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1.
J Phys Chem A ; 128(12): 2399-2408, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38484115

ABSTRACT

The global warming potential (GWP) is a relative measure of the capability of a molecule to trap the Earth's infrared radiation as heat. The measurement or prediction of the GWP of a molecule is based on two factors: the radiative efficiency and atmospheric lifetime of a molecule. While the calculation of the radiative efficiency of a molecule using the computational chemistry approach, such as density functional theory (DFT), is well-established and robust, the development of a computational approach to estimate the atmospheric lifetime remains challenging and limited to date. In this contribution, we developed a machine learning (ML) approach to estimate a molecule's atmospheric lifetime and GWP100 based on electronic and geometrical features. We benchmarked the state-of-the-art computational workflow with the developed ML model in estimating the atmospheric lifetime and GWP100. The developed ML model outperforms the existing approach with the mean absolute error values of 0.234 (ML-predicted atmospheric lifetime) and 0.249 (direct ML model for GWP100) compared with 0.535 (Atkinson's method) and 0.773 (Kazakov et al.) from previous works. The developed models were used to screen >7000 molecules in PubChem and bigQM7 data sets in a search for SF6 replacement gas for the electric industry and identified 84 potential candidates.

2.
J Mater Sci Mater Med ; 35(1): 33, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38900208

ABSTRACT

Phosphate bioactive glass has been studied for its advanced biodegradability and active ion release capability. Our previous research found that phosphate glass containing (P2O5)-(Na2O)-(TiO2)-(CaO)-(SrO) or (ZnO) showed good biocompatibility with MG63 and hMSCs. This study further investigated the application of 5 mol% zinc oxide or 17.5 mol% strontium oxide in titanium-doped phosphate glass for bone tissue engineering. Ti-Ca-Na-Phosphate glasses, incorporating 5% zinc oxide or 17.5% strontium oxide, were made with melting quenching technology. The pre-osteoblast cell line MC3T3-E1 was cultured for indirect contact tests with graded diluted phosphate glass extractions and for direct contact tests by seeding cells on glass disks. The cell viability and cytotoxicity were analysed in vitro over 7 days. In vivo studies utilized the tibial defect model with or without glass implants. The micro-CT analysis was performed after surgery and then at 2, 6, and 12 weeks. Extractions from both zinc and strontium phosphate glasses showed no negative impact on MC3T3-E1 cell viability. Notably, non-diluted Zn-Ti-Ca-Na-phosphate glass extracts significantly increased cell viability by 116.8% (P < 0.01). Furthermore, MC3T3-E1 cells cultured with phosphate glass disks exhibited no increase in LDH release compared with the control group. Micro-CT images revealed that, over 12 weeks, both zinc-doped and strontium-doped phosphate glasses demonstrated good bone incorporation and longevity compared to the no-implant control. Titanium-doped phosphate glasses containing 5 mol% zinc oxide, or 17.5 mol% strontium oxide have promising application potential for bone regeneration research.


Subject(s)
Bone Regeneration , Cell Survival , Glass , Phosphates , Strontium , Titanium , Strontium/chemistry , Strontium/pharmacology , Bone Regeneration/drug effects , Animals , Mice , Phosphates/chemistry , Phosphates/pharmacology , Glass/chemistry , Titanium/chemistry , Cell Survival/drug effects , Materials Testing , Zinc/chemistry , Cell Line , Osteoblasts/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Tissue Engineering/methods , Bone Substitutes/chemistry , Bone Substitutes/pharmacology , X-Ray Microtomography
3.
Int J Mol Sci ; 25(6)2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38542065

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) has emerged as a significant liver ailment attributed to factors like obesity and diabetes. While ongoing research explores treatments for NAFLD, further investigation is imperative to address this escalating health concern. NAFLD manifests as hepatic steatosis, precipitating insulin resistance and metabolic syndrome. This study aims to validate the regenerative potential of chimeric fibroblast growth factor 21 (FGF21) and Hepatocyte Growth Factor Receptor (HGFR) in NAFLD-afflicted liver cells. AML12, a murine hepatocyte cell line, was utilized to gauge the regenerative effects of chimeric FGF21/HGFR expression. Polysaccharide accumulation was affirmed through Periodic acid-Schiff (PAS) staining, while LDL uptake was microscopically observed with labeled LDL. The expression of FGF21/HGFR and NAFLD markers was analyzed by mRNA analysis with RT-PCR, which showed a decreased expression in acetyl-CoA carboxylase 1 (ACC1) and sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP) with increased expression of hepatocellular growth factor (HGF), hepatocellular nuclear factor 4 alpha (HNF4A), and albumin (ALB). These findings affirm the hepato-regenerative properties of chimeric FGF21/HGFR within AML12 cells, opening novel avenues for therapeutic exploration in NAFLD.


