正交试验方差分析的Excel通用计算与应用

以一L9( 34)拟水平正交试验为例,介绍了一种用Excel表格进行极差和方差分析的数据处理模型.此模型计算过程直观明了、层次分明,结果准确快速,函数设置易于理解,而且能以其它正交表用于进行数据处理的新模型构建.     

医药数理统计中正交试验方法研究

结合Excel及SPSS软件的应用,对正交试验在解决实际问题中的若干数据处理方法进行比较,目的是使学生更好地掌握正交试验设计的方法,把它更广泛地应用到药学、药理学的实验设计中,提高试验的科学性,达到简便、快捷和准确的统计效果。     

应用正交试验解决肌苷口服液色泽问题

本文应用正交试验法选取最佳生产工艺，解决了肌苷口服液的色译问题，提高了产品质量，降低了生产成本，取得了明显的经济效益．     

正交试验法优选蜘蛛香挥发油-β-环糊精包合工艺

采用正交试验法,以挥发油的利用率为指标,通过L9(34)正交试验筛选出蜘蛛香挥发油-β-环糊精包合物最佳包合条件。结果显示最佳包合条件为:β-环糊精:挥发油=1∶8、包合温度65℃、时间2.0h。影响包合效果的主要因素为包合温度。     

正交试验解决0.9%NaCl输液成品乳光问题

0．9％NaCl输液投入生产后,在成品灯检时出现乳光问题,使产品不合格率大大提高．本文采用正交试验法解决这一问题,取得了满意的结果．     

正交试验对松冬舒活乳剂分层的观察

用正交试验法对松冬舒活乳剂在留样观察中发现的分层现象进行了试验，结果表明，混合乳化剂的比例，成乳过程中的搅伴时间、油／水两相合并时的温度控制三个因素影响该乳剂的稳定性。     

正交试验优选野菊花中总黄酮的提取工艺

目的：优选野菊花中总黄酮的提取工艺。方法：以乙醇质量分数、加醇倍数、提取时间为考察因素,以野菊花总黄酮含量为评价指标,采用正交试验优选提取工艺。结果：最佳提取工艺为加12倍量50％乙醇,回流2次,每次1h。结论：所选工艺合理、可行,可用于野菊花中总黄酮的提取。     

关于中药提取正交试验设计的疑问与探讨

本文探讨与总结了如何设计中药提取正交试验中的提取时间、加水倍数因素,并提出了包含提取成本的评价方法.     

正交试验设计优选多聚甲醛的解聚方法

目的优选多聚甲醛快速简单的解聚方法。方法采用正交试验法,以解聚状态为考察指标,对影响解聚的主要因素（温度、加热时间、振摇时间）进行优选。结果加热至95℃左右、120min时多聚甲醛完全解聚,含量符合规定。结论该方法快速、简单,可直接用于稀甲醛的配制,适用于医院制剂室推广。     

正交试验优选八角莲中鬼臼类化合物的提取工艺研究

目的研究回流提取法中各因素对八角莲中鬼臼毒素,4’-去甲鬼臼毒素提取效果的影响。方法采用L9(34)正交试验,以鬼臼毒素,4’-去甲鬼臼毒素含量为指标,确定回流提取法各因素对八角莲中有效物质提取效果的影响,结果八角莲最佳回流提取工艺为:料液比为1∶5,温度80℃,90%乙醇提取3次每次1h。     

Prenatal nicotine exposure in rhesus monkeys compromises development of brainstem and cardiac monoamine pathways involved in perinatal adaptation and sudden infant death syndrome: amelioration by vitamin C

