Modulators of platelet function in aging

Abstract

Platelets are small, anucleated effector cells that play an important role in linking the hemostatic and inflammatory processes in the body. Platelet function is known to be altered under various inflammatory conditions including aging. A gain in platelet function during aging can increase the risk of thrombotic events, such as stroke and acute myocardial infarction. Anti-platelet therapy is designed to reduce risk of serious cerebrovascular and cardiovascular events, but the adverse consequences of therapy, such as risk for bleeding increases with aging as well. Age-associated comorbidities such as obesity, diabetes, and hyperlipidemia also contribute to increased platelet activity and thus can enhance the risk of thrombosis. Therefore, identification of unique mechanisms of platelet dysfunction in aging and in age-associated comorbidities is warranted to design novel antiplatelet drugs. This review outlines some of the current areas of research on aging-related mechanisms of platelet hyperactivity and addresses the clinical urgency for designing anti-platelet therapies toward novel molecular targets in the aging population.     

山西省出生缺陷高发区土壤元素分布特征

目的 了解出生缺陷高发区土壤中元素分布特征,为出生缺陷的干预和治疗提供理论依据.方法 于2005年1-5月,选择山西省吕梁山区出生缺陷高发的中阳县和交口县作为出生缺陷高发区,以人口相对集中的河道两侧为采样点,共涉及8个乡镇,79个行政村;选择晋中盆地出生缺陷低发的祁县作为出生缺陷对照区,采样点均匀分布,共涉及6个乡镇,27个行政村.采集距耕地表层10～20cm深的土壤,共采集样品131件.采用ICP-电感耦合等离子发射光谱法,对土壤样品中的16种元素进行测定.结果 高发区土壤中元素总量明显高于低发区.与祁县相比,交口县土壤中元素含量偏高的有As、Mo、Pb、Ni、V,含量偏低的元素有Se,差异均有统计学意义(P＜0.05);中阳县土壤中含量偏高的元素为Sn、Se、Mo、Zn、Sr、Pb、Ni、Fe、V、Ca、Cu、Al,偏低的元素为Mg和Na,差异均有统计学意义(P＜0.05).土壤中元素含量(μg/g)与出生缺陷发病率的(1/万)逐步回归分析显示,交口县土壤中Mo、Al、As、Ni、Pb、Zn元素对病情影响有统计学意义(均P＜0.01),其标准的逐步回归判别方程为:y=-1.321 1.106 Mo-0.509 Al 0.117 As 0.663 Ni-0.429 Pb-0.262 Zn(R2a=0.891);中阳县土壤中Pb、Mg、Ca、Al、Zn元素对病情影响有统计学意义(均P＜0.05),其标准回归方程为:y=-1.757 0.441 Pb-0.264Mg 0.309 Ca-0.186Al 0.162Zn (R2a2=0.839).结论 交口县和中阳县土壤中Pb、Mo、Al等含量异常可能是两县出生缺陷高发的原因之一.     

Urodynamic studies in the evaluation of young men presenting with lower urinary tract symptoms

AIM: To evaluate the usefulness of urodynamic study in young men with lower urinary tract symptoms (LUTS). METHODS: We reviewed the charts of 50 men with LUTS aged 50 years and below. Those with neurological diseases, urethral trauma or strictures were excluded. All underwent multichannel urodynamic studies (UDS). The pre- and post-UDS diagnoses and treatment modalities were compared. RESULTS: Mean age was 38.1 years (17-49). The main pre-UDS diagnoses included prostatitis in seven (14%), overactive bladder in seventeen (34%) and benign prostatic hyperplasia in nine (18%). Pre-UDS management ranged from anticholingeric agents for thirteen (26%), alpha-adrenergic antagonists for nine (18%), antibiotics for six (12%). Abnormal UDS were noted in 36 (72%), including detrusor overactivity in 9 (18%), detrusor underactivity/acontractility in 5 (10%) and bladder outlet obstruction in 21 (42%). Fourteen (28%) had primary bladder neck dysfunction and five (10%) had benign prostatic hyperplasia. Post-UDS management included anticholingeric agents for ten (26%), alpha-adrenergic antagonists for seventeen (34%), catheterization for four (10%), behavioral therapy for three (6%), surgery for three (6%). None were prescribed antibiotics. Following UDS, the diagnosis had to be updated in 40 (80%) and concomitant change in management was required in 34 (68%). CONCLUSION: Young men presenting with LUTS have different underlying etiologies. Clinical diagnosis and treatment are often empiric and inaccurate. Urodynamic study is useful in the evaluation of this group of patients as it aids in arriving at an accurate diagnosis and guides treatment therapy.     

