Efficacy and tolerability of ophthalmic epinastine: a randomized, double-masked, parallel-group, active- and vehicle-controlled environmental trial in patients with seasonal allergic conjunctivitis

BACKGROUND: Epinastine hydrochloride is an antihistamine with mast cell-stabilizing and anti-inflammatory activity. OBJECTIVE: The aim of this study was to assess the efficacy and tolerability of ophthalmic epinastine in patients with seasonal allergic conjunctivitis (SAC) exposed to environmental allergens. METHODS: This randomized (age-stratified), double-masked, parallel-group, active- and vehicle-controlled, environmental, Phase III clinical trial was conducted at 6 ophthalmology clinics in the United States. Patients aged >or=9 years diagnosed with SAC and who had a positive reaction in a conjunctival allergen challenge were enrolled. Patients were randomly assigned in a 2:2:1 ratio to receive 1 drop/eye BID of epinastine hydrochloride 0.05% ophthalmic solution, levocabastine hydrochloride 0.05% ophthalmic suspension, or vehicle of epinastine, respectively, for 8 weeks. The primary end point was ocular itching, and secondary end points included ocular hyperemia, chemosis, ocular mucous discharge (all assessed on a 5-point scale), eyelid swelling (assessed on a 4-point scale), and tearing (present or absent). Efficacy analyses used assessments from the two 1-week periods with the highest pollen counts. For tolerability assessment slit-lamp biomicroscopy and visual acuity examinations were conducted at each study visit (weeks 0, 2, 4, 6, and 8). RESULTS: Two-hundred ninety-eight patients (159 females, 139 males; mean [SD] age, 32.7 [14.6] years [range, 9-71 years]) entered the study; 118 received epinastine, 118 received levocabastine, and 62 received vehicle. Epinastine-treated patients reported significantly less ocular itching than those receiving vehicle (P=0.045); scores for hyperemia were similar between these 2 groups. Ocular itching and hyperemia scores were similar between the epinastine and levocabastine groups. No clinically or statistically significant between-group differences were seen in slit-lamp biomicroscopy findings, changes in visual acuity from baseline, or the incidence of treatment-related adverse effects. CONCLUSIONS: In this study of patients with SAC, ophthalmic epinastine instilled twice daily was more effective than vehicle for the control of ocular itching and was similar in efficacy to levocabastine for control of ocular itching and hyperemia. Epinastine was well tolerated.     

冠状动脉粥样硬化性心脏病患者升主动脉弹性与颈动脉内-中膜厚度的相关性

目的:观察冠状动脉粥样硬化性心脏病(简称冠心病)患者升主动脉弹性与颈动脉内膜-中层厚度及粥样斑块发生的相关性。方法:于2005-08/2006-04选择石河子大学医学院第一附属医院心内科行冠状动脉造影检查患者97例,根据冠状动脉造影结果分为正常对照组41例和冠心病组56例,对两组患者进行超声检查,分别测量升主动脉扩张性D、僵硬度指数β、测量升主动脉前壁收缩期S波以及舒张期E波、A波的速度、颈动脉内膜-中层厚度及粥样斑块发生率。僵硬度指数β=In(收缩压/舒张压)/[(收缩期内径-舒张期内径)/舒张期内径]。动脉扩张性D=2(收缩期内径-舒张期内径)/[舒张期内径(收缩压-舒张压)]×10-3m2/N。结果:纳入患者97例,均进入结果分析。①冠心病组升主动脉扩张性D低于正常对照组,差异有显著性意义[分别为(15.02±9.99)×10-4,(34.75±20.80)×10-3m2/N,P=0.001];僵硬度指数β高于正常对照组(分别为28.20±21.06,15.23±25.32,P=0.001);升主动脉前壁S波和E波速度低于正常对照组[分别为(0.08±0.01),(0.10±0.03)m/s;(0.05±0.01),(0.07±0.02)m/s,P=0.001];颈动脉内膜-中层厚度和颈动脉斑块发生率高于正常对照组[分别为(0.90±0.15),(0.66±0.09)mm;41.03%,5.88%,P=0.001]。②升主动脉前壁S波速度与扩张性呈正相关(r=0.43,P=0.003),与僵硬度指数呈负相关(r=-0.47,P=0.002)。升主动脉前壁E波速度与扩张性呈正相关(r=0.47,P=0.002),与僵硬度指数无相关性。升主动脉前壁A波速度与扩张性和僵硬度指数均无相关性。③升主动脉扩张性D与颈动脉内膜-中层厚度呈负相关(r=-0.49,P=0.004),而僵硬度指数β与内膜-中层厚度则呈正相关(r=0.46,P=0.003)。S波速度与内膜-中层厚度无相关性(r=-0.26,P=0.15)。结论:冠心病患者升主动脉弹性降低即动脉扩张性降低、僵硬度指数升高、升主动脉前壁S波速度下降,颈动脉内膜-中层厚度增厚及粥样斑块发生率增高,将这些参数结合可作为冠心病很有价值的预测指标。     

