Microstructural imaging of early gel layer formation in HPMC matrices

A real-time confocal fluorescence imaging method has been developed which allows the critical early stages of gel layer formation in hydroxypropylmethylcellulose (HPMC) matrices to be examined. Congo Red, a fluorophore whose fluorescence is selectively intensified when bound to beta-D-glucopyranosyl sequences, has allowed mapping of hydrated polymer regions within the emerging gel layer, and revealed for the first time, the microstructural sequence of polymer hydration during development of the early gel layer. Liquid penetration and swelling can be examined in unprecedented detail. The earliest images revealed an initial phase of liquid ingress into the tablet pore network, followed by the progressive formation of a coherent gel layer by outward columnar swelling and coalescence of hydrated HPMC particles. Salts can markedly affect HPMC matrix behaviour. Gel layer growth in 0.1-0.5 M NaCl was progressively suppressed until at 0.75 M, particles clearly failed to coalesce into a gel layer, although with considerable polymer swelling. The failure to form a limiting diffusion barrier resulted in enhanced liquid penetration of the core, and the swelling of particles that did not coalesce culminated in surface disintegration. This provides direct evidence of physical mechanisms that contribute to salts accelerating drug release from HPMC matrices.     

盐酸多西环素注射用缓释凝胶的体内释药研究

目的考察盐酸多西环素注射用缓释凝胶的体内释放特性及体内外相关性。方法将含药凝胶注射到家兔牙龈内 ,用HPLC法测定不同时间凝胶中的残余药量 ,从而计算药物的释放量。结果 7d盐酸多西环素的释放度达 99 7%。结论药物可缓释 7d ,体内外相关。     

Use of strips containing tetracycline hydrochloride or metronidazole for the treatment of advanced periodontal disease

Strips containing tetracycline hydrochloride or metronidazole 25% in polyhydroxybutyric acid as a biodegradable polymer matrix, showed sustained release in simulated gingival fluid pH 6.6 at 37 degrees C. When evaluated in patients suffering from advanced periodontal disease, the greatest response to therapy was observed with tetracycline hydrochloride strips inserted into periodontal pockets at four-day intervals for 16 days, compared with an untreated control group. A reduction in plaque index, gingival index and pocket depth was observed. A favourable alteration occurred in the microbial flora of treated pockets with an increase in the proportion of cocci and decrease in gram-negative rods, fusiforms and spirochetes. Metronidazole strips or root-planning tended not to be as effective. The clinical improvement produced by each treatment was not maintained when treatment was terminated.     

膝关节类风湿性关节炎的MRI诊断

目的探讨磁共振成像(MRI)技术在类风湿性关节炎(RA)患者膝关节病变临床诊断中的应用价值.方法对32例51个膝关节进行磁共振检查,并分析其表现.结果MRI显示了RA患者膝关节的滑膜增生及血管翳形成、关节软骨破坏、骨质受侵、关节囊积液及周围邻近软组织的改变,并可通过血管翳的信号和强化程度判断疾病的时期.结论MRI能直接显示RA患者膝关节的各种改变,与X线及CT比较有明显优势,有助于疾病的早期诊断和临床分期.     

磁共振成像造影剂的临床应用研究

综述磁共振成像造影剂在临床的应用，着重介绍磁共振造影剂的组成成分，在人体内代谢的详细过程，不同序列上信号的不同，造影剂如何是病灶弛豫时间发生改变，从而使我们在临床工作中能够准确的诊断疾病，为临床治疗提供依据。     

Magnetic resonance imaging of the rat brain following acute carbon monoxide poisoning.

