Molecular mechanisms of pulmonary response progression in crystalline silica exposed rats

An understanding of the mechanisms underlying diseases is critical for their prevention. Excessive exposure to crystalline silica is a risk factor for silicosis, a potentially fatal pulmonary disease. Male Fischer 344 rats were exposed by inhalation to crystalline silica (15?mg/m³, six hours/day, five days) and pulmonary response was determined at 44 weeks following termination of silica exposure. Additionally, global gene expression profiling in lungs and BAL cells and bioinformatic analysis of the gene expression data were done to understand the molecular mechanisms underlying the progression of pulmonary response to silica. A significant increase in lactate dehydrogenase activity and albumin content in BAL fluid (BALF) suggested silica-induced pulmonary toxicity in the rats. A significant increase in the number of alveolar macrophages and infiltrating neutrophils in the lungs and elevation in monocyte chemoattractant protein-1 (MCP-1) in BALF suggested the induction of pulmonary inflammation in the silica exposed rats. Histological changes in the lungs included granuloma formation, type II pneumocyte hyperplasia, thickening of alveolar septa and positive response to Masson’s trichrome stain. Microarray analysis of global gene expression detected 94 and 225 significantly differentially expressed genes in the lungs and BAL cells, respectively. Bioinformatic analysis of the gene expression data identified significant enrichment of several disease and biological function categories and canonical pathways related to pulmonary toxicity, especially inflammation. Taken together, these data suggested the involvement of chronic inflammation as a mechanism underlying the progression of pulmonary response to exposure of rats to crystalline silica at 44 weeks following termination of exposure.     

Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling

A proper understanding of the mechanisms underlying crystalline silica-induced pulmonary toxicity has implications in the management and potential prevention of the adverse health effects associated with silica exposure including silicosis, cancer and several auto-immune diseases. Human lung type II epithelial cells and rat lungs exposed to crystalline silica were employed as experimental models to determine global gene expression changes in order to understand the molecular mechanisms underlying silica-induced pulmonary toxicity. The differential gene expression profile induced by silica correlated with its toxicity in the A549 cells. The biological processes perturbed by silica exposure in the A549 cells and rat lungs, as identified by the bioinformatics analysis of the differentially expressed genes, demonstrated significant similarity. Functional categorization of the differentially expressed genes identified cancer, cellular movement, cellular growth and proliferation, cell death, inflammatory response, cell cycle, cellular development, and genetic disorder as top ranking biological functions perturbed by silica exposure in A549 cells and rat lungs. Results of our study, in addition to confirming several previously identified molecular targets and mechanisms involved in silica toxicity, identified novel molecular targets and mechanisms potentially involved in silica-induced pulmonary toxicity. Further investigations, including those focused on the novel molecular targets and mechanisms identified in the current study may result in better management and, possibly, reduction and/or prevention of the potential adverse health effects associated with crystalline silica exposure.     

Pulmonary toxicity and global gene expression changes in response to sub-chronic inhalation exposure to crystalline silica in rats

Exposure to crystalline silica results in serious adverse health effects, most notably, silicosis. An understanding of the mechanism(s) underlying silica-induced pulmonary toxicity is critical for the intervention and/or prevention of its adverse health effects. Rats were exposed by inhalation to crystalline silica at a concentration of 15 mg/m³, 6 hr/day, 5 days/week for 3, 6 or 12 weeks. Pulmonary toxicity and global gene expression profiles were determined in lungs at the end of each exposure period. Crystalline silica was visible in lungs of rats especially in the 12-week group. Pulmonary toxicity, as evidenced by an increase in lactate dehydrogenase (LDH) activity and albumin content and accumulation of macrophages and neutrophils in the bronchoalveolar lavage (BAL), was seen in animals depending upon silica exposure duration. The most severe histological changes, noted in the 12-week exposure group, consisted of chronic active inflammation, type II pneumocyte hyperplasia, and fibrosis. Microarray analysis of lung gene expression profiles detected significant differential expression of 38, 77, and 99 genes in rats exposed to silica for 3-, 6-, or 12-weeks, respectively, compared to time-matched controls. Among the significantly differentially expressed genes (SDEG), 32 genes were common in all exposure groups. Bioinformatics analysis of the SDEG identified enrichment of functions, networks and canonical pathways related to inflammation, cancer, oxidative stress, fibrosis, and tissue remodeling in response to silica exposure. Collectively, these results provided insights into the molecular mechanisms underlying pulmonary toxicity following sub-chronic inhalation exposure to crystalline silica in rats.     

