Differential effects of postconditioning on myocardial stunning and infarction: a study in conscious dogs and anesthetized rabbits

Postconditioning, i.e., brief intermittent episodes of myocardial ischemia-reperfusion performed at the onset of reperfusion, reduces infarct size after prolonged ischemia. Our goal was to determine whether postconditioning is protective against myocardial stunning. Accordingly, conscious chronically instrumented dogs (sonomicrometry, coronary balloon occluder) were subjected to a control sequence (10 min coronary artery occlusion, CAO, followed by coronary artery reperfusion, CAR) and a week apart to postconditioning with four cycles of brief CAR and CAO performed at completion of the 10 min CAO. Three postconditioning protocols were investigated, i.e., 15 s CAR/15 s CAO (n=5), 30 s CAR/30 s CAO (n=7), and 1 min CAR/1 min CAO (n=6). Left ventricular wall thickening was abolished during CAO and similarly reduced during subsequent stunning in control and postconditioning sequences (e.g., at 1 h CAR, 33+/-4 vs. 34+/-4%, 30+/-4 vs. 30+/-4%, and 33+/-4 vs. 32+/-4% for 15 s postconditioning, 30 s postconditioning, and 1 min postconditioning vs. corresponding control, respectively). We confirmed this result in anesthetized rabbits by demonstrating that shortening of left ventricular segment length was similarly depressed after 10 min CAO in control and postconditioning sequences (4 cycles of 30 s CAR/30 s CAO). In additional rabbits, the same postconditioning protocol significantly reduced infarct size after 30 min CAO and 3 h CAR (39+/-7%, n=6 vs. 56+/-4%, n=7 of the area at risk in postconditioning vs. control, respectively). Thus, contrasting to its beneficial effects on myocardial infarction, postconditioning does not protect against myocardial stunning in dogs and rabbits. Conversely, additional episodes of ischemia-reperfusion with postconditioning do not worsen myocardial stunning.     

D1 and D2 Dopaminergic Regulation of Acetylcholine Release from Striata of Freely Moving Rats

The effects of selective D1 and D2 dopaminergic agents on the extracellular acetylcholine (ACh) content in striata of freely moving rats were determined by the microdialysis technique. LY 171555, a selective D2 agonist, reduced ACh output by approximately 30% within 20 min at the dose of 0.2 mg/kg, i.p., whereas the D2 antagonists (-)-remoxipride (10 mg/kg, s.c.) and L-sulpiride (50 mg/kg, i.p.) induced maximal increases of approximately 50% within 10 and 20 min, respectively. In contrast, the D1 antagonist SCH 23390 (0.25 mg/kg, s.c.) decreased the extracellular ACh content by approximately 30% in 20 min, but lower doses--0.025 and 0.05 mg/kg--had no such effect. The stimulation of ACh release by LY 171555 was prevented by (-)-remoxipride but not by SCH 23390 (0.25 mg/kg, s.c.). In addition, the D1 agonist SKF 38393 failed to modify the ACh increasing effect of (-)-remoxipride. Thus, the D1 and D2 receptors subserve opposing functions on ACh release. The D1/D2 dopaminergic agonist R-apomorphine, at the does of 1 mg/kg, i.p., reduced ACh output by approximately 35% only when D1 receptors were blocked by SCH 23390 (0.025 mg/kg, s.c.). The results provide clear in vivo evidence of the tonic inhibition exerted by dopaminergic nigrostriatal input on the cholinergic system of the basal ganglia through D1 and D2 receptors.     

