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An adjustment of vancomycin dosing regimen for a young patient with augmented renal clearance: A case report / Úprava dávkového režimu vankomycínu pre mladého pacienta so zvýšeným renálnym klírensom: Kazuistika
Pub Date : 2015-12-01 DOI: 10.1515/afpuc-2015-0025
Maria Goboova, Magdaléna Kuželová, Viera Kissova, Dasa Bodakova, Elena Martišová
Abstract Augmented renal clearance (ARC) is a recently reported condition in pathophysiology of critically ill patients in the intensive care unit. ARC refers to the enhanced renal elimination of circulating solutes. These patients are either young or previously healthy people who have undergone surgery or multiple trauma. This case report describes an adjustment of dosing regime of vancomycin to a young patient, who demonstrated ARC with severe polytrauma, overcome crush syndrome and sepsis. This 16-year old male patient was crushed by a tractor, which caused severe tissue damaged in the right lower limb. He gradually developed a serious crush syndrome. When kidneys resumed their function, creatinine clearance reached the value that indicated ARC (339.81 mL/min/1.73 m2). Vancomycin was included in the patient’s treatment regime by administering conventional dose of 1 g per 12 hours. The residual measured levels were very low. The dose of vancomycin had to be adjusted to double and then to triple the conventional dose. Without the therapeutic drug monitoring (TDM) and subsequent interpretation of the results by the clinical pharmacists, such high doses would not have been considered for administration. ARC responds strongly to sub-therapeutic serum vancomycin levels. Our case report confirms the significance of TDM and the consecutive interpretation of the results in critically ill patients.
增强肾清除率(Augmented renal clearance, ARC)是最近报道的重症监护病房危重患者的病理生理状况。ARC是指肾脏对循环溶质的消除增强。这些患者要么是年轻人,要么是以前健康的人,他们经历了手术或多重创伤。本病例报告描述了一个调整万古霉素给药方案的年轻患者,谁证明了ARC与严重多发创伤,克服挤压综合征和败血症。这名16岁的男性患者被拖拉机碾压,导致右下肢严重组织损伤。他逐渐患上了严重的挤压综合症。当肾脏恢复功能时,肌酐清除率达到ARC指示值(339.81 mL/min/1.73 m2)。万古霉素纳入患者的治疗方案,每12小时给予常规剂量1g。残留测量水平非常低。万古霉素的剂量必须调整到常规剂量的两倍,然后是三倍。如果没有治疗药物监测(TDM)和临床药师随后对结果的解释,如此高的剂量是不会被考虑给药的。ARC对亚治疗期血清万古霉素水平反应强烈。我们的病例报告证实了TDM的重要性以及对危重患者结果的连续解释。
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引用次数: 5
A current view of the diagnostics and treatment of phenylketonuria in Slovakia 斯洛伐克苯丙酮尿症的诊断和治疗现状
Pub Date : 2015-12-01 DOI: 10.1515/afpuc-2015-0016
Oto Ürge
Abstract An overview of the diagnostics and treatment of phenylketonuria in Slovakia is presented in this paper. The nature of diseases, incidence and prevalence in Slovakia, its genetic characteristics, current laboratory diagnostics and treatment options are defined. A new method of phenylketonuria screening in Slovakia, which has brought substantial improvement in early detection of the disease and shortening time for definitive diagnosis since 1995 as well as the importance of a tandem MS/MS (mass spectrometry) introduced in the diagnosis of inherited metabolic disorders, is presented. The current state of phenylketonuria treatment focusing on low-protein dietary treatment and supplementation of amino acid mixtures is analysed. The use of sapropterin, enzyme replacement therapy, large neutral amino acids supplementation and gene therapy are also discussed.