Molecular insights into the progression of crystalline silica‐induced pulmonary toxicity in rats

Identification of molecular target(s) and mechanism(s) of silica‐induced pulmonary toxicity is important for the intervention and/or prevention of diseases associated with exposure to silica. Rats were exposed to crystalline silica by inhalation (15 mg m^?3, 6 h per day, 5 days) and global gene expression profile was determined in the lungs by microarray analysis at 1, 2, 4, 8 and 16 weeks following termination of silica exposure. The number of significantly differentially expressed genes (>1.5‐fold change and <0.01 false discovery rate P‐value) detected in the lungs during the post‐exposure time intervals analyzed exhibited a steady increase in parallel with the progression of silica‐induced pulmonary toxicity noticed in the rats. Quantitative real‐time PCR analysis of a representative set of 10 genes confirmed the microarray findings. The number of biological functions, canonical pathways and molecular networks significantly affected by silica exposure, as identified by the bioinformatics analysis of the significantly differentially expressed genes detected during the post‐exposure time intervals, also exhibited a steady increase similar to the silica‐induced pulmonary toxicity. Genes involved in oxidative stress, inflammation, respiratory diseases, cancer, and tissue remodeling and fibrosis were significantly differentially expressed in the rat lungs; however, unresolved inflammation was the single most significant biological response to pulmonary exposure to silica. Excessive mucus production, as implicated by significant overexpression of the pendrin coding gene, SLC26A4, was identified as a potential novel mechanism for silica‐induced pulmonary toxicity. Collectively, the findings of our study provided insights into the molecular mechanisms underlying the progression of crystalline silica‐induced pulmonary toxicity in the rat. Published 2012. This article is a US Government work and is in the public domain in the USA.     

基因芯片筛查外周血中胃癌转移相关基因

目的应用基因芯片筛查外周血中胃癌转移相关基因,为探究外周血中胃癌转移分子标志物提供线索。方法采用phalanx人全基因组表达谱芯片检测胃癌发生转移患者与未发生转移患者外周血中基因表达谱差异,利用生物信息学技术分析检测结果。结果从外周血中筛选出胃癌转移相关差异表达基因157个,表达上调基因92个,表达下调基因65个,涉及细胞粘附和运动基因、蛋白水解酶基因等。结论胃癌转移过程涉及多个不同功能基因表达的改变,运用基因芯片技术可初步从外周血中筛选出胃癌转移相关基因。     

Pulmonary chemokine and mutagenic responses in rats after subchronic inhalation of amorphous and crystalline silica.