长期慢病患者单次精准功率运动前后脉搏波波形特征个体化分析研究*

目的: 观察研究长期慢病患者的静息桡动脉脉搏波及单次个体化运动后脉搏波的变化情况。方法: 选取被明确诊断为高血压和（或）糖尿病和（或）高脂血症的长期（病程≥5年）慢病患者16例,完成症状限制性极限心肺运动试验（CPET）,计算Δ50%功率为个体化精准运动强度,完成持续30 min的单次个体化运动。于运动前和运动后10 min、20 min、30 min分别测量50 s桡动脉脉搏波,得到每个脉搏波特征点：起始点（B）、主波波峰点（P1）、重搏波波谷点（PL）、重搏波波峰点（P2）、结束点（E）,从仪器中导出各点对应的横坐标（时间T）和纵坐标（幅值Y）的原始数据,将上一个脉搏波的结束点E视为下一个波的起始点B,TB归零,得到主要观察指标：YB、YP1、YPL、YP2及TP1、TPL、TP2、TE,并计算出ΔYP1、ΔYPL、ΔYP2,TE-TPL、（TE-TPL）/TPL、脉率,S1、S2,ΔYP2-ΔYPL、TP2-TPL作为次要观察指标;计算波峰明显的重搏波出现率;对每位患者运动前后的50 s脉搏波数据个体化分析,再将所有数据求均值进行整体分析。结果: ①16例长期慢病患者(男14女2）,年龄（53.7±12.6,28~80）岁,身高（171.7±6.6, 155~183）cm,体质量（80.0±13.5, 54~98）kg。2静息时YB（91.5±10.8,71.1~108.6）、YP1（203.6±24.7,162.7~236.3）、YPL（127.1±6.2,118.2~140.3）、YP2（125.9±6.2,115.7~137.7）、TP1（137.2±22.3,103.0~197.1）、TPL（368.7±29.5,316.3~434.0）、TP2（422.7±32.8,376.9~494.7）、TE（883.4±95.0,672.2~1003.3）,ΔYP1（112.1±33.8,60.3~157.5）、ΔYPL（35.5±14.2,17.5~66.2）、ΔYP2（34.4±13.3,20.0~62.9）、TE-TPL（514.6±85.4,341.4~621.9）、(TE-TPL)/TPL（1.4±0.2,1.0~1.7）、脉率（68.8±8.4,59.8~89.3）、S1（0.9±0.3,0.4~1.4）、S2（0.0±0.0,-0.1~0.0）、ΔYP2-ΔYPL（-1.2±2.6, -6.5 ~2.5）、TP2-TPL（54.0±10.8,33.6~81.1）。③运动后10 min,YB、 YPL、YP2、TPL、TE减小,YP1增大;ΔYPL、TE-TPL、（TE-TPL）/TPL减小,而ΔYP1、脉率、S1、ΔYP2-ΔYPL、 TP2-TPL增大（P均<0.05）。运动后20 min和30 min的脉搏波变化趋势与运动后10 min保持一致,但从10 min后大部分指标逐渐向静息水平恢复。④静息时16例长期慢病患者波峰明显的重搏波出现率为28.6%,运动后10 min（65.7%）、20 min（77.1%）、30 min（73.7%）的出现率明显提高（P均<0.01）。其中6例患者运动后波峰明显的重搏波出现率显著升高,且能持续到30 min;3例患者运动后10 min出现率上升明显,20 min时开始下降;1例患者运动后20 min出现率才开始升高;2例患者运动后10 min出现率升高后随即下降;1例患者运动后20 min出现率短暂升高后下降;1例患者运动后出现率下降,20 min时开始回升;2例患者运动后出现率不升,30 min时稍有升高。结论: 长期慢病患者的桡动脉脉搏波波形矮小,重搏波不明显甚至消失,单次精准功率运动后,主波增高,重搏波位置降低、幅度增大;具体反应情况应个体化分析。     

Endogenous adenosine protects preconditioned heart during early minutes of reperfusion by activating Akt

Ischemic preconditioning (IPC) is thought to protect by activating survival kinases during reperfusion. We tested whether binding of adenosine receptors is also required during reperfusion and, if so, how long these receptors must be populated. Isolated rabbit hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. IPC reduced infarct size from 32.1 +/- 4.6% of the risk zone in control hearts to 7.3 +/- 3.6%. IPC protection was blocked by a 20-min pulse of the nonselective adenosine receptor blocker 8-(p-sulfophenyl)-theophylline when started either 5 min before or 10 min after the onset of reperfusion but not when started after 30 min of reperfusion. Protection was also blocked by either 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1-selective receptor antagonist, or MRS1754, an A2B-selective antagonist, but not by 8-(3-chlorostyryl)caffeine, an A2A-selective antagonist. Blockade of phosphatidylinositol 3-OH kinase (PI3K) with a 20-min pulse of wortmannin also aborted protection when started either 5 min before or 10 or 30 min after the onset of reperfusion but failed when started after 60 min of reflow. U-0126, an antagonist of MEK1/2 and therefore of ERK1/2, blocked protection when started 5 min before reperfusion but not when started after only 10 min of reperfusion. These studies reveal that A1 and/or A2B receptors initiate the protective signal transduction cascade during reperfusion. Although PI3K activity must continue long into the reperfusion phase, adenosine receptor occupancy is no longer needed by 30 min of reperfusion, and ERK activity is only required in the first few minutes of reperfusion.     