摘要本文介绍了斯洛伐克苯丙酮尿症的诊断和治疗概况。定义了斯洛伐克的疾病性质、发病率和流行程度、遗传特征、目前的实验室诊断和治疗方案。提出了一种新的苯丙酮尿筛查方法,自1995年以来,该方法在疾病的早期发现和缩短确诊时间方面取得了实质性进展,并介绍了串联质谱法(MS/MS)在遗传性代谢疾病诊断中的重要性。分析了目前苯丙酮尿的治疗现状,主要集中在低蛋白饮食治疗和补充氨基酸混合物。此外,还讨论了沙普霉素的使用、酶替代治疗、大中性氨基酸补充和基因治疗。
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引用次数: 0
Modelling of absorption, distribution and physicochemical properties of AT1 receptor antagonists / Modelovanie absorpcie, distribúcie a fyzikálnochemických vlastnosti antagonistov AT1 receptorov AT1受体拮抗剂的吸收、分布和理化性质建模/ Modelovanie absorpcie, distribúcie a fyzikálnochemických vlastnosti antagonistov AT1受体
Pub Date : 2015-12-01 DOI: 10.1515/afpuc-2015-0028
Pavol Ježko, Viera Žufková, Milan Remko
Abstract The theoretical chemistry methods were used to elucidate absorption, distribution and physicochemical properties of AT1 receptor antagonists and dual angiotensin II and endothelin A receptor antagonist (PS-433540). Computed partition coefficients (ALOGPS method) studied for drugs varied between 2.98 and 6.66. Neutral compounds are described as lipophilic drugs. Telmisartan is a drug with the highest lipophilicity. The neutral forms of the studied AT1 receptor antagonists are practically insoluble in water, and their computed solubilities is in interval between 2.04 and 22.65 mg/l (ALOGpS method). The calculated pKa values for tetrazolyle moiety are in the range 3.92-5.00 and for carboxylic moiety 3.12-5.50. Telmisartan (polar surface area = 72.95 A) and irbesartan (polar surface area = 87.14 A) belong to the AT1 receptor antagonists with increased absorption.
摘要采用理论化学方法研究了AT1受体拮抗剂和血管紧张素II和内皮素A受体双拮抗剂(PS-433540)的吸收、分布和理化性质。计算分割系数(ALOGPS法)在2.98 ~ 6.66之间。中性化合物被描述为亲脂性药物。替米沙坦是一种亲脂性最高的药物。所研究的AT1受体拮抗剂的中性形式几乎不溶于水,它们的计算溶解度在2.04和22.65 mg/l之间(ALOGpS方法)。计算得到四唑基的pKa值为3.92 ~ 5.00,羧基的pKa值为3.12 ~ 5.50。替米沙坦(极性表面积= 72.95 A)和厄贝沙坦(极性表面积= 87.14 A)属于吸收增加的AT1受体拮抗剂。
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引用次数: 3
Sjögren’s syndrome Sj em gren’s综合症
Pub Date : 2015-12-01 DOI: 10.1515/afpuc-2015-0019
V. Mlynáriková, D. Mičeková, J. Rovensky, E. Šteňová
Abstract Sjögren’s syndrome is a slowly progressive, inflammatory autoimmune disease primarily affecting exocrine glands. Lymphocytic infiltrates replace functional epithelium and lead to decreased exocrine secretion of salivary and lacrimal glands - xerocrinopathy. Glands of intestinal system and pulmonary tract, skin and vaginal mucosa may also be affected. The most common extraglandular manifestations of primary Sjögren’s syndrome include skin vasculitis, Raynaud’s phenomenon, functional renal abnormalities, neuropathy and arthritis symptoms. This disorder may appear separately as a primary Sjögren’s syndrome or in connection with other inflammatory rheumatic diseases as secondary Sjögren’s syndrome. Treatment of the disease is based on topical ocular and oral therapy, extraglandular manifestations need to be treated with hydroxychloroquine and severe cases even with corticosteroid or immunosuppressive drugs.
