Integrin alpha2beta1 affects mechano-transduction in slowly and rapidly adapting cutaneous mechanoreceptors in rat hairy skin

The role of a transmembrane protein, integrin alpha2beta1, to modulate the neural responses of cutaneous mechanoreceptors to mechanical indentation was examined using an isolated skin-nerve preparation in a rat model. Skin and its intact innervation were harvested from the medial thigh of the hindlimb and placed in a dish containing synthetic interstitial fluid. Using a standard teased nerve preparation, the neural responses of single slowly or rapidly adapting mechanoreceptors (SA or RA, respectively) were identified and the afferents categorized according to standard protocols (i.e. response to constant stimuli). The most sensitive spot of a mechanoreceptor's receptive field was identified and then stimulated using controlled compressive stress (constant or dynamic loads between threshold and saturation load for SAs and RAs, respectively). Loads were applied before, during, and after passive diffusion into the skin of a function-blocking anti-integrin alpha2 monoclonal antibody (FBmAb) or one of two types of control antibodies (immunoglobulin G or a FBmAb conjugated with a secondary antibody). The sensitivities of both SA and RA mechanoreceptors were profoundly reduced in the presence of the FBmAb, while not changing the waveforms of their action potentials or their adaptation properties. Both control antibodies had no significant effect on mechanoreceptors' sensitivities. Following removal of the FBmAb, the effects in some neurons were partially reversible. Taken together, the data from this study support the hypothesis that integrin alpha2beta1 plays a significant role in modulating mechanoreceptive response to compressive indentation.     

Quasi-living surface graft polymerization with phosphorylcholine group(s) at the terminal end

A surface graft polymer with one or two phosphorylcholine (PC) polarheads at the terminus of the growing chain end was prepared by sequential reactions on a glass substrate. The dithiocarbamate group covalently bound to glass surfaces was derivatized with one or two PC groups and then irradiated with ultraviolet light in the presence of N,N-dimethylacrylamide (DMAAm). X-ray photoelectron spectroscopy, wettability measurements and dye staining experiment for the PC group showed that the resultant graft copolymers were produced via iniferter-based quasi-living radical polymerization, in which the polyDMAAm graft chain contains one or two PC groups at the terminal end of the graft chain. These polymer surface grafts may help provide biocompatibility.     

双相气道正压无创机械通气上呼吸道影像分析

目的应用多层螺旋CT对患者不同通气状态下上呼吸道放射性成像,证实在全身麻醉无自主呼吸的条件下,双相气道正压(bi-level positive airway pressure,BiPAP)无创机械通气能克服上呼吸道阻力,实施有效的机械通气。方法选择拟实施全身麻醉的择期手术患者10例,分别对患者清醒自主呼吸、麻醉诱导后自主呼吸停止、BiPAP无创通气时头颈部正位和侧位作螺旋CT扫描。监测扫描过程的无创血压(NIBP)、脉搏氧饱和度(SpO2)、心率(HR)、自主呼吸频率(RR)。测量上呼吸道各软组织区(软腭后区RP、舌根后区RG、会厌区EPG)的最窄气道横截面左右径、前后径线长度及相应横截面积。结果头部正位麻醉诱导后各软组织区的最窄横截面左右径、前后径线长度及相应横截面积均比清醒时缩小(P<0.05),BiPAP通气时各截面径线和面积与清醒期比较差异仍有统计学意义(P<0.05,P<0.01)。头部侧位BiPAP通气时各径线和截面积与清醒时比较,差异无统计学意义。EPG区和RG区在BiPAP通气期的侧位截面积明显比正位时增大(P<0.05,P<0.01)。诱导期正、侧位SpO2均明显下降(P<0.01);头部正位BiPAP通气时与诱导期的SpO2比较虽有改善,但差异无统计学意义(P>0.05);头部侧位BiPAP通气时SpO2较诱导期明显升高(P<0.01),基本恢复到清醒期水平(P>0.05)。结论麻醉诱导后上呼吸道的通气面积明显减少,气道通畅度下降;头颈部侧位时上呼吸道各软组织区最狭窄处的通气截面积比正位时显著改善,以会厌区最明显。无明显上呼吸道梗阻性病史的成年患者全身麻醉时,头部侧位BiPAP无创通气能克服上呼吸道阻力,实施有效的机械通气,保证通气和氧合正常。     

高压氧治疗重度颅脑损伤后临床、脑电地形图及预后的探讨

目的:探讨高压氧治疗重度颅脑损伤的疗效。方法:重度颅脑损伤患者35例为治疗组,20例为对照组,观察高压的氧治疗前后临床、脑电地形图的变化及预后。结果:治疗组临床(GCS)、脑电地形图及预后经高压氧治疗后均明显改善,而对照组改善不明显。结论:高压氧能够明显改善重度颅脑损伤患者的临床,脑电地形图及预后。     

组蛋白去乙酰化酶抑制剂与5-FU合用对肝癌细胞HepG2的影响

目的：探讨MS-275和5-Fu联用对HepG2细胞周期和凋亡的影响，并对其机制进行初步探讨。方法：将细胞分成对照组、MS-275组、5-FU组和联合用药组。流式细胞仪检测各组细胞凋亡和周期变化；Westernblot分析各组Bcl-2、Bax、CyclinD1、P21蛋白表达。结果：MS-275和5-Fu联用能抑制肝癌细胞生长，诱导G0—G1期阻滞，促进细胞凋亡。上述效应具有时间和剂量依赖性。二者联用可以使P21蛋白上调，Bcl-2、CyclinD1蛋白下调，Bax蛋白无明显变化。结论：5-Fu和MS-275联用能提高HepG2细胞凋亡率和周期阻滞，其机制与下调CyclinD1、Bcl-2蛋白的表达、上调P21蛋白表达有关。     

