Moisture-Induced Aggregation of Lyophilized DNA and its Prevention

Purpose To investigate the moisture-induced aggregation (i.e., a loss of solubility in water) of DNA in a solid state and to develop rational strategies for its prevention.Methods Lyophilized calf thymus DNA was exposed to relative humidity (RH) levels from 11% to 96% at 55°C. Following a 24-h incubation under these stressed conditions, the solubility of DNA in different aqueous solutions and the water uptake of DNA were determined. The effects of solution pH and NaCl concentration and the presence of excipients (dextran and sucrose) on the subsequent moisture-induced aggregation of DNA were examined. The extent of this aggregation was compared with that of a supercoiled plasmid DNA.Results Upon a 24-h incubation at 55°C, calf thymus DNA underwent a major moisture-induced aggregation reaching a maximum at a 60% RH; in contrast, the single-stranded DNA exhibited the maximal aggregation at a 96% RH. Moisture uptake and aqueous solubility studies revealed that the aggregation was primarily due to formation of inter-strand hydrogen bonds. Aggregation of DNA also proceeded at 37°C, albeit at a slower rate. Solution pH and NaCl concentration affected DNA aggregation only at higher RH levels. This aggregation was markedly reduced by co-lyophilization with dextran or sucrose (but not with PEG). The aggregation pattern of a supercoiled plasmid DNA was similar to that of its linear calf thymus counterpart.Conclusions The moisture-induced aggregation of lyophilized DNA is caused mainly by non-covalent cross-links between disordered, single-stranded regions of DNA. At high RH levels, renaturation and aggregation of DNA compete with each other. The aggregation is minimized at low RH levels, at optimal solution pH and salt concentration prior to lyophilization, and by co-lyophilizing with excipients capable of forming multiple hydrogen bonds, e.g., dextran and sucrose.     

Comparison of the incidence of influenza in relation to climate factors during 2000–2007 in five countries

Relatively few international comparisons of the incidence of influenza related to climate parameters have been performed, particularly in the Eastern hemisphere. In this study, the incidence of influenza and climate data such as temperature, relative humidity, and rainfall, from cities at different latitudes with contrasting climates: Singapore, Hong Kong (China), Ulaanbaatar (Mongolia), Vancouver (Canada), and three Australian cities (Brisbane, Melbourne and Sydney) were examined to determine whether there was any overall relationship between the incidence of influenza and climate. Applying time‐series analyses to the more comprehensive datasets, it was found that relative humidity was associated with the incidence of influenza A in Singapore, Hong Kong, Brisbane, and Vancouver. In the case of influenza B, the mean temperature was the key climate variable associated with the incidence of influenza in Hong Kong, Brisbane, Melbourne, and Vancouver. Rainfall was not significantly correlated with the incidence of influenza A or B in any of these cities. J. Med. Virol. 82:1958–1965, 2010. © 2010 Wiley‐Liss, Inc.     

眩晕定颗粒的吸湿性研究

目的:研究眩晕定颗粒的吸湿性,确定眩晕定颗粒生产过程中合理的湿度条件及暴露时间。方法:通过测定眩晕定颗粒的吸湿速度及平衡吸湿量,建立其动力学模型,提取吸湿速度参数并比较大小。结果:眩晕定颗粒在不同湿度下的吸湿动力学符合房室模型,吸湿量达到6%对应的相对湿度为56.11%,在此湿度下包装前最久可摆放10.15h。结论:眩晕定颗粒生产中应控制环境湿度在56%以下,分装时暴露时间不可超过10.15h。     

Organic solvents vapor pressure and relative humidity effects on the phase transition rate of α and β forms of tegafur

The objective of this work was to investigate the relative humidity (RH) and solvent vapor pressure effects on the phase transition dynamics between tegafur polymorphic forms that do not form hydrates and solvates. The commercially available α and β modifications of 5-fluoro-1-(tetrahydro-2-furyl)-uracil, known as the antitumor agent tegafur, were used as model materials for this study. While investigating the phase transitions of α and β tegafur under various partial pressures of methanol, n-propanol, n-butanol, and water vapor, it was determined that the phase transition rate increased in the presence of solvent vapors, even though no solvates were formed. By increasing the relative air humidity from 20% to 80%, the phase transition rate constant of α and β tegafur was increased about 60 times. After increasing the partial pressure of methanol, n-propanol, or n-butanol vapor, the phase transition rate constant did not change, but the extent of phase transformation was increased. In the homologous row of n-alcohols, the phase transition rate constant decreased with increasing carbon chain length. The dependence of phase transformation extent versus the RH corresponded to the polymolecular adsorption isotherm with a possible capillary condensation effect.     

Sorption of antimicrobial agents in blow-fill-seal packs

The present work studies the interaction of methyl paraben (MPB) and propyl paraben (PPB), two widely used antimicrobial agents in multi-dose ophthalmic formulations, with 5?mL, low density polyethylene (LDPE) and polypropylene (PP) blow-fill-seal (BFS) packs, by subjecting the systems to accelerated stability conditions of 40°C/25% RH. The effect of pH, paraben concentration, and relative humidity (RH) on the sorption loss of both the parabens was studied. Additionally, the effects of buffer species and buffer strength on MPB sorption were studied. LDPE packs showed significantly higher loss compared to PP packs which showed < 5% loss in all cases. PPB showed a significantly higher loss (40–50%) than MPB (9–16%) in LDPE. pH (3.0, 5.0, 7.0) did not have a statistically significant effect on sorption. However, concentration, humidity and buffer at pH 7 affected paraben sorption. The application of the power law suggested that the MPB followed non-Fickian diffusion while PPB showed non-Fickian to Case II diffusion in LDPE packs. In conclusion, caution should be exercised while using parabens in LDPE BFS packs because substantial losses of the antimicrobial agent during the shelf-life can compromise the preservative effectiveness against ‘in-use’ contamination.     