犬脂肪间充质干细胞体外分离培养及其多向分化潜能

目的:为进一步分析脂肪间充质干细胞的生物学特性,建立犬脂肪间充质干细胞的体外分离培养方法,并对其表面标志和多向分化潜能进行鉴定。方法:实验于2006-09/2007-04在解放军第四军医大学组织工程中心完成。①实验方法:1岁龄家犬麻醉后,无菌条件下取犬腹股沟皮下脂肪组织,用Ⅰ型胶原酶消化,离心弃上层脂肪及上清,沉淀用含体积分数为0.1胎牛血清的D/F12培养基制成单细胞悬液,按2×108L-1接种于培养瓶中,细胞长满80%时用胰酶消化传代。②实验评估:分别取第3,5,10代脂肪间充质干细胞,倒置显微镜下连续观察细胞形态变化;MTT法检测细胞增殖活性;采用免疫细胞化学和体外诱导分化方法对脂肪间充质干细胞表面分子标志和多向分化潜能进行鉴定。结果:①细胞形态观察:原代培养1d多数贴壁细胞呈圆形;3d时贴壁细胞数量明显增加,大部分呈梭形、三角形;6d后细胞呈团簇状生长,形成集落;9～10d后细胞融合超过80%。传代后2～4h开始贴壁,经过较短的潜伏期后开始增殖,3d即可长满培养瓶底壁。②细胞增殖活性:培养的细胞分裂增殖能力强,无明显的生长滞缓期,第3天进入对数生长期,第7天达到生长峰值,第8天后进入平台期。第3,5,10代细胞传代接种后的潜伏期、对数生长期、平台期无明显差异,传10代后细胞无明显的衰老征象。③细胞表面分子标志的鉴定:第3代脂肪间充质干细胞CD29,CD44均呈阳性表达。④脂肪间充质干细胞的多向分化潜能:向脂肪细胞诱导第6天胞质中出现透亮的小脂滴,油红染色呈阳性;向神经细胞预诱导24h后,细胞由梭形变为栅栏样,正式诱导0.5h后细胞呈双极或多极,3h后细胞形态不再发生变化,神经元特异性烯醇化酶、胶质原纤维酸性蛋白均呈阳性;向成骨细胞诱导第21天可见钙化结节。结论:体外分离培养的犬脂肪间充质干细胞生长稳定、增殖较快,存在脂肪组织来源干细胞的相关标志分子CD29及CD44,诱导后能向脂肪细胞、神经细胞和成骨细胞分化。     

