Flow and injection characteristics of pharmaceutical parenteral formulations using a micro-capillary rheometer

A micro-capillary rheometer consisted of a fine needle with an internal diameter of 347 μm attached to a 1 ml removable-needle syringe within an Instron device that operated in compression mode to provide various crosshead speeds ranging from 150 to 950 mm min⁻¹ covering typical clinical injection rates, and that determined the resulting force on the plunger. The crosshead speed and the resulting force were used to calculate the shear rate and the shear stress respectively. These were used in standard capillary flow expressions together with an independent measurement of the wall frictional force and allowed the viscosity of parenteral Newtonian solutions and non-Newtonian suspensions to be measured quantitatively and their rheological behaviour in needles of clinical dimensions to be established. Commercial pharmaceutical parenteral formulations consisting of three oil-based solutions and three aqueous suspensions were chosen for this study. The net injection forces were also obtained and it was shown that both the oil-based solutions and the aqueous suspensions covered similar ranges. The viscosities for the parenteral solutions were determined from the slope of the linear regression (R²>0.97) between shear stress and shear rate and ranged between 0.029 and 0.060 Pa s. For the aqueous suspensions examined, viscosities decreased from low shear rate to high shear rate, following a power-law model and indicating a pseudo plastic behaviour. Standardisation of the micro-capillary rheometer with Newtonian silicone oils calibrated with a Rheometrics Fluids Spectrometer showed viscosity values consistent between the rotational flow measurements and capillary flow measurements which were within 5% and showed very high degrees of reproducibility between replicate samples. This degree of reproducibility allowed differences in the contribution of the wall frictional force to the required plunger force for both the oil-based and aqueous parenteral formulations to be determined reliably. The wall frictional force values for all formulations were similar (0.6–1.6 N) but the frictional forces of aqueous systems were found to decline significantly with plunger speed. The micro-capillary rheometer has been used to evaluate the impact of concentration changes due to sedimentation on the injectability of one of the aqueous suspensions, where it was shown that not only the viscosity increased but the shear thinning behaviour ceased at higher shear rates. The micro-capillary rheometer which was able to operate in clinical shear rate ranges has been shown to detect deteriorations in the injectable rheology of suspensions, which in the case here was due to pre-injection sedimentation.     

Computational fluid dynamics prediction of blood damage in a centrifugal pump

This study explores a quantitative evaluation of blood damage that occurs in a continuous flow left ventricular assist device due to fluid stress. Computational fluid dynamics (CFD) analysis is used to track the shear stress history of 388 particle streaklines. The accumulation of shear and exposure time is integrated along the streaklines to evaluate the levels of blood trauma. This analysis, which includes viscous and turbulent stresses, provides a statistical estimate of possible damage to cells flowing through the pump. In vitro normalized index of hemolysis values for clinically available ventricular assist devices were compared to our damage indices. This allowed for an order of magnitude comparison between our estimations and experimentally measured hemolysis levels, which resulted in a reasonable correlation. This work ultimately demonstrates that CFD is a convenient and effective approach to analyze the Lagranian behavior of blood in a heart assist device.     

搬运邮袋的生物力学分析及工效学评价

本研究采用生物力学分折方法,分析了14名健康男性受试者搬运两种不同设计(有或无帆布提手)、三种重量(4.5Kg,18.2Kg,31.8Kg)的邮袋时机体的受力情况。结果表明,邮袋增设握手以后,减轻了搬运过程中腰部弯曲程度,在搬运18.2Kg 和31.8Kg 两种重量的邮袋时,腰部所受水平切力明显减少(P<0.01),并可缩短搬运时间(14.1%,35.9%)。提示有提手的设计有利于保护工人健康和提高工作效率。     

剪切力增高对大鼠腹主动脉管径及管壁MMP-9表达的影响

目的:观察腹主动脉局部剪切力增高对其管径及管壁MMP-9表达的影响,分析剪切力增高在动脉重塑中的作用。方法:SD大鼠48只，随机分8组，实验组和对照组各4 组。实验组行肾动脉下腹主动脉-下腔静脉细针穿刺造瘘，术后1，7，14，28 d取标本，观察动脉管径及管壁结构的变化。对照组除不造瘘外，操作同实验组。结果:实验组术后1 d，瘘口近端动脉管径明显增大（P＜0.05),管壁变薄（P＜0.05)，随时间的延长，管径不断增大，管壁不断变薄。MMP-9于术后1 d开始表达，术后7d达高峰（P＜0.01）,并持续高表达(P＜0.01)。结论:剪切力增高可使大鼠腹主动脉出现管径增大，管壁变薄的正性重塑，并导致管壁MMP-9表达上调；此正性重塑与MMP-9表达密切关联；剪切力增高，MMP-9表达增多是导致动静脉瘘形成后瘘口近远端逐渐膨大的重要因素。     

Innovative technology for tissue disruption by explosive-induced shock waves

We have developed a novel, less invasive, shock wave source that can be introduced into an arbitrary position in a human body percutaneously. Using this technique we can disrupt cells locally. The shock wave source consists of an explosive, an optical fiber, a balloon catheter, and a Nd:YAG laser, which generates a spherical explosive shock wave. The destructive potential of the present source for injuring tissue was confirmed and the subsequent cell elongation and split in the direction of the shock wave has been observed.     

