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Experimental Cardiac Toxicity Induced by the Injection of Uracoan Rattlesnake (Crotalus vegrandis) and the Black Rattlesnake (Crotalus pifanorum) Venoms Uracoan rattlesake (Crotalus vegrandis)和黑响尾蛇(Crotalus pifanorum)毒液注射对心脏毒性的实验研究
Pub Date : 2022-12-30 DOI: 10.17140/tfmoj-7-139
D. Colombet, Roger Rivas-Calero, Leiser Salcedo, M. Riera, A. Mogollón, José Mendoza, A. Rodríguez-Acosta, H. Rodríguez-Angulo
Background Snakebite is a collective health problem that afflicts areas with poor healthcare coverage. Venezuela has an important population of snakes, including the endemic species Crotalus vegrandis and Crotalus pifanorum, whose venom has not been fully characterized, especially of those aspects related to cardiac electrophysiology. Aims In this sense, this work aims to characterize the electrocardiographic and histopathological effect of crude venom of C. vegrandis and C. pifanorum on albino Naval Medical Research Institute (NMRI) mice. Results For this, mice were gathered in C. pifanorum and C. vegrandis experimental groups, including normal controls and envenomed mice injected with commercial antivenom. C. vegrandis venom showed a significant T and S wave flattening and pulmonic (pulmonary) regurgitation (PR) enlargement, in addition to atrial ectopic activity, notched R wave, triggered activity, and T wave inversion. C. pifanorum was the only group that registered triggered activity. Antivenom was able to revert conduction disorders showing a statistical increase in arrhythmogenic compared by χ2 . The multidimensional comparison confirmed the statistical differences between C. vegrandis and C. pifanorum venoms and between antivenom vs non-antivenom groups, detecting variables associated with cardiac conduction, as the most important variables. Conclusion In conclusion, this work demonstrated, as far as we know, for the first time the cardiotoxic effects associated with C. vegrandis and C. pifanorum venom injection, subsequently suggesting the duty of including an electrocardiogram in the consultation of any accident caused by these species.
蛇咬伤是一种集体健康问题,困扰着医疗保险覆盖面较差的地区。委内瑞拉有一个重要的蛇种群,包括特有物种Crotalus vegrandis和Crotalus pifanorum,其毒液尚未完全表征,特别是与心脏电生理有关的那些方面。目的在此基础上,研究黄颡鱼和皮棘鱼粗毒液对美国海军医学研究所(Naval Medical Research Institute, NMRI)白化小鼠的心电图和组织病理学影响。结果本实验将小鼠分为pifanorum实验组和C. vegrandis实验组,包括正常对照组和注射商业抗蛇毒血清的中毒小鼠。维氏蛇毒具有明显的T波、S波扁平化、肺返流(PR)增大、心房异位活动、R波切迹、触发活动和T波倒置等特点。皮棘菊是唯一有触发活性的组。抗蛇毒血清能够恢复传导障碍,显示心律失常发生的统计学增加。多维度比较证实了C. vegrandis和C. pifanorum毒液之间以及抗蛇毒血清组和非抗蛇毒血清组之间的统计学差异,检测到与心脏传导相关的变量是最重要的变量。总之,据我们所知,本研究首次证明了维氏锥虫和皮法诺锥虫毒液注射对心脏的毒性作用,从而提示在对这些物种引起的任何事故进行会诊时应包括心电图检查。
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引用次数: 0
Immunotoxic Effects of Cypermethrin in Male Wistar Rats: Attenuation by Co-Administration of Zinc and Alpha-Lipoic Acid 氯氰菊酯对雄性Wistar大鼠的免疫毒性作用:锌和α -硫辛酸共同给药的衰减作用
Pub Date : 2021-12-31 DOI: 10.17140/tfmoj-6-135
A. Paramanik, A. D. Chaudhuri, Barun Chakraborty, Dibyendu Giri, A. Majumder, D. Chatterjee, A. Pradhan, P. Maiti, S. Choudhury
Aim The present study investigated the effects of cypermethrin exposure on humoral and cellular immune response in rat and its attenuation by zinc and alpha-lipoic acid. Methods Cypermethrin at the dose levels of 40 mg and 80 mg/kg body weight were orally administered and pre-treatment of zinc (227 mg/L in drinking water) and alpha-lipoic acid (35 mg/kg body wt.) were done. Total leukocyte and differential leukocyte counts (DLC), phagocytic index, serum nitric oxide (NO) activity, total immunoglobulin concentration, quantitative hemolysis, proliferation assay of blood mononuclear cells were estimated and histological examination of spleen was accomplished. Results Total white blood cell (WBC) count and percentage of lymphocyte, serum nitric oxide activity (p<0.001) and quantitative hemolysis were increased significantly increased whereas neutrophil %, total serum immunoglobulin, and blood mononuclear cell proliferation (p<0.001) and the phagocytic function of peritoneal macrophages were significantly reduced in cypermethrin treated rats compared to control group rats at a dose-dependent manner. Zinc and alpha-lipoic acid pre-treatment reversed the results. Conclusion From the findings it can be concluded that the co-administration of zinc and alpha-lipoic acid significantly attenuated the immunotoxic effects in cypermethrin exposed rat.