Chronic inhalation of crystalline silica can produce lung tumors in rats whereas this has not been shown for amorphous silica. At present the mechanisms underlying this rat lung tumor response are unknown, although a significant role for chronic inflammation and cell proliferation has been postulated. To examine the processes that may contribute to the development of rat lung tumors after silica exposure, we characterized the effects of subchronic inhalation of amorphous and crystalline silica in rats. Rats were exposed for 6 h/day, on 5 days/week, for up to 13 weeks to 3 mg/m(3) crystalline or 50 mg/m(3) amorphous silica. The effects on the lung were characterized after 6.5 and 13 weeks of exposure as well as after 3 and 8 months of recovery. Exposure concentrations were selected to induce high pulmonary inflammatory-cell responses by both compounds. Endpoints characterized after silica exposure included mutation in the HPRT gene of isolated alveolar cells in an ex vivo assay, changes in bronchoalveolar lavage fluid markers of cellular and biochemical lung injury and inflammation, expression of mRNA for the chemokine MIP-2, and detection of oxidative DNA damage. Lung burdens of silica were also determined. After 13 weeks of exposure, lavage neutrophils were increased from 0.26% (controls) to 47 and 55% of total lavaged cells for crystalline and amorphous silica, with significantly greater lavage neutrophil numbers after amorphous silica (9.3 x 10(7) PMNs) compared to crystalline silica (6.5 x 10(7) PMNs). Lung burdens were 819 and 882 microg for crystalline and amorphous silica, respectively. BAL fluid levels of LDH as an indicator of cytotoxicity were twice as high for amorphous silica compared to those of crystalline silica, at the end of exposure. All parameters remained increased for crystalline silica and decreased rapidly for amorphous silica in the 8-month recovery period. Increased MIP-2 expression was observed at the end of the exposure period for both amorphous and crystalline silica. After 8 months of recovery, those markers remained elevated in crystalline silica-exposed rats, whereas amorphous silica-exposed rats were not significantly different from controls. A significant increase in HPRT mutation frequency in alveolar epithelial cells was detected immediately after 13 weeks of exposure to crystalline, but not to amorphous silica. A significant increase in TUNEL staining was detected in macrophages and terminal bronchiolar epithelial cells of amorphous silica-exposed rats at the end of the exposure period; however, crystalline silica produced far less staining. The observation that genotoxic effects in alveolar epithelial cells occurred only after crystalline but not amorphous silica exposure, despite a high degree of inflammatory-cell response after subchronic exposure to both types of silica, suggests that in addition to an inflammatory response, particle biopersistence, solubility, and direct or indirect epithelial cell cytotoxicity may be key factors for the induction of either mutagenic events or target cell death.     

末梢血与静脉血检测糖化血红蛋白结果的对比分析

目的 探讨用末梢血与静脉血检测糖化血红蛋白(HbA1c)结果的可比性.方法 313例研究对象同时取末梢血与静脉血用Primus PDQ PLUS糖化血红蛋白分析仪检测HbA1c,对检测结果进行相关性分析和配对t检验.结果 用末梢血与静脉血检测HbA1c的结果数据经统计学分析有显著相关性(健康组、糖尿病组、全体分别r=0.97、0.98、0.99,均P＜0.01),差异无统计学意义(健康组、糖尿病组、全体分别P=-0.77,P=0.72,P=0.75).结论 可以用末梢血检测HbA1c,其结果与静脉血检测HbA1c的结果无明显差异,可作为糖尿病患者的血糖检测指标.     

阿奇霉素对阿霉素肾病大鼠基因表达谱的影响

目的 利用基因芯片技术了解阿霉素肾病大鼠基因表达谱及其经阿奇霉素干预后的变化。方法 将81只大鼠随机分为对照组、模型组、阿奇霉素组,通过尾静脉注射法建立阿霉素肾病模型,检测第4、8周时大鼠血生化指标及24 h尿蛋白变化。利用Agilent公司生产的Agilent SurePrint G3 Rat Gene Expression(8×60 k)基因芯片检测第8周时各组大鼠的肾脏基因表达谱,并利用生物信息学方法对检测结果进行分析。结果 与模型组比较,阿奇霉素组24 h尿蛋白、总胆固醇、血肌酐均显著降低(P < 0.01),白蛋白、总蛋白、内生肌酐清除率均明显升高(P < 0.01)。通过芯片检测得到了各组大鼠的肾脏基因表达谱。与对照组比较,模型组共有185个基因发生差异性表达;而与模型比较,阿奇霉素组共有824个基因发生差异性表达。结论 阿霉素肾病的发生涉及众多基因的改变,阿奇霉素干预治疗可以改变其基因表达谱及在基因水平上使其肾组织异常的基因表达实现回归,对进一步探索阿奇霉素干预阿霉素肾病的作用机制提供了线索。     

Differential gene expression in human peripheral blood mononuclear cells induced by cigarette smoke and its constituents.