Magnetic resonance (MR) may be used for repeatedly and non-invasively imaging the brain. Until now, no studies have used this approach to study the effects of carbon monoxide (CO) poisoning in a defined animal model. Conscious, Levine-prepared female rats (unilateral carotid artery and jugular vein occlusion) were exposed to 2400 ppm CO for 90 min, with or without the infusion of 50% glucose solution; CO-stimulated increases in blood glucose and lactate occurred in both groups, while blood pressure and body temperature fell. One to four hours following termination of CO exposure, increased cortical pixel intensity, cortical surface area and brain midline shift were observed on the operated side of the brain in some rats of both groups (i.e. responders = R), providing evidence of edema. At sacrifice, 5 h following termination of CO exposure, gross water content was increased on the left side in the corresponding cortical slices in R rats, providing another measure of edema. Significant positive correlations were found between left to right pixel intensity difference and water content difference, and between the extent of midline shift and water content difference. The elevations of blood glucose and lactate concentrations, and the magnitudes of CO-induced hypothermia and hypotension were similar to those in past studies, but appeared to exert no effect on the severity of cortical edema in terms of differences in pixel intensity, surface area, midline shift or gross tissue water content. Thus, the observed differences between the R rats is not explained by the available data.(ABSTRACT TRUNCATED AT 250 WORDS)     

Magnetic resonance imaging investigation of the mixing-segregation process in a pharmaceutical blender.

Magnetic Resonance Imaging (MRI) was used to study the mixing process of binary mixtures of free flowing sugar beads in a Turbula mixer. In order to make particles MRI-sensitive, some reference beads were doped with an organic oil. Doped and undoped particles were mixed and MRI was used to non-destructively image the particle bed for a given number of mixer rotations (NR), bead diameter ratio (R=d(ref)/d(i)) and rotation speed (V). All the results were quantified on the basis of image analysis to characterise the degree of mixing. Studies showed that for binary mixtures of identical particle size, the mixing was complete after 30 rotations, whereas for beads of different size (R=2.8) a segregated steady state was obtained after nearly 10 rotations. Experiments revealed that segregation appeared as soon as R=0.9. Moreover, the lower the rotation speed, the more segregated the final state was. It appeared that for a filling level greater than 80%, dead regions appeared in the centre of the powder bed. In conclusion, when the particles are non-cohesive, the Turbula blender perfectly mixes identical beads but segregation occurs for beads of different size after just a few rotations.     

盐酸川芎嗪眼用原位温敏凝胶的制备及体外释药特性研究

目的：制备盐酸川芎嗪眼用原位温敏凝胶并对其体外释药特性进行考察。方法采用泊洛沙姆407和泊洛沙姆188为温敏基质制备眼用温敏凝胶,采用无膜溶出模型,研究药物在某一时间的累积释放百分率与时间的变化,对曲线进行拟合分析,研究川芎嗪的体外释放特性。结果所制得凝胶为均匀稍带黏性的澄清溶液,该制剂的体外释放行为遵循零级动力学方程（r ＝0．9887）,由 Ritger －Peppas 方程拟合的 n 值为0．7533。结论盐酸川芎嗪眼用温敏凝胶体外释药是由药物扩散和凝胶溶蚀双重机制控制。     

Magnetic resonance imaging of the rabbit knee: detection of cartilage proteoglycan degradation.

Intra-articular (i.a.) injection of papain causes a reversible loss of proteoglycan in intact rabbit knees. Twelve rabbits were scanned with magnetic resonance imaging (MRI) at 0, 24, 48 and 72 hours after 5 units of papain i.a. in a 1.5 Tesla Signa with a three inch surface coil using spin echo sequence. Total cartilage thickness in proton density images was 1.08 +/- 0.09 mm prior to papain injection. The magnetic resonance images showed a reduction in articular cartilage thickness in papain-treated rabbit femurs at 24 hours to 0.69 +/- 0.18 mm and partial restoration by 72 hours to 0.77 +/- 0.21 mm.     