Sjögren综合征是一种缓慢进展的炎症性自身免疫性疾病,主要影响外分泌腺。淋巴细胞浸润取代功能性上皮,导致唾液腺和泪腺外分泌减少-干眼病。肠系统和肺部的腺体、皮肤和阴道粘膜也可能受到影响。原发性Sjögren综合征最常见的腺外表现包括皮肤血管炎、雷诺现象、肾功能异常、神经病变和关节炎症状。这种疾病可以单独表现为原发性Sjögren综合征,也可以与其他炎性风湿病一起表现为继发性Sjögren综合征。该疾病的治疗基于局部眼和口服治疗,腺外表现需要用羟氯喹治疗,严重者甚至使用皮质类固醇或免疫抑制药物。
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引用次数: 0
Kinetic Modelling of Drug Release from Pentoxifylline Matrix Tablets based on Hydrophilic, Lipophilic and Inert Polymers 基于亲水、亲脂和惰性聚合物的己酮茶碱基质片药物释放动力学建模
Pub Date : 2015-12-01 DOI: 10.1515/afpuc-2015-0026
E. Mircia, L. Vlase, G. Hancu, M. Budău, R. Soare
Abstract Pentoxifylline is a xanthine derivative used in the treatment of peripheral vascular disease, which because of its pharmacokinetic and pharmacologic profile is an ideal candidate for the development of extended release formulations. The aim of this study is to present a kinetic analysis of the pentoxifylline release from different extended release tablets formulations, using mechanistic and empirical kinetic models. A number of 28 formulations were prepared and analysed; the analysed formulations differed in the nature of the matrix forming polymers (hydrophilic, lipophilic, inert) and in their concentrations. Measurements were conducted in comparison with the reference product Trental 400 mg (Aventis Pharma). The conditions for the dissolution study were according to official regulations of USP 36: apparatus no. 2, dissolution medium water, volume of dissolution medium is 1,000 mL, rotation speed is 50 rpm, spectrophotometric assay at 274 nm. Six mathematical models, five mechanistic (0 orders, 1st-order release, Higuchi, Hopfenberg, Hixson-Crowell) and one empirical (Peppas), were fitted to pentoxifylline dissolution profile from each pharmaceutical formulation. The representative model describing the kinetics of pentoxifylline release was the 1st-order release, and its characteristic parameters were calculated and analysed.
己酮茶碱是一种用于治疗周围血管疾病的黄嘌呤衍生物,由于其药代动力学和药理学特征,是开发缓释制剂的理想候选者。本研究的目的是利用力学和经验动力学模型,对不同缓释片剂型的己酮茶碱的释放进行动力学分析。编制和分析了28种配方;所分析的配方在基质形成聚合物的性质(亲水、亲脂、惰性)和浓度上有所不同。测量结果与参考产品Trental 400mg (Aventis Pharma)进行了比较。溶出度研究的条件按照USP 36:仪器号的官方规定。2、溶解介质为水,溶解介质体积为1000ml,转速为50rpm,分光光度测定在274nm。6个数学模型,5个机制模型(0阶、1阶释放、Higuchi、Hopfenberg、Hixson-Crowell)和1个经验模型(Peppas),拟合了每种药物制剂中己酮茶碱的释放谱。己酮茶碱释放动力学的代表性模型为一级释放,并对其特征参数进行了计算和分析。
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引用次数: 3
Guidelines for complex genetic analysis of hereditary breast ovarian cancer syndrome in slovak population 斯洛伐克人群遗传性乳腺癌综合征复杂遗传分析指南
Pub Date : 2015-12-01 DOI: 10.1515/afpuc-2015-0017
M. Konečný, I. Mlkva, J. Simko, L. Copáková, L. Kádasi, F. Cisárik, L. Dolesova, K. Závodná, J. Markus
Abstract Genetic diagnostics of hereditary breast and ovarian cancer (HBOC) has been performed in Slovakia in many different forms before the year 2000. Complex HBOC genetic analysis consists of many steps, including the initial genetic consultation, laboratory testing of genes associated with HBOC, interpretation and report of DNA analysis results, secondary explanatory genetic consultation and recommendation of clinical management for pathological mutation carriers. Many clinicians are participating on this workflow, such as clinical geneticists, laboratory diagnosticians as well as gynaecologists, oncologists or radio-diagnosticians. Currently, genetic testing is still technically and financially demanding and aimed only at selected families or patients who fulfil the defined clinical indication criteria. Positive result of DNA analysis, that is, detection of pathological mutation in genes associated with HBOC syndrome means that the risk of breast/ovarian cancer onset in mutation carriers is amplified. This predisposition markedly affects the clinical management and treatment of patient and other members of the family, thus creating the demand to establish widely accepted specific recommendations for genetic diagnostics of HBOC. In the past, the analysis of HBOC in Slovakia followed various technical approaches and indication criteria depending on the workflow of specific laboratory. The guidelines reported below adhere to the current trends in DNA analysis and clinical healthcare, define the criteria for diagnostic laboratories, conditions for genetic testing and determine indications for selection of HBOC families and further clinical management of mutation carriers.