Effects of temperature, relative humidity, absolute humidity, and evaporation potential on survival of airborne Gumboro vaccine virus

Survival of airborne virus influences the extent of disease transmission via air. How environmental factors affect viral survival is not fully understood. We investigated the survival of a vaccine strain of Gumboro virus which was aerosolized at three temperatures (10°C, 20°C, and 30°C) and two relative humidities (RHs) (40% and 70%). The response of viral survival to four metrics (temperature, RH, absolute humidity [AH], and evaporation potential [EP]) was examined. The results show a biphasic viral survival at 10°C and 20°C, i.e., a rapid initial inactivation in a short period (2.3 min) during and after aerosolization, followed by a slow secondary inactivation during a 20-min period after aerosolization. The initial decays of aerosolized virus at 10°C (1.68 to 3.03 ln % min(-1)) and 20°C (3.05 to 3.62 ln % min(-1)) were significantly lower than those at 30°C (5.67 to 5.96 ln % min(-1)). The secondary decays at 10°C (0.03 to 0.09 ln % min(-1)) tended to be higher than those at 20°C (-0.01 to 0.01 ln % min(-1)). The initial viral survival responded to temperature and RH and potentially to EP; the secondary viral survival responded to temperature and potentially to RH. In both phases, survival of the virus was not significantly affected by AH. These findings suggest that long-distance transmission of airborne virus is more likely to occur at 20°C than at 10°C or 30°C and that current Gumboro vaccination by wet aerosolization in poultry industry is not very effective due to the fast initial decay.     

Fetal blood volume responses to fetal haemorrhage: autonomic nervous contribution

The purpose of this study was to determine whether the autonomic nervous system contributes to short-term fetal blood volume restitution following fetal haemorrhage. Unanaesthetized, chronically catheterized fetal sheep averaging 130 days gestation (term = 145-150 days) were studied 5 days after catheter implantation. Blockade of the autonomic nervous system was produced with a bolus intravenous injection of hexamethonium. In 7 blocked fetuses, an average of 17.6% of the initial blood volume was removed over 5 min and this was not different from the 16.5% blood volume removed in 7 control fetuses. However, blood volume restoration averaged 44.6% after 30 min in the blocked fetuses and this was significantly less than the 60.2% volume restoration in the control fetuses (P less than 0.05). Thus blood volume restoration averaged 74% of control in the blocked fetuses. Following blood reinfusion over 5 min, blood volume was transiently elevated in the control group, but averaged 3.4, 4.7, and 5.3% below normal (P less than 0.05) at 10, 20 and 30 min post reinfusion in the blocked group. In addition, arterial pressure was lower after haemorrhage in the blocked group and increased twice that in the control group during reinfusion. Thus, the present data suggest that the fetal autonomic nervous system plays a significant role in mediating the short-term changes in fetal blood volume and vascular pressures following fetal haemorrhage and reinfusion.     

Acute renal venous obstruction is more detrimental to the kidney than arterial occlusion: implication for murine models of acute kidney injury

In this study, we compared the traditional murine model with renal pedicle clamp with models that clamped the renal artery or vein alone as well as to a whole body ischemia-reperfusion injury (WBIRI) model. Male C57BL/6J mice underwent either clamping of the renal artery, vein, or both (whole pedicle) for 30 or 45 min followed by reperfusion, or 10 min of cardiac arrest followed by resuscitation up to 24 h. After 30 min of ischemia, the mice with renal vein clamping showed the mostly increased serum creatinine and the most severe renal tubule injury. After 45 min of ischemia, all mice with renal vasculature clamping had a comparable increase in serum creatinine but the renal tubule injury was most severe in renal artery-clamped mice. Renal arterial blood flow was most decreased in mice with a renal vein clamp compared with a renal artery or pedicle clamp. A 30-or 45-min renal ischemia time led to a significant increase in the protein level of interleukin-6, keratinocyte-derived chemokine (KC), and granular colony-stimulating factor in the ischemic kidney, but the KC was the highest in the renal pedicle-clamped kidney and the lowest in the renal vein-clamped kidney. Of note, 10 min of WBIRI led to kidney dysfunction and structural injury, although less than longer time clamping of isolated renal vasculature. Our data demonstrate important differences in ischemic AKI models. Understanding these differences is important in designing future experimental studies in mice as well as clinical trials in humans.     

