应用沉淀法消除HLAP患者生化标本乳糜状态的探讨

目的探索磷钨酸镁沉淀法在高脂血症性急性胰腺炎(HLAP)患者标本进行生化检验前对重度乳糜状态的消除作用。方法取外观正常标本经磷钨酸镁处理后做各项生化检验,与处理前数据进行相关性分析;以脂肪乳液配制轻、中、重3组模拟乳糜血清做回收试验,计算各生化项目的回收率;收集HLAP患者标本做实证试验,观察乳糜消除效果和生化检验效果。结果除了二氧化碳结合力(CO2CP)、总胆红素(TBil)、直接胆红素(DBil)、肌酸激酶同工酶MB(CK-MB)、乳酸脱氢酶同工酶1(LD-1)、半胱氨酸蛋白酶抑制剂C(Cys C)、高敏C反应蛋白(hs-CRP)外,钾离子(K+)、钠离子(Na+)、氯离子(Cl-)、钙离子(Ca2+)、血糖(Glu)、尿素(Urea)、尿酸(UA)、肌酐(Cr)、淀粉酶(AMY)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、γ-谷氨酰基转移酶(GGT)、碱性磷酸酶(ALP)、胆碱酯酶(CHE)、总蛋白(TP)、白蛋白(Alb)、总胆汁酸(TBA)、肌酸激酶(CK)、乳酸脱氢酶(LD)、α-羟丁酸脱氢酶(α-HBDH)经磷钨酸镁处理后均可正确检测,且与处理前呈高度的直线相关,拟合曲线显著性检验显示P均0.01。回收试验中3组模拟乳糜血清各生化项目的回收率最低为98.03%,最高为103.44%,回收效果良好。HLAP患者标本经磷钨酸镁处理后可正确检测的生化项目与相关性分析实验中外观正常的标本一致,甘油三酯(TG)10 mmol/L或TG40 mmol/L的标本乳糜消除效果明显,TG为10~40 mmol/L的标本需先做稀释使TG10 mmol/L再做处理。结论磷钨酸镁沉淀法清除血脂效果显著,对绝大多数的生化检验不会产生干扰,适用于重度乳糜状态的HLAP患者标本生化检验前的处理。     

2006-2010年成都市气温、降雨量与蚊密度监测

目的分析平均气温与降水量对成都监测点蚊密度监测的影响,为提高国家病媒生物监测质量提供参考。方法使用2006-2010年国家成都病媒监测点蚊密度(诱蚊灯)监测结果,与监测日当旬平均气温与旬旬降水量由SPSS软件计算Spearman秩相关系数,偏相关系数。结果成都蚊密度监测结果与平均气温呈不同程度正相关(r∶0.21-0.91,P∶0.00-0.04),降水量则与蚊密度关系较弱(r∶-0.04-0.59,P∶0.02-0.05)。结论降雨量对蚊密度监测结果有正反两方面影响(r∶-0.32-0.38,P∶0.02-0.04),蚊密度监测需注意规避降雨日。     

Precipitation in the small intestine may play a more important role in the in vivo performance of poorly soluble weak bases in the fasted state: Case example nelfinavir

The aim of this study was to evaluate the utility of biorelevant dissolution tests coupled with in silico simulation technology to forecast in vivo bioperformance of poorly water-soluble bases, using nelfinavir mesylate as a model compound.An in silico physiologically based pharmacokinetic (PBPK) model for poorly water-soluble, weakly basic drugs was used to generate plasma profiles of nelfinavir by coupling dissolution results and estimates of precipitation with standard gastrointestinal (GI) parameters and the disposition pharmacokinetics of nelfinavir. In vitro dissolution of nelfinavir mesylate film-coated tablets was measured in biorelevant and compendial media. Drug precipitation in the small intestine was estimated from crystal growth theory. GI parameters (gastric emptying rate and fluid volume) appropriate to the dosing conditions (fasting and fed states) were used in the PBPK model. The disposition parameters of nelfinavir were estimated by fitting compartmental models to the in vivo oral PK data. The in vivo performance in each prandial state was simulated with the PBPK model, and predicted values for AUC and C_max were compared to observed values.Dissolution results in FaSSIF-V2 and FeSSIF-V2, simulating the fasting and fed small intestinal conditions, respectively, correctly predicted that there would be a positive food effect for nelfinavir mesylate, but overestimated the food effect observed in healthy human volunteers. In order to better predict the food effect, an in silico PBPK simulation model using STELLA® software was evolved. Results with the model indicated that invoking drug precipitation in the small intestine is necessary to describe the in vivo performance of nelfinavir mesylate in the fasted state, whereas a good prediction under fed state conditions is obtained without assuming any precipitation. In vitro–in silico–in vivo relationships (IVISIV-R) may thus be a helpful tool in understanding the critical parameters that affect the oral absorption of poorly soluble weak bases.     