目的研究氯氰菊酯暴露对大鼠体液和细胞免疫反应的影响以及锌和硫辛酸对免疫反应的抑制作用。方法采用高效氯氰菊酯40 mg和80 mg/kg体重口服,锌(饮水227 mg/L)和α -硫辛酸(35 mg/kg体重)预处理。测定白细胞总数、差异白细胞计数(DLC)、吞噬指数、血清一氧化氮(NO)活性、总免疫球蛋白浓度、定量溶血、单核细胞增殖试验,并进行脾脏组织学检查。结果与对照组相比,氯氰菊酯处理大鼠外周血总白细胞(WBC)计数、淋巴细胞百分比、血清一氧化氮活性(p<0.001)和溶血量显著增加,中性粒细胞%、血清总免疫球蛋白、血液单核细胞增殖(p<0.001)和腹腔巨噬细胞吞噬功能显著降低,且呈剂量依赖性。锌和α -硫辛酸预处理逆转了这一结果。结论锌与硫辛酸联合施用可显著降低氯氰菊酯暴露大鼠的免疫毒性。
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引用次数: 0
A Case Report of Severe Theophylline Poisoning: Management and Review of Literature 重度茶碱中毒1例:处理及文献复习
Pub Date : 2021-12-31 DOI: 10.17140/tfmoj-6-138
Z. Sim, I. Z. Hong, P. R
Background Theophylline poisoning leads to multisystem toxicity. Management of theophylline overdose is focused on stabilizing cardiovascular manifestations of arrhythmia and hypotension, correcting metabolic derangements, aborting seizures and removing the drug from the system. We present a case of refractory seizures and haemodynamic instability from theophylline poisoning and reviewed the literature to update the management of severe theophylline overdose. Case Presentation A 73-year-old Chinese gentleman presenting with chills and rigor was admitted for management of sepsis. While admitted suffered seizures which were refractory to benzodiazepine and anti-epileptic drugs. Based on his previous admission for theophylline overdose, serum levels were done confirming severe theophylline poisoning. He was resuscitated and subsequently started on haemodialysis following which seizures were eventually aborted when theophylline levels were successfully reduced. Conclusion Severe theophylline poisoning should be identified early and appropriate treatment initiated promptly. In the management of refractory hypotension, methylene blue and venoarterial-extracorporeal membrane oxygenation are reasonable rescue therapies to consider. Multi-dose activated charcoal and extracorporeal treatments for elimination of drugs should be administered in severe theophylline poisoning.