Maternal smoking during pregnancy greatly enhances perinatal morbidity/mortality and is the major risk factor for Sudden Infant Death Syndrome (SIDS). Studies in developing rodents indicate that nicotine is a neuroteratogen that targets monoamine pathways involved in the responses to hypoxia that are in turn, hypothesized to contribute to these adverse events. We administered nicotine to pregnant Rhesus monkeys from gestational day 30 through 160 by continuous infusion, achieving maternal plasma levels comparable to those in smokers; we examined neurochemical parameters immediately after Cesarean delivery at the end of the exposure period. Nicotine evoked elevations in brainstem serotonin levels and serotonin turnover, indicating hyperactivity of these pathways. The same treatment evoked a deficit in cardiac norepinephrine levels. Both effects were offset by coadministration of the antioxidant, Vitamin C. Brainstem serotonin hyperinnervation is a hallmark of SIDS, and the hyperactivity seen here can also account for the downregulation of serotonin receptors noted in this disorder. Deficient cardiac sympathetic innervation is also consistent with increased vulnerability to hypoxia during delivery or in the agonal event in SIDS. Our results thus indicate that nicotine exposure in a primate model produces brainstem and autonomic abnormalities of the key monoamine systems that govern the response to hypoxia, indicate an important role of oxidative stress in the adverse effects, and point to potential amelioration strategies that could offset these particular effects of nicotine.     

我院2003～2006年非甾体抗炎药动态分析与评价

目的:评价非甾体抗炎药(NSAIDs)的应用现状及趋势。方法:对我院2003～2006年NSAIDs的销售金额、用药频度、日均费用等进行回顾性分析。结果:NSAIDs销售金额2005、2006年增长迅速,平均增长率分别为18·54%和25·18%;用药频度年增长率平均为4·94%;部分特异性环氧化酶-2抑制剂在抗炎、抗风湿应用中有逐步取代传统NSAIDs的趋势。结论:应着力开发不良反应少的NSAIDs新制剂,对现有NSAIDs应加强不良反应监测。     

Methylphenidate alters monoaminergic and metabolic pathways in the cerebellum of adolescent rats

Abnormalities in the cerebellar circuitry have been suggested to contribute to some of the symptoms associated with attention deficit hyperactivity disorder (ADHD). The psychostimulant methylphenidate (MPH) is the major drug for treating this condition. Here, the effects of acute (2.0?mg/kg and 5.0?mg/kg) and chronic (2.0?mg/kg, twice daily for 15 days) MPH treatments were investigated in adolescent (35–40 days old) rats on monoaminergic and metabolic markers in the cerebellum. Data acquired indicates that acute MPH treatment (2.0?mg/kg) decreased cerebellar vesicular monoamine transporter (VMAT2) density, while chronic treatment caused an increase. In contrast, protein levels of tyrosine hydroxylase (TH) and the dopamine D1 receptor were not significantly altered by neither acute nor chronic MPH treatment. In addition, while chronic but not acute MPH treatment significantly enhanced dopamine turnover (DOPAC/dopamine) in the cerebellum, levels of dopamine and homovanillic acid (HVA) were not altered. Acute MPH (5.0?mg/kg) significantly modified levels of a range of cerebellar metabolites with similar trends also detected for the lower dose (2.0?mg/kg). In this regard, acute MPH tended to decrease cerebellar metabolites associated with energy consumption and excitatory neurotransmission including glutamate, glutamine, N-acetyl aspartate, and inosine. Conversely, levels of some metabolites associated with inhibitory neurotransmission, including GABA and glycine were reduced by acute (5.0?mg/kg) MPH, together with acetate, aspartate and hypoxanthine. In conclusion, this study demonstrated that MPH alters cerebellar biochemistry, and that this effect depends on both dose and duration of treatment. The therapeutic significance of these results requires further investigation.     

一测多评法测定枣仁安神胶囊中丹参酮ⅡA、五味子醇甲与五味子醇乙的含量

【】目的：建立枣仁安神胶囊中丹参酮ⅡA、五味子醇甲与五味子醇乙含量的一测多评方法。方法：采用高效液相法测定丹参酮ⅡA与五味子醇甲和五味子醇乙间的相对校正因子,考察其重现性,比较计算值与测得值的差异。结果：用一测多评法对6批枣仁安神胶囊中丹参酮ⅡA、五味子醇甲与五味子醇乙进行测定,与外标法实测值基本一致。结论：该方法可靠,结果准确,可用于枣仁安神胶囊的质量控制。     

Prevention and management of diabetic retinopathy in STZ diabetic rats by Tinospora cordifolia and its molecular mechanisms