Alteration of the transmembrane K+ gradient during development of delayed rectifier in isolated rat pulmonary arterial cells

The properties of the tail current associated with the delayed rectifier K+ current (IK) in isolated rat pulmonary artery smooth muscle cells were examined using the whole cell patch clamp technique. The tail currents observed upon repolarization to -60 mV after brief (e.g., 20 ms) or small (i.e. to potentials negative of 0 mV) depolarizations were outwardly directed, as expected given the calculated K+ reversal potential of -83 mV. The tail currents seen upon repolarization after longer (e.g., 500 ms) and larger (e.g., to +60 mV) depolarizations tended to be inwardly directed. Depolarizations of intermediate strength and/or duration were followed by biphasic tail currents, which were inwardly directed immediately upon repolarization, but changed direction and became outwardly directed before deactivation was complete. When cells were depolarized to +60 mV for 500 ms both IK and the subsequent inward tail current at -60 mV were similarly blocked by phencyclidine. Both IK and the inward tail current were also blocked by 4-aminopyridine. Application of progressively more depolarized 30 s preconditioning potentials inactivated IK, and reduced the inward tail current amplitude with a similar potential dependency. These results indicated that the inward tail current was mediated by IK. The reversal potential of the tail current became progressively more positive with longer depolarizations to +60 mV, shifting from -76.1 +/- 2.2 mV (n = 10) after a 20-ms step to -57.7 +/- 3.5 mV (n = 9) after a 500-ms step. Similar effects occurred when extracellular K+ and Na+ were replaced by choline. When extracellular K+ was raised to 50 mM, the tail current was always inwardly directed at -60 mV, but showed little change in amplitude as the duration of depolarization was increased. These observations are best explained if the dependencies of tail current direction and kinetics upon the duration of the preceding depolarization result from an accumulation of K+ at the external face of the membrane, possibly in membrane invaginations. A mathematical model which simulates the reversal potential shift and the biphasic kinetics of the tail current on this basis is presented.     

Free fatty acid-induced peripheral insulin resistance augments splanchnic glucose uptake in healthy humans

To investigate the effect of elevated plasma free fatty acid (FFA) concentrations on splanchnic glucose uptake (SGU), we measured SGU in nine healthy subjects (age, 44 +/- 4 yr; body mass index, 27.4 +/- 1.2 kg/m(2); fasting plasma glucose, 5.2 +/- 0.1 mmol/l) during an Intralipid-heparin (LIP) infusion and during a saline (Sal) infusion. SGU was estimated by the oral glucose load (OGL)-insulin clamp method: subjects received a 7-h euglycemic insulin (100 mU x m(-2) x min(-1)) clamp, and a 75-g OGL was ingested 3 h after the insulin clamp was started. After glucose ingestion, the steady-state glucose infusion rate (GIR) during the insulin clamp was decreased to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in GIR during the period after glucose ingestion from the ingested glucose load. [3-(3)H]glucose was infused during the initial 3 h of the insulin clamp to determine rates of endogenous glucose production (EGP) and glucose disappearance (R(d)). During the 3-h euglycemic insulin clamp before glucose ingestion, R(d) was decreased (8.8 +/- 0.5 vs. 7.6 +/- 0.5 mg x kg(-1) x min(-1), P < 0.01), and suppression of EGP was impaired (0.2 +/- 0.04 vs. 0.07 +/- 0.03 mg x kg(-1) x min(-1), P < 0.01). During the 4-h period after glucose ingestion, SGU was significantly increased during the LIP vs. Sal infusion study (30 +/- 2 vs. 20 +/- 2%, P < 0.005). In conclusion, an elevation in plasma FFA concentration impairs whole body glucose R(d) and insulin-mediated suppression of EGP in healthy subjects but augments SGU.     