Subject(s)
Non-alcoholic Fatty Liver Disease , Animals , Mice , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Proto-Oncogene Proteins c-met/metabolism , Liver/metabolism , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism
4.
J Nanobiotechnology ; 20(1): 367, 2022 Aug 11.
Article in English | MEDLINE | ID: mdl-35953847

ABSTRACT

BACKGROUND: Astrocyte is a key regulator of neuronal activity and excitatory/inhibitory balance via gliotransmission. Recently, gliotransmission has been identified as a novel target for neurological diseases. However, using the properties of nanomaterials to modulate gliotransmission has not been uncovered. RESULTS: We prepared non-invasive CNT platforms for cells with different nanotopography and properties such as hydrophilicity and conductivity. Using CNT platforms, we investigated the effect of CNT on astrocyte functions participating in synaptic transmission by releasing gliotransmitters. Astrocytes on CNT platforms showed improved cell adhesion and proliferation with upregulated integrin and GFAP expression. In addition, intracellular GABA and glutamate in astrocytes were augmented on CNT platforms. We also demonstrated that gliotransmitters in brain slices were increased by ex vivo incubation with CNT. Additionally, intracellular resting Ca2+ level, which is important for gliotransmission, was also increased via TRPV1 on CNT platforms. CONCLUSION: CNT can improve astrocyte function including adhesion, proliferation and gliotransmission by increasing resting Ca2+ level. Therefore, our study suggests that CNT would be utilized as a new therapeutic platform for central nervous system diseases by modulating gliotransmission.


Subject(s)
Nanotubes, Carbon , Astrocytes , Brain , Neurons/metabolism , Synaptic Transmission/physiology
5.
Bioorg Med Chem ; 51: 116493, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34781082

ABSTRACT

Cancer has become one of the main reasons for human death in recent years. Around 18 million new cancer cases and approximately 9.6 million deaths from cancer reported in 2018, and the annual number of cancer cases will have increased to 22 million in the next two decades. These alarming facts have rekindled researchers' attention to develop and apply different approaches for cancer therapy. Unfortunately, most of the applied methods for cancer therapy not only have adverse side effects like toxicity and damage of healthy cells but also have a short lifetime. To this end, introducing innovative and effective methods for cancer therapy is vital and necessary. Among different potential materials, carbon nanomaterials can cope with the rising threats of cancer. Due to unique physicochemical properties of different carbon nanomaterials including carbon, fullerene, carbon dots, graphite, single-walled carbon nanotube and multi-walled carbon nanotubes, they exhibit possibilities to address the drawbacks for cancer therapy. Carbon nanomaterials are prodigious materials due to their ability in drug delivery or remedial of small molecules. Functionalization of carbon nanomaterials can improve the cancer therapy process and decrement the side effects. These exceptional traits make carbon nanomaterials as versatile and prevalent materials for application in cancer therapy. This article spotlights the recent findings in cancer therapy using carbon nanomaterials (2015-till now). Different types of carbon nanomaterials and their utilization in cancer therapy were highlighted. The plausible mechanisms for the action of carbon nanomaterials in cancer therapy were elucidated and the advantages and disadvantages of each material were also illustrated. Finally, the current problems and future challenges for cancer therapy based on carbon nanomaterials were discussed.


Subject(s)
Antineoplastic Agents/therapeutic use , Carbon/chemistry , Nanostructures/chemistry , Neoplasms/drug therapy , Animals , Antineoplastic Agents/chemistry , Humans , Molecular Structure
6.
BMC Anesthesiol ; 21(1): 125, 2021 04 21.
Article in English | MEDLINE | ID: mdl-33882838

