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Liponax® sol, A Patented Food Supplement in Liquid Dosage Form: Study of Pharmacokinetics Parameters of R-α-Lipoic Acid in Healthy Volunteers Liponax®溶胶,一种液体剂型的专利食品补充剂:健康志愿者中R-α-硫辛酸的药代动力学参数研究
Pub Date : 2021-03-15 DOI: 10.19080/oajt.2021.05.555651
Nicola D'Anzi
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引用次数: 0
Further studies in translatable model systems are needed to predict the impacts of human microplastic exposure. 需要在可转化的模型系统中开展进一步研究,以预测人类接触微塑料的影响。
Pub Date : 2020-06-01 Epub Date: 2020-06-05
Sarah E Morgan, Lisa A DeLouise

Microplastics are a pervasive environmental contaminant that have been found in many media including water sources, soils, and foodstuff. Due to the worldwide presence and persistence of microplastic debris, human exposure is inevitable. Human exposure occurs predominantly through ingestion, although dermal and inhalation exposures are probable. Microplastic single exposure studies in aquatic species and fish have shown various toxic effects including those on reproduction and survival. In addition to potential intrinsic toxicity, microplastics often have chemicals adsorbed to their surfaces. Studies report that these chemicals can have innate toxicity that is modulated by the composition of microplastics. Both the impacts of microplastics alone and co-exposures with adsorbed chemicals exhibit size dependent effects. Analysis of the current literature has revealed published studies predominantly investigate the toxicity of microplastic exposure in fish and other aquatic species, with limited knowledge about the effects in mammals and cell lines. Toxicity has been shown to vary widely between taxonomic groups, suggesting inferring human health relevance will require model systems where human routes of exposure can be mimicked. Although it may be difficult to extrapolate the results from aquatic model systems to relevant human health impacts, they may suggest effects to investigate. In order to best estimate the short- and long-term impacts of human microplastic exposure, it is imperative that studies in model systems with increased similarity to human anatomy and cellular processes be done.

微塑料是一种普遍存在的环境污染物,在水源、土壤和食品等多种介质中都有发现。由于微塑料碎片在全球范围内的存在和持久性,人类不可避免地会接触到它们。人类主要通过摄入接触微塑料碎片,但也可能通过皮肤和吸入接触微塑料碎片。对水生物种和鱼类进行的微塑料单次接触研究显示了各种毒性影响,包括对繁殖和存活的影响。除了潜在的内在毒性外,微塑料表面通常还吸附有化学物质。研究报告称,这些化学物质可能具有先天毒性,并受微塑料成分的影响。无论是单独接触微塑料还是与吸附的化学物质共同接触,其影响都与尺寸有关。对现有文献的分析表明,已发表的研究主要调查微塑料暴露对鱼类和其他水生物种的毒性,对哺乳动物和细胞系的影响了解有限。不同分类群组之间的毒性差异很大,这表明要推断与人类健康的相关性,需要模拟人类接触途径的模型系统。虽然很难将水生模型系统的结果推断为对人类健康的相关影响,但它们可能会提出一些需要研究的影响。为了最好地估计人类接触微塑料的短期和长期影响,必须在与人体解剖结构和细胞过程更加相似的模型系统中进行研究。
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引用次数: 0
Inappropriate Use of Risk Assessment in Addressing Health Hazards Posed by Civil Aircraft Cabin Air 在处理民用飞机客舱空气构成的健康危害时不适当使用风险评估
Pub Date : 2020-02-27 DOI: 10.19080/OAJT.2020.04.555634
Howard Cv
Toxicological reviews of data on Aerotoxic Syndrome that have been widely referenced by the airline industry tend to use a toxicological endpoint, Organo-Phosphate Induced Neuropathy (OPIDN), that is acknowledged to be the result of a very high dose of organophosphate exposure. Additionally, the reviews tend to only address one chemical, Tri-Ortho Cresyl Phosphate (TOCP), ignoring the presence of other toxic compounds in a complex mixture. In using this to justify the safety of the continued use of unfiltered engine bleed air to ventilate civil aircraft cabins, this represents a misuse of toxicological risk assessment. The approach totally ignores the scientific literature on repeated low-dose exposure to OPs over extended periods, the constant presence of a complex mixture of OPs in engine bleed air and their overall toxicity and the variable susceptibility of individuals to toxicological damage. This paper lists the above-mentioned studies and reviews a sub-set. We present the scientific literature that should be considered to make a realistic risk assessment of the hazards of aircraft engine bleed air.