Presynaptic opioid kappa-receptor and regulation of the release of Met-enkephalin in the rat brainstem

Opioid kappa-agonists had much more potent inhibitory effects on the high K+-evoked Met-enkephalin release from rat brain slices than did the mu- or delta-agonists. The opioid kappa- antagonist, MR2266 enhanced the evoked release of Met-enkephalin to a greater extent than did mu- or delta-antagonists in vitro and had a potent analgesia in mice in vivo. These findings suggest that the release of Met-enkephalin may be regulated in vitro and in vivo, mainly by presynaptic kappa-receptor-mediated mechanisms.     

Brachydactyly type A3 is caused by a novel 13 bp HOXD13 frameshift deletion in a Chinese family

Brachydactyly type A (BDA) is defined as short middle phalanges of the affected digits and is subdivided into four types (BDA1‐4). To date, the molecular cause is unknown. However, there is some evidence that pathogenic variants of HOXD13 could be associated with BDA3 and BDA4. Here, we report a Chinese autosomal dominant BDA3 pedigree with a novel HOXD13 mutation. The affected individuals presented with an obviously shorter fifth middle phalanx. The radial side of the middle phalanx was shorter than the ulnar side, and the terminal phalanx of the fifth finger inclined radially and formed classical clinodactyly. Interestingly, the index finger was normal. The initial diagnosis was BDA3. However, the distal third and fourth middle phalanges were also slightly affected, resulting in mild radial clinodactyly. Both feet showed shortening of the middle phalanges, which were fused to the distal phalanges of the second to the fifth toes, as reported in BDA4. Therefore, this pedigree had combined BDA3 and atypical BDA4. By direct sequencing, a 13 bp deletion within exon 1 of HOXD13 (NM_000523.4: c.708_720del13; NP_000514.2: p.Gly237fs) was identified. The 13 bp deletion resulted in a frameshift and premature termination of HOXD13. This study provides further evidences that variants in HOXD13 cause BDA3‐BDA4 phenotypes.     

Cortical dendritic pathology in human immunodeficiency virus encephalitis.

Previous neuropathological and morphometric studies of the cerebral cortex of patients with human immunodeficiency virus encephalitis (HIVE) have shown a decrease in the population of large neurons, moderate loss in synaptophysin immunoreactivity, and pathological changes in dendrites. To further characterize and quantify alterations in the dendritic tree of neocortical pyramidal neurons, we performed a modified Golgi impregnation technique on Formalin fixed blocks from the frontal cortex of 5 HIVE cases, 5 human immunodeficiency virus seropositive control cases without encephalitis, and 5 human immunodeficiency virus seronegative controls. Apical dendrites of HIVE cases were dilated, vacuolated, and tortuous with decreased length and branching. Basal and oblique dendrites also showed these alterations, but to a lesser extent. Some dendrites presented lacunae and filopodia consistent with remodeling. Computer aided quantification of HIVE cases showed a 40-60% decrease in spine density throughout the entire length of dendrites. Laser confocal imaging of Golgi impregnated sections displayed aberrant spines in regions of abnormal second order dendritic branches. These observations support the role of primary dendritic damage in HIVE in contrast to other neurodegenerative disorders where the primary pathology is presynaptic.     

Physics-Driven CFD Modeling of Complex Anatomical Cardiovascular Flows—A TCPC Case Study

Recent developments in medical image acquisition combined with the latest advancements in numerical methods for solving the Navier-Stokes equations have created unprecedented opportunities for developing simple and reliable computational fluid dynamics (CFD) tools for meeting patient-specific surgical planning objectives. However, for CFD to reach its full potential and gain the trust and confidence of medical practitioners, physics-driven numerical modeling is required. This study reports on the experience gained from an ongoing integrated CFD modeling effort aimed at developing an advanced numerical simulation tool capable of accurately predicting flow characteristics in an anatomically correct total cavopulmonary connection (TCPC). An anatomical intra-atrial TCPC model is reconstructed from a stack of magnetic resonance (MR) images acquired in vivo. An exact replica of the computational geometry was built using transparent rapid prototyping. Following the same approach as in earlier studies on idealized models, flow structures, pressure drops, and energy losses were assessed both numerically and experimentally, then compared. Numerical studies were performed with both a first-order accurate commercial software and a recently developed, second-order accurate, in-house flow solver. The commercial CFD model could, with reasonable accuracy, capture global flow quantities of interest such as control volume power losses and pressure drops and time-averaged flow patterns. However, for steady inflow conditions, both flow visualization experiments and particle image velocimetry (PIV) measurements revealed unsteady, complex, and highly 3D flow structures, which could not be captured by this numerical model with the available computational resources and additional modeling efforts that are described. Preliminary time-accurate computations with the in-house flow solver were shown to capture for the first time these complex flow features and yielded solutions in good agreement with the experimental observations. Flow fields obtained were similar for the studied total cardiac output range (1–3 l/min); however hydrodynamic power loss increased dramatically with increasing cardiac output, suggesting significant energy demand at exercise conditions. The simulation of cardiovascular flows poses a formidable challenge to even the most advanced CFD tools currently available. A successful prediction requires a two-pronged, physics-based approach, which integrates high-resolution CFD tools and high-resolution laboratory measurements.