In current molecular epidemiology studies, a wide range of methods are used to monitor early biological effects after exposure to xenobiotic agents. Gene expression profiling is considered a promising tool that may provide more sensitive, mechanism-based biomarkers. As a first step toward obtaining information on the applicability of gene expression profiles as a biomarker for early biological effects of carcinogen exposure, we conducted in vitro studies on human peripheral blood mononuclear cells (PBMC). We used cigarette smoke condensate (CSC) and a selection of its genotoxic constituents as model agents, applying cDNA microarray technology to investigate modulated gene expression. In independent experiments using cells from several donors, quiescent PBMC were exposed for 18 h, followed by gene expression analyses on a microarray containing 600 toxicologically relevant genes. The search for candidate biomarker genes was binomial: first we looked for genes responding similarly to all agents; second, for agent-specific genes. Many genes were significantly deregulated by all compounds, but as the direction of deregulation frequently differed per agent, they are not useful as generic biomarkers. Cigarette smoke condensate modulated the expression of many more genes than any of its constituents, with the largest effect in SERPINB2. The affected genes are involved in immune or stress responses, but surprisingly no genes involved in DNA damage response were modulated, and only a few in DNA repair. In conclusion, several genes have been identified as potential biomarkers for population studies on early biological effects caused by cigarette smoke exposure, but no genes were identified that represent a generic biomarker.     

风湿性二尖瓣狭窄患者外周血细胞因子的基因表达谱

目的 利用基因芯片技术。比较风湿性二尖瓣狭窄病人和健康人外周血细胞因子基因表达的差异，从整体上认识风湿性二尖瓣狭窄的心脏瓣膜病的细胞因子表达状况。方法 单纯性二尖瓣狭窄的病人3人，以健康人5人作为对照，应用Trizol法分别提取他们的外周血总RNA，逆转录合成cDNA，用Cy5、Cy3分别标记病人、对照组的cDNA。混合后在细胞因子表达谱芯片上杂交。结果经对原始数据的标准化和SAM芯片数据软件的应用，获得CXCR4，RGS2和IRAK13种显著性差异表达的细胞因子基因，均为表达上调的细胞因子基因．并对各自的作用进行归纳、分析。结论 获得风湿性二尖瓣狭窄外周血细胞因子的基因表达图谱，并证实了风湿性二尖瓣狭窄的心脏瓣膜病是炎症反应和抗炎反应相互作用的结果，为进一步临床研究该病与细胞因子的关系提供一定的方向。     

Progression of lung inflammation and damage in rats after cessation of silica inhalation.

Human epidemiologic studies have found that silicosis may develop or progress even after occupational exposure has ended, suggesting that there is a threshold lung burden above which silica-induced pulmonary disease progresses without further exposure. We previously described the time course of rat pulmonary responses to silica inhalation as biphasic, the initial phase characterized by increased but controlled pulmonary inflammation and damage. However, after a threshold lung burden was exceeded, rapid progression of silica-induced pulmonary disease occurred. To test the hypothesis that there is a threshold lung burden above which silica-induced pulmonary disease progresses without further exposure we initiated a study to investigate the relationship between silica exposure, the initiation and progression of silica-induced pulmonary disease, and recovery. Rats were exposed to silica (15 mg/m(3), 6 h/day) for either 20, 40, or 60 days. A portion of the rats from each exposure were maintained without further exposure for 36 days to examine recovery. The major findings of this study are: (1) silica-exposed rats were not in pulmonary overload, and lung silica burden decreased with recovery; (2) pulmonary inflammation, damage and lipidosis increased with recovery for rats exposed to silica for 40 and 60 days, but not 20 days; (3) histopathology revealed changes in silica-induced alveolitis, epithelial hypertrophy and hyperplasia, and alveolar lipoproteinosis consistent with bronchoalveolar lavage (BAL) endpoints; and (4) pulmonary fibrosis developed even when exposure was stopped prior to its initial development.     

Effects of subacute oral warfarin administration on peripheral blood granulocytes in rats