航空工业广泛引用的航空中毒综合征数据的毒理学审查倾向于使用一个毒理学终点,即有机磷诱导的神经病变(OPIDN),这被认为是非常高剂量的有机磷暴露的结果。此外,这些评论往往只涉及一种化学物质,三邻甲酰磷酸(TOCP),而忽略了复杂混合物中其他有毒化合物的存在。用这一点来证明继续使用未经过滤的发动机引气给民用飞机机舱通风的安全性,这是对毒理学风险评估的误用。这种方法完全忽略了科学文献关于长时间重复低剂量暴露于有机磷化合物、发动机引气中持续存在的复杂有机磷化合物混合物及其总体毒性以及个体对毒理学损害的不同易感性。本文列举了上述研究,并对其中的一个子集进行了综述。我们提出了对飞机发动机引气危害进行现实风险评估时应考虑的科学文献。
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引用次数: 6
Transdermal Methimazole for Feline Hyperthyroidism 甲巯咪唑透皮给药治疗猫甲状腺功能亢进症
Pub Date : 2019-08-19 DOI: 10.19080/oajt.2019.04.555630
Pilar Z Murphy
Hyperthyroidism is a common disorder in older cats causing detrimental adverse effects if left untreated. The three most recommended treatment options include thyroidectomy, radioiodine treatment, and antithyroid medication therapy. Oral methimazole has been the most widely used option due to low cost and accessibility. The topical application of transdermal methimazole is an ideal route of administration for cat owners. The purpose of this review article is to give insight into the efficacy and recommended indication for use of the pluronic lecithin organogel (PLO) formulated transdermal delivery system of methimazole, in the treatment of feline hyperthyroidism. PLO compounded methimazole is uniquely transported through the skin, and chronic use has been shown effective in treating feline hyperthyroidism. In many cases, once daily application of the gel has provided enough methimazole activity for lowering hormone levels. The compounded formulation also allows for more individualized dosing than the oral tablets. There is limited information regarding long-term treatment of PLO methimazole, however, the formulation continues to satisfy both veterinarians and owners, and effectively lower serum thyroxine (T4) concentrations.
甲状腺机能亢进是老年猫的一种常见疾病,如果不及时治疗,会造成有害的不良影响。三种最推荐的治疗方案包括甲状腺切除术、放射性碘治疗和抗甲状腺药物治疗。口服甲巯咪唑由于成本低和可及性而成为最广泛使用的选择。局部应用透皮甲巯咪唑是一个理想的途径,管理猫的主人。这篇综述文章的目的是深入了解多元卵磷脂有机凝胶(PLO)配制的甲巯咪唑透皮给药系统治疗猫甲状腺机能亢进的疗效和推荐适应症。PLO复合甲巯咪唑是独特的通过皮肤运输,长期使用已被证明对治疗猫甲状腺功能亢进有效。在许多情况下,一旦每天应用凝胶提供了足够的甲巯咪唑活性,以降低激素水平。复合制剂也允许比口服片剂更个体化的给药。关于PLO甲巯咪唑长期治疗的信息有限,然而,该配方继续满足兽医和饲主,并有效降低血清甲状腺素(T4)浓度。
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引用次数: 0
Anti-Contractile Mechanism of Resveratrol in Non-Vascular Smooth Muscle Under α1Adrenoceptor Stimulation involves IP3 Receptor, Protein Kinase-C and NADPH Oxidase α - 1肾上腺素受体刺激下白藜芦醇在非血管平滑肌中的抗收缩机制涉及IP3受体、蛋白激酶- c和NADPH氧化酶
Pub Date : 2019-04-08 DOI: 10.19080/oajt.2019.04.555627
Carolina Baraldi Araujo Restini
con-Abstract Reactive oxygen species (ROS) are products from enzymatic systems that are responsible for several biological disturbances when uncontrolled. Superoxide anion (O 2- ), increases intracellular calcium-regulated contractile/relaxation responses in smooth muscles. Activation of α1-adrenoceptors promotes these contractions through the Gq pathway involving protein kinase C (PKC) and calcium mobilization. It has been reported that Gq pathway is related to ROS production. It has also been shown that resveratrol (RESV), an antioxidant agent, decreases vascular smooth muscle contraction. The effect of RESV was not yet demonstrated in the anococcygeus smooth muscle contraction. Since ROS are present in rat anococcygeus smooth muscle and RESV has an antioxidant effect, the hypothesis for the current work is that the contractile response, under α1-adrenoceptor stimulation, can be decreased by RESV through decreasing ROS production related to the pathways of PKC and calcium mobilization. Thus, the aims were to investigate if the RESV interferes with the non-vascular smooth muscle contractile reactivity stimulated by the α1-adrenoceptor agonist, phenylephrine (PE) and to analyze its potential mechanisms. Anococcygeus smooth muscles were isolated from male Wistar rats and placed in organ baths to evaluate isometric tension. RESV enhanced the decreased contractions after incubation with α1-adrenoceptor and IP3-receptor (RIP3) antagonists as well as PKC and NADPH oxidase inhibitors. Under α1-adrenoceptor stimulation, the anococcygeus smooth muscle contractions are indeed related to the pathway of ROS production, involving inhibition of Ca 2+ mobilization, PKC activation and NADPH oxidase that are all sensitive to RESV.
