Effects of barbiturate administration on hepatic and renal biochemical parameters in new zealand white rabbits.

To assess the initial response of various plasma hepatic and renal biochemical parameters to barbiturates, we assigned 30 new Zealand White rabbits to three treatment groups (n = 10 each): control (saline solution injected intravenously), pentobarbitone (30 mg/kg intravenously), and thiopentone (20 mg/kg intravenously). Blood samples were obtained from the central ear artery at six time points: before injection injection of the anesthetics or saline and at 10, 30, 60, and 120 min and 24 h afterward. Plasma alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamiltransferase, blood urea nitrogen, and creatinine levels were measured using an autoanalyzer, and those of the treatment groups were compared with control group levels. The administration of thiopentone significantly increased plasma levels of alanine aminotransferase, aspartate aminotransferase, gamma glutamiltransferase and blood urea nitrogen, but that of plasma alkaline phosphatase significantly decreased. Plasma alkaline phosphatase and gamma glutamiltransferase levels significantly increased after pentobarbitone administration. From these results, we concluded that plasma levels of some hepatic and renal enzyme concentrations increase significantly within a short time after administration of thiopentone or pentobarbitone. Therefore, caution is required in interpreting data on plasma biochemical parameters from rabbits anesthetized with pentobarbitone or thiopentone.     

Acute effects of cocaine on plasma adrenocorticotropic hormone, luteinizing hormone and prolactin levels in cocaine-dependent men.

Acute cocaine administration alters secretion of anterior pituitary hormones in experimental animals, and cocaine abuse may compromise neuroendocrine function in humans. The goal of this study was to examine cocaine's acute effects on neuroendocrine hormones in cocaine-dependent men. Plasma adrenocorticotropic hormone (ACTH), luteinizing hormone and prolactin levels were measured in 18 men before and after i.v. administration of cocaine (30 mg) or placebo. Each subject served as his own control during the i.v. placebo and cocaine administration conditions. Plasma cocaine levels peaked at 260 ng/ml within 5 min after the i.v. injection. Plasma ACTH levels increased significantly above base-line levels at 5, 15, 30 (P < .01) and 45 min (P < .05) after i.v. cocaine. Plasma luteinizing hormone levels increased significantly above base-line levels at 5 (P < .05) and at 15 min (P < .01) after i.v. cocaine. No changes in plasma ACTH or luteinizing hormone levels were found after i.v. placebo injection. Plasma prolactin levels decreased significantly at 30, 45, 60, 90 and 120 min (P < .01) after both i.v. cocaine and placebo administration. Cocaine-induced increases in plasma ACTH levels may be due to its effects on dopaminergic systems which modulate corticotropin-releasing factor release in brain.     

Effects of intravenous cocaine and cigarette smoking on luteinizing hormone,testosterone, and prolactin in men

Cocaine and nicotine have a number of similar behavioral and neurobiological effects. This study compared the acute effects of cocaine and cigarette smoking on luteinizing hormone (LH), testosterone (T), and prolactin. Twenty-four men who met American Psychiatric Association Diagnostic and Statistical Manual criteria for cocaine abuse or nicotine dependence were given intravenous cocaine (0.4 mg/kg) or placebo-cocaine, or smoked a low or high nicotine cigarette under controlled conditions. Placebo-cocaine or low nicotine cigarette smoking did not change LH, T, or prolactin. Peak plasma levels of 254 +/- 18 ng cocaine/ml and 22.6 +/- 3.4 ng nicotine/ml were measured at 8 and 14 min, respectively. LH increased significantly after both i.v. cocaine and high nicotine cigarette smoking (P < 0.01). These LH increases were significantly correlated with increases in cocaine and nicotine plasma levels (P < 0.001-0.003), and high nicotine cigarette smoking stimulated significantly greater increases in LH release than i.v. cocaine (P < 0.05). Testosterone levels did not change significantly after either cocaine or after high nicotine cigarette smoking. After i.v. cocaine, prolactin decreased significantly and remained below baseline levels throughout the sampling period (P < 0.05-0.01). After high nicotine cigarette smoking, prolactin increased to hyperpro-lactinemic levels within 6 min and remained significantly above baseline levels for 42 min (P < 0.05-0.03). The rapid increases in LH and reports of subjective "high" after both i.v. cocaine and high nicotine cigarette smoking illustrate the similarities between these drugs and suggest a possible contribution of LH to their abuse-related effects.     

