白细胞介素1及白细胞介素8在心肌缺血再灌注损伤中的动态演变及药物干预效果

目的:在心肌缺血再灌注损伤中,炎症细胞因子参与其过程的多个环节。实验拟验证白细胞介素1、白细胞介素8因子在此过程中的动态变化,并分析其与药物干预的关系。方法:实验于2005-10/2006-11在新乡医学院形态学实验室完成。①实验分组:选择健康Wistar成年大鼠70只,按随机数字表法分为3组:对照组(n=10)、模型组(n=30)和药物组(n=30)。后两组又分为缺血0.5h,再灌注2,4,8,12,24h6个时相点,每个时相点5只。对照组只设12h一个时相点作为总体对照。②实验方法:大鼠麻醉后,药物组在右股静脉注入甲泼尼龙(30mg/kg),对照组及模型组注入生理盐水(0.75mg/kg)。采用夹闭左冠状动脉前降支建立大鼠心肌缺血再灌注损伤模型。对照组只开胸不夹闭。③实验评估:在各时相点观察各组大鼠缺血再灌注后的心肌细胞改变;血清学检测白细胞介素1、白细胞介素8因子的动态表达。结果:①模型组缺血再灌注12h炎细胞浸润最显著,药物组炎细胞呈散在浸润。②模型组和药物组白细胞介素1、白细胞介素8因子质量浓度明显高于对照组[缺血再灌注8h为例,白细胞介素1分别为(99.21±14.37),(85.77±11.31),(21.87±10.32)ng/L;白细胞介素8分别为(794.85±24.07),(536.95±19.72),(103.94±11.59)ng/L,P<0.05],峰值分别在缺血再灌注4,8h;同时相点药物组白细胞介素1、白细胞介素8因子质量浓度明显低于模型组(P<0.05)。结论:白细胞介素1和白细胞介素8因子在心肌缺血再灌注损伤的炎症反应中发挥着重要作用;甲泼尼龙对缺血再灌注损伤心肌有保护作用。     

亮度知觉效应与视觉加工方式研究

目的:利用微持续与微间隔时间技术,设计了两组相关的实验,对亮度知觉效应和视觉加工方式进行探讨。方法:实验于2006-06在中南民族大学物理楼脑认知实验室进行,所有受试者为年龄20～25岁的大学本科生,视力(含矫正视力)正常,均为右利手。①实验1:被试为10名(男5名,女5名),要求被试分别对n屏依次呈现的亮块的明度和n 1屏依次呈现的亮块的明度进行比较(n≤17)。②实验2:被试为28名(男13名,女15名),实验涉及两个刺激物,先呈现的刺激物由左右两个大小相同、亮度不同的亮块a和b组成,后呈现的刺激物把a和b的位置进行对调,当这两个刺激物依次显示时,要求被试报告左右两边的明度是否存在差异,存在何种差异。结果:①实验1∶1≤n≤3时,100%的被试报告,n 1屏的明度大于n屏的亮度,即n 1>n;4≤n≤10时,70%～90%的被试报告n 1>n;n>10时,50%～70%的被试报告n 1>n;随着n值的增加明度差异也在减小,大约在n=17时达到稳定,n屏和n 1屏的明度区别将很难被看出。②实验2:在L(a)b a,随着a和b的亮度差异减小,左右两边呈现的明度越相似;同样当L(a)相似文献   

Can blood pressure responses to tests unmask future blood pressure trends and the need for antihypertensive medication? Ten years of follow‐up

An exaggerated blood pressure (BP) response to test may unmask the subjects who have a high risk of developing hypertension. In this prospective 10 years of follow-up, we examined whether the predictive value of casual BP measurements on future BP level and need for antihypertensive medication could be improved by using BP responses to different physical tests. At baseline, BP was recorded by casual measurements and intra-arterial monitoring. During the intra-arterial BP recording, standardized postural and exercise tests were performed on 97 healthy, untreated men (34 normotensive, 29 borderline hypertensive, and 34 mild hypertensive). After 10 years of follow-up, 87 of them (90%) returned for casual and non-invasive 24-h BP measurements. At follow-up, 20 (23%) of the men had antihypertensive medication. The prediction of casual systolic blood pressure (SBP) was best improved by SBP at 10 min after the dynamic exercise test (adj. R2 = 0.448; adj. R2 = 0.356 for casual SBP alone). The prediction of casual diastolic blood pressure (DBP) was most improved by DBP at 10 min after the dynamic exercise test (adj. R2 = 0.282; adj. R = 0.259 for casual BP alone). SBP in the supine test best improved the prediction of 24-h SBP (adj. R2 = 0 448; adj. R2 = 0.275 for casual SBP alone). DBP in the standing test best improved the prediction of 24-h DBP (adj. R2 = 0.252; adj. R2 = 0.214 for casual DBP alone). Pre-exercise DBP and casual SBP were the best predictors of the need for antihypertensive medication (Cox-Snell R2 = 0.256; Cox-Snell R2 = 0.164 for casual SBP alone). In conclusion the prediction of future BP and need for antihypertensive medication can be improved by using BP measurements during postural and exercise tests. Future SBP is more predictable than DBP.     