肌腱玻璃化法冷冻保存的体外实验

目的:目前临床上常用低温冷冻法来保存同种异体肌腱,但操作较复杂费时,并且所保存的肌腱活性较低而限制其应用。采用已筛选的玻璃化法冷冻保存鸡屈趾深肌腱,并将复温后的玻璃化肌腱进行体外检测,探索其作为肌腱移植材料的可行性。方法:实验于2003-11/2005-02在解放军总医院骨科研究所完成。①实验材料及分组:来亨鸡16只,雄性,体质量2.5kg左右,随机分为2组,玻璃化组为玻璃化肌腱,新鲜肌腱组为新鲜肌腱,每组8只。②实验过程:切取来亨鸡屈趾深肌腱,置入玻璃化液内快速投入液氮保存2周制备玻璃化肌腱。③实验评估:将2组肌腱在体外进行大体、组织学及超微结构观察,羟脯氨酸含量测定,生物力学性能检测,并对两组肌腱进行细胞培养与鉴定。结果:①玻璃化组肌腱的大体、组织学及超微结构与新鲜肌腱组相似,其细胞及细胞外结构得以良好保存。②应用碱解法测定玻璃化肌腱内的羟脯氨酸含量为69.27mg/g,与新鲜肌腱组间差异无统计学意义。③玻璃化组肌腱破裂强度为165.58MPa,弹性模量1.41GPa,与新鲜肌腱组的力学性能差异无统计学意义。④将玻璃化组肌腱进行细胞培养,细胞第8天自组织块长出,第21天后传代,培养3代后出现明显的退化现象,其生物学特性与新鲜肌腱组相似。⑤将两组肌腱培养的细胞分别进行免疫组织化学染色,经鉴定均为肌腱细胞。结论:玻璃化法保存的肌腱具有良好的细胞活性、细胞外结构及力学性能,其生物学及生物力学特性无明显变异。     

丘脑卒中患者认知功能损害及其临床判别

目的:探讨丘脑卒中后认知损害的特点,尝试应用回归函数方程推测和判别这种损害程度。方法:①选择2004-04/12大连市第二人民医院和大连市海港医院收治,并经CT确诊的丘脑卒中患者21例为丘脑卒中组;按1∶3匹配原则,将63例年龄与性别与丘脑卒中组匹配的非脑部疾病者入选为对照组。②丘脑卒中组住院后进行影像学和生理、生化学指标检查,对所有入组人员进行神经心理学测查其认知功能,内容包括4个纬度(智能纬度、执行功能纬度、注意机能纬度和记忆纬度)13个认知因子,以韦氏成人智力量表、韦氏记忆量表和威斯康星卡片分类实验等为测查工具。③将对照组每项认知因子均数根据其在认知中的作用不同,加或减1.64标准差为界值,以判断丘脑卒中组认知损害程度,并建立回归方程和认知损害程度表达式。结果:84例均进入结果分析。①丘脑卒中组在13个认知指标中有9个指标与对照组相比差异显著(P<0.05),4个纬度均有涉及。②建立丘脑组认知损害程度函数表达式,计算出每例认知损害程度函数值(F0)。以丘脑组每例认知损害程度函数值为应变量,以临床影响因子为自变量建立了回归方程Y=43.679-2.304*β。以Y值推测F0值。当Y<0.98,可考虑为轻度认知损害,当Y=0.98～8.15时可考虑为中度认知损害,当Y>8.15时可考虑为重度认知损害。结论:①丘脑卒中可引起广泛的认知损害。②临床可以根据影响因素建立回归方程,计算出Y值,以Y值推测F0值。     

The complete sequence of Drosophila beta-spectrin reveals supra-motifs comprising eight 106-residue segments.

The alpha and beta chains of spectrin are homologous, yet they have acquired different structural features that work in synergy to give the multimer its overall properties. The primary amino acid sequence of each spectrin subunit is dominated by tandemly repeated 106-residue motifs. By comparing the complete Drosophila beta-spectrin sequence with other spectrins we have discovered evidence that a higher-order, 848-amino acid supra-motif is tandemly repeated in both alpha- and beta-spectrin. These data argue that alpha- and beta-spectrin, rather than evolving independently from sequences encoding the ancestral 106-residue motifs, must have arisen after the establishment of a large supra-motif composed of eight of the 106-residue motifs. Our data suggest the segment structure of a progenitor gene that gave rise to both alpha- and beta-spectrin as well as dystrophin. The structural differences that evolved after the split between the alpha- and beta-spectrin genes confer the independent functions that exist in their products today.     