Ultrasonic exposure modifies platelet morphology and function in vitro

Samples of human platelet rich plasma (PRP) exposed to 1 MHz ultrasonic irradiation contained more cellular debris than their controls, indicating that a small population of the cells had been disrupted, possibly by some form of cavitation-like activity. The surviving cells appeared undamaged under the electron microscope and functioned as well as their controls in forming a platelet thrombus when tested immediately after the ultrasonic exposure but not after a 30 min incubation at 22°C. Parallel studies showed that incubation of control platelets with substances released from damaged or disrupted platelets could mimic the changes seen in incubated samples which had previously been exposed to ultrasound.     

Quadrant Analysis of Quantitative Computed Tomography Scans of the Femoral Neck Reveals Superior Region-Specific Weakness in Young and Middle-Aged Men With Type 1 Diabetes Mellitus

We have previously shown that the intertrochanter of young and middle-aged patients with type 1 diabetes mellitus (T1DM) showed higher buckling ratio (an index of cortical instability) and lower volumetric bone mineral density (vBMD). However, we have not yet reported the detailed findings regarding the mechanical and density properties of the femoral neck. Therefore, we present a subanalysis of our previous study with the aim of further evaluating the middle third of the femoral neck via quadrant quantitative computed tomography in young and middle-aged patients with T1DM. Bone parameters in 4 anatomical quadrants (superoanterior [SA], inferoanterior [IA], inferoposterior [IP], and superoposterior [SP]) were cross-sectionally evaluated in 17 male T1DM patients and 18 sex-matched healthy controls aged between 18 and 49?yr using quadrant quantitative computed tomography analysis. Patients with T1DM had a thinner cortical thickness in the SP quadrant and a significantly lower cortical vBMD in the SA quadrant than the controls. The serum insulin-like growth factor-1 values in patients with T1DM were positively correlated with the average cortical thickness in the SA quadrant and the average trabecular vBMD in the SP quadrant of the femoral neck. The cortical thickness in controls was negatively correlated with age in the SP and IP quadrants. The cortical thickness in patients with T1DM showed no correlation with age in all quadrants. The fragility of the femoral neck was remarkable in the superior region of patients with T1DM. Insulin-like growth factor-1 may play an important role in superior cortical thinning and in lowering cortical vBMD. Furthermore, in young and middle-aged men with T1DM, the structure of the femoral neck exhibits similar changes as those observed with aging.     

剪切波超声弹性成像技术和表面肌电图在颈肩肌筋膜疼痛综合征疗效评估中的应用

目的:探讨剪切波超声弹性成像(SWE)技术和表面肌电图(sEMG)在颈肩肌筋膜疼痛综合征(MPS)疗效评估中的应用价值。方法:回顾性分析2017年10月~2019年10月间医院收治的90例颈肩(MPS)患者的临床资料,所有患者均接受4个疗程(7d为1疗程)的针刺联合推拿治疗,根据治疗后1个月的疗效划分为A组(54例)、B组(36例)。于治疗前、后采用SWE检测两组患者的杨氏模量值、触发点厚度、组织弹性图评分,并使用sEMG检测平均振幅值、平均频率斜率值,并使用受试者工作曲线(ROC)分析以上指标对颈肩MPS患者疗效的评估价值。结果:治疗前,两组患者的组织弹性图评分、杨氏模量值、筋膜厚度、平均振幅值、平均频率斜率等比较,差异均无统计学意义(P_均>0.05)。治疗后,两组患者的组织弹性图评分、杨氏模量值、筋膜厚度等均低于治疗前(A组B组),差异均具有统计学意义(P_均<0.05)。ROC曲线显示,组织弹性图评分、杨氏模量值、筋膜厚度、平均振幅值、平均频率斜率评估颈肩MPS患者疗效的AUC分别为0.750、0.744、0.836、0.812、0.752,具有一定的价值,且联合检查的价值较高(AUC=0.957,P<0.01)。结论:剪切波超声弹性成像技术联合表面肌电图可用于颈肩肌筋膜疼痛综合征疗效评估。     

Breast mass characterization using shear wave elastography and ultrasound

Purpose

To evaluate the role of SWE in characterizing breast masses and ascertain whether additional use of SWE to ultrasound for evaluating BI-RADS 3 and 4a masses could help reduce long-term follow-up and unnecessary biopsies of these suspicious breast masses.

剪切波弹性成像离散度指标诊断恶性乳腺肿块的价值

目的探讨剪切波速度的变异系数诊断乳腺癌的价值。方法对109个乳腺肿块行剪切波弹性成像,分别测量肿块内最高、最低、中等剪切波速度,根据均数和标准差计算变异系数,并比较乳腺良恶性肿块变异系数的差异。结果乳腺恶性肿块剪切波速度的变异系数明显高于乳腺良性肿块(0.302±0.093vs 0.167±0.057;t=9.361,P0.001)。以剪切波速度的变异系数=0.225为界值诊断乳腺恶性肿块的敏感度为85.00%(34/40),特异度为89.86%(62/69),阳性预测值为82.93%(34/41),阴性预测值为91.18%(62/68)。结论乳腺剪切波速度变异系数能反映乳腺肿块的离散度,是鉴别乳腺良恶性肿块的一个重要指标。