ABSTRACT

BACKGROUND: Predicting difficult airway is challengeable in patients with limited airway evaluation. The aim of this study is to develop and validate a model that predicts difficult laryngoscopy by machine learning of neck circumference and thyromental height as predictors that can be used even for patients with limited airway evaluation. METHODS: Variables for prediction of difficulty laryngoscopy included age, sex, height, weight, body mass index, neck circumference, and thyromental distance. Difficult laryngoscopy was defined as Grade 3 and 4 by the Cormack-Lehane classification. The preanesthesia and anesthesia data of 1677 patients who had undergone general anesthesia at a single center were collected. The data set was randomly stratified into a training set (80%) and a test set (20%), with equal distribution of difficulty laryngoscopy. The training data sets were trained with five algorithms (logistic regression, multilayer perceptron, random forest, extreme gradient boosting, and light gradient boosting machine). The prediction models were validated through a test set. RESULTS: The model's performance using random forest was best (area under receiver operating characteristic curve = 0.79 [95% confidence interval: 0.72-0.86], area under precision-recall curve = 0.32 [95% confidence interval: 0.27-0.37]). CONCLUSIONS: Machine learning can predict difficult laryngoscopy through a combination of several predictors including neck circumference and thyromental height. The performance of the model can be improved with more data, a new variable and combination of models.


Subject(s)
Laryngoscopy , Machine Learning , Neck/anatomy & histology , Thyroid Cartilage/anatomy & histology , Datasets as Topic , Humans , Sensitivity and Specificity
7.
J Appl Toxicol ; 41(7): 1038-1049, 2021 07.
Article in English | MEDLINE | ID: mdl-33085125

ABSTRACT

Recent research on in vitro systems has focused on mimicking the in vivo situation of cells within the respiratory system. However, few studies have predicted inhalation toxicity using conventional and simple submerged two-dimensional (2D) cell culture models. We investigated the conventional submerged 2-D cell culture model as a method for the prediction of acute inhalation toxicity. Median lethal concentration (LC50 ) (rat, inhalation, 4 h) and half maximal inhibitory concentration (IC50 ) (lung or bronchial cell, 24 h) data for 59 substances were obtained from the literature and by experiments. Cytotoxicity assays were performed on 44 substances with reported LC50 , but without IC50 , data to obtain the IC50 values. A weak correlation was observed between the IC50 and LC50 of all substances. Semi-volatile organic compounds (SVOCs) and non-VOCs (NVOCs) (16 substances) with a water solubility of ≥1 g/L were strongly correlated between 24-h IC50 and 4-h LC50 , and this had an excellent predictive ability to distinguish between Categories 1-3 and 4 (Globally Harmonized System classification for acute inhalation toxicity). Our results suggest that the submerged 2-D cell culture model may be used to predict in vivo acute inhalation toxicity for substances with a water solubility of ≥1 g/L in SVOCs and NVOCs.


Subject(s)
Epithelial Cells/drug effects , Inhalation Exposure , Lung/drug effects , Toxicity Tests/methods , Administration, Inhalation , Animal Testing Alternatives , Animals , Cell Culture Techniques , Cell Line , Humans , Lethal Dose 50 , Rats
8.
J Appl Toxicol ; 41(3): 470-482, 2021 03.
Article in English | MEDLINE | ID: mdl-33022792

ABSTRACT

Cetylpyridinium chloride (CPC), a quaternary ammonium compound and cationic surfactant, is used in personal hygiene products such as toothpaste, mouthwash, and nasal spray. Although public exposure to CPC is frequent, its pulmonary toxicity has yet to be fully characterized. Due to high risks of CPC inhalation, we aimed to comprehensively elucidate the in vitro and in vivo toxicity of CPC. The results demonstrated that CPC is highly cytotoxic against the A549 cells with a half-maximal inhibitory concentration (IC50 ) of 5.79 µg/ml. Following CPC exposure, via intratracheal instillation (ITI), leakage of lactate dehydrogenase, a biomarker of cell injury, was significantly increased in all exposure groups. Further, repeated exposure of rats to CPC for 28 days caused a decrease in body weight of the high-exposure group and the relative weights of the lungs and kidneys of the high recovery group, but no changes were evident in the histological and serum chemical analyses. The bronchoalveolar lavage fluid (BALF) analysis showed a significant increase in proinflammatory cytokines interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α levels. ITI of CPC induced focal inflammation of the pulmonary parenchyma in rats' lungs. Our study demonstrated that TNF-α was the most commonly secreted proinflammatory cytokine during CPC exposure in both in vitro and in vivo models. Polymorphonuclear leukocytes in the BALF, which are indicators of pulmonary inflammation, significantly increased in a concentration-dependent manner in all in vivo studies including the ITI, acute, and subacute inhalation assays, demonstrating that PMNs are the most sensitive parameters of pulmonary toxicity.


