valuable information for comparative immunology studies. Peptidylarginine deiminases (PADs) are calcium dependent enzymes that are phylogenetically conserved and cause protein deimination via conversion of arginine to citrulline. This post-translational modification can lead to structural and functional protein changes contributing to protein moonlighting in health and disease. PAD-mediated regulation of extracellular vesicle (EV) release, a critical component of cellular communication, has furthermore been identified to be a phylogenetically conserved mechanism. PADs, protein deimination and EVs have hitherto not been studied in the horseshoe crab and were assessed in the current study.
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