Warfarin affects mainly vitamin K dependent (VKD) processes, but the effects on some non-VKD-related activities such as tumor growth inhibition and mononuclear cell-mediated immune reactions were shown as well. In this study, the effect of subchronic (30 days) oral warfarin (0.35 mg/l and 3.5 mg/l) intake on peripheral blood granulocytes in rats was investigated. Increase in prothrombin and partial thromboplastin time at high warfarin dose reflected its basic activity. Priming effect for respiratory burst was noted at both warfarin doses, while only high warfarin dose resulted in priming for adhesion, the rise in intracellular myeloperoxidase content/release and stimulation of nitric oxide production. Differential effects of high warfarin dose were noted on granulocyte cytokines IL-6 (lack of the effect), TNF-α (decreased release and mRNA expression) and IL-12 (increase in mRNA for IL-12 subunits p35 and p40). Changes in granulocytes seems not to rely on mitogen activated kinases p38 and ERK. Warfarin intake was associated with an increase in circulating IL-6, fibrinogen and haptoglobin and with changes in the activity of erythrocyte antioxidant enzymes superoxide dismutase and catalase. The effects of oral warfarin intake on peripheral blood granulocytes demonstrated in this study might be relevant for oral anticoagulant therapy strategies in humans.     

基于血浆代谢组学的新生化颗粒对急性血瘀大鼠作用机制研究

目的 研究新生化颗粒对急性血瘀大鼠血浆中内源性代谢物的影响,探讨新生化颗粒治疗急性血瘀证的可能机制。方法 将50只SD大鼠随机分为对照组、模型组、复方丹参滴丸（阳性药,0.10 g·kg^-1）组和新生化颗粒低、高剂量（4.86、9.72 g·kg^-1）组,给药体积10 mL·kg^-1,对照组和模型组大鼠ig给予等体积0.5%羧甲基纤维素钠（CMC-Na）,每天早晚各ig给药1次,共7次。第5次给药后,除对照组外,采用sc盐酸肾上腺素和冰水浴制备大鼠急性血瘀模型。通过测定全血黏度（WBV）、血浆黏度（PV）、活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）、纤维蛋白原（FIB）和凝血酶时间（TT）,观察不同剂量的新生化颗粒对急性血瘀大鼠血液流变学和凝血功能的影响;采用超高效液相色谱-四极杆飞行时间质谱联用（UHPLCQTOF-MS）法检测各组大鼠血浆中的内源性代谢物,通过多变量统计分析筛选潜在生物标志物,结合质谱信息、数据库检索和标准品比对鉴定潜在生物标志物,并将鉴定到的生物标志物导入MetaboAnalyst 5.0数据库推测其可能的代谢通路。结果 与模型组比较,新生化颗粒显著降低急性血瘀大鼠WBV、PV和FIB,显著延长APTT、PT和TT（P＜0.05、0.01）。代谢组学结果显示,从急性血瘀大鼠血浆中共鉴定出21个差异代谢物（准确鉴定7个）,与对照组比较,模型组大鼠血浆中乳酸、肉碱和肌酐等10个内源性代谢物显著上调,苹果酸、琥珀酸和色胺等11个内源性代谢物显著下调（P＜0.05、0.01）;除了硫酸吲哚酚和脱氧胞苷外,新生化颗粒对其他19个生物标志物均有显著回调作用（P＜0.05、0.01）。这些标志物主要涉及苯丙氨酸、酪氨酸和色氨酸生物合成、苯丙氨酸代谢、亚油酸代谢、三羧酸循环和色氨酸代谢。结论 新生化颗粒对急性血瘀大鼠体内紊乱代谢物有较好的回调作用,其作用机制主要与调节苯丙氨酸、酪氨酸和色氨酸生物合成,苯丙氨酸代谢,亚油酸代谢,三羧酸循环和色氨酸代谢通路有关。     