We investigated the potential of Tinospora cordifolia (TC) in treatment of diabetic retinopathy in STZ-induced rats due to its antihyperglycemic, angiogenic, antiinflammatory and antioxidant effects. The diabetic rats, treated for 24 weeks with TC extract (250 mg/kg), were evaluated for lenticular and fundus changes. Biochemical parameters were estimated and histopathological studies performed. TC significantly reduced blood glucose and glycated hemoglobin in treated rats. It prevented cataract development in treated group. Angiogenic markers VEGF and PKC increased in diabetic retina, which reduced significantly with TC. Anti-inflammatory parameters TNF-α and IL-1β elevated in diabetic group unlike that in treated group. TC also provided defense against depletion of antioxidant enzymes- glutathione and catalase. Histopathological studies revealed thickening of basement membrane of the retinal and glomerular vasculature of diabetic rat, but no basement membrane widening was seen in treated animals. Destruction of pancreatic islet structure was observed in diabetic group, but not in treated. Thus, TC reduces blood glucose and inhibits overexpression of angiogenic and inflammatory mediators, which are distinct markers of diabetic retinopathy. It also prevents retinal oxidative stress and restores antioxidant enzyme levels. These data provide evidence for the safety and potential effect of TC in the management of experimental diabetic retinopathy.     

In vivo and in vitro cardiovascular effects of Papuan taipan (Oxyuranus scutellatus) venom: Exploring "sudden collapse"

'Sudden collapse' following envenoming by some Australasian elapids is a poorly understood cause of mortality. We have previously shown that Oxyuranus scutellatus venom causes cardiovascular collapse in anaesthetized rats. Prior administration of a sub lethal dose of venom attenuated the response to subsequent administration of higher (lethal) venom doses. In this study, we investigated the possible mechanisms mediating this 'protective effect'. Papuan taipan venom (5μg/kg, i.v.) produced a small transient hypotension in anaesthetized rats, while 10μg/kg resulted in a 73±12% decrease in arterial pressure. Venom (20μg/kg or 50μg/kg) produced cardiovascular collapse in all animals tested (n=12). Cardiovascular collapse by 50μg/kg venom was prevented by prior administration of 'priming' doses of venom (5, 10 and 20μg/kg). Also, prior administration of indomethacin (30mg/kg, i.v.) or heparin (300units/kg, i.v.) prevented sudden collapse induced by venom (20μg/kg). Venom was without effect in isolated hearts indicating that a direct cardiac effect was unlikely to be responsible for 'sudden collapse'. Venom induced endothelium-dependent and -independent relaxation in pre-contracted rat mesenteric artery rings which was inhibited by indomethacin, IbTx and Rp-8-CPT-cAMPs. This relaxation was markedly reduced upon second exposure. Our results indicate that cardiovascular collapse induced by O. scutellatus venom may be due to a combination of release of dilator autacoids and to direct relaxation of vascular smooth muscle involving the cAMP/protein kinase A cascade. Further work will involve identification of the venom component(s) responsible for this action and may provide insight into the management of envenomed patients.     

Evaluation of a Biologic Formulation Using Customized Design of Experiment and Novel Multidimensional Robustness Diagrams

Formulation development includes selection of appropriate excipients to stabilize the active pharmaceutical ingredient throughout its recommended shelf life, against potential excursions in its life cycle and sometimes to aid in the delivery of therapeutics into the patient. Identity and quantity of every ingredient in a therapeutic formulation are critical to achieve their intended purpose. Deviations from a target composition can result in manufacturing, safety, and efficacy challenges. It is mandatory to establish robustness of a formulation for the expected changes in its composition arising from the qualified “process variability” of the impacting process steps during manufacture. The approach for carrying out a robustness study evolved through improved understanding of a therapeutic stability and exploration of new tools, including the quality by design elements strongly recommended by regulatory agencies. An approach is presented here to study formulation robustness in multidimensional space using a customized experimental design and novel multidimensional diagrams, which present a unique way of identifying robustness limits. The concept is universally applicable to any multivariate analysis and such diagrams would be useful to comprehend the outcome on all variables at a glance. Interpretation of these diagrams is discussed, some of which are applicable in general to any statistical design of experiment.     