在2000年之前,斯洛伐克以许多不同的形式进行了遗传性乳腺癌和卵巢癌(HBOC)的遗传诊断。复杂的HBOC遗传分析包括初始遗传咨询、HBOC相关基因的实验室检测、DNA分析结果的解释和报告、二次解释性遗传咨询和病理突变携带者的临床管理建议等多个步骤。许多临床医生都参与了这一工作流程,如临床遗传学家、实验室诊断医生以及妇科医生、肿瘤学家或放射诊断医生。目前,基因检测在技术上和经济上仍然要求很高,而且只针对符合明确临床指征标准的选定家庭或患者。DNA分析阳性,即检测到HBOC综合征相关基因的病理突变,意味着突变携带者发生乳腺癌/卵巢癌的风险增大。这种易感性显著影响患者和其他家庭成员的临床管理和治疗,因此需要建立广泛接受的HBOC遗传诊断的具体建议。过去,斯洛伐克的HBOC分析根据特定实验室的工作流程采用各种技术方法和指示标准。以下报告的指南遵循了DNA分析和临床保健的当前趋势,定义了诊断实验室的标准、基因检测的条件,并确定了选择HBOC家族和进一步临床管理突变携带者的适应症。
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引用次数: 0
Increased expression and secretion of recombinant hIFNγ through amino acid starvation-induced selective pressure on the adjacent HIS4 gene in Pichia pastoris 通过氨基酸饥饿诱导的HIS4基因的选择性压力,毕赤酵母中重组hIFNγ的表达和分泌增加
Pub Date : 2015-12-01 DOI: 10.1515/afpuc-2015-0031
Ali Razaghi, R. Huerlimann, L. Owens, K. Heimann
Abstract Transcriptional co-regulation of adjacent genes has been observed for prokaryotic and eukaryotic organisms, alike. High levels of gene adjacency were also found in a wide variety of yeast species with a high frequency of co-regulated gene sets. The aim of this research was to study how selective pressure on the Histidinol dehydrogenase gene (HIS4), using amino acid starvation, affects the level of expression and secretion of the adjacent human interferon gamma gene (hIFNγ) in the recombinant Pichia pastoris GS115 strain, a histidine-deficient mutant. hIFNγ was cloned into the pPIC9 vector adjacent to the HIS4 gene, a gene essential for histidine biosynthesis, which was then transformed into P. pastoris. The transformed P. pastoris was cultured under continuous amino acid starvation in amino acid-free minimal medium for ten days, with five inoculations into unspent medium every second day. Under these conditions, only successfully transformed cells (hIFNγ -HIS4+) are able to synthesise histidine and therefore thrive. As shown by ELISA, amino acid starvation-induced selective pressure on HIS4 improved expression and secretion of the adjacent hIFNγ by 55% compared to unchallenged cells. RT-qPCR showed that there was also a positive correlation between duration of amino acid starvation and increased levels of the hIFNγ RNA transcripts. According to these results, it is suggested that these adjacent genes (hIFNγ and HIS4) in the transformed P. pastoris are transcriptionally co-regulated and their expression is synchronised. To the best of the knowledge of the authors; this is the first study demonstrating that amino acid starvationinduced selective pressure on HIS4 can alter the regulation pattern of adjacent genes in P. pastoris.