胫骨平台骨折软组织损伤磁共振成像分析及前瞻性流行病学研究

目的确定胫骨平台骨折病例伴发的膝关节周围主要软组织结构损伤的发病率及其流行病学特点。方法采用前瞻性队列研究方法。选取2004年1月至2008年12月内我院诊治的胫骨平台骨折病例共102例,其中87例接受手术治疗而入组。所有人组病例于急诊情况下进行膝关节标准x光检查,包括前后位、侧位影像。术前准备阶段均接受MRI检查。基于x线影像以Schatzker分类对胫骨平台骨折进行分型。基于MRI影像对膝关节周围软组织结构损伤情况进行评估。在MRI影像上主要评估膝关节周围4个重要软组织结构,包括交叉韧带、侧副韧带、半月板及后外侧角结构的16种损伤类型,损伤情况以阳性或阴性表示。结果胫骨平台骨折时膝关节周围主要软组织结构损伤的总发生率为100％。所有入组病例均有不同程度的软组织结构损伤。68例患者（78．2％）有外侧半月板损伤;40例（46．0％）存在内侧半月板撕裂。有61例（70．1％）存在前交叉韧带的损伤;35例（40．2％）存在后交叉韧带的损伤。66例（75．9％）有外侧副韧带部分或完全撕裂;80例（92．0％）存在内侧副韧带损伤。64例患者（73．6％）存在一处或多处后外侧角结构损伤。入组病例中最常见的骨折类型是SchatzkerlI型（41．4％）。高能量损伤类型SchatzkerⅣ、Ⅴ、Ⅵ型骨折发生率分别为12．6％、16．1％和13．8％。其中SchatzkerⅢ型的发生率为5．7％。结论胫骨平台骨折时膝关节周围软组织结构损伤发病率较高。其中Ⅲ型骨折仍存在一定发生率。在胫骨平台骨折各类型骨折模式中各种软组织损伤发生率各不相同、各有特点。软组织损伤特点不仅反应了损伤机制,同时也为骨折手术治疗方案提供佐证。术前需要认真分析骨折及软组织损伤特点。     

Magnetic resonance imaging and transient elastography in the management of Nonalcoholic Fatty Liver Disease (NAFLD)

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and cirrhosis worldwide and the second most common cause of liver transplantation in major medical centers. Because liver steatosis and fibrosis severity are related to disease morbidity and mortality, the extent of disease, and disease progression, they need to be assessed and monitored. In addition, innovation with new drug developments requires disease staging and monitoring in both phase 2 and 3 clinical trials. Currently, disease assessment in both clinical practice and research is mostly performed by liver biopsy, an invasive, procedure with risks. Noninvasive, highly accurate tests are needed that could be used in clinical trials as surrogate endpoints and in clinical practice for monitoring patients.

Area Covered: We discuss noninvasive tests, transient elastography (TE) with controlled attenuation parameter (CAP), magnetic resonance imaging (MRI), and MR elastography (MRE), summarize the available evidence of their usefulness for assessing steatosis and fibrosis. Therefore they could be used as clinical trials outcomes and in disease monitoring in clinical practice.

Expert Commentary: TE with CAP, MRI and MRE are highly accurate noninvasive diagnostic tools for quantifying hepatic steatosis and fibrosis. Therefore they could be used as clinical trials outcomes and in disease monitoring in clinical practice.     

盐酸曲马多多层控释骨架片的体外释药规律

以羟丙基甲基纤维素为主要骨架材料 ,将高水溶性药物盐酸曲马多制成多层控释骨架片 ,研究了影响多层骨架片体外释药速率的因素。结果表明 ,通过改变盐酸曲马多多层骨架片各层组成 ,可以灵活地改变其释药速率。多层骨架片系统可以避免初始的突释现象 ,而且其体外释药规律可以接近零级。因此 ,多层骨架片系统是制备高水溶性药物控释制剂的有效方法     

磁共振造影剂的处方筛选和稳定性研究

目的预得到超顺磁流体制剂的最优处方 ,然后对其注射液的稳定性进行了初步研究。方法运用均匀设计进行处方筛选 ,经典恒温法预测有效期。结果其注射液在 pH值为中性时比较稳定 ,光照无影响 ,有效期约 3年。结论超顺磁流体注射液的稳定性较好     

Application of FTIR spectroscopic imaging to study the effects of modifying the pH microenvironment on the dissolution of ibuprofen from HPMC matrices

