scholarly journals In-Vitro Experimental Modeling of Oscillatory Respiratory Flow in a CT-Scanned OSAHS Tract

2020 ◽  
Vol 10 (22) ◽  
pp. 7979
Author(s):  
Zhenshan Zhu ◽  
Yaping Ju ◽  
Chuhua Zhang
Keyword(s):  
Flow Velocity ◽  
Clinical Medicine ◽  
Experimental Modeling ◽  
Respiratory Disorder ◽  
Optical Index ◽  
Respiratory Flow ◽  
Index Matching ◽  
Obstructive Sleep ◽  
Eta Model

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a highly prevalent respiratory disorder. The knowledge of respiratory flow is an essential prerequisite for the establishment and development of OSAHS physiology, pathology, and clinical medicine. We made the first in-vitro experimental attempt to measure the oscillatory flow velocity in a computed tomography (CT) scanned extra-thoracic airway (ETA) model with OSAHS by using the particle image velocimetry (PIV) technique. In order to mimic respiration flow, three techniques were adopted to address difficulties in in-vitro experimental modeling: (1) fabricating the obstructive ETA measurement section with the CT-scanned data of an OSAHS patient airway; (2) maintaining the measurement accuracy by using the optical index-matching technique; (3) reproducing the oscillatory respiratory flow rates with the compiled clinical data of transient tidal volumes. The in-vitro measurements of oscillatory respiratory flow velocity manifested the time evolution of the complex OSAHS flow patterns, and the potential wall collapse of the ETA model with OSAHS.

Rapid Maxillary Expansion in Obstructive Sleep Apnea in Young Patients: Cardio-Respiratory Monitoring

2017 ◽  
Vol 41 (4) ◽  
pp. 312-316 ◽  
Author(s):  
Alfio Buccheri ◽  
Fabio Chinè ◽  
Giovanni Fratto ◽  
Licia Manzon
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Young Patients ◽  
Rapid Maxillary Expansion ◽  
Respiratory Monitoring ◽  
Respiratory Disorder ◽  
Maxillary Expansion ◽  
Mean Values ◽  
Obstructive Sleep ◽  
The Mean

Objective(s): Obstructive sleep apnea syndrome (OSAS) is a respiratory disorder which affects from 1 to 3 % of people during development. OSAS treatment may be pharmacological, surgical or based on application of intraoral devices to increase nasal respiratory spaces. The purpose of this study was to determine the efficacy of the Rapid Maxillary Expander in OSAS young patients by measuring cardio-respiratory monitoring parameters (AHI, the average value of complete and incomplete obstructed respiration per hour of sleep, and SAO2, the percentage of oxygen saturation). Study design: The study was conducted on 11 OSAS young subjects (mean age 6.9±1.04 years), all treated with rapid maxillary expansion (RME). Cardio-respiratory monitoring (8-channel Polymesam) was performed at the beginning (diagnostic, T0) and after 12 months of treatment. Results: The mean values of cardio-respiratory parameters at TO were: AHI=6.09±3.47; SAO2=93.09%±1.60. After 12 months of treatment, the mean values of the same polysomnographic parameters were: AHI=2.36 ± 2.24;SAO2=96.81% ±1.60. These changes were associated with an improvement in clinical symptoms, such as reduction of snoring and sleep apnea. Conclusion(s): This study confirms the therapeutic efficacy of RME in OSAS young patients. This orthopedic-orthodontic treatment may represent a good option in young patients affected by this syndrome.

scholarly journals Prospects for use of peptides and their derivatives, structurally corresponding to the G protein-coupled receptors, in medicine

2015 ◽  
Vol 61 (1) ◽  
pp. 19-29 ◽  
Author(s):  
A.O. Shpakov ◽  
E.A. Shpakova
Keyword(s):  
G Protein ◽  
Intracellular Signaling ◽  
High Efficiency ◽  
Clinical Medicine ◽  
Inflammatory Diseases ◽  
G Protein Coupled Receptors ◽  
Signaling Cascades ◽  
G Protein Coupled