Clozapine bioactivation induces dose-dependent, drug-specific toxicity of human bone marrow stromal cells: a potential in vitro system for the study of agranulocytosis

Clozapine, an atypical antipsychotic drug effective in treatment of refractory schizophrenia causes potentially life-threatening agranulocytosis. The drug undergoes bioactivation to a toxic, chemically reactive intermediate with capacity to target stromal cells, central components of the bone marrow microenvironment implicated in neutrophil development. To identify possible mechanisms underpinning disruption of stroma as a site of drug bioactivation, toxicity was induced in vitro. Therefore metabolite generation procedures utilizing HOCl or HRP-H(2)O(2) as primary components involved in clozapine metabolism were adapted for stromal culture and coupled with viability determinations. Drug oxidation by HOCl was less toxic to stromal cells than HRP-H(2)O(2) based methods. More specifically, clozapine bioactivation by HRP-H(2)O(2) caused dose-dependent inhibition of stromal viability at therapeutically relevant concentrations. Differences in susceptibility of HAS303 and LP101 cells to the clozapine nitrenium ion were also evident. Stromal cell death was attributed to clozapine in the presence of a complete metabolising system comprising HRP and H(2)O(2). In the absence of a complete metabolising system clozapine was not cytotoxic. For LP101 cells, drug plus HRP (minus H(2)O(2)) also induced toxicity. Importantly, other antipsychotic drugs including risperidone, olanzapine and haloperidol when bioactivated, were not cytotoxic, indicating system specificity for clozapine. Exogenous GSH, N-acetylcysteine, l-ascorbic acid, catalase, and sodium azide afforded protection to cells whereas S-methylGSH, GSSG, ketoprofen and proadifen did not. Thus functional data derived from the in vitro stromal system defined in these studies may enable further investigation of the mechanisms subserving stromal impairment in clozapine-induced agranulocytosis and direct attention to improved methods for its prevention.     

Sustained antagonism of acute ethanol-induced ataxia following microinfusion of cyclic AMP and cpt-cAMP in the mouse cerebellum

Ataxia is a conspicuous physical manifestation of alcohol consumption in humans and laboratory animals. Previously we reported possible involvement of cAMP in ethanol-induced ataxia. We now report a sustained antagonism of ataxia due to multiple ethanol injections following intracerebellar (ICB) cAMP or cpt-cAMP microinfusion. Adenylyl cyclase drugs cAMP, cpt-cAMP, Sp-cAMP, Rp-cAMP, adenosine A₁ agonist, N⁶-cyclohexyladenosine (CHA) and GABA_A agonist muscimol were directly microinfused into the cerebellum of CD-1 male mice to evaluate their effect on ethanol (2 g/kg; i.p.) ataxia. Drug microinfusions were made via stereotaxically implanted stainless steel guide cannulas. Rotorod was used to evaluate the ethanol's ataxic response. Intracerebellar cAMP (0.1, 1, 10 fmol) or cpt-cAMP (0.5, 1, 2 fmol) 60 min before ethanol treatment, dose-dependently attenuated ethanol-induced ataxia in general agreement with previous observations. Intracerebellar microinfusion of cAMP (100 fmol) or cpt-cAMP (2 fmol) produced a sustained attenuation of ataxia following ethanol administration at 1, 4, 7 and 25 h or 31 h post-cAMP/cpt-cAMP microinfusion. At 31 h post-cAMP, the ataxic response of ethanol reappeared. Additionally, marked antagonism to the accentuation of ethanol-induced ataxia by adenosine A₁ and GABA_A agonists, CHA (34 pmol) and muscimol (88 pmol), respectively, was noted 24 h after cAMP and cpt-cAMP treatment. This indicated possible participation of AC/cAMP/PKA signaling in the co-modulation of ethanol-induced ataxia by A₁ adenosinergic and GABAergic systems. No change in normal motor coordination was noted when cAMP or cpt-cAMP microinfusion was followed by saline. Finally, Rp-cAMP (PKA inhibitor, 22 pmol) accentuated ethanol-induced ataxia and antagonized its attenuation by cAMP whereas Sp-cAMP (PKA activator, 22 pmol) produced just the opposite effects, further indicating participation of cAMP-dependent PKA downstream. Overall, the results support a role of AC/cAMP/PKA signaling in the expression of ethanol-induced ataxia and its co-modulation by adenosine A₁ and GABA_A receptors.