缺血性眩晕大鼠模型的建立

目的建立缺血性眩晕大鼠模型,为研究相关治疗药物奠定基础。方法采用手术结扎右侧颈总动脉（common carotid artery,CCA）和右侧锁骨下动脉（subclavian artery,SCA）致大鼠右侧半脑不完全脑缺血建立缺血性眩晕大鼠模型。记录逃避电刺激所需的时间（潜伏期）作为衡量眩晕严重程度的指标,测量造模前后右侧前庭神经核组织血流量,计算血流量变化率,评价脑供血状况。结果 1.与假手术组相比,模型组大鼠潜伏期明显延长（P〈0.01）,造模成功;与模型组比较,盐酸地芬尼多和天保宁能够明显缩短大鼠潜伏期（分别缩短61.9%、52.0%,P〈0.01）。2.结扎右侧CCA及SCA后,与对照组相比,模型组大鼠前庭神经核组织血流量明显减少（P〈0.01）,造模成功;与模型组相比,天保宁能明显增加结扎动脉后组织血流量,在结扎后5、10、15、20、25、30 min血流量分别增加92.8%、83.8%、77.3%、77.9%、65.7%、55.8%（P〈0.01）。结论该模型持久稳定,动物脑部缺血明显,并且能够很好地反映动物眩晕时间及眩晕程度,可有效应用于抗缺血性眩晕药物的实验研究。     

20-Hydroxyecdysone accelerates the flow of cells into the G1 phase and the S phase in a male accessory gland of the mealworm pupa (Tenebrio molitor)

The cells of the bean-shaped accessory glands of mealworms proliferate through the first 7 days of the 9-day pupal stage. Immediately after larval-pupal ecdysis, 25-27% of the cells were in the G1 phase, 60-65% were in the G2 phase, and the balance were in S phase. Over the first 4 days of normal development, the S fraction gradually increased, to reach its highest level in the mid-pupa at the time of the major ecdysteroid peak (Delbecque et al., 1978). Thereafter, the S fraction declined until over 95% of the cells had accumulated in G2 on Day 8. When 0-day pupal glands were explanted into Landureau's S-20 medium for 6 days, the G1 fraction remained fairly constant (25-30%) while S and the G2 fractions fluctuated. On the first day in vitro, the G2 fraction declined and the S fraction rose. On the second day in basal media, the S fraction fell and G2 rose correspondingly until 70% of the cells reached G2 when cycling stopped on the third day. With addition of 20-hydroxyecdysone to 0-day cultures, the S fraction increased quite sharply. It remained large for all 6 days of the experiment in the continuing presence of hormone. A 1-day pulse of hormone produced a transient increase in S. We blocked cell cycling with hydroxyurea in a stathmokinetic experiment and showed that 20-hydroxyecdysone accelerated the flow of cells from the G2 phase to the G1 phase by 2.5-fold. An increase in the G1 fraction was detected within 10 hr of hormone administration and the effect was dose-dependent with an ED50 of 5 X 10(-7) M for 20-hydroxyecdysone. We conclude that 20-hydroxyecdysone acts at a control point in the G2 phase. Incubation of the glands with 20-hydroxyecdysone for only 30-60 min followed by washout stimulated the flow from G2 to G1 and the effect persisted after transfer of the tissues to hormone-free media. Dose-dependent stimulation also occurred with ponasterone A (ED50 3 X 10(-9] but not with cholesterol.     

Complement-requiring neutralizing antibody in guinea pigs with primary and recurrent genital herpes

Guinea pigs inoculated intravaginally with herpes simplex virus type 2 (HSV-2) strain 1868 produced a serum complement-requiring neutralizing (CRN) antibody during primary acute infection, i.e., 10 days postinoculation. The CRN antibody titers in the guinea pig sera decreased to less than 1:10 after heating at 56 degrees C for 30 min. It was found that 32 units of complement were necessary to obtain a satisfactory HSV-2 neutralizing antibody titer. Nonheated sera significantly reduced virus infectivity titers when mixed with 3.5 log10 PFU of HSV-2 and incubated at 37 degrees C for 20 to 60 min (P less than 0.001), whereas the same sera after heating at 56 degrees C for 30 min showed no inhibitory effect. Only 27.3% of infected guinea pigs had low serum non-CRN antibody titers ranging from 1:20 to 1:40. In addition, no evidence of increase in CRN antibody titers was noted during spontaneous recurrent genital herpes infection.     