The regulation of signaling pathways involved in the control of many physiological functions is carried out via the heterotrimeric G protein-coupled receptors (GPCR). The search of effective and selective regulators of GPCR and intracellular signaling cascades coupled with them is one of the important problems of modern fundamental and clinical medicine. Recently data suggest that synthetic peptides and their derivatives, structurally corresponding to the intracellular and transmembrane regions of GPCR, can interact with high efficiency and selectivity with homologous receptors and influence, thus, the functional activity of intracellular signaling cascades and fundamental cellular processes controlled by them. GPCR-peptides are active in both in vitro and in vivo. They regulate hematopoiesis, angiogenesis and cell proliferation, inhibit tumor growth and metastasis, and prevent the inflammatory diseases and septic shock. These data show greatest prospects in the development of the new generations of drugs based on GPCR-derived peptides, capable of regulating the important functions of the organism.

scholarly journals H3K23/H3K36 hypoacetylation and HDAC1 up-regulation are associated with adverse consequences in obstructive sleep apnea patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yung-Che Chen ◽  
Po-Yuan Hsu ◽  
Chien-Hung Chin ◽  
Chang-Chun Hsiao ◽  
Chia-Wei Liou ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Mononuclear Cells ◽  
Gene Promoter ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Reactive Protein ◽  
Primary Snoring ◽  
Obstructive Sleep

AbstractThe aim of this study is to determine the roles of global histone acetylation (Ac)/methylation (me), their modifying enzymes, and gene-specific histone enrichment in obstructive sleep apnea (OSA). Global histone modifications, and their modifying enzyme expressions were assessed in peripheral blood mononuclear cells from 56 patients with OSA and 16 matched subjects with primary snoring (PS). HIF-1α gene promoter-specific H3K36Ac enrichment was assessed in another cohort (28 OSA, 8 PS). Both global histone H3K23Ac and H3K36Ac expressions were decreased in OSA patients versus PS subjects. H3K23Ac expressions were further decreased in OSA patients with prevalent hypertension. HDAC1 expressions were higher in OSA patients, especially in those with excessive daytime sleepiness, and reduced after more than 6 months of continuous positive airway pressure treatment. H3K79me3 expression was increased in those with high C-reactive protein levels. Decreased KDM6B protein expressions were noted in those with a high hypoxic load, and associated with a higher risk for incident cardiovascular events or hypertension. HIF-1α gene promoter-specific H3K36Ac enrichment was decreased in OSA patients versus PS subjects. In vitro intermittent hypoxia with re-oxygenation stimuli resulted in HDAC1 over-expression and HIF-1α gene promoter-specific H3K36Ac under-expression, while HDAC1 inhibitor, SAHA, reversed oxidative stress through inhibiting NOX1. In conclusions, H3K23/H3K36 hypoacetylation is associated with the development of hypertension and disease severity in sleep-disordered breathing patients, probably through up-regulation of HDAC1, while H3K79 hypermethylation is associated with higher risk of cardiovascular diseases, probably through down-regulation of KDM6B.

scholarly journals Pilot study of intracranial venous physiology in craniosynostosis

2018 ◽  
Vol 21 (6) ◽  
pp. 626-631 ◽  
Author(s):  
Martijn J. Cornelissen ◽  
Robbin de Goederen ◽  
Priya Doerga ◽  
Iris Cuperus ◽  
Marie-Lise van Veelen ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pilot Study ◽  
Flow Velocity ◽  
Outpatient Clinic ◽  
Early Stage ◽  
Cerebral Vein ◽  
Type I ◽  
Venous Blood Flow ◽  
Flow Waveform ◽  
Obstructive Sleep

OBJECTIVEIn addition to craniocerebral disproportion, other factors, such as Chiari malformation type I, obstructive sleep apnea, and venous outflow obstruction, are considered to have a role in the occurrence of intracranial hypertension in craniosynostosis. This pilot study examined cerebral venous flow velocity to better characterize the complex intracranial venous physiology of craniosynostosis.METHODSThe authors performed a prospective cohort study of craniosynostosis patients (n = 34) referred to a single national (tertiary) craniofacial unit. Controls (n = 28) consisted of children who were referred to the unit’s outpatient clinic and did not have craniosynostosis. Transfontanelle ultrasound scans with venous Doppler flow velocity assessment were performed at the first outpatient clinic visit and after each surgery, if applicable. Mean venous blood flow velocities of the internal cerebral vein (ICVv) and the superior sagittal sinus (SSSv) were recorded and blood flow waveform was scored.RESULTSPreoperatively, SSSv was decreased in craniosynostosis patients compared with controls (7.57 vs 11.31 cm/sec, p = 0.009). ICVv did not differ significantly between patients and controls. Postoperatively, SSSv increased significantly (7.99 vs 10.66 cm/sec, p = 0.023). Blood flow waveform analyses did not differ significantly between patients and controls.CONCLUSIONSPremature closure of cranial sutures was associated with decreased SSSv but not ICVv; indicating an effect on the superficial rather than deep venous drainage. Further Doppler ultrasound studies are needed to test the hypothesis that at an early stage of craniosynostosis pathology SSSv, but not pulsatility, is abnormal, and that abnormality in both SSSv and the superficial venous waveform reflect a more advanced stage of evolution in suture closure.