在原核生物和真核生物中都观察到邻近基因的转录共调控。高水平的基因邻接也被发现在各种各样的酵母物种与高频率的共调节基因集。本研究的目的是研究利用氨基酸饥饿对组氨酸脱氢酶基因(HIS4)的选择性压力如何影响组氨酸缺乏突变体毕赤酵母GS115重组菌株中邻近人干扰素γ基因(hIFNγ)的表达和分泌水平。hIFNγ被克隆到HIS4基因附近的pPIC9载体中,HIS4基因是组氨酸生物合成所必需的基因,然后将其转化为P. pastoris。转化后的巴斯德梭菌在无氨基酸最小培养基中连续氨基酸饥饿培养10天,每隔一天在未消耗的培养基中接种5次。在这些条件下,只有成功转化的细胞(hIFNγ -HIS4+)能够合成组氨酸并因此茁壮成长。ELISA结果显示,氨基酸饥饿诱导的HIS4选择性压力使邻近hIFNγ的表达和分泌比未激食细胞提高55%。RT-qPCR结果显示,氨基酸饥饿持续时间与hIFNγ RNA转录物水平升高之间也存在正相关。根据这些结果,这些邻近基因(hIFNγ和HIS4)在转化的帕斯德酵母中受到转录共调控,其表达是同步的。尽作者所知;这是首次证明氨基酸饥饿诱导的HIS4选择性压力可以改变巴斯德酵母中邻近基因的调控模式的研究。
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引用次数: 4
Genetics of alkaptonuria – an overview 尿酸钾的遗传学综述
Pub Date : 2015-12-01 DOI: 10.1515/afpuc-2015-0021
A. Zaťková, M. Némethová
Abstract Alkaptonuria (AKU) is the first described inborn error of metabolism and a classical example of rare autosomal recessive disease. AKU patients carry homozygous or compound heterozygous mutations of the gene coding for enzyme homogentisate dioxygenase (HGD) involved in metabolism of tyrosine. The metabolic block in AKU causes accumulation of homogentisic acid (HGA) that, with advancing age of the patient, leads to severe and painful ochronotic arthropathy. HGD gene was mapped to chromosome 3q13.3 and is composed of 14 exons. In about 400 patients, 142 pathogenic variants were reported that are listed in HGD mutations database (http://hgddatabase.cvtisr.sk/). In this review, we summarise different aspects of AKU genetics and impact of the HGD variants on enzyme function.
Alkaptonuria (AKU)是第一个被描述的先天性代谢错误,是一种罕见的常染色体隐性遗传病的典型例子。AKU患者携带参与酪氨酸代谢的酶均质双加氧酶(HGD)基因编码纯合或复合杂合突变。AKU中的代谢阻滞导致均质酸(HGA)的积累,随着患者年龄的增长,导致严重和痛苦的慢性关节病。HGD基因定位于染色体3q13.3,由14个外显子组成。在大约400名患者中,报告了142种致病变异,这些变异被列在HGD突变数据库(http://hgddatabase.cvtisr.sk/)中。在这篇综述中,我们总结了AKU遗传学的不同方面以及HGD变异对酶功能的影响。
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引用次数: 1
Phenylcarbamic acid derivatives with integrated n-phenylpiperazine moiety in the structure – kinetics of alkaline hydrolysis study / Deriváty kyseliny fenylkarbámovej s integrovanou n-fenylpiperazínovou zložkou v štruktúre – štúdium kinetiky alkalickej hydrolýzy
Pub Date : 2015-12-01 DOI: 10.1515/AFPUC-2015-0032
M. Stankovicová, V. Miháliková, Ľ. Mezovský, A. Lašáková, V. Medlenová, I. Malík
Slovak abstract Acta Fac. Pharm. Univ. Comen. LXII, 2015 (2): 38-42. ISSN 1338-6786 (online) and ISSN 0301-2298 (print version), DOI: 10.1515/afpuc-2015-0032 Received September 22, 2015, accepted October 28, 2015 Original research article/Review * E-mail: stankovicm@fpharm.uniba.sk Deriváty kyseliny fenylkarbámovej – alkalická hydrolýza – chemická kinetika – antiarytmiká – stabilita Kľúčové slová: Univerzita Komenského v Bratislave, Farmaceutická Fakulta, Katedra Farmaceutickej Chémie, Bratislava, Slovenská republika Comenius University in Bratislava, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Bratislava, Slovak Republic / Phenylcarbamic acid derivatives with integrated n-phenylpiperazine moiety in the... Stankovičová M. et al. Acta Fac. Pharm. Univ. Comen. LXII, 2015 (2): 38-42. 