Subject(s)
A549 Cells/drug effects , Anti-Infective Agents, Local/toxicity , Cell Survival/drug effects , Cetylpyridinium/toxicity , Pneumonia/chemically induced , Pneumonia/physiopathology , Animals , Disease Models, Animal , Humans , Male , Rats , Rats, Sprague-Dawley
9.
Transfusion ; 60(7): 1424-1433, 2020 07.
Article in English | MEDLINE | ID: mdl-32583456

ABSTRACT

INTRODUCTION: Red cell exchange (RCE) therapy is increasingly used to treat patients with acute or chronic manifestations of sickle cell disease (SCD). However, little is known regarding the most safe and effective practice parameters associated with this particular therapy. METHODS: A SCD subcommittee of members of the American Society for Apheresis (ASFA) developed a 122-question survey and administered it via email to other ASFA members. The survey inquired about clinical indications for treatment, practice patterns, and transfusion policies for RCE when used for patients with SCD. RESULTS: Ninety-nine distinct institutions completed the survey. Twenty-one (21%) were from outside of the US. Twenty-two (22%) provided chronic transfusion therapy to >10 patients, and both adult (25%) and pediatric-focused services (20%) were represented. Common acute indications for RCE included acute chest syndrome, acute ischemic stroke, and pre-surgical prophylaxis. Common chronic indications included primary stroke prophylaxis, secondary stroke prophylaxis, and recurrent acute chest syndrome. Respondents most commonly set a post-RCE treatment target of 30% for the hematocrit and hemoglobin S levels, regardless of the therapeutic indication. Units for RCE were phenotypically matched in 95% of cases. About 40% of respondents reported using isovolemic hemodilution. CONCLUSIONS: This survey solicited the current practice variations in RCE from a diverse range of practice sites. Many sites reported similar practice patterns and challenges but some variations emerged. To our knowledge, this survey represents the largest and most in-depth investigation of the use of RCE for patients with SCD, and could inform future studies in the field.


Subject(s)
Anemia, Sickle Cell/therapy , Electronic Mail , Erythrocyte Transfusion , Health Policy , Surveys and Questionnaires , Adult , Anemia, Sickle Cell/epidemiology , Child , Humans , Male
10.
J Clin Apher ; 35(1): 25-32, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31705563

ABSTRACT

IMPORTANCE: Neuromyelitis optica/neuromyelitis optica spectrum disorder patients' response to therapeutic plasma exchange (TPE) is currently incompletely characterized. OBJECTIVE: Our study aims to understand the clinical status improvement of neuromyelitis optica/neuromyelitis optica spectrum disorder patients treated with TPE. DESIGN, SETTING, AND PARTICIPANTS: This is a multicenter retrospective study conducted between 1 January 2003 and 31 July 2017 at 13 US hospitals performing apheresis procedures. Subjects studied were diagnosed with neuromyelitis optica/neuromyelitis optica spectrum disorder who received TPE during presentation with acute disease. MAIN OUTCOMES AND MEASURES: The primary outcome was clinical status improvement in patients treated with TPE. Secondary measures were procedural and patient characteristics associated with response to treatment. RESULTS: We evaluated 114 patients from 13 institutions. There was a female predilection. The largest ethnic group affected was non-Hispanic Caucasian. The average age of diagnosis was 43.1 years. The average time to diagnosis was 3.1 years. On average, five procedures were performed during each treatment series. The most commonly performed plasma volume exchange was 1.0 to 1.25 using 5% albumin as replacement fluid. Most patients (52%) did not require an additional course of TPE and noted "mild" to "moderate" clinical status improvement. Maximal symptom improvement appeared by the fourth or fifth TPE treatment. CONCLUSION AND RELEVANCE: TPE improved the clinical status of patients. Adults responded more favorably than children. Procedural characteristics, including number of TPEs, plasma volume exchanged, and replacement fluid used, were similar between institutions. TPE was well-tolerated and had a low severe adverse event profile.