Bronchial edema alters (99m)Tc-DTPA clearance from the airway surface in sheep.

Airway wall edema, prominent in inflammatory airways disease, may alter barrier properties at the airway air-liquid interface such that normal absorption of soluble substances into the airway circulation is altered. We studied the effects of bradykinin-induced airway wall edema on the clearance of the soluble tracer technetium-99m-labeled diethylenetriamine pentaacetic acid ((99m)Tc-DTPA) from subcarinal airways in sheep (n = 8). (99m)Tc-DTPA (6-10 microl) was delivered by a microspray nozzle inserted through a bronchoscope to a fourth-generation bronchus both before and 1 h after bradykinin (20 ml; 10(-6) M) had been infused through a cannulated and perfused bronchial artery. Airway retention (by scintigraphy) and blood levels of radiolabel were monitored for 30 min after the local deposition of (99m)Tc-DTPA. During control conditions, 85-90% of the tracer cleared from the deposition site within 30 min. The maximum blood level during that time was 17% of the total delivered tracer. However, 1 h after bradykinin infusion, there was significant retention of the marker at the deposition site with clearance within 30 min reduced to 63-70% and decreased blood levels of radiolabel (8%; both P < 0.05). These results demonstrate that moderate airway wall edema alters blood uptake and removal of soluble substances delivered to the subcarinal airways. We suggest that the interplay between vascular and mucociliary clearance routes will impact the resident time for clearance of soluble air toxins and/or therapeutic agents from the epithelial surface.     

Central transmural venous pressure and plasma arginine vasopressin during negative pressure breathing in man

After overnight food and fluid restriction, 8 normal healthy males were examined in the upright sitting position before (prestudy), during and after (recovery) negative pressure breathing (NPB) with a pressure (P = difference between airway pressure and barometric pressure) of -9.6 +/- 0.5 to -10.4 +/- 0.4 mm Hg for 30 min. Plasma arginine vasopressin (pAVP) did not change significantly comparing prestudy with 10 and 30 min of NPB or comparing recovery with NPB at 10, 20 or 30 min. However, at 20 min of NBP, pAVP was slightly lower than at prestudy (p less than 0.05). Central venous pressure (CVP) decreased significantly during NPB, and central transmural venous pressure (CVP-P) increased significantly from -0.9 +/- 0.8 mm Hg to 3.8 +/- 0.7, 4.3 +/- 0.7 and 4.5 +/- 0.6 mm Hg (p less than 0.001) after 10, 20 and 30 min, respectively. Systolic, diastolic and mean arterial pressure and heart rate did not change significantly during NPB. Diuresis, natriuresis, kaliuresis, osmotic excretion and clearance were slightly increased during the recovery hour after NPB compared to prestudy, while urine osmolality decreased during NPB (n = 6). However, none of these changes were significant. There was no significant correlation between CVP-P and pAVP. In conclusion, -10 mm Hg NPB for 30 min in upright sitting subjects did not change pAVP consistently, while CVP-P was significantly increased and HR and arterial pressures were unchanged. This lends support to the concept that arterial baroreceptors and not cardiopulmonary mechanoreceptors are of importance in regulating AVP secretion in man.     

Effect of traditional floor sitting on postural control after standing

Seiza is a Japanese traditional floor sitting style, sitting down with both legs set at about a 180 degree angle and both femurs on both lower legs. We examined the influence of the somatic dysesthesia and decrease in voluntary toe flexion strength (VTF) induced by Seiza on the center of pressure (COP) sway. Fifteen adults participated in this experiment. COP Sway was measured immediately after a chair resting (pre-test), when a plantar dysethesia occurred (post-test A), and when a decrease (under 30% of maximal voluntary contraction (MVC)) in the VTF set in (post-test B). Tissue oxygenation kinetics in the soleus muscle and plantar somatosensory thresholds (ST) were measured just before each COP test and during Seiza. From starting Seiza, oxygenated hemoglobin/myoglobin decreased markedly and reached a plateau within about 6 min. ST abruptly increased at about 19 min from starting Seiza. VTF decreased to less than 30% MVC in 33% of the participants after 10 min from the acute increase in ST, and in 100% after 20 min. When sustaining Seiza for 19 min, ST rose and sway velocity and antero-posterior sway increased. With continued Seiza, VTF decreased to below 30% MVC at 10 - 20 min, and the above stated body sway further markedly increase.     