高湿环境中不同性别人群血清TK-1水平差异性的研究

目的探讨高湿环境对不同性别人群血清胸苷激酶1（TK-1）水平的影响。方法选择来自高湿环境的健康体检者51例,其中,男20例,女31例。采用酶联免疫印迹化学发光法进行TK-1检测。结果 20例男性体检者中,血清TK-1阳性者3例（15.0%）;31例女性体检者中,血清TK-1阳性者13例（41.9%）。女性体检者血清TK-1阳性率明显高于男性（P〈0.05）。结论高湿环境中,女性细胞增殖明显比男性活跃。     

Physiologic Model for Seasonal Patterns in Flu Transmission

Seasonal patterns in flu transmission have observational validity in temperate climates. However, there is no consensus mechanism explaining the increased incidence of flu during the winter. The physiologic effects of cold weather and dry air on the upper respiratory system may contribute to immune dysfunction and increased susceptibly to flu-causing pathogens. Low temperature limits the absolute humidity of air. Persistent exposure to dry air leads to airway desiccation and failure of the mucociliary system. The resultant physiologic and histopathologic changes that occur in the airway increase susceptibility to flu-causing pathogens. Laryngoscope, 130:309–313, 2020     

可见光连续环境消毒系统对手术室消毒前后菌群生物气溶胶浓度的影响

目的探讨可见光连续环境消毒系统(CED)对手术室真菌和细菌气溶胶浓度的影响以及与环境因素的相关性。方法以焦作市第二人民医院5间手术室作为研究对象,分别对CED应用前后手术室内生物气溶胶浓度进行检测,并进行真菌和细菌培养,将检测结果进行比较,并与同期检测的消毒前后的室内温度和湿度相关性进行分析。结果消毒前和消毒后强化消毒模式下手术室内细菌、真菌浓度均较常规消毒模式降低,其次术后消毒完成后强化消毒模式下室内相对湿度相比常规消毒降低,差异均有统计学意义(P<0.05)。消毒过程中手术室的相对湿度标准值为(41.12±4.06)%,温度为(23.41±2.07)℃。经Spearman相关分析显示,消毒后真菌和细菌浓度与相对湿度标准值呈正相关(r=0.109,0.107;P=0.034,0.037),与温度无相关性(P>0.05)。结论常规消毒措施上加用可见光连续环境消毒系统能大大降低手术室的菌群生物气溶胶浓度,同时维持室内相对湿度减少细菌和真菌的繁殖。     

Bronchoconstrictor responses to sulfur dioxide or sulfur dioxide plus sodium chloride droplets in allergic,nonasthmatic adolescents

Eight atopic adolescent subjects without diagnosis of clinical asthma but with signs of hyperactive airways were studied. The subjects were exposed for 30 min at rest followed by 10 min during moderate exercise on a treadmill to the following: (1) filtered air, (2) 1 mg/m³ NaCl droplet aerosol, (3) 1 ppm SO₂ and NaCl droplet aerosol, or (4) 1 ppm SO₂. All exposures were at 75% relative humidity and 22 °C. Exposures to either SO₂ mode produced statistically significant changes in pulmonary function, whereas sham exposures to air on NaCl did not. These results are similar to those seen earlier in a group of extrinsic asthmatic adolescent subjects and are three to 22 times greater than changes we saw in a group of normal adolescent subjects. The changes seen after inhalation of SO₂ were not statistically different from those seen after inhalation of SO₂ and NaCl droplet aerosol. Our results indicate that inhalation of 1 ppm SO₂ by a group of atopic adolescents can produce exercise-induced bronchospasm at a level of exercise that has no effect by itself.     

丹参胶囊的系统稳定性考察

目的:制备丹参提取物和丹参胶囊,研究二者在高湿、高温和光照条件下的稳定性,并考察丹参胶囊及相关物料的吸湿特性。方法:采用UPLC测定丹参素、迷迭香酸、紫草酸和丹酚酸B的含量,流动相0. 05%磷酸水溶液(A)-乙腈(B)梯度洗脱(0～2 min,93%～79. 2%A; 2～6 min,79. 2%～75%A; 6～9 min,75%～65%A; 9～10. 5 min,65%～10%A; 10. 5～11 min,10%～93%A),流速0. 4 mL·min~(-1),检测波长280 nm。通过测定丹参胶囊及相关物料的吸湿增重,绘制吸湿等温曲线,测算临界相对湿度(CRH)。结果:丹参提取物和丹参胶囊分别在温度40℃,相对湿度75%和92. 5%,光照强度(4 500±500) Lx条件下放置10 d后,4个酚酸成分含量波动均在±10%以内,无明显变化趋势;高温60℃条件,二者中的丹参素变化率分别为47. 45%和32. 24%,丹酚酸B变化率分别为-6. 39%和-9. 64%。吸湿性考察显示,淀粉基丸CRH=58. 5%,丹参提取物CRH=72. 34%,包衣丸CRH=72. 85%,丹参胶囊CRH=73. 55%。结论:高温环境会影响丹参提取物和丹参胶囊中酚酸类指标成分的稳定性,为确保丹参提取物及丹参胶囊质量稳定,应避免高温环境。为防止丹参胶囊及其相关物料过度吸湿,淀粉基丸、丹参提取物、丹参包衣丸和丹参胶囊的生产、贮存环境中相对湿度应控制在相应CRH以下。