Subject(s)
Neuromyelitis Optica/therapy , Plasma Exchange/methods , Adolescent , Adult , Aged , Aged, 80 and over , Autoantibodies , Blood Component Removal , Child , Child, Preschool , Humans , Infant , Infant, Newborn , Middle Aged , Plasmapheresis , Registries , Retrospective Studies , United States , Young Adult
11.
Scand J Gastroenterol ; 54(8): 1058-1063, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31430183

ABSTRACT

Background: The benefits of narrow band imaging (NBI) for improving the detection rate of colorectal polyps remain unclear. New generation NBI using the 290 system (290-NBI) provides an at least two-fold brighter image than that of the previous version. We aimed to compare polyp miss rates between 290-NBI colonoscopy and high-definition white light endoscopy (HDWL). Methods: In total, 117 patients were randomized to undergo either 290-NBI or HDWL from June 2015 to February 2017. In the HDWL group, we performed HDWL as an initial inspection, followed by a second inspection with NBI. In the 290-NBI group, NBI was performed as the initial inspection, followed by a second inspection with HDWL. We compared polyp and adenoma detection rates and polyp miss rates (PMR) between the two groups and analyzed the factors associated with the PMR. Results: In total, 127 polyps were detected in the 117 patients. No differences in adenoma or polyp detection rates were observed between the two groups. The PMR for 290-NBI was 20.6% and that for HDWL was 33.9% (p = .068). However, the non-adenomatous PMR for 290-NBI was significantly lower than that of HDWL (11.5% vs. 52.2%, p = .002). Furthermore, the miss rates of polyps on the left side of the colon, flat-type polyps, and non-adenomatous polyps were significantly lower in the 290-NBI than HDWL. Conclusions: New generation NBI may reduce PMR, especially of flat-type and non-adenomatous polyps and those on the left side of the colon. (UMIN000025505).


Subject(s)
Adenoma/diagnosis , Colonic Polyps/diagnosis , Colonoscopy/methods , Narrow Band Imaging , Adenoma/pathology , Colonic Polyps/pathology , Colonoscopy/instrumentation , Female , Humans , Image Enhancement/methods , Male , Middle Aged , Missed Diagnosis/prevention & control , Missed Diagnosis/statistics & numerical data , Precancerous Conditions/pathology , Prospective Studies , Republic of Korea , Tertiary Care Centers
12.
Chem Rev ; 117(15): 9874-9906, 2017 Aug 09.
Article in English | MEDLINE | ID: mdl-28640612

ABSTRACT

Genome editing offers promising solutions to genetic disorders by editing DNA sequences or modulating gene expression. The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) technology can be used to edit single or multiple genes in a wide variety of cell types and organisms in vitro and in vivo. Herein, we review the rapidly developing CRISPR/Cas9-based technologies for disease modeling and gene correction and recent progress toward Cas9/guide RNA (gRNA) delivery based on viral and nonviral vectors. We discuss the relative merits of delivering the genome editing elements in the form of DNA, mRNA, or protein, and the opportunities of combining viral delivery of a transgene encoding Cas9 with nonviral delivery of gRNA. We highlight the lessons learned from nonviral gene delivery in the past three decades and consider their applicability for CRISPR/Cas9 delivery. We also include a discussion of bioinformatics tools for gRNA design and chemical modifications of gRNA. Finally, we consider the extracellular and intracellular barriers to nonviral CRISPR/Cas9 delivery and propose strategies that may overcome these barriers to realize the clinical potential of CRISPR/Cas9-based genome editing.


Subject(s)
CRISPR-Cas Systems/genetics , Gene Editing , Gene Transfer Techniques , Genetic Therapy/methods , Models, Biological , Humans
13.
Dig Dis Sci ; 64(9): 2607-2613, 2019 09.
Article in English | MEDLINE | ID: mdl-30977077

ABSTRACT

BACKGROUND: Colonic bubbles obscure the colonic mucosa during colonoscopy following bowel preparation with polyethylene glycol plus ascorbic acid (PEG-Asc). Simethicone is used to enhance visualization during colonoscopy. We aimed to determine the optimal timing of simethicone addition to improve bowel preparation using PEG-Asc. METHODS: This prospective, randomized study enrolled patients undergoing elective colonoscopy from April 2017 to January 2018. They were randomly assigned to one of the following three groups: PEG-Asc only (control) or simethicone addition in the morning on the day of colonoscopy (PEG-S1) or in the evening of the day prior to colonoscopy (PEG-S2). The primary outcome was the quality of colon cleansing, and the secondary outcomes were the adenoma detection rate (ADR), polyp detection rate (PDR), and diminutive (≤ 5 mm) ADR. RESULTS: In total, 240 patients were randomly allocated to the three groups; six patients were withdrawn. Of the 234 patients evaluated, 78, 79, and 77 were allocated to the control, PEG-S1, and PEG-S2 groups, respectively. The bubble scores of all colonic segments were lowest in the PEG-S2 group. There was no significant difference in ADR or PDR among the three groups. However, the diminutive ADR was significantly higher in the PEG-S2 group compared to the other two groups (control 5.1% vs. PEG-S1 8.9% vs. PEG-S2 20.8%; P = 0.009). CONCLUSION: Addition of simethicone to PEG-Asc at the optimal time prevents the formation of air bubbles and so improves the quality of bowel preparation, especially enhancing diminutive ADR.