Intermittent, Repetitive Corticosteroid-Induced Upregulation of Platelet Levels After Adenovirus-Mediated Transfer to the Liver of a Chimeric Glucocorticoid-Responsive Promoter Controlling the Thrombopoietin cDNA

Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 822-833 ◽  
Author(s):  
Ko Narumi ◽  
Motoyoshi Suzuki ◽  
Wenru Song ◽  
Malcolm A.S. Moore ◽  
Ronald G. Crystal
Keyword(s):  
Clinical Medicine ◽  
Intraperitoneal Administration ◽  
Fold Increase ◽  
Inducible Promoter ◽  
Pharmacologic Agent ◽  
Before And After ◽  
American Society ◽  
Pharmacologic Agents

Abstract For many in vivo gene therapy clinical applications, it is desirable to control the expression of the transferred transgene using pharmacologic agents. To evaluate the feasibility of accomplishing this using corticosteroids, pharmacologic agents widely used in clinical medicine, we constructed replication deficient adenoviral (Ad) vectors containing an expression cassette with a chimeric promoter comprised of five glucocorticoid response elements (GRE) and the chloramphenicol acetyltransferase reporter gene (AdGRE.CAT) or the murine thrombopoietin cDNA (AdGRE.mTPO). In vitro studies showed the vectors functioned as expected, with marked glucocorticoid-induced upregulation of the CAT or mTPO transgenes. To evaluate the inducibility of the GRE promoter in vivo, the AdGRE.CAT vector was administered intravenously to C57B1/6 mice, and CAT activity was quantified in liver before and after intraperitoneal administration of dexamethasone. The GRE promoter activity was dependent on the dexamethasone dose, with a 100-fold increase in CAT expression with 50 μg dexamethasone, similar to the levels observed in vivo with the Rous sarcoma virus long terminal repeat constitutive promoter. After dexamethasone administration, maximum CAT activity was observed at day 2, with a slow decline to baseline levels by 2 weeks. Based on these observations, we hypothesized that a single administration of an Ad vector-mediated transfer of the chimeric GRE inducible promoter driving the mTPO cDNA would enable repetitive administration of corticosteroids to repetitively upregulate platelet levels for 1 to 2 weeks. The data show that this occurs, with dexamethasone administration every 3 weeks associated with 1-week elevations (at each 3-week interval) of serum mTPO levels, megakaryocyte numbers in bone marrow, and platelet levels fourfold to sixfold over baseline. Thus, with the appropriate promoter, it is possible to use a commonly used pharmacologic agent to upregulate the expression of a newly transferred gene on demand. © 1998 by The American Society of Hematology.

Selected Contribution: Improved anoxic tolerance in rat diaphragm following intermittent hypoxia

2001 ◽  
Vol 90 (6) ◽  
pp. 2508-2513 ◽  
Author(s):  
Thomas L. Clanton ◽  
Valerie P. Wright ◽  
Peter J. Reiser ◽  
Paul F. Klawitter ◽  
Nanduri R. Prabhakar
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Intermittent Hypoxia ◽  
Contractile Function ◽  
Myosin Heavy Chain Isoforms ◽  
Adaptive Responses ◽  
Low Frequencies ◽  
Myosin Heavy Chain Isoform ◽  
Obstructive Sleep