Marked microglial reaction in normal aging human substantia nigra: correlation with extraneuronal neuromelanin pigment deposits

Multiple reports have documented an age-related loss, estimated at about 10% per decade, of the pigmented neurons in the substantia nigra. This is associated with motor dysfunction, including bradykinesia, stooped posture and gait disturbance. As microglia are activated by cell death and neuromelanin pigment, we hypothesized that there should be a significant microglial reaction in normal aging human substantia nigra. Sections of substantia nigra from elderly subjects (N = 15; mean 81.3; SD 7.0) and younger subjects (N = 7; mean 30.3; SD = 8.7), all of which had no specific neurologically or neuropathologically defined disorders, were stained immunohistochemically for MHC Class II and the area occupied by microglia was quantified in substantia nigra pars compacta. All elderly subjects showed a pronounced microglial reaction in the substantia nigra, with frequent, intensely stained hypertrophic microglia, while immunoreactive nigral microglia were much less frequent in the younger subjects. Quantification showed that in older subjects, the percentage of substantia nigra area occupied by microglial bodies and processes was significantly greater than for younger subjects (mean 19.6 vs. 3.6; P = 0.005). Extraneuronal neuromelanin deposits were present in all the older subjects but were absent or rare in the younger subjects. The neuromelanin deposit abundance score in the older subjects correlated significantly with the area occupied by immunoreactive microglia. The marked microglial reaction in normal aging human substantia nigra, together with the previously reported 35–80% pigmented neuron loss, indicates the presence of a powerful pathologic process that may be additive with specific age-related neurodegenerative diseases, including Parkinson’s disease.     

Naproxen, meloxicam and methylprednisolone inhibit urokinase plasminogen activator and inhibitor and gelatinases expression during the early stage of osteoarthritis

BACKGROUND: To test the hypothesis that naproxen, meloxicam and methylprednisolone down-regulate the plasminogen activator (PA)/plasmin system and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] expression during early development of osteoarthritis (OA). METHODS: Samples of human OA articular cartilage, meniscus and synovium were obtained at knee arthroscopy and cultured ex vivo with or without naproxen, meloxicam or methylprednisolone. MMP-2 and MMP-9 levels were evaluated by gelatin zymography and urokinase-type PA (u-PA) and PA inhibitor-1 (PAI-1) levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Gelatin zymography revealed that naproxen, meloxicam and methylprednisolone could suppress MMP-2 secretion in all tissue cultures and MMP-9 production in meniscal and synovial cultures. ELISA showed that naproxen and meloxicam reduced u-PA secretion in chondral and synovial cultures at 48 h except in naproxen-treated chondral cultures. On PAI-1 secretion, naproxen and meloxicam had the suppressive effects in all cultures at 48 h but not in naproxen-treated meniscal cultures. Methylprednisolone also decreased u-PA secretion in chondral and synovial cultures and PAI-1 production in synovial cultures at 48 h. CONCLUSION: Naproxen, meloxicam and methylprednisolone can down-regulate the PA/plasmin system and gelatinases expression in the early osteoarthritic knee of humans, thereby possibly have a potential structure-modifying activity in a limited use.     

Coronary artery diameters in infants and children with congenital heart disease as determined by computed tomography

This study was conducted to establish reference curves and formulas for the diameters of the coronary arteries in infants and children using computed tomography. A total of 145 children (57 female, 88 male) ranging in age from 2 days to 19 years, 11 months (mean 5 years, 10 months), were retrospectively identified, and the diameters of their coronary arteries were quantified. The measurability of the coronary arteries, coronary arterial size differences between the genders, and relations of the diameters of the coronary arteries to age, height, weight, body surface area, and the diameter of the descending aorta were examined. Independent-samples Student's t tests, 2-tailed Pearson's correlations, and linear regression were used in statistical analysis. The measurability of all coronary arteries was 73.3%. No difference in coronary arterial size was found between the genders. The diameter of the descending aorta correlated most strongly with coronary arterial size. In conclusion, predictive formulas and reference curves for coronary arterial diameters in infants and children were obtained.