Subject(s)
Adenoma/diagnostic imaging , Antifoaming Agents/administration & dosage , Colonic Polyps/diagnostic imaging , Colonoscopy , Colorectal Neoplasms/diagnostic imaging , Simethicone/administration & dosage , Adenoma/pathology , Adult , Aged , Ascorbic Acid , Cathartics , Colorectal Neoplasms/pathology , Double-Blind Method , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Polyethylene Glycols , Prospective Studies
14.
J Clin Apher ; 34(6): 692-699, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31566780

ABSTRACT

BACKGROUND AND OBJECTIVES: Estimation of the total blood volume (TBV) is fundamental to the control of automated red cell exchange (RCE). Error in the TBV estimate can produce outcomes that deviate from the prescribed targets, and may endanger the patient. Both the Spectra Optia and the COBE Spectra use the Nadler formulae to estimate TBV. There is a potential for large overestimates of TBV when the Nadler formula for males is applied to prepubertal boys. MATERIALS AND METHODS: This study uses our large clinical experience with RCE to examine procedure outcomes when RCE in prepubertal boys is programed with the female parameter instead of male. We determined the differences between programmed and measured values for three outcomes: (a) Programmed End Hematocrit - Post spun HCT by Hemata Stat II, (b) Programmed End Hematocrit - Post CBC HCT, and (c) Predicted Post Hgb S+C - Measured Post Hgb S+C. We defined the experimental group as Male-Female, where the biological sex was male but programmed sex was female, and two control groups where programmed and biological sex were the same. RESULTS: Small but statistically significant differences were demonstrated between the mean programmed-to-observed deviations of these outcome measures in all but two group and subgroup comparisons; however, the absolute magnitudes of the observed differences were not clinically significant. The suggested weight cutoff to begin programming males as male is 35 kg. CONCLUSION: The study provides experiential validation that performing RCE in prepubertal boys using the female parameter is safe.


Subject(s)
Blood Volume , Cytapheresis/methods , Erythrocyte Transfusion/methods , Erythrocytes/cytology , Child , Female , Humans , Male , Pediatrics , Sex Factors
15.
Am J Physiol Lung Cell Mol Physiol ; 315(1): L59-L65, 2018 07 01.
Article in English | MEDLINE | ID: mdl-29516782

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease involving degenerative breathing capacity. Fibrotic disease is driven by dysregulation in mechanical forces at the organ, tissue, and cellular level. While it is known that, in certain pathologies, diseased cells are stiffer than healthy cells, it is not known if fibroblasts derived from patients with IPF are stiffer than their normal counterparts. Using IPF patient-derived cell cultures, we measured the stiffness of individual lung fibroblasts via high-resolution force maps using atomic force microscopy. Fibroblasts from patients with IPF were stiffer and had an augmented cytoskeletal response to transforming growth factor-ß1 compared with fibroblasts from donors without IPF. The results from this novel study indicate that the increased stiffness of lung fibroblasts of IPF patients may contribute to the increased rigidity of fibrotic lung tissue.


Subject(s)
Fibroblasts/metabolism , Idiopathic Pulmonary Fibrosis/metabolism , Lung/metabolism , Signal Transduction , Transforming Growth Factor beta1/metabolism , Adult , Aged , Female , Fibroblasts/pathology , Humans , Idiopathic Pulmonary Fibrosis/pathology , Lung/pathology , Male , Middle Aged
16.
Int J Mol Sci ; 19(1)2018 Jan 04.
Article in English | MEDLINE | ID: mdl-29300346

ABSTRACT

The fibronectin type 10-peptide amphiphile (FNIII10-PA) was previously genetically engineered and showed osteogenic differentiation activity on rat bone marrow stem cells (rBMSCs). In this study, we investigated whether FNIII10-PA demonstrated cellular activity on polycaprolactone (PCL) fibers. FNIII10-PA significantly increased protein production and cell adhesion activity on PCL fibers in a dose-dependent manner. In cell proliferation results, there was no effect on cell proliferation activity by FNIII10-PA; however, FNIII10-PA induced the osteogenic differentiation of MC3T3-E1 cells via upregulation of bone sialoprotein (BSP), collagen type I (Col I), osteocalcin (OC), osteopontin (OPN), and runt-related transcription factor 2 (Runx2) mitochondrial RNA (mRNA) levels; it did not increase the alkaline phosphatase (ALP) mRNA level. These results indicate that FNIII10-PA has potential as a new biomaterial for bone tissue engineering applications.


