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   Table of Contents - Current issue
October-December 2019
Volume 9 | Issue 4
Page Nos. 170-240

Online since Monday, December 30, 2019

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Nitric oxide p. 170
Zhi-Lu Yang, Qiang Zhao, Qianjun He
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Effects of nitric oxide donor N,N’-di-sec-butyl-N,N’-dinitroso-1,4-phenylenediamine on the expression of interferon-gamma in tumor infiltrating lymphocytes p. 171
Jing Fan, Zhen Gao, De-Peng Zhao, Ping Wang, Zheng-Zhong Wu, Xue-Mei Li
Nitric oxide (NO) has been proven to be a key regulator in the mammalian immune response, such as the innate and adaptive immune responses to tumors. The messenger NO involves T helper cell differentiation and lymphocyte biofunctions. In this study, we employed N,N’-di-sec-butyl-N,N’-dinitroso-1,4-phenylenediamine as NO donor and released NO around tumor infiltrating lymphocytes in vitro by short-time blue light irradiation. The interferon-γ secretion of tumor infiltrating lymphocytes was investigated to study the functional changes caused by the accurate spatio-temporal delivery of NO. The downregulation of interferon-γ in tumor infiltrating lymphocytes after NO treatment indicates promising biological applications to potentially play a role in the treatment of autoimmune diseases. The study was approved by the Medical Ethics Committee of the Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, China (approved No. 065) on February 12, 2018.
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Micelle-embedded coating with ebselen for nitric oxide generation p. 176
Li Yang, Lin-Hua Li, Lu Jiang, Jun-Qiang Pan, Ri-Fang Luo, Yun-Bing Wang
Nitric oxide generation is considered to be a key factor to mimic endothelial function in terms of anti-coagulation and anti-hyperplasia. Herein, ebselen which could play the similar role as glutathion peroxidase-like was loaded into micelles and was further assembled into a layer-by-layer coating. The ability of nitric oxide generation and corresponding biological effect were investigated. Endothelial-mimetic surface has now attracted huge attention in blood-contacting materials, due to its inherent ability of secreting nitric oxide. Among those categories, nitric oxide generation surface is considered to be safe and tunable in the modification of vascular biomedical devices. How to adsorb or immobilize glutathion peroxidase-like catalyst and maintain sustained/safe nitric oxide generation is full of interest. This study aimed at developing a functional coating constructed via layer-by-layer assembly to introduce the catalyst into the coating by pre-loading ebselen in micelles. We firstly introduced phenylboronic acid moiety into the micelle molecule backbone and grafted catechol moiety to chitosan backbone. Then, chitosan, micelles (containing ebselen) and heparin were adopted as polyelectrolytes and then alternatively assembled onto the substrate via layer-by-layer protocol. The catechol was conjugated to the amine groups of chitosan by Schiff base reaction to synthesize chitosan-catechol. The hydrophobic cholesterol was conjugated to the one end of the hydrophilic hyaluronic acid, and the hydroxymethylphenylboronic acid was conjugated to the other end via the esterification of carboxyl (–COOH) and hydroxyl (–OH). The modified hyaluronic acid could spontaneously form micelles in aqueous solution. Ebselen was the loaded into the as-prepared micelles. Chitosan-catechol, heparin, and micelles were alternatively assembled onto the substrate layer by layer to form a micelle-embedded coating. The micelle-embedded coating with ebselen was successfully obtained and the nitric oxide generation ability was in a safe level which was close to healthy endothelial cells. The coating could effectively inhibit platelet adhesion and smooth muscle cell proliferation. The use of ebselen preloaded into micelles could provide a sustained release of catalyst for in situ nitric oxide generation. Besides, this method could also be used to load diverse drugs and regulate desired properties. The study was approved by the Institutional Review Board of the West China Hospital in Sichuan University on March 3, 2018, with approval No. K2018044.
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Recent developments in nitric oxide-releasing biomaterials for biomedical applications p. 184
Han Yu, Lin-Xian Cui, Nan Huang, Zhi-Lu Yang
Nitric oxide (NO) is an endogenous gas with several physiological activities. Owing to the NO physiological functions, such as inhibition of platelet aggregation and adhesion, vascular muscle relaxation, modulation of inflammation and immune response, antibacterial and anticancer activity, increasing attensions have been paid to the development of biomaterials with the ability to release this medical gas. Nowadays, numerous prodrugs have been developed to release NO in vivo. However, due to the low payloads and non-controlled delivery of the prodrug, the NO-releasing devices do not fulfil the expectations, which restricts their widespread application. Recently, several methods have been proposed to address the issue above, including physical and chemical methods and specific designs. This review aims to briefly introduce the latest achievements with recent 3 years involving coatings which mimic the vascular endothelium to treat atherosclerosis, nanocarriers which generate NO for a sustained anticancer treatment, and a framework which modifies the prodrug as a stable cardiovascular stent or as an anticancer targeted drug.