Reference antigen-free and antibody-free LTD-IDMS assay for influenza H7N9 vaccine in vitro potency determination

Influenza vaccines are the most effective intervention to prevent the substantial public health burden of seasonal and pandemic influenza. Hemagglutinin (HA), as the main antigen in inactivated influenza vaccines (IIVs), elicits functional neutralizing antibodies and largely determines IIV effectiveness. HA potency has been evaluated by single-radial immunodiffusion (SRID), the standard in vitro potency assay for IIVs, to predict vaccine immunogenicity with a correlation to protective efficacy. We previously reported that limited trypsin digestion (LTD) selectively degraded stressed HA, so that an otherwise conformationally insensitive biophysical quantification technique could specifically quantify trypsin-resistant, immunologically active HA. Here, we demonstrate that isotope dilution mass spectrometry (IDMS), a method capable of quantifying the absolute HA concentration without reference antigen use, can be further expanded by adding LTD followed with precipitation to selectively quantify the active HA. We test the LTD-IDMS assay on H7N9 vaccines stressed by low pH, raised temperature, or freeze/thaw cycles. This method, unlike SRID, has no requirement for strain-specific reference antigens or antibodies and can generate potency values that correlate with SRID. Thus, LTD-IDMS is a promising alternative in vitro potency assay for influenza vaccines to complement and potentially replace SRID in a pandemic when strain specific reagents may not be readily available.     

From Precipitation to Inhibition of Seizures: Rationale of a Therapeutic Paradigm

Summary:  Epileptic seizures can be triggered by both nonspecific facilitating factors such as sleep withdrawal, fever, or excessive alcohol intake, and specific reflex epileptic mechanisms. These consist of sensory or cognitive inputs activating circumscribed cortical areas or functional anatomic systems that, due to some functional instability, respond with an epileptic discharge. Interruption of seizure activity at the stage of the aura (i.e., locally restricted discharge) also can be achieved by nonspecific (e.g., relaxation or concentration techniques or vagal nerve stimulation) or by specific focus-targeted sensory or cognitive inputs. The latter, again, activate circumscribed cortical areas. Intriguingly, in some patients, the same stimulus can either precipitate or abort a seizure. The response depends on the state of cortical activation: seizure precipitation occurs in the resting condition, and seizure interruption occurs when the epileptic discharge has begun close to the activated area. These relations can be understood on the background of experimental data showing that an intermediate state of neuronal activation is a precondition for the generation of paroxysmal depolarization shifts, whereas a hyperpolarized neuron will remain subthreshold, and a depolarized neuron that already produces action potentials is not recruitable for other activity. Sensory input meeting an intermediately activated pool of potentially epileptic neurons is adequate to produce a seizure. In another condition, the same stimulus can depolarize a neuron pool in the same area sufficiently to block the further propagation of nearby epileptic activity. Understanding these interactions facilitates the development of successful nonpharmaceutical therapeutic interventions for epilepsy.     