Subject(s)
Cell Differentiation/drug effects , Fibronectins/pharmacology , Osteogenesis/drug effects , Peptides/pharmacology , Polyesters/chemistry , Surface-Active Agents/chemistry , Amino Acid Sequence , Animals , Cell Adhesion/drug effects , Cell Line , Cell Proliferation/drug effects , Fibronectins/chemistry , Mice
17.
J Clin Apher ; 32(5): 342-367, 2017 Oct.
Article in English | MEDLINE | ID: mdl-27723109

ABSTRACT

The American Society for Apheresis (ASFA) conducted a one-day consensus conference on red blood cell exchange (RBCx) in sickle cell disease (SCD) during its annual meeting in San Antonio, TX, on May 5, 2015. The authors of this article, a subcommittee of ASFA's Clinical Applications Committee, developed several questions with regard to pathophysiology of SCD and use of RBCx in the management of various complications. These questions were provided to the seven invited speakers who are the experts in the field of SCD. Two experts in the field moderated the proceedings of the conference, which was attended by more than 150 participants. After each presentation, there was a summary of the main points by the moderators and an open discussion with questions from the audience. A video recording of the proceedings, as well as each presentation, was made available to the authors. Each author's summary was reviewed and approved by the respective speaker before submission of this manuscript. The subcommittee also developed several key questions to generate a consensus amongst the speakers on key issues for using RBCx for patients with SCD.


Subject(s)
Anemia, Sickle Cell/therapy , Blood Component Removal/methods , Erythrocyte Transfusion/methods , Acute Chest Syndrome/diagnosis , Acute Chest Syndrome/etiology , Acute Chest Syndrome/therapy , Anemia, Hemolytic/etiology , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/physiopathology , Blood Component Removal/adverse effects , Erythrocyte Transfusion/adverse effects , Hemolysis , Humans , Hypertension, Pulmonary/etiology , Societies, Medical , Stroke/prevention & control , United States
18.
J Clin Apher ; 32(1): 5-11, 2017 Feb.
Article in English | MEDLINE | ID: mdl-26946363

ABSTRACT

BACKGROUND: Anti-muscle specific kinase antibody positive (MuSK Ab) myasthenia gravis (MG) patients are known to have different clinical course compared to anti-acetylcholine receptor Ab positive MG patients. Therapeutic plasma exchange (TPE) has been reported to be effective; however, little is known of the response and of TPE procedural information. An ASFA Apheresis Registry was developed to analyze those data. METHODS: The study collected detailed de-identified patient data, TPE procedures, and treatment outcome/complications. Collected data was described in aggregate. RESULTS: A total of 15 MuSK Ab MG patients with exacerbation of MG symptoms, 13 females/2 males, median age 44, were investigated. Thirty TPE courses (median 5 procedures/course, total 145 procedures) were evaluated. All TPE procedures were performed with citrate anticoagulation, 1 - 1.25 plasma volume exchange in 100% fluid balance, and 90% of courses used only albumin as replacement. Calcium was added to albumin or given orally as needed. TPE was performed every other day in 55% of courses. Adverse events occurred in 3.4% of procedures. Ten patients (67%) experienced relapses within a median of 7 weeks. Objective symptoms were resolved in more than 75% of courses. Overall subjective improvement rates were 94.1%/93.3% after 3/4 TPE procedures, respectively. Thirty-one percent of patients responded poorly with minimal recovery. CONCLUSION: Overall subjective improvement was seen up to 94% of patients after one course of TPE. Some patients were poor-responders. Five TPE may be adequate for initial course with additional TPE as needed. Based upon this preliminary data, we will modify our future data collection. J. Clin. Apheresis 32:5-11, 2017. © 2016 Wiley Periodicals, Inc.