茶碱中毒可导致多系统中毒。茶碱过量的管理主要集中在稳定心律失常和低血压的心血管表现,纠正代谢紊乱,中止癫痫发作和从系统中清除药物。我们报告一例茶碱中毒引起的难治性癫痫发作和血流动力学不稳定,并回顾文献以更新严重茶碱过量的处理。一位73岁的中国男士,以寒战和僵硬为表现,因脓毒症入院治疗。入院时癫痫发作,对苯二氮卓类药物及抗癫痫药物均难治。根据患者先前因茶碱过量入院,测定血清水平,确认严重茶碱中毒。他被复苏,随后开始进行血液透析,在成功降低茶碱水平后,癫痫最终停止。结论对严重茶碱中毒应及早发现,及时采取适当治疗。在难治性低血压的治疗中,亚甲基蓝和静脉-体外膜氧合是合理的抢救治疗方法。严重茶碱中毒应多剂量活性炭和体外清除药物治疗。
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引用次数: 0
Autonomic Dysreflexia: Atypical Complication from Immediate Release Tapentadol 自主神经反射障碍:立即释放他他多的非典型并发症
Pub Date : 2021-12-31 DOI: 10.17140/TFMOJ-6-136
Claudia M. Diaz, Veli Solyali
Neurological disorders are a ubiquitous part of our lives, and with innovative technological advancements there are increasing numbers of people being diagnosed with a variety of conditions. While these advances uncover the underlying pathological process, the requisite need to manage a patient’s condition necessitates renewed vigour in the realm of key therapeutics. This case study looks at a patient with a rare neurological condition, transverse myelitis (TM), and a complication that many spinal cord injury patients suffer, autonomic dysreflexia (AD). However, what makes this case unique is when the patient was administered with immediate-release Tapentadol, a synthetic opioid, the patient suffered more frequent and prolonged attacks of AD. The exploration of the functional anatomy of TM as it applies to this case is highlighted, and how the role of Tapentadol was a causative agent in increasing the patient’s AD.
神经系统疾病是我们生活中无处不在的一部分,随着创新技术的进步,越来越多的人被诊断出患有各种疾病。虽然这些进展揭示了潜在的病理过程,但管理患者病情的必要需求需要在关键治疗领域重新焕发活力。本病例研究的患者患有罕见的神经系统疾病,横贯脊髓炎(TM)和许多脊髓损伤患者患有的并发症,自主神经反射障碍(AD)。然而,这个病例的独特之处在于,当患者服用了一种合成阿片类药物塔他他多(Tapentadol)后,患者的阿尔茨海默病发作更频繁、时间更长。强调了TM的功能解剖探索,因为它适用于本病例,以及他他多是如何在增加患者AD的致病因子中的作用。
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引用次数: 0
Vitamin C, E and Zinc Ameliorates Cadmium-Toxicity Induced Biochemical Changes in Male Albino Rats 维生素C、E和锌改善镉中毒引起的雄性白化大鼠的生化变化
Pub Date : 2021-12-31 DOI: 10.17140/tfmoj-6-137
M. Renuka, Yenukolu Aparna, Poli Venkataramanaiah, M. S. Reddy
Background Environmental toxicants have become a major source of health hazards to humans, thereby negatively impacting the health and overall well-being of exposed individuals. Among these environmental toxicants, heavy metals stand out as the major cause of tissue pathologies and threaten an individual’s health status. One such heavy metal is cadmium (CD) whose exposure has been linked to various tissue toxicities including nervous, respiratory, reproductive, cardiovascular, hepatic and renal tissues. Cadmium is a non-biodegradable heavy metallic which possesses a long half of lifestyles and comfortably accumulates inside the tissues in which it produces tissue toxicities main to tissue disorder. The present study was aimed to determine the amelioration capabilities of Vitamin C, E and Zinc from the harmful effects of CD in Wistar rats. Methods The Wistar strain male albino rats weighing 225±10 g were administered with CD along co-administered with Vitamin C, E and Zinc, individually and also in combinations. After the completion of 45-days of experimentation, certain specific enzymatic parameters were assayed in plasma serum to assess the impact of CD and protective effect of Vitamin C, E and Zinc. Results Soon after the co-administration of CD along with Vitamin C, E and Zinc, either individually and in combinations, Body weights, liver weight and histo-somatic index (HSI) of liver and certain specific enzymes of plasma including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), creatinine, glucose and urea were monitored. All the parameters monitored showed a significant (p<0.05) increase during CD administration except ALP. All the parameters selected in the present study were shown to be significantly (p<0.05) reversed due to co-administration of Vitamin C, E and Zinc either individually or in combination, due to the protective effect from CD toxicity in wistar rats. Conclusion Our results demonstrate that co-administration of Vitamin C, E and Zinc ably protects the toxicity of CD in Wistar rats significantly.