活性氧(ROS)是酶系统的产物,当不受控制时,它会引起几种生物干扰。超氧阴离子(o2 -),增加细胞内钙调节的平滑肌收缩/松弛反应。α - 1肾上腺素受体的激活通过Gq途径促进这些收缩,该途径涉及蛋白激酶C (PKC)和钙动员。有报道称Gq通路与ROS的产生有关。研究还表明,白藜芦醇(RESV),一种抗氧化剂,可以减少血管平滑肌收缩。RESV在无尾肌平滑肌收缩中的作用尚未得到证实。由于大鼠无尾肌平滑肌中存在ROS,而RESV具有抗氧化作用,本研究假设RESV可通过减少与PKC和钙动员通路相关的ROS生成,从而降低α - 1肾上腺素能受体刺激下的收缩反应。因此,目的是研究RESV是否干扰α - 1肾上腺素受体激动剂苯肾上腺素(PE)刺激的非血管平滑肌收缩反应性,并分析其潜在机制。从雄性Wistar大鼠中分离出肛门尾骨平滑肌,置于器官浴中评估等长张力。RESV与α - 1肾上腺素受体、ip3受体(RIP3)拮抗剂以及PKC和NADPH氧化酶抑制剂孵育后,增强了收缩功能的减弱。在α - 1肾上腺素能受体刺激下,ano尾肌平滑肌收缩确实与ROS的产生途径有关,涉及对RESV敏感的ca2 +动员、PKC激活和NADPH氧化酶的抑制。
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引用次数: 1
Safe and Effective Dosing of Over-The-Counter Melatonin use for Sleep Disturbances in Children with Autism: A Literature Review 非处方褪黑素治疗自闭症儿童睡眠障碍的安全有效剂量:文献综述
Pub Date : 2019-02-12 DOI: 10.19080/oajt.2019.03.555624
Pilar Z Murphy
With the increasing prevalence of autism, it is important to identify if the over-the-counter (OTC) melatonin use for sleep disorders in autistic children is safe and effective. Since there are no FDA-approved medications for children with insomnia, this literature review aims to cast helpful insight for caregivers and physicians concerning the safe and effective use of OTC melatonin in autistic children for sleep disturbance relief. PubMed, International Pharmaceutical Abstracts (IPA), and Google Scholar were utilized in the search for studies for this literature review. Two randomized placebo-controlled crossover trials, one randomized placebo-controlled clinical trial, and two open-label trials were looked at for dosage strength, efficacy, and safety. From these trials, melatonin use seems effective and safe within the dosing ranges of 1mg to 10mg. Titration may be needed in some children depending upon if they are a slow or fast metabolizer of melatonin. Improvements in sleep and in behavior were documented. Therefore, melatonin is seemingly safe and effective in helping autistic children with sleep disturbances by helping them go to sleep faster and stay asleep longer, thus giving them a better night’s rest. Children Sleep Habits Questionnaire
随着自闭症患病率的增加,确定非处方(OTC)褪黑激素用于治疗自闭症儿童睡眠障碍是否安全有效是很重要的。由于没有fda批准的治疗失眠症儿童的药物,本文献综述旨在为护理人员和医生提供有关安全有效地在自闭症儿童中使用OTC褪黑激素缓解睡眠障碍的有用见解。本文献综述使用PubMed, International Pharmaceutical Abstracts (IPA)和谷歌Scholar检索研究。两项随机安慰剂对照交叉试验、一项随机安慰剂对照临床试验和两项开放标签试验对剂量强度、疗效和安全性进行了研究。从这些试验来看,褪黑素在1mg到10mg的剂量范围内似乎是有效和安全的。一些儿童可能需要根据他们是褪黑激素的缓慢代谢者还是快速代谢者而进行滴定。睡眠和行为的改善被记录在案。因此,褪黑素在帮助患有睡眠障碍的自闭症儿童方面似乎是安全有效的,它能帮助他们更快入睡,保持更长时间的睡眠,从而让他们在晚上得到更好的休息。儿童睡眠习惯问卷
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引用次数: 0
Sustainable Ship Recycling Methods and Process for Global Major Ship Recycling Players 全球主要船舶回收参与者的可持续船舶回收方法和流程
Pub Date : 2018-11-15 DOI: 10.19080/oajt.2018.03.555622
Khandakar Akhter Hossain
The world-wide ship recycling industry dismantles around 1,000 large ocean-going vessels per year, such as container ships, cargo & bulkers, oil & gas tankers (LNG, LPG), passenger ships and other types of ships, to recover steel and other valuable metals or recyclable items[1]. However, at present almost all ship recycling activities are concentrated in five countries: the three South East Asian countries (India, Bangladesh, and Pakistan), China, and Turkey[2]. Further capacity is available in North America (US, Canada, Mexico) and within the European Union (amongst others Denmark, Belgium and UK). At present, South East Asia is undoubtedly the global center for ship recycling activities.South East Asia contributes to more than ninety percent of global ship recycling activities[3]. Countries such as Pakistan, India, Bangladesh and China are the major ship recycling player and centers of the world.