Selected Nonpharmacological Therapies for Chronic Pain: The Therapeutic Use of the Placebo Effect

Chronic pain is a common problem requiring a multidisciplinary approach. Nursing can offer diverse therapies complementary to the medical-surgical approach. Guidelines for practice and challenges for research are outlined for selected nonpharmacological chronic pain therapies. This article discusses the placebo effect, which is common to all therapies. Placebos can therapeutically empower patients to stimulate their psychophysiologic self-regulation abilities. Effects, theories, ethics, and therapeutic methods of stimulating the placebo effect are explored.     

Transfection of oocytes and other types of ovarian cells in rabbits after direct injection into uterine arteries of adenoviruses and plasmid/liposomes

Transfection of oocytes should be avoided in somatic gene therapy. However, several viral vectors including adenoviruses can transfect zona-pellucida-free eggs in vitro. During early stages of development, oocytes of postnatal ovaries lack the zona pellucida. Therefore, they may be susceptible to gene transfer and unintended toxic effects. The purpose of this study was to see whether the injection of adenoviruses (1 x 10(10) PFU) or plasmid (500 microg)/DOTMA:DOPE (1:2) liposomes directly into uterine arteries in pregnant rabbits leads to transfection of oocytes and other types of ovarian cells. LacZ and herpes simplex virus thymidine kinase (HSV-TK) were used as transgenes. It was found that both adenovirus and plasmid vectors transfected oocytes at the primordial and primary follicle stage when they were not protected by the zona pellucida, whereas no transfection was seen in oocytes surrounded by the zona pellucida. Efficient transfection of corpus luteum and granulosa cells was also detected by adenoviral and plasmid vectors. Transfection of oocytes and other ovarian cells was verified by X-gal staining and laser microdissection, followed by PCR analysis. HSV-TK gene transfer, followed by ganciclovir treatment, led to destruction of a significant number of oocytes, whereas HSV-TK gene transfer alone did not lead to toxic effects. It is concluded that the presence of a high concentration of adenovirus or plasmid vectors via the uterine artery may lead to transfection of zona-pellucida-free oocytes and other ovarian cells.     

Inhibition of angiotensin-converting enzyme with quinapril (CI-906): investigation of antihypertensive mechanisms in spontaneously hypertensive rats

Treatment for 8 days with a new nonsulfhydryl angiotensin-converting enzyme inhibitor, quinapril (CI-906), produced a marked and progressive reduction in the blood pressure of spontaneously hypertensive rats. Quinapril was given p.o. in a dose of 20 or 40 mg/kg once daily. Both doses increased plasma renin activity and decreased the urinary excretion of aldosterone. These results, together with a marked decrease in serum angiotensin-converting enzyme activity, indicate that the drug produced a considerable fall in circulating angiotensin II. The urinary excretion of vasopressin was not altered by the smaller dose of quinapril but was reduced by the larger dose, which increased water intake and urine excretion. Quinapril did not affect plasma kininogen or the urinary excretion of kallikrein. The urinary excretion of neither the prostacyclin metabolite 6-keto-prostaglandin F1 alpha nor the thromboxane metabolite thromboxane B2 were altered by the drug. However, quinapril did produce a temporary decrease in the excretion of prostaglandin E2, the effect passing off with the continuation of the treatment. These data indicate that vasodilatory prostanoids do not contribute to the blood pressure lowering effect of quinapril in spontaneously hypertensive rats. The inhibition of the renin-angiotensin system is probably the principal mechanism of the drug's antihypertensive action, but these results do not rule out the possibility that an increase in vasodilatory kinins may also be involved.     