Subject(s)
Myasthenia Gravis/therapy , Plasma Exchange/methods , Registries , Adult , Autoantibodies , Female , Humans , Male , Myasthenia Gravis/immunology , Plasma Exchange/adverse effects , Receptor Protein-Tyrosine Kinases/immunology , Receptors, Cholinergic/immunology , Retrospective Studies , Treatment Outcome
19.
J Clin Apher ; 32(4): 215-223, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27442906

ABSTRACT

BACKGROUND: Although many apheresis centers offer extracorporeal photopheresis (ECP), little is known about current treatment practices. METHODS: An electronic survey was distributed to assess ECP practice internationally. RESULTS: Of 251 responses, 137 met criteria for analysis. Most respondents were from North America (80%). Nurses perform ECP at most centers (84%) and the majority of centers treat adults only (52%). Most centers treat fewer than 50 patients/year (83%) and perform fewer than 300 procedures/year (70%). Closed system devices (XTS and/or Cellex) are used to perform ECP at most centers (96%). The most common indications for ECP are acute/chronic skin graft versus host disease (89%) and cutaneous T-cell lymphoma (63%). The typical wait time for ECP treatment is less than 2 weeks (91%). Most centers do not routinely perform quality control assessment of the collected product (66%). There are device-specific differences in treatment parameters. For example, XTS users more frequently have a minimum weight limit (P = 0.003) and use laboratory parameters to determine eligibility for treatment (P = 0.03). Regardless of device used, the majority of centers assess the clinical status of the patient before each procedure. Greater than 50% of respondents would defer treatment for hemodynamic instability due to active sepsis or heart failure, positive blood culture in the past 24 h or current fever. CONCLUSION: This survey based study describes current ECP practices. Further research to provide evidence for optimal standardization of patient qualifications, procedure parameters and product quality assessment is recommended.


Subject(s)
Photopheresis/methods , Practice Patterns, Physicians'/standards , Graft vs Host Disease/therapy , Humans , Lymphoma, T-Cell, Cutaneous/therapy , Patient Selection , Practice Patterns, Physicians'/trends , Quality Assurance, Health Care , Skin Transplantation/adverse effects , Surveys and Questionnaires
20.
Cell Tissue Res ; 363(2): 525-40, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26174955

ABSTRACT

The current study deals with the fabrication and characterization of blended nanofibrous scaffolds of tropical tasar silk fibroin of Antheraea mylitta and poly (Є-caprolactone) to act as an ideal scaffold for bone regeneration. The use of poly (Є-caprolactone) in osteogenesis is well-recognized. At the same time, the osteoconductive nature of the non-mulberry tasar fibroin is also established due to its internal integrin binding peptide RGD (Arg-Gly-Asp) sequences, which enhance cellular interaction and proliferation. Considering that the materials have the required and favorable properties, the blends are formed using an equal volume ratio of fibroin (2 and 4 wt%) and poly (Є-caprolactone) solution (10 wt%) to fabricate nanofibers. The nanofibers possess an average diameter of 152 ± 18 nm (2 % fibroin/PCL) and 175 ± 15 nm (4% fibroin/PCL). The results of Fourier transform infrared spectroscopy substantiates the preservation of the secondary structure of the fibroin in the blends indicating the structural stability of the neo-matrix. With an increase in the fibroin percentage, the hydrophobicity and thermal stability of the matrices as measured from melting temperature Tm (using DSC) decrease, while the mechanical strength is improved. The blended nanofibrous scaffolds are biodegradable, and support the viability and proliferation of human osteoblast-like cells as observed through scanning electron and confocal microscopes. Alkaline phosphatase assay indicates the cell proliferation and the generation of the neo-bone matrix. Taken together, these findings illustrate that the silk-poly (Є-caprolactone) blended nanofibrous scaffolds have an excellent prospect as scaffolding material in bone tissue engineering.


Subject(s)
Bone and Bones/physiology , Fibroins/pharmacology , Nanofibers/chemistry , Oligopeptides/pharmacology , Polyesters/pharmacology , Tissue Engineering/methods , Alkaline Phosphatase/metabolism , Animals , Bone and Bones/drug effects , Calcification, Physiologic/drug effects , Calorimetry, Differential Scanning , Cell Adhesion/drug effects , Cell Line , Cell Proliferation/drug effects , Cell Shape/drug effects , Endopeptidase K/metabolism , Humans , Nanofibers/ultrastructure , Osteoblasts/cytology , Osteoblasts/drug effects , Osteoblasts/metabolism , Spectroscopy, Fourier Transform Infrared , Stress, Mechanical , Temperature , Tensile Strength/drug effects , Tissue Scaffolds/chemistry
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