环境毒物已成为危害人类健康的主要来源,从而对接触者的健康和整体福祉产生负面影响。在这些环境毒物中,重金属是引起组织病变和威胁个体健康状况的主要原因。其中一种重金属是镉(CD),其暴露与各种组织毒性有关,包括神经、呼吸、生殖、心血管、肝脏和肾脏组织。镉是一种不可生物降解的重金属,具有很长的寿命,在人体组织中容易积累,并产生组织毒性,主要是导致组织紊乱。本研究旨在探讨维生素C、E和锌对Wistar大鼠CD损伤的改善作用。方法Wistar系雄性白化病大鼠体重225±10 g,分别与维生素C、E、锌联合或单独给药。实验结束45 d后,测定血浆中某些特定酶参数,以评估维生素C、E和锌对CD的影响和保护作用。结果CD与维生素C、E和锌单独或联合给药后,监测各组大鼠体重、肝重、肝脏组织-体指数(HSI)及血浆特定酶如天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)、γ-谷氨酰转移酶(GGT)、乳酸脱氢酶(LDH)、肌酐、葡萄糖和尿素的变化。除ALP外,其余各项指标均显著升高(p<0.05)。由于维生素C、E和锌单独或联合给药对wistar大鼠CD毒性的保护作用,本研究所选择的所有参数均显示出显著(p<0.05)逆转。结论维生素C、E和锌对Wistar大鼠CD毒性有明显的保护作用。
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引用次数: 3
Fingerstick Plasma Drug Testing of Chronic Pain Patients: Comparison of Paired Fingerstick Plasma and Urine Specimens 慢性疼痛患者指戳血浆药物检测:指戳血浆与尿液配对比较
Pub Date : 2020-12-19 DOI: 10.17140/tfmoj-5-131
MP George, Irving Texas Usa Firstox Laboratories, R. George, Jessica Almonds
Aim A clinical study was conducted to evaluate fingerstick blood as a viable biological matrix for monitoring prescription and illicit drugs in a clinical setting on patients undergoing pain and addiction treatment. The current standard for monitoring patients’ medication use, misuse, and diversion is urine drug testing (UDT). Materials and Methods This study compared 632 paired urine and fingerstick blood specimens collected at three pain management clinics and one suboxone clinic for 35 drugs and/or metabolites. Plasma from the fingerstick blood was used for the analysis. The urine and plasma specimens were analyzed by validated liquid chromatography–tandem mass spectrometry (LC-MS-MS) procedures. The urine cutoff used by most pain testing laboratories were used to identify positive and negative drugs in urine. Limit of quantitation was used to identify positive and negative drugs in plasma. Drugs and/or metabolites were quantified in both urine and plasma using deuterium-labeled internal standards. Results Results were tabulated for urine and plasma specimens for data analysis. The results showed that 8.7% of plasma specimens detected more drugs compared to the corresponding urine specimens, and 2.2% of the urine specimens detected a drug that was negative in the corresponding plasma specimen. Overall 89.1% of the specimens had complete agreement between urine and plasma specimens for detection. The observed Cohen’s Kappa value for overall drug detection was 0.96 an “almost perfect” agreement as characterized by Landis and Koch. Conclusion Based on the observed data, the authors conclude that plasma collected from fingerstick blood is a better matrix to monitor patients currently prescribed pain medications or patients currently undergoing medication-assisted opioid treatment compared to urine drug testing.
目的通过一项临床研究,评估手指刺血作为一种可行的生物基质,在临床环境中监测正在接受疼痛和成瘾治疗的患者的处方药和非法药物。目前监测患者药物使用、滥用和转移的标准是尿液药物检测(UDT)。材料与方法本研究比较了在3个疼痛管理诊所和1个suboxone诊所收集的632对尿液和手指血样本,检测35种药物和/或代谢物。手指刺血中的血浆被用于分析。尿液和血浆标本采用经验证的液相色谱-串联质谱(LC-MS-MS)方法进行分析。大多数疼痛检测实验室采用尿切断法来鉴别尿中药物的阳性和阴性。用定量限法鉴别血浆中阳性和阴性药物。使用氘标记内标对尿液和血浆中的药物和/或代谢物进行定量。结果将尿液和血浆标本结果制成表格,进行数据分析。结果显示,8.7%的血浆标本比相应尿液标本检出更多的药物,2.2%的尿液标本检出相应血浆标本中阴性的药物。总的来说,89.1%的标本尿液和血浆标本的检测结果完全一致。观察到的总体药物检测的Cohen’s Kappa值为0.96,与Landis和Koch所描述的“几乎完美”一致。根据观察到的数据,作者得出结论,与尿液药物检测相比,从手指刺血中收集的血浆是一种更好的基质,用于监测正在服用止痛药或正在接受药物辅助阿片类药物治疗的患者。
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引用次数: 0
Haematological Presentations in Acute and Chronic Tramadol Intoxication 急性和慢性曲马多中毒的血液学表现
Pub Date : 2020-12-19 DOI: 10.17140/tfmoj-5-134
Loveday U. Zebedee, Owubokiri N. Jeremiah, Anthony E. Soroh, Agoro Es