Intermittent hypoxia (IH), associated with obstructive sleep apnea, initiates adaptive physiological responses in a variety of organs. Little is known about its influence on diaphragm. IH was simulated by exposing rats to alternating 15-s cycles of 5% O2 and 21% O2 for 5 min, 9 sets/h, 8 h/day, for 10 days. Controls did not experience IH. Diaphragms were excised 20–36 h after IH. Diaphragm bundles were studied in vitro or analyzed for myosin heavy chain isoform composition. No differences in maximum tetanic stress were observed between groups. However, peak twitch stress ( P < 0.005), twitch half-relaxation time ( P < 0.02), and tetanic stress at 20 or 30 Hz ( P < 0.05) were elevated in IH. No differences in expression of myosin heavy chain isoforms or susceptibility to fatigue were seen. Contractile function after 30 min of anoxia (95% N2-5% CO2) was markedly preserved at all stimulation frequencies during IH and at low frequencies after 15 min of reoxygenation. Anoxia-induced increases in passive muscle force were eliminated in the IH animals ( P < 0.01). These results demonstrate that IH induces adaptive responses in the diaphragm that preserve its function in anoxia.

scholarly journals Effect of continuous positive airway pressure treatment on permeability, inflammation and mucus production of human epithelial cells

2020 ◽  
Vol 6 (2) ◽  
pp. 00327-2019
Author(s):  
Sandra Grau-Bartual ◽  
Ahmed M. Al-Jumaily ◽  
Paul M. Young ◽  
Daniela Traini ◽  
Maliheh Ghadiri
Keyword(s):  
Continuous Positive Airway Pressure ◽  
Airway Pressure ◽  
Positive Airway Pressure ◽  
Nasal Congestion ◽  
Positive Pressure ◽  
Cpap Therapy ◽  
Upper Airways ◽  
Mucus Production ◽  
Obstructive Sleep

Continuous positive airway pressure (CPAP) therapy is the gold standard treatment for obstructive sleep apnoea, which affects millions of people worldwide. However, this therapy normally results in symptoms such as dryness, sneezing, rhinorrhoea, post-nasal drip, nasal congestion and epistaxis in the upper airways.Using bronchial epithelial (Calu-3) and nasal epithelial (RPMI 2650) cells in an in vitro respiratory model, this study, for the first time, investigates the effect of CPAP positive pressure on the human respiratory epithelial mechanisms that regulate upper airways lubrication characteristics. To understand how the epithelium and mucus are affected by this therapy, several parameters were determined before and after positive pressure application.This work demonstrates that the positive pressure not only compresses the cells, but also reduces their permeability and mucus secretion rate, thus drying the airway surface liquid layer and altering the mucus/water ratio. It is also observed that the respiratory epithelia is equally inflamed without or with external humidification during CPAP application.These findings clearly identify the causes of the side-effects reported by patients under CPAP therapy.

Derivation of human embryonic stem cell lines after blastocyst microsurgery

2010 ◽  
Vol 88 (3) ◽  
pp. 479-490 ◽  
Author(s):  
Guoliang Meng ◽  
Shiying Liu ◽  
Xiangyun Li ◽  
Roman Krawetz ◽  
Derrick E. Rancourt
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Cell Lines ◽  
Clinical Medicine ◽  
Inner Cell Mass ◽  
Cell Mass ◽  
Embryonic Stem ◽  
Hesc Lines

Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of the blastocyst. Because of their ability to differentiate into a variety of cell types, human embryonic stem cells (hESCs) provide an unlimited source of cells for clinical medicine and have begun to be used in clinical trials. Presently, although several hundred hESC lines are available in the word, only few have been widely used in basic and applied research. More and more hESC lines with differing genetic backgrounds are required for establishing a bank of hESCs. Here, we report the first Canadian hESC lines to be generated from cryopreserved embryos and we discuss how we navigated through the Canadian regulatory process. The cryopreserved human zygotes used in this study were cultured to the blastocyst stage, and used to isolate ICM via microsurgery. Unlike previous microsurgery methods, which use specialized glass or steel needles, our method conveniently uses syringe needles for the isolation of ICM and subsequent hESC lines. ICM were cultured on MEF feeders in medium containing FBS or serum replacer (SR). Resulting outgrowths were isolated, cut into several cell clumps, and transferred onto fresh feeders. After more than 30 passages, the two hESC lines established using this method exhibited normal morphology, karyotype, and growth rate. Moreover, they stained positively for a variety of pluripotency markers and could be differentiated both in vitro and in vivo. Both cell lines could be maintained under a variety of culture conditions, including xeno-free conditions we have previously described. We suggest that this microsurgical approach may be conducive to deriving xeno-free hESC lines when outgrown on xeno-free human foreskin fibroblast feeders.

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