全球船舶回收行业每年拆除约1000艘大型远洋船舶,如集装箱船、货物和散货船、石油和天然气油轮(LNG、LPG)、客船和其他类型的船舶,以回收钢铁和其他贵重金属或可回收物品[1]。然而,目前几乎所有的船舶回收活动都集中在五个国家:东南亚三国(印度、孟加拉国和巴基斯坦)、中国和土耳其[2]。北美(美国、加拿大、墨西哥)和欧盟(丹麦、比利时和英国等国)还有更多产能。目前,东南亚无疑是全球船舶回收活动的中心。东南亚对全球船舶回收活动的贡献率超过90%[3]。巴基斯坦、印度、孟加拉国和中国等国是主要的船舶回收参与者和世界中心。
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引用次数: 0
An Improved Method to Conjugation of KLH-Diazinon 一种改进的klh -二嗪酮偶联方法
Pub Date : 2018-11-15 DOI: 10.19080/oajt.2018.03.555621
M. Sankian
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引用次数: 0
Is Brca-Associated Protein (Bap1) A New Drug Target to Combat Metastatic Uveal Melanoma? brca相关蛋白(Bap1)是治疗转移性葡萄膜黑色素瘤的新药物靶点吗?
Pub Date : 2018-09-10 DOI: 10.19080/oajt.2018.03.555619
Rhonda J Rosengren
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引用次数: 1
On the Adverse Effects of Glibenclamide Administration 格列本脲给药的不良反应
Pub Date : 2018-08-24 DOI: 10.19080/oajt.2018.03.555618
Olga V Akopova
Glibenclamide (glyburide) is a sulfonylurea derivative, N-p[2-(5-Chloro-2-methoxybenzamido) ethyl] benzene sulfonylN′-cyclohexylurea (C23H28ClN3O5S), which is widely used as a blocker of ATP-sensitive potassium channels (KATP channels) ubiquitously present in plasma membranes and mitochondria. KATP channel is an octameric multiprotein complex that comprises four pore-forming Kir subunits, which are inwardrectifier K+ channels, and four sulfonylurea receptors (SUR) [1]. Molecular composition of mitochondrial KATP channel (mKATP) channel remains yet undisclosed and the most part of the notions on the properties of mKATP channel was obtained from the studies on plasmalemmal KATP channels. It is known that glibenclamide binds to SUR subunits to block KATP channel [1,2]. SUR subunit of KATP channel belongs to ATP binding cassette proteins that bind ATP upon its hydrolysis [1-3]. MgATPase activity of SUR subunits is thought to be required for KATP channel functioning, its activation by KATP channels openers and the channel blockage by glibenclamide [3]. The same mechanism is supposed to underlie KATP channel blockage in mitochondria. Generally, no blockage of KATP channels was observed either in the absence of MgATP, or in the presence of Mg2+ or ATP alone [4,5]. Glibenclamide binds to mKATP channels with high affinity, however values of Ki (~1-6 μM [4]) obtained for mKATP channels were by the order higher than inhibition constants obtained for sKATP channels [1]. This was used by Garlid’s group for semiquantitative estimation of the density of mKATP channels in mitochondria from various tissues with fluorescent glibenclamide derivative [6]. Glibenclamide is a widely applied antidiabetic drug, known to stimulate insulin release by blocking sKATP channels in betacells. However, the application of sulfonylureas (glibenclamide and tolbutamide) produced adverse effects in heart and brain, such as increased cardiovascular mortality in patients with diabetes [7], and increased neurodegeneration after hypoxic brain injury [8]. In our work we observed one of the adverse effects of glibenclamide application in vivo caused by the direct effects of this drug on mitochondrial functions.
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引用次数: 1
期刊
Open access journal of toxicology
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