Introduction Tramadol is a synthetic centrally acting analgesic used worldwide for pain relief, but now abused as a euphoria generating substance. The short- and long-term implications of tramadol intoxication on blood cells and its components are still hazy and controversial. Aim Our primary aim was to evaluate the alterative pattern of haematological parameters resulting from acute or chronic tramadol intoxication. Method The study was made of acute and chronic phases of sixty male rats (Rattusnorvegicus) randomly pair-divided into established groups of six male rats each. The acute stage consisted of a control group of 6 rats administered with normal saline solution, and a treatment group of 6 rats administered with lethal dose of tramadol. The control group for the chronic stage consisted of 6 rats that were administered normal saline solution. Whereas, the tramadol-dependent groups comprised of 3 groups of 6 rats each administered orally with 50 mg/kg, 100 mg/kg, and 200 mg/kg of tramadol for 90 days respectively. Statistical analyses consisted of the one-way analysis of variance (ANOVA), Student’s t-test, and Pearson’s Correlation using the JMP statistical discovery™ software version 14.1. Blood samples were collected after anesthetic sacrifice by cardiac puncture for the analysis of full blood count and red cell indices using SYSMEX Automated Blood Count machine (SYSMEX KX-21N ANALYZER) and microscopy for blood film reading. Results Results of the acute phase of the study showed that the packed cell volume (PCV) in the treatment group (51.00±2.96%) was significantly higher (t=3.99, p=0.002) than control (37.83±1.43%). Similarly, the haemoglobin concentration (Hb) in the treatment group (14.70±0.46 g/dL) was significantly higher (t=5.10, p=0.005) than control (11.55±0.41 g/dL). The mean cell haemoglobin concentration (MCHC) was significantly lower (t=2.67, p=0.02) in the control group (28.30±0.52 g/dL) than treatment (30.43±0.61 g/dL). However, that of the chronic phase exhibited a progressive increase in platelet count which was proportional to increasing dosage of treatment (t=8.59, p=0.007). Conclusion This study has demonstrated that tramadol administration could cause haematological alterations which could be beneficial if administrated optimally and deleterious, if abused. Therefore, indiscriminate and prolonged use of tramadol should be monitored to avert haemotoxicity.
曲马多是一种用于缓解疼痛的合成中枢镇痛药,但现在被滥用为一种产生欣快感的物质。曲马多中毒对血细胞及其成分的短期和长期影响仍然是模糊和有争议的。我们的主要目的是评估急性或慢性曲马多中毒引起的血液学参数的变化模式。方法选用褐家鼠雄性大鼠60只,随机分成两组,每组6只。急性期对照组6只大鼠给予生理盐水,治疗组6只大鼠给予曲马多致死剂量。慢性期对照组6只,给予生理盐水。曲马多依赖组分为3组,每组6只,分别口服曲马多50 mg/kg、100 mg/kg和200 mg/kg,持续90 d。统计分析包括单因素方差分析(ANOVA)、学生t检验和Pearson相关性分析,使用JMP统计发现™软件版本14.1。麻醉牺牲后心脏穿刺采血,采用SYSMEX全自动血细胞计数仪(SYSMEX KX-21N ANALYZER)和镜检法进行全血细胞计数和红细胞指标分析。结果急性期研究结果显示,治疗组细胞堆积体积(PCV)(51.00±2.96%)显著高于对照组(37.83±1.43%)(t=3.99, p=0.002)。同样,治疗组血红蛋白(Hb)浓度(14.70±0.46 g/dL)显著高于对照组(11.55±0.41 g/dL) (t=5.10, p=0.005)。对照组的平均细胞血红蛋白浓度(MCHC)为28.30±0.52 g/dL,显著低于治疗组(30.43±0.61 g/dL) (t=2.67, p=0.02)。而慢慢期患者血小板计数呈进行性增加,与治疗剂量的增加成正比(t=8.59, p=0.007)。结论本研究表明曲马多给药可引起血液学改变,如果给药合理则有益,如果滥用则有害。因此,应监测曲马多的滥用和长期使用,以避免血液毒性。
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引用次数: 1
Effect of Statins Therapy in Diabetogenesis 他汀类药物治疗在糖尿病发生中的作用
Pub Date : 2020-12-19 DOI: 10.17140/tfmoj-5-130
A. S. Olagunju, Olayinka A. Adebayo, S. O. Kosemani, Toluwanimi P. Iroko