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Nitric oxide detection methods in vitro and in vivo p. 192
Ekta Goshi, Gaoxin Zhou, Qianjun He
Initially being considered as an environmental pollutant, nitric oxide has gained the momentum of research since its discovery as endothelial derived growth factor in 1987. Extensive researches have revealed the various pathological and physiological roles of nitric oxide such as inflammation, vascular and neurological regulation functions. Hence, the development of methods for quantifying nitric oxide concentration and its metabolites will be beneficial to well know about its biological functions and effects. This review summaries various methods for in vitro and in vivo nitric oxide detection, and introduces their merits and demerits.
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Respiratory effects of occupational exposure to low concentration of hydrochloric acid among exposed workers: a case study in steel industry p. 208
Hamidreza Heidari, Abolfazl Mohammadbeigi, Ahmad Soltanzadeh, Mohadese Darabi, Mahdi Asadi-Ghalhari
Occupational exposure to hydrochloric acid in pickling of steel for remove rust or iron oxide scale from iron processing occurs at low concentration. This study aimed to investigate the respiratory symptoms and pulmonary dysfunction caused by exposure to low concentration of hydrochloric acid in acid washing unit in one of the steel industries. A case control study was carried out in the acid washing unit of the cold rolling of the steel industry in 2017. The exposed group included 45 male workers, and another 41 unexposed employees from official employees were enrolled as control group. A questionnaire was used to collect personal and occupational data and pulmonary function tests, including forced vital capacity (FVC), forced expiratory volume in the first second and peak expiratory flow rate followed guidelines given by the American Thoracic Society and measured with a portable calibrated vitalograph spirometer. For determination of acid concentration, 21 breathing zone air samples were collected in accordance with Method 7903 NIOSH. The findings showed that nose sensitivity, throat irritation and shortness of breath were the highest prevalence symptoms among exposed persons (30.4% to 32.6%). Also, the results showed that FVC and forced expiratory volume in the first second had highest and direct or positive correlation with height (0.965 and 0.927, respectively). Age and weight put in the next priorities (P < 0.01). On the other hand, based on the results of multivariate linear regression, exposing to the acid and job history are two main predictor factors for FVC. So that, the exposing to acid, by itself can reduce FVC as 4.386 units. This value is equal to 1.117 for the job history. Exposure to low concentrations of hydrochloric acid alone could increase the risk of respiratory tract damage and pulmonary function disorders. But the extent to which it can cause respiratory complications for occupational exposure is still unknown and requires further study. This study was approved by Ethical Committee of Qom University of Medical Sciences (approval No. IR.MUQ.REC.1397.118) on November 6, 2018.
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Numerical analysis of mechanical ventilation using high concentration medical gas mixtures in newborns p. 213
Ira Katz, Aude Milet, Matthieu Chalopin, Géraldine Farjot
When administered in relatively high concentrations the mechanical properties of inhaled gas can become significantly different from air. This fact has implications in mechanical ventilation where adequate respiration and injury to the lungs or respiratory muscles can worsen morbidity and mortality. Here we use an engineering pressure loss model to analyze the administration of medical gas mixtures in newborns. The model is used to determine the pressure distribution along the gas flow path. Numerical experiments comparing medical gas mixtures with helium, nitrous oxide, argon, xenon, and medical air as a control, with and without an endotracheal tube obstruction were performed. The engineering pressure loss model was incorporated into a model of mechanical ventilation during pressure control mode, a ventilator mode that is often used for neonates. Results are presented in the form of Rohrer equations relating pressure loss to flow rate for each gas mixture with and without obstruction. These equations were incorporated into a model for mechanical ventilation resulting in pressure, flow rate, and volume curves for the inhalation-exhalation cycle. In terms of accuracy, published values of airway resistance range from 50 to 150 cmH2O/L per second for a normal 3 kg infant. With air, the current results are 55 to 80 cmH2O/L per second for 0.3 to 5 L/min. It is shown that density through inertial pressure losses has a greater influence on airway resistance than viscosity in spite of relatively low flow rates and small airway dimensions of newborns. The results indicate that the high-density xenon mixture can be problematic during mechanical ventilation. On the other hand, low density heliox (a mixture of helium and oxygen) provides a wider margin of safety for mechanical ventilation than the other gas mixtures. The argon or nitrous oxide mixtures considered are only slightly different from air in terms of mechanical ventilation performance.