Present Status of Apheresis Technologies: Part 2. Membrane Plasma Fractionator

Abstract: This article is the second of a 4 part series describing currently available apheresis devices and technologies. The sections will include: Part 1: Membrane Plasma Separator (published in Vol. 1); Part 2: Membrane Plasma Fractionator; Part 3: Leukocyte Filter; and Part 4: Adsorbent.—     

Physical Stability and Dissolution of Lumefantrine Amorphous Solid Dispersions Produced by Spray Anti-Solvent Precipitation

This study aims to develop amorphous solid dispersion (ASD) of lumefantrine with a cost-effective approach of spray anti-solvent precipitation. Four acidic polymers, hydroxypropylmethylcellulose phthalate (HPMCP), hydroxypropylmethylcellulose acetate succinate (HPMCAS), poly(methacrylic acid–ethyl acrylate) (EL100) and cellulose acetate phthalate (CAP) were studied as excipients at various drug-polymer ratios. Of the studied polymers, satisfactory physical stability was demonstrated for HPMCP- and HPMCAS-based ASDs with no observed powder X-ray diffraction peaks for up to 3 months of storage at 40 °C/75% RH. HPMCP and HPMCAS ASDs also achieved greater drug release levels in the dissolution study than other polymers. The HPMCP-based ASDs with a drug:polymer ratio of 2:8 exhibited a maximum drug release of 140 μg/mL for up to 2 h, which is significantly higher than the currently marketed formulation of Coartem® (<80 ng/mL). Relatively, the CAP and EL100 ASDs indicated a higher water content and crystallized within a day when stored at 40 °C/75% RH. The choice of polymer, and the drug-polymer ratio played a crucial role in the solubility enhancement of lumefantrine. Our study indicates that the developed spray anti-solvent precipitation method could be an affordable approach for producing ASDs.     

Electrocrystallization of calcium carbonate on carbon-based electrodes

Calcium carbonate was deposited by electrochemical reduction of oxygen to hydroxyl ions at various carbon-based electrodes. Although some vaterite was observed during earlier stages of the electrodeposition, the predominant polymorph during later stages was calcite. The average crystal size reached a value of 15 μm after 10 h at a glassy carbon electrode but the crystal growth rate was substantially accelerated when oxygen was catalytically reduced. The same average size of the calcite crystals in this case (Pt/C electrode) was reached within a period of 1.5 h. Efficient removal of CaCO₃ from water was demonstrated when using a porous aerogel carbon electrode and a potential sufficiently negative to promote reduction of water molecules within the pores.     

沈阳市大气微生物的研究5、大气真菌粒子的沉降量

本文用平皿沉降法对沈阳市大气真菌粒子沉降量进行了一年的观测.结果表明,沈阳市大气真菌粒子的年平均沉降量为15.1个/皿5min;一年中,大气真菌粒子沉降量秋季大,冬季明显小;一天中,21:00时为大气真菌粒子沉降量的高峰时;造纸厂大气真菌粒子沉降量大,市郊清洁区沉降量小。     

Intermediate phases in the basic solution preparation of alkaline earth phosphates

The first solid to appear in the precipitation of calcium phosphates from basic solutions is structurally non-crystalline. The existence, however, of a solution-prepared, non-crystalline orthophosphate salt is not unique only to the calcium phosphate system. Non-crystalline magnesium phosphates and magnesium ammonium phosphates can also be prepared under comparable conditions, but unlike the calcium salt, which converts into hydroxyapatite, these latter compounds are apparently solution stable. Preparations of strontium and barium orthophosphates from basic solution do not yield non-crystalline intermediates. For strontium, the intermediate phase is Sr₃(PO₄)₂·4H₂O, whereas the barium precipitates immediately as a stable barium hydroxyapatite. The tristrontium phosphate, however, converts autocatalytically into strontium hydroxyapatite. The analogous stoichiometry and identical kinetic behavior of the strontium intermediate with that of the amorphous calcium phosphate suggest that the latter could be a tricalcium phosphate rather than a cryptocrystalline Ca-deficient hydroxyapatite. This supports the possibility that the non-crystalline phase in bone mineral may not be an apatite but instead a distinct and separate compound.This work supported in part by PHS Grant DE-09145 from the National Institute of Dental Research, USA. Publication Number 44 from The Laboratory of Ultrastructural Biochemistry.