Statins are widely used in the management or inhibition of several processes that lead to the development of cardiovascular diseases. Increased statin therapy has been related to the induction of type II diabetes (DM), a state which predisposes to cardiovascular disease (CVD). Statins are well-known to possess anti-inflammatory properties and the ability to disrupt de novo biosynthesis of cholesterol and lipid homeostasis has been implicated in the induction of inflammatory responses within pancreatic β-cells. Inhibition of β-hydroxy β-methyl glutaryl-CoA (HMG-CoA) results an increased level of low-density lipoproteins (LDL) receptors. Increased LDL receptor numbers will replenish exhausted intracellular supplies, resulting in higher levels of intracellular cholesterol. Therefore, stimulating immunological response and inflammatory reactions, disrupt the functional integrity of the β-cell via oxidation of the plasma-derived low-density lipoprotein. Despite the pleiotropic effects of statins on the pancreatic β-cell, they have also been reported to affect a number of other cell types associated with the development of diabetes. Inhibition of the biosynthesis of isoprenoid by statins has been associated with the down-stream regulation of glucose transporter (GLUT 4) in adipose tissues, which facilitates the uptake of glucose. This effect resulted in increasing resistance to insulin in the liver, muscle, and adipose tissue. Adiponectin, a plasma protein released by adipocytes, alters fatty acids and carbohydrate metabolism both in the muscle cells and liver. This process indirectly influences resistance to insulin by the attendant decrease in hepatic gluconeogenesis and to upregulate muscular β-oxidation and glucose uptake.
他汀类药物被广泛用于管理或抑制导致心血管疾病发展的几个过程。他汀类药物治疗的增加与II型糖尿病(DM)的诱导有关,这是一种易患心血管疾病(CVD)的状态。众所周知,他汀类药物具有抗炎特性,并且能够破坏胆固醇和脂质稳态的新生生物合成,这与胰腺β细胞内炎症反应的诱导有关。抑制β-羟基β-甲基戊二酰辅酶a (HMG-CoA)导致低密度脂蛋白(LDL)受体水平升高。增加的LDL受体数量将补充耗尽的细胞内供应,导致细胞内胆固醇水平升高。因此,刺激免疫反应和炎症反应,通过氧化血浆来源的低密度脂蛋白破坏β细胞的功能完整性。尽管他汀类药物对胰腺β细胞有多效性作用,但据报道,它们也会影响与糖尿病发展相关的许多其他细胞类型。他汀类药物抑制类异戊二烯的生物合成与脂肪组织中葡萄糖转运蛋白(GLUT 4)的下游调节有关,这有助于葡萄糖的摄取。这种效应导致肝脏、肌肉和脂肪组织对胰岛素的抵抗力增加。脂联素是一种由脂肪细胞释放的血浆蛋白,可以改变肌肉细胞和肝脏中的脂肪酸和碳水化合物代谢。这一过程通过肝脏糖异生的减少和肌肉β氧化和葡萄糖摄取的上调间接影响胰岛素抵抗。
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引用次数: 0
A Cycle of Altered Proteasome and Reactive Oxygen Species Production in Renal Proximal Tubular Cells. 肾近端小管细胞中蛋白酶体改变和活性氧产生的循环。
Pub Date : 2019-01-01 Epub Date: 2019-05-15 DOI: 10.17140/tfmoj-4-128
Nirmala Parajuli
Aims An intricate relationship exists between the mitochondrial function and proteasome activity. Our recent report showed in a rat model of renal transplantation that mitochondrial dysfunction precedes compromised proteasome function and this results in a vicious cycle of mitochondrial injury and proteasome dysfunction. In this study, we studied whether reactive oxygen species (ROS) has a role in proteasome alteration in renal cells and vice versa. Methods We used the genomic and pharmacologic approach on rat normal kidney proximal tubular (NRK) cell lines. First, we knocked down β5 or Rpt6 subunit of the proteasome using small interfering RNA (siRNA) in NRK cells. We also treated NRK cells with Bortezomib, a proteasome inhibitor, and peroxynitrite (a potent ROS). Results Studies with RNA interference showed increased mitochondrial ROS following knockdown of β5 or Rpt6 subunit in NRK cells. Similarly, pharmacological inhibition of the proteasome in NRK cells using Bortezomib also showed an increase of mitochondrial ROS in a dose-dependent manner. Next, exposing NRK cells to different concentrations of peroxynitrite provided evidence that the higher levels of peroxynitrite exposure decreased the key subunits (β5 and α3) of the proteasome in NRK cells. Conclusion Our results suggest that proteasome inhibition/downregulation increases ROS, which then impairs proteasome subunits in renal proximal tubular cells.