Aspirin before reperfusion blunts the infarct size limiting effect of atorvastatin

We assessed whether aspirin (acetylsalicylic acid, ASA), administered before reperfusion, abrogates the infarct size (IS)-limiting effect of atorvastatin (ATV). Statins reduce IS. This dose-dependent effect is mediated by upregulation of cycloxygenase-2 (COX2) and PGI(2) production. Administration of selective COX2-inhibitors either with ATV for 3 days or immediately before coronary occlusion blocks the IS-limiting effect of ATV. Sprague-Dawley rats received 3-day ATV (10 mg x kg(-1) x day(-1)) or water alone. Rats underwent 30 min coronary artery occlusion and 4 h reperfusion (IS protocol, n=8 in each group), or rats underwent 30 min coronary artery occlusion and 10 min reperfusion (enzyme expression and activity protocol, n=4 in each group). Immediately before reperfusion rats received intravenous ASA (5, 10, or 20 mg/kg) or saline. Area-at-risk (AR) was assessed by blue dye and IS by triphenyltetrazolium chloride. ATV reduced IS (10.1 +/- 1.4% of the AR) compared with controls (31.0 +/- 2.2%). Intravenous ASA alone did not affect IS (29.0 +/- 2.6%); however, ASA dose dependently (5, 10, and 20 mg/kg) attenuated the protective effect of ATV on IS (15.8 +/- 0.9%, 22.0 +/- 1.6%, and 23.7 +/- 3.8%, respectively). ASA dose dependently blocked the upregulation of COX2 by ATV. COX2 activity was as follows: control, 8.93 +/- 0.90 pg/mg; ATV, 75.85 +/- 1.08 pg/mg; ATV + ASA5, 34.39 +/- 1.48 pg/mg; ATV + ASA10, 19.87 +/- 1.10 pg/mg; and ATV + ASA20, 9.36 +/- 0.94 pg/mg. ASA, administered before reperfusion in doses comparable to those used in the clinical setting, abrogates the IS-limiting effect of ATV in a model with mechanical occlusion of the coronary artery. This potential adverse interaction should be further investigated in the clinical setting of acute coronary syndromes.     

Gliclazide mainly affects insulin secretion in second phase of type 2 diabetes mellitus.

We studied the effect of the acute administration of gliclazide at 160 mg on insulin release during hyperglycaemic clamps in 12 type 2 diabetes patients, age 50 +/- 9.0 years, diabetes duration 5.5 +/- 4.8 years, fasting blood glucose 9.6 +/- 2.1 mmol/L (means +/- SD). After a 210 min of hyperinsulinaemic euglycaemic clamp (blood glucose 4.6 +/- 0.14mmol/L), gliclazide or placebo (randomised, double-blind, cross-over) was administered; 60 minutes later, a hyperglycaemic clamp (4hr) at 8mmol/L was started. Plasma C-peptide levels increased significantly after the administration of gliclazide (increment 0.17 +/- 0.15 vs. 0.04 +/- 0.07 nmol/L, p = 0.024) before the clamp. After the start of the hyperglycaemic clamp, the areas under the curve (AUC) for insulin and C-peptide did not differ from 0-10 min (first phase) with gliclazide. However, second-phase insulin release (30-240 min) was markedly enhanced by gliclazide. AUC plasma insulin (30 to 240 min) was statistically significantly higher after gliclazide (12.3 +/- 13.9 vs. -0.56 +/- 9.4 nmol/L x 210 min, p = 0.022); similarly, AUC plasma C-peptide (30 to 240 min) was also higher: 128 +/- 62 vs. 63 +/- 50 nmol/L x 210 min, p = 0.002). In conclusion, in long-standing type 2 diabetes the acute administration of gliclazide significantly enhances second phase insulin release at a moderately elevated blood glucose level. In contrast to previous findings in mildly diabetic subjects, these 12 type 2 diabetes patients who had an inconsiderable first phase insulin release on the placebo day, only showed an insignificant increase in first phase with gliclazide.     