This work presents the novel application of attenuated total reflection-Fourier transform infrared spectroscopic (ATR-FTIR) imaging to study the dissolution of ibuprofen form tablets in which the internal pH of the matrix has been modified by addition of acidic and basic powders to the formulations. Acidic additives to the matrix retarded the dissolution of crystalline ibuprofen domains. Basic additives formed both soluble and insoluble salts with the ibuprofen depending on the pH modifier added. Tablets consisting of hydroxypropyl methylcellulose, ibuprofen, and an acidic or basic additive were studied. FTIR imaging in ATR mode was used for analysis of water ingress into the tablet and the presence, distribution, and chemical state of the drug. The FTIR imaging data showed distinct changes in the dissolution of crystalline ibuprofen between the formulations with different pH modifiers. In the basic formulations, FTIR imaging identified the formation of salts. The sodium salt formed was highly soluble and enhanced dissolution, whereas the calcium salt was highly insoluble and slowed the dissolution. FTIR imaging has produced important data concerning the internal matrix dissolution performance.     

磁共振评估急性心肌梗死患者心肌活性及与超敏C反应蛋白的相关性

目的用磁共振评估急性心肌梗死(AMI)患者心肌活性,并分析其与超敏C反应蛋白(hs-CRP)的相关性。方法选择AMI患者43例,健康对照组30名,利用磁共振灌注及延迟成像将AMI患者分为透壁增强组、非透壁增强组和混合组。AMI患者于经皮冠状动脉介入治疗(PCI)术前及术后6个月分别行心脏磁共振分析梗死心肌质量、左室射血分数及室壁运动异常评分的变化。AMI患者分别于病程第7日及PCI术后6个月抽取肘静脉血测血清hs-CRP水平。健康对照组抽1次血测血清hs-CRP水平。分析PCI术前及术后血清hs-CRP水平的变化及与磁共振检测结果的相关性。结果梗死心肌质量及室壁运动异常评分在PCI术后均减少,梗死心肌质量在非透壁增强组及混合组中减少差异有统计学意义(P<0.05),室壁运动异常评分在非透壁增强组降低(P<0.05);左室射血分数在3组患者PCI术后均增加,在非透壁增强组及混合组中增加差异有统计学意义(P<0.05)。PCI术前及术后6个月血清hs-CRP较健康对照组均降低,但术前与健康对照组比较差异有统计学意义(P<0.05)。PCI术后6个月血清中hs-CRP较术前明显降低(P<0.05)。PCI术前的左室射血分数与血清中hs-CRP独立相关(R2=0.318,P<0.05)。结论磁共振灌注技术可以有效预测心肌梗死患者的心肌活性,对临床治疗及评估预后具有较为重要的临床价值。检测血清hs-CRP对预测心肌活性,评估冠状动脉缺血严重程度及判断预后具有一定的临床意义。     

Magnetic resonance imaging and computational fluid dynamics (CFD) simulations of rabbit nasal airflows for the development of hybrid CFD/PBPK models

The percentages of total airflows over the nasal respiratory and olfactory epithelium of female rabbits were calculated from computational fluid dynamics (CFD) simulations of steady-state inhalation. These airflow calculations, along with nasal airway geometry determinations, are critical parameters for hybrid CFD/physiologically based pharmacokinetic models that describe the nasal dosimetry of water-soluble or reactive gases and vapors in rabbits. CFD simulations were based upon three-dimensional computational meshes derived from magnetic resonance images of three adult female New Zealand White (NZW) rabbits. In the anterior portion of the nose, the maxillary turbinates of rabbits are considerably more complex than comparable regions in rats, mice, monkeys, or humans. This leads to a greater surface area to volume ratio in this region and thus the potential for increased extraction of water soluble or reactive gases and vapors in the anterior portion of the nose compared to many other species. Although there was considerable interanimal variability in the fine structures of the nasal turbinates and airflows in the anterior portions of the nose, there was remarkable consistency between rabbits in the percentage of total inspired airflows that reached the ethmoid turbinate region (~50%) that is presumably lined with olfactory epithelium. These latter results (airflows reaching the ethmoid turbinate region) were higher than previous published estimates for the male F344 rat (19%) and human (7%). These differences in regional airflows can have significant implications in interspecies extrapolations of nasal dosimetry.