Trimethoprim pharmacokinetics in children with renal insufficiency

We studied the pharmacokinetics of trimethoprim in 14 children (two neonates) with renal insufficiency. They were 1 week to 16.4 years old and had glomerular filtration rates (GFR) between 10.8 to 72.3 ml/min/1.73 m2. The half-life (t1/2) of trimethoprim was inversely related to the GFR. The relation followed a power curve (correlation of t1/2 with GFR: r = -0.86; P less than 0.001). The slower elimination rate was mainly the result of lowered renal clearance of trimethoprim. The volume of distribution (Varea) was, in most patients, in the upper normal range for children. In some of the patients, chiefly infants with severe renal insufficiency, the Varea was larger than normal. In some individuals the pharmacokinetics of trimethoprim deviated from that to be expected from the GRF. We recommend reduced daily doses of trimethoprim if the GFR is less than 30 ml/min/1.73 m2. The reduction should be proportional to the reduction in GFR and primarily take the form of a prolonged dose interval.     

Characterization of the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-provoked strong and rapid aversion to unfamiliar foodstuffs in rats

A conspicuous but scantly studied feature of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity is avoidance of unfamiliar foodstuffs, which seems to be one of the very few exquisitely sensitive behavioural effects in adult laboratory animals. Here we characterized this peculiar response further after low doses of TCDD. The time-course of the novelty avoidance, the role of nutriment form and dependence of the aversion on the time lag between TCDD exposure and the presentation of a novel food item was determined using rats with different sensitivities to lethality of TCDD. Rats were offered chocolate, liquid nutriment or familiar feed with an unfamiliar texture and the consumptions were measured for varying periods. Aversion to a novel food item (chocolate) emerged within 5.5h after TCDD exposure. A lag of a week or more between TCDD exposure and the presentation of chocolate abolished the avoidance whereas simultaneous presentation of chocolate with TCDD treatment rendered the rats oblivious to the chocolate's presence for over 40 days. Rats avoided also liquid nutriments when these were coupled with TCDD administration but this faded much sooner than chocolate aversion. Even a change in feed texture at the exposure was able to elicit the response. However, habituation was found to interfere with the aversion. These findings indicate that temporal proximity to TCDD exposure is a requisite for the avoidance response which emerges rapidly and may linger on for extended periods, but is not strictly confined to any specific food type. The molecular mechanisms of this tantalizing behavioural alteration remain to be determined.     

Immediate and highly sensitive aversion response to a novel food item linked to AH receptor stimulation

Aversion to novel food items was studied in male rats and mice after 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure using chocolate consumption as an indicator. The correlation of this phenomenon with susceptibility to acute toxicity and CYP1A1 induction was examined by determining the dose-response of chocolate aversion in differently dioxin-sensitive rat lines after TCDD (0.01-10 μg/kg). Furthermore, the dependence of this behavioral alteration on the AH receptor (AHR) was studied employing AHR-deficient and wild-type mice. We offered chocolate for both species as a novel food item immediately after the exposure, and it was available with standard rodent chow for 3 days. The ED₅₀ value for the extremely resistant rat line A (LD₅₀ value > 10,000 μg/kg) was 0.36 μg/kg, for the semi-resistant line B (LD₅₀ value 830 μg/kg) 1.07 μg/kg and for the TCDD-sensitive line C (LD₅₀ value 40 μg/kg) 0.34 μg/kg. Interestingly, the ED₅₀ values for chocolate aversion were very similar to those for CYP1A1 induction in these rat lines. Findings on AHR-deficient and wild-type mice implied the involvement of the AHR in this intriguing response, which may thus represent a mechanism to restrict exposure to potentially toxic dietary substances causing hepatic induction of drug-metabolizing enzymes.     

Convulsive and nonconvulsive epilepsy in rats: effects on behavioral response to novelty stress

Behavioral response to a new environment of Wistar and WAG/Rij rats with absence and/or audiogenic seizures (AGSs) was investigated. Behavior was observed in open-field (OF) and light-dark choice (LD) tests. Correlations of test performance with seizure parameters were evaluated. AGS-susceptible Wistar rats exhibited reduced exploration (rearing) in both tests and a tendency toward hyperlocomotion in the OF test. Genetically absence-epileptic WAG/Rij rats demonstrated agitation (increased vertical/horizontal locomotion, enhanced defecation/urination) in the LD test, whereas they exhibited reduced exploration, increased grooming, and hyperlocomotion in the OF test. Anxiety level, as estimated by grooming time in the OF test and latency to first "risk assessment" in the LD test, correlated positively with the propensity for absence seizures in WAG/Rij rats not susceptible to AGSs. It can be concluded that the behavioral response to novelty stress in epileptic subjects depends on the type and severity of seizures.