硫化氢供体对高肺血流性肺动脉高压大鼠肺动脉胶原含量及代谢的影响

目的探讨硫化氢供体硫氢化钠(sodium hydrosulfide,NaHS)对高肺血流性肺动脉高压大鼠肺动脉胶原含量及代谢的影响。方法32只♂SD大鼠随机分为分流组(n=8)、分流+NaHS组(n=8)、假手术组(n=8)和假手术+NaHS组(n=8)。对分流组和分流+NaHS组大鼠行腹主动脉-下腔静脉穿刺建立高肺血流动物模型。分流11wk后,以右心导管法测定大鼠肺动脉收缩压(systolic pulmonary arteryp ressure,SPAP)、以敏感硫电极法测定肺组织硫化氢(hydro-gen sulfide,H2S)含量、以免疫组织化学法测定肺动脉胶原Ⅰ和胶原Ⅲ、基质金属蛋白酶-13(matrix metalloproteinase,MMP-13)及其抑制物-1(tissue inhibitor of metalloproteinase,TIMP-1)的表达。结果分流11wk后,大鼠SPAP明显增高(P<0.05);肺组织H2S含量明显降低(P<0.05);应用NaHS干预11wk后,分流+NaHS组大鼠H2S含量明显升高,而SPAP明显降低(P<0.05);分流+NaHS组大鼠胶原Ⅰ和胶原Ⅲ蛋白表达比分流组明显降低(P<0.05);分流+NaHS组大鼠MMP-13、TIMP-1的蛋白表达及MMP-13/TIMP-1比值比分流组明显升高(P<0.05)。结论NaHS可能通过增加肺动脉壁胶原成分的降解、减少胶原含量,从而在高肺血流性肺动脉高压形成中发挥调节作用。     

Comparative cardiopulmonary toxicity of exhausts from soy-based biofuels and diesel in healthy and hypertensive rats

Abstract

Increased use of renewable energy sources raise concerns about health effects of new emissions. We analyzed relative cardiopulmonary health effects of exhausts from (1) 100% soy biofuel (B100), (2) 20% soy biofuel?+?80% low sulfur petroleum diesel (B20), and (3) 100% petroleum diesel (B0) in rats. Normotensive Wistar–Kyoto (WKY) and spontaneously hypertensive rats were exposed to these three exhausts at 0, 50, 150 and 500?μg/m³, 4?h/day for 2 days or 4 weeks (5 days/week). In addition, WKY rats were exposed for 1 day and responses were analyzed 0?h, 1 day or 4 days later for time-course assessment. Hematological parameters, in vitro platelet aggregation, bronchoalveolar lavage fluid (BALF) markers of pulmonary injury and inflammation, ex vivo aortic ring constriction, heart and aorta mRNA markers of vasoconstriction, thrombosis and atherogenesis were analyzed. The presence of pigmented macrophages in the lung alveoli was clearly evident with all three exhausts without apparent pathology. Overall, exposure to all three exhausts produced only modest effects in most endpoints analyzed in both strains. BALF γ-glutamyl transferase (GGT) activity was the most consistent marker and was increased in both strains, primarily with B0 (B0?>?B100?>?B20). This increase was associated with only modest increases in BALF neutrophils. Small and very acute increases occurred in aorta mRNA markers of vasoconstriction and thrombosis with B100 but not B0 in WKY rats. Our comparative evaluations show modest cardiovascular and pulmonary effects at low concentrations of all exhausts: B0 causing more pulmonary injury and B100 more acute vascular effects. BALF GGT activity could serve as a sensitive biomarker of inhaled pollutants.     

N-乙酰半胱氨酸对肺间质纤维化大鼠肺损伤及外周血单核细胞DNA损伤的保护作用

目的观察肺间质纤维化大鼠氧化-抗氧化状态、外周血单核细胞(PBMCs)DNA损伤情况和N-乙酰半胱氨酸(NAC)的保护作用及其机制。方法气管内灌注博来霉素建立大鼠肺纤维化模型,设正常对照组、模型组、NAC小剂量组(NAC 50mg·kg~(-1)·d~(-1))、NAC大剂量组(NAC 200mg·kg~(-1)·d~(-1))和氢化可的松组(氢化可的松100mg·kg~(-1)·d~(-1)),每组18只。于给药后d7、14、28,观察各组肺组织病理学改变和羟脯氨酸(HYP)、丙二醛(MDA)以及谷胱甘肽过氧化物酶(GSH-Px)含量及PBMCs DNA损伤情况。结果与正常对照组比较,模型组肺泡腔、肺间质均可见大量胶原纤维和成纤维细胞。给药后d28,NAC组肺泡炎和肺纤维化程度均较模型组改善(P<0.05)。模型组肺组织HYP、MDA和PBMCs彗星率高于正常对照组,GSH-Px低于正常对照组(P<0.01)。与模型组比较,NAC大、小剂量组鼠肺组织HYP和MDA水平降低、GSH-Px含量升高、PBMCs彗星率降低,差异均非常显著(P<0.01)。结论 NAC能减轻博来霉素诱导的大鼠肺纤维化,这种作用有可能是通过改善体内氧化应激状态、减轻PBMCs DNA损伤实现的。     