目的:线粒体功能与蛋白酶体活性之间存在着复杂的关系。我们最近的报告显示,在大鼠肾移植模型中,线粒体功能障碍先于蛋白酶体功能受损,这导致线粒体损伤和蛋白酶体功能障碍的恶性循环。在这项研究中,我们研究了活性氧(ROS)是否在肾细胞的蛋白酶体改变中起作用,反之亦然。方法:采用基因组学和药理学方法对大鼠正常肾近端小管(NRK)细胞系进行研究。首先,我们在NRK细胞中使用小干扰RNA (siRNA)敲除蛋白酶体的β5或Rpt6亚基。我们还用硼替佐米(一种蛋白酶体抑制剂)和过氧亚硝酸盐(一种强效ROS)处理NRK细胞。结果:RNA干扰研究表明,NRK细胞中β5或Rpt6亚基下调后,线粒体ROS增加。同样,使用硼替佐米对NRK细胞中蛋白酶体的药理学抑制也显示线粒体ROS以剂量依赖的方式增加。接下来,将NRK细胞暴露于不同浓度的过氧亚硝酸盐中提供了证据,表明较高水平的过氧亚硝酸盐暴露降低了NRK细胞蛋白酶体的关键亚基(β5和α3)。结论:我们的研究结果表明,蛋白酶体抑制/下调会增加ROS,从而损害肾近端小管细胞中的蛋白酶体亚基。
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引用次数: 4
In Vitro Cytotoxicity of Cyanuric Acid and Selected Derivatives 氰尿酸及其衍生物的体外细胞毒性
Pub Date : 2018-12-30 DOI: 10.17140/TFMOJ-3-125
T. Batsalova, Desislava Kolchakova, B. Dzhambazov
Copyright 2018 by Dzhambazov B. This is an open-access article distributed under Creative Commons Attribution 4.0 International License (CC BY 4.0), which allows to copy, redistribute, remix, transform, and reproduce in any medium or format, even commercially, provided the original work is properly cited. 14 cc Original Research Original Research | Volume 3 | Number 1| Background Cyanuric acid and its derivatives belong to the group of s-triazines. They have wide industrial application, generally in the production of pesticides, bleaching agents and disinfectants. Recent reports showed significant negative effect of cyanuric acid in combination with melamine but low general cytotoxicity of cyanuric acid alone. However, evaluations of cyanuric acid toxicity against different human cell types using a panel of in vitro assays have not been performed. In addition, little is known about the cytotoxicity and potential antitumor effects of certain cyanuric acid derivatives, for example trichloroisocyanuric acid and 1,3,5-tris(2-hydroxyethyl) isocyanurate.
Dzhambazov B.版权所有2018。这是一篇根据知识共享署名4.0国际许可证(CC by 4.0)分发的开放获取文章,该许可证允许以任何媒介或格式进行复制、重新分发、混音、转换和复制,即使是商业性的,只要原作被正确引用。14 cc原创研究原创研究|第3卷|第1号|背景氰尿酸及其衍生物属于s-三嗪类。它们具有广泛的工业应用,通常用于生产杀虫剂、漂白剂和消毒剂。最近的报道显示氰尿酸与三聚氰胺联合使用具有显著的负面作用,但单独使用氰尿酸的总体细胞毒性较低。然而,尚未使用一组体外测定法对氰尿酸对不同人类细胞类型的毒性进行评估。此外,对某些氰尿酸衍生物的细胞毒性和潜在的抗肿瘤作用知之甚少,例如三氯异氰尿酸和1,3,5-三(2-羟乙基)异氰尿酸盐。
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引用次数: 2
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Toxicology and forensic medicine : open journal
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