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The role of medical gas in stroke: an updated review p. 221
Ze-Yu Zhang, Yuan-Jian Fang, Yu-Jie Luo, Cameron Lenahan, Jian-Ming Zhang, Sheng Chen
Medical gas is a large class of bioactive gases used in clinical medicine and basic scientific research. At present, the role of medical gas in neuroprotection has received growing attention. Stroke is a leading cause of death and disability in adults worldwide, but current treatment is still very limited. The common pathological changes of these two types of stroke may include excitotoxicity, free radical release, inflammation, cell death, mitochondrial disorder, and blood-brain barrier disruption. In this review, we will discuss the pathological mechanisms of stroke and the role of two medical gases (hydrogen and hydrogen sulfide) in stroke, which may potentially provide a new insight into the treatment of stroke.
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The role of oxygen in cluster headache p. 229
Xiao-Ning Guo, Jia-Jie Lu, Jian-Qiang Ni, Hai-Feng Lu, Hong-Ru Zhao, Gang Chen
High-flow oxygen inhalation is one of the most effective acute treatments for cluster headache. The therapy was first described for the treatment of cluster headache in 1952 by Horton, and has exhibited some advantages and efficacy compared to other acute medicines. The mechanism is not very clear, but some evidence has demonstrated its relationship to the trigeminovascular system and neuroinflammation. High-flow oxygen inhalation via a non-rebreather mask during cluster headache attacks has been widely recommended. Patients with frequent attacks and/or intolerance to drugs may prefer the oxygen treatment.
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Ozone and oxidation therapies as a solution to the emerging crisis in infectious disease management: a review of current knowledge and experience Highly accessed article p. 232
Robert Jay Rowen
Medicine faces crisis with emerging “super bugs,” lethal viruses (Ebola), and stealth pathogens such as tick-borne infections. Thousands are dying worldwide of once easily treatable diseases. Ozone therapy, extensively studied, may be a valuable adjunctive or stand-alone therapy. Ebola again ravages Africa with over 2000 already dead, carrying a 65% mortality rate. The world desperately needs safe, inexpensive and effective anti-infective therapy to which microbes will not develop resistance. Oxidation therapies have shown an extremely high safety profile, lacking credible reports of significant injury beyond vein irritation. Ozone therapy, the most studied and least expensive to perform, is in itself a germicide, not an antibiotic, and improves several physiological parameters essential for infection defense. Recent reports indicate very favorable responses to both bacterial and viral disease, inclusive of Ebola. Despite lack of commercial profitability (not patentable), medicine would do well to revisit its pre-antibiotic era oxidation therapy roots, especially ozone in the current crisis.
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Revisiting the expanded use of hyperbaric oxygen therapy for treatment of resistant migraines p. 238
David V Matera, Brian Smith, Benjamin Lam
There are currently 13 indications approved by the U.S. Food and Drug Administration for use of hyperbaric oxygen therapy. The European Consensus Conference on Hyperbaric Medicine has 28 indications approved for its use. However, neither includes the use of hyperbaric oxygen therapy for neurological conditions such as migraines with aura. Recent research has made the attempt to fully understand the use of hyperbaric therapy in treatment of neurological conditions, but results have so far been inconclusive. We report a 23-year-old female with an 11-year history of migraines with aura who has received inadequate pharmacological treatment for her migraines since she began having them. Migraines have led her to significant loss of function. The patient underwent treatment at 1.5 absolute atmospheres in a hyperbaric chamber Monday through Friday for 1 hour each day for a total of 40 sessions but reported missing a few sessions over the 8-week period. No more than 1 session during a given week was missed and the patient received no other treatments for her migraines throughout this time period. By her 24th treatment, the patient had only experienced a single migraine with aura but without debilitating pain. The patient stated she had never had a migraine with such little intensity prior to initiation of hyperbaric treatment and did not have to take any days off from work or school. Follow-up at the end of her 40-day treatment period revealed a highly-satisfied patient who had only experienced the single episode of a mild migraine during the entire course of treatment. Thus, we believe that further research needs to be done to realize the full potential of hyperbaric oxygen therapy in the treatment of neurological conditions as this case highlights the potential for using hyperbaric oxygen therapy as prophylaxis against attacks in patients with treatment resistant migraines with aura.
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Correction: Preventing explosions of hydrogen gas inhalers  

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