40 39 parameters, i.e. activation energy EA determined from temperature dependence of the rate constants. Following the evaluation of complex physicochemical properties of basic esters, the aim of this work is the study of kinetics of their alkaline hydrolysis. In terms of fundamental structural aspects, the influence of alkoxy side chain attached to phenyl ring as well as the substitution on N-phenylpiperazin-1-yl moiety within the structure on the stability is evaluated. MATERIALS AND METHODS
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引用次数: 0
Spirulina maxima and its effect on antioxidant activity in fructose induced oxidative stress with histopathological observations 大螺旋藻及其对果糖诱导氧化应激抗氧化活性的影响及组织病理学观察
Pub Date : 2015-12-01 DOI: 10.1515/afpuc-2015-0027
Urmila Jarouliya, A. Zacharia, Raj K. Keservani, G. Prasad
Abstract Diabetes mellitus is a metabolic disorder characterised by hyperglycemia and oxidative stress. The aim of the present study is to explore the antioxidant effect of Spirulina maxima in rat model along with the histopathological observations. Diabetes was induced by feeding 10% fructose solution orally to Wistar rats (n = 6) for 30 days, analysed for plasma blood glucose and the markers of the oxidative stress [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and thiobarbituric acid reactive substances (TBARS)]. These biochemical studies were associated with histopathological examination of liver and kidney sections. The microalga Spirulina maxima being rich in proteins and other essential nutrients is widely used as a food supplement. S. maxima at a dose of 5 and 10% per kg and the metformin (500 mg/kg) as reference drug were given orally for 30 days to the diabetic rats. Diabetic rats showed significant (p < 0.001) elevations in plasma blood glucose, thiobarbituric acid-reactive substances and significant reduction in catalase, superoxide dismutase and reduced glutathione activity. Oral administration of 5 and 10% aqueous extract of S. maxima for 30 days restored not only of blood glucose levels but also markers of oxidative stress. Histopathological observations of tissues manifested that the S. maxima administration had the protective and therapeutic effects against fructose-induced abnormalities in diabetic rats. It is concluded that S. maxima is effective in reinstating the antioxidant activity in addition to its antidiabetic effect in type 2 diabetic rats.
糖尿病是一种以高血糖和氧化应激为特征的代谢紊乱。本研究旨在探讨最大螺旋藻在大鼠模型中的抗氧化作用,并进行组织病理学观察。采用口服10%果糖溶液诱导Wistar大鼠(n = 6) 30 d,测定其血浆血糖和氧化应激标志物[过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、还原性谷胱甘肽(GSH)和硫代巴比妥酸反应性物质(TBARS)]。这些生化研究与肝脏和肾脏切片的组织病理学检查相关联。最大螺旋藻是一种富含蛋白质和其他必需营养素的微藻,被广泛用作食品补充剂。分别以5%和10%的剂量给药,并以500 mg/kg的二甲双胍作为对照药,给药30 d。糖尿病大鼠血浆血糖、硫代巴比妥酸活性物质显著升高(p < 0.001),过氧化氢酶、超氧化物歧化酶和谷胱甘肽活性显著降低。口服5%和10%的水提物30天,不仅能恢复血糖水平,还能恢复氧化应激指标。组织病理学观察表明,给药对果糖诱导的糖尿病大鼠异常具有保护和治疗作用。由此可见,在2型糖尿病大鼠的抗氧化活性恢复的同时,大黄霉还具有抗糖尿病作用。
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引用次数: 6
期刊
Acta Facultatis Pharmaceuticae Universitatis Comenianae
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