Effect of Cytochalasin B on the Cytokinesis of Thuricola folliculata (Ciliophora,Peritrichida)1

ABSTRACT. Binary fission of the sessiline loricate peritrich Thuricola folliculata was examined by light microscopy. Cytokinesis, which occurs in the oral-aboral median plane, is 35-40 min in duration. Cytochalasin B (CB) was used at final concentrations of 50–100 μg/ml in dimethyl sulfoxide (DMSO). A transition point occurs at about 20 min after the beginning of binary fission and about 10 min before cytokinesis. In most cases, 50 μg/ml and 100 μg/ml CB added to cells before the transition point resulted in delays of cytokinesis which were significant compared to DMSO controls; sometimes, cytokinesis was blocked completely. If added after the transition point, CB had no effect on cells.     

Effects of hypercapnia on brain pHi and phosphate metabolite regulation by 31P-NMR

The ability of brain cells to regulate intracellular pH (pHi) and several phosphate metabolites was evaluated during 1 h of hypercapnia (inspiratory CO2 fraction of 0.10 and 0.05) in anesthetized rats by 31P high-field (145.6 MHz) nuclear magnetic resonance spectroscopy. Body temperature was maintained at 37 +/- 0.5 degrees C. Fully relaxed spectra were obtained for controls and 30-50 min after CO2 loading and CO2 withdrawal. Spectra were taken serially every 2.5 min after gas mixtures were changed. Brain pHi decreased 0.10 +/- 0.02 units [7.06 +/- 0.01 (SE)] to 6.96 +/- 0.01 (P less than 0.001) after 30-50 min of 10% CO2 breathing, and arterial pH decreased 0.24 +/- 0.01 units. Brain pHi decreased by 0.045 +/- 0.01 units (7.05 +/- 0.01 to 7.01 +/- 0.01, P less than 0.05) during 5% CO2 breathing. Brain pHi returned to control values after 30-50 min of CO2 washout in both groups. In three of six animals breathing 10% CO2, there was an undershoot in brain pHi by 0.07-0.09 units between 2.5 and 20 min of hypercapnia. Three animals exhibited an overshoot in pHi by 0.06-0.11 units between 7.5 and 17.5 min during CO2 washout. Phosphocreatine-to-Pi and Pi-to-beta-ATP ratios changed during hypercapnia and returned to base line after withdrawal of CO2. The findings of a smaller brain pHi change than arterial pH change and undershoots and overshoots in pHi support the view that pHi regulation involves active processes such as transmembrane ion transport.     

Beneficial haemodynamic effect of indomethacin during endotoxin shock in anaesthetized pigsputative involvement of nitric oxide?

Endotoxin shock was induced in 31 anaesthetized pigs by infusion of 5 mug/kg of Escbeicbia coli endotoxin (LPS) over 60 min into the superior mesenteric artery. Fifteen of these pigs died within 30 min of the start of LPS infusion whereas the remaining 16 survived the experimental period of 2 h. In a group of nine pigs indomethacin (2 mg/kg, i.v.)was inected 20-25 rain after the start of LPS infusion at which time mean arterial blood pressure (MABP) had decreased below 40 mmHg indicating imminent death. Indomethacin immediately reversed the hypotension. In another group of five pigs, N(G)-nitro L-arginine-methyl ester (L-NAME, 1 and 3 mg/kg)was iniected 10 and 5 min, respectively, before the expected death without any beneficial effect on the hypotension. Three rain after the last dose of L-NAME, indomethacin (2 mg/kg, i.v.) was iniected. In three animals the hypotension was reserved by indomethacin, although this beneficial effect was delayed in comparison with the LP-Streated group not receiving L-NAME. Four pigs were pretreated with L-NAME, 3 mg/kg, i.v., 10 min prior to LPS infusion. All pretreated animals tended to die within 30 min of the start of the LPS infusion. Five rain before the expected death (20-25 rain after the start of LPS infusion) indomethacin (2 mg/kg) was inected. In three of these animals indomethacin reversed hypotenston and prevented death. Interestingly, this rise in the MABP developed very slowly. These results suggest that the beneficial effect of indomethacin in endotoxin shock might be related partially to interference with nitric oxide, which is not the only factor determining blood pressure levels during endotoxic shock.