Experimentally induced,synergistic late effects of a single dose of radiation and aging: significance in LKS fraction as compared with mature blood cells

The number of murine mature blood cells recovered within 6 weeks after 2‐Gy whole‐body irradiation at 6 weeks of age, whereas in the case of the undifferentiated hematopoietic stem/progenitor cell (HSC/HPC) compartment [cells in the lineage‐negative, c‐kit‐positive and stem‐cell‐antigen‐1‐positive (LKS) fraction], the numerical differences between mice with and without irradiation remained more than a year, but conclusively the cells showed numerical recovery. When mice were exposed to radiation at 6 months of age, acute damages of mature blood cells were rather milder probably because of their maturation with age; but again, cells in the LKS fraction were specifically damaged, and their numerical recovery was significantly delayed probably as a result of LKS‐specific cellular damages. Interestingly, in contrast to the recovery of the number of cells in the LKS fraction, their quality was not recovered, which was quantitatively assessed on the basis of oxidative‐stress‐related fluorescence intensity. To investigate why the recovery in the number of cells in the LKS fraction was delayed, expression levels of genes related to cellular proliferation and apoptosis of cells in the bone marrow and LKS fraction were analyzed by real‐time polymerase chain reaction (RT‐PCR). In the case of 21‐month‐old mice after radiation exposure, Ccnd1, PiK3r1 and Fyn were overexpressed solely in cells in the LKS fraction. Because Ccnd1and PiK3r1 upregulated by aging were further upregulated by radiation, single‐dose radiation seemed to induce the acceleration of aging, which is related to the essential biological responses during aging based on a lifetime‐dependent relationship between a living creature and xenobiotic materials. Copyright © 2014 John Wiley & Sons, Ltd.     

Comparison of nebivolol and atenolol on blood pressure, blood sugar, and lipid profile in patients of essential hypertension

Background:

Nebivolol is a third-generation β-blocker, with highest β₁ selectivity and nitric-oxide-derived vasodilatation. It also exhibits antiproliferative and antioxidant property that has beneficial metabolic profile compared to second-generation β blockers like atenolol. This study was planned to study the comparative effects of nebivolol and atenolol on metabolic parameters in patients with essential hypertension.

Materials and Methods:

A prospective, randomized, parallel, open-label clinical study was carried out on patients with essential hypertension. The patients were randomly assigned to receive tablet atenolol (Group A) and nebivolol (Group B) for a period of 24 weeks. Investigations were carried out at baseline and at the end of study period, that is, 24 weeks. Out of 69 patients, 60 completed the study and the data was analyzed using student''s t-test. P < 0.05 was considered statistically significant.

Results:

Atenolol and nebivolol both showed significant (P < 0.001) antihypertensive action after 24 weeks. Mean blood sugar and lipid profile were found to be significantly (P < 0.001) elevated after 24 weeks of treatment with atenolol but not with nebivolol. Heart rate was significantly (P < 0.001) decreased in both groups at 24 weeks.

Conclusion:

In view of metabolic adverse effects of atenolol, nebivolol is the better choice whenever β-blockers have to be used in essential hypertension.     

外周血Bcl-2／IgH融合基因检测的可行性探讨

目的探讨外周血作为Bcl-2／IgH融合基因检测的标本来源的可行性。方法以SYBR Green I荧光染料实时定量PCR方法检测20例患者外周血和5例骨髓Bcl-2／IgH融合基因的阳性率及表达水平。结果骨髓和外周血Bcl-2／IgH融合基因的阳性检出率分别是80％与65％，两者阳性率经统计学分析差异无显著性（P=0．64）；外周血和骨髓融合基因相对拷贝数x^-±sd分别为2．73±2．54和4．23±4．06，经统计学分析差异无显著性（P=0．107）。结论以外周血作为Bcl-2／IgH融合基因观测的标本来源有一定的可行性，值得进一步研究。