藤茶提取物的抗炎作用研究

目的：采用几种不同类型的炎症动物模型对AGE的抗炎作用进行研究。方法：大鼠角叉菜胶性足肿胀，醋酸诱导的小鼠腹腔毛细血管通透性增高，小鼠羧甲基纤维素囊中的白细胞数目，大鼠巴豆油性气囊肿的形成。结果：连续灌胃给药5天，AGE（5、10g/kg）可以显著抑制角叉菜胶所致的大鼠足肿胀、醋酸所致的小鼠腹腔毛细血管通透性增高、小鼠羧甲基纤维素囊中白细胞的游出数目以及大鼠巴豆油性气囊的形成。结论：藤茶提取物具有显著的抗炎活性。     

Normal obstetric ultrasound reduces the risk of Down syndrome in fetuses of older mothers

The objective of this study is to determine whether a normal fetal morphology ultrasound scan in women older than 35 years reduces the risk of aneuploidy. We reviewed the results of amniocentesis and second trimester sonogram in all women older than 35 years from 1991 to 1995. None had prior screening. We excluded fetuses with structural anomalies. We determined the sensitivity and specificity of minor markers in detecting Down syndrome and also determined the reduction in risk of a normal sonogram. Among the 2060 women older than 35 years giving birth during the study period, 16 (0.78%) delivered an infant with Down syndrome. Of the 16 fetuses, two had no prenatal testing or ultrasound, two had invasive testing but no second trimester sonogram, five had a normal sonogram and seven had one or more sonographic markers of Down syndrome. At least 17% of women older than 35 years did not participate in prenatal testing or ultrasound. Ultrasound detected Down syndrome with a sensitivity of 59% (95% confidence interval: 45–72%), a false‐positive rate of 10.6% (9.4–11.8%) and a positive predictor value of 1 in 9. The likelihood of having normal karyotype if the sonogram was normal was 0.46 (0.31–0.61). In women older than 35 years, a normal second trimester sonogram reduces the risk of Down syndrome by more than 50%. At least 17% of women older than 35 years do not participate in prenatal testing or ultrasound.     

Effects of periodic weight support in a simulated weightless environment in preventing bone demineralisation.

Anti Orthostatic Hypokinetic posture in rats by tail suspension for 15 days (d) simulates the deconditioning effects of weightlessness on the weight bearing bones. The present study evaluates the effects of daily 4 hour (h) weight support (WS) during simulated weightlessness (S-W) in preventing these changes. Adult male albino rats were divided into three groups as (i) Control (CON, n = 12), (ii) Hind limb unweighing by tail suspension for 15 d (HU, n = 18), (iii) HU with daily 4 h WS (4 HRWS, n = 11). After 15 d tibia from all the animals were removed and subsequently dried, ashed and then calcium content of the bones were determined. HU showed reductions in the water content by 35.8%, organic matrix by 12.2% and calcium content by 33.4% of tibia. 4 h WS during S-W resulted in complete prevention of water loss and organic matrix loss and partial prevention of the loss of calcium content. Calcium content of tibia in 4 HRWS remained 15.2% less as compared to CON. These findings indicate that 4 h WS is partially successful in preventing the demineralisation effects of S-W on weight bearing bone tibia.     

A tracer kinetic model for 18F-FHBG for quantitating herpes simplex virus type 1 thymidine kinase reporter gene expression in living animals using PET.

Reporter probe 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine (18F-FHBG) and reporter gene mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) have been used for imaging reporter gene expression with PET. Current methods for quantitating the images using the percentage injected dose per gram of tissue do not distinguish between the effects of probe transport and subsequent phosphorylation. We therefore investigated tracer kinetic models for 18F-FHBG dynamic microPET data and noninvasive methods for determining blood time-activity curves in an adenoviral gene delivery model in mice. METHODS: 18F-FHBG (approximately 7.4 MBq [approximately 200 microCi]) was injected into 4 mice; 18F-FHBG concentrations in plasma and whole blood were measured from mouse heart left ventricle (LV) direct sampling. Replication-incompetent adenovirus (0-2 x 10(9) plaque-forming units) with the E1 region deleted (n = 8) or replaced by HSV1-sr39tk (n = 18) was tail-vein injected into mice. Mice were dynamically scanned using microPET (approximately 7.4 MBq [approximately 200 microCi] 18F-FHBG) over 1 h; regions of interest were drawn on images of the heart and liver. Serial whole blood 18F-FHBG concentrations were measured in 6 of the mice by LV sampling, and 1 least-squares ratio of the heart image to the LV time-activity curve was calculated for all 6 mice. For 2 control mice and 9 mice expressing HSV1-sr39tk, heart image (input function) and liver image time-activity curves (tissue curves) were fit to 2- and 3-compartment models using Levenberg-Marquardt nonlinear regression. The models were compared using an F statistic. HSV1-sr39TK enzyme activity was determined from liver samples and compared with model parameter estimates. For another 3 control mice and 6 HSV1-sr39TK-positive mice, the model-predicted relative percentage of metabolites was compared with high-performance liquid chromatography analysis. RESULTS: The ratio of 18F-FHBG in plasma to whole blood was 0.84 +/- 0.05 (mean +/- SE) by 30 s after injection. The least-squares ratio of the heart image time-activity curve to the LV time-activity curve was 0.83 +/- 0.02, consistent with the recovery coefficient for the partial-volume effect (0.81) based on independent measures of heart geometry. A 3-compartment model best described 18F-FHBG kinetics in mice expressing HSV1-sr39tk in the liver; a 2-compartment model best described the kinetics in control mice. The 3-compartment model parameter, k3, correlated well with the HSV1-sr39TK enzyme activity (r2 = 0.88). CONCLUSION: 18F-FHBG equilibrates rapidly between plasma and whole blood in mice. Heart image time-activity curves corrected for partial-volume effects well approximate LV time-activity curves and can be used as input functions for 2- and 3-compartment models. The model parameter k3 from the 3-compartment model can be used as a noninvasive estimate for HSV1-sr39TK reporter protein activity and can predict the relative percentage of metabolites.