肠内注射卡巴胆碱对缺血-再灌注大鼠血浆炎症介质的影响

目的　研究肠内注射拟胆碱药卡巴胆碱对缺血再灌注大鼠血浆炎症介质的影响及其意义。方法　成年雄性 Wistar大鼠 ,戊巴比妥钠腹腔麻醉 ,动脉夹阻断肠系膜上动脉血流 (SMAO) ,1h后松夹恢复灌流。大鼠随机分为预防、治疗和对照 3组 ,预防组和治疗组分别在夹闭后 30 m in和再灌后 30 min肠内注射卡巴胆碱 (0 .1mg/ kg,稀释至 1ml生理盐水中 ) ,对照组注射生理盐水。各组分别于夹闭后 1.0、2 .5和 6 .0 h测定血浆中肿瘤坏死因子 α(TNFα)、白细胞介素 10 (IL 10 )和皮质醇含量。结果　治疗组及预防组血浆TNFα含量明显低于对照组 (P均 <0 .0 1) ,IL 10和皮质醇含量变化不明显。结论　卡巴胆碱肠道给药能抑制肠缺血再灌注大鼠全身促炎细胞因子的产生 ,而对抗炎细胞因子的释放及呼吸、循环功能的影响轻微 ,有助于减轻缺血再灌注损伤后的全身性炎症反应。     

Plasma arginine vasopressin response to intravenous methadone and naloxone in conscious dogs

The effect of naloxone and methadone on the systemic release of arginine vasopressin (AVP) was studied in six conscious dogs. After i.v. methadone administration (1 mg/kg b.wt.) plasma AVP levels rose significantly to a mean maximum value of 102.8 +/- 18.8 pg/ml at 15 min postinjection. Plasma sodium and plasma osmolality did not change significantly, whereas plasma potassium decreased significantly. Blood gas variables showed the development of a slight respiratory acidosis. Mean arterial blood pressure increased and heart rate decreased, both significantly, after methadone administration. Naloxone (0.1 mg/kg b.wt.) administered i.v., 15 min before methadone, prevented the changes in plasma AVP levels as well as other variables, with the exception of the heart rate. Naloxone administration itself did not induce changes in any variable recorded. The dose-response study showed increasing plasma AVP levels upon administration of increasing doses of methadone above the 0.5 mg/kg level. On account of the magnitude of response and the lack of changes in biochemical and hemodynamic variables sufficient to explain the documented AVP response, we conclude that methadone exerts a stimulatory influence on the systemic release of AVP. We consider the documented release of AVP to be a direct effect of the methadone administration, on account of the findings from the dose-response study and on account of the total blockade of the response after naloxone administration before methadone.     

Effects of selective iNOS inhibition on systemic hemodynamics and mortality rate on endotoxic shock in streptozotocin-induced diabetic rats

The purpose of this study was to examine whether selective iNOS inhibition can restore the hemodynamic changes and reduce the nitrotyrosine levels in the cerebral cortex of rats with streptozotocin-induced diabetes during endotoxin-induced shock. The study was designed to include three sets of experiments: (1) measurement of changes in systemic hemodynamics, (2) measurement of biochemical variables, including iNOS activity and nitrotyrosine formation in the brain, and (3) assessment of mortality rate. Rats were randomly divided into four groups: group 1, control; group 2, LPS: Escherichia coli endotoxin, 10.0 mg/kg (i.v.) bolus; group 3 (i.v.) LPS and L-N6-(1-iminoethyl)-lysine (L-NIL), 4mg/kg (i.p.); and group 4, LPS and NG-nitro-L-arginine methyl ester (L-NAME), 5 mg/kg (i.p.). In nondiabetic rats, administration of L-NIL prevented the hemodynamic and biochemical changes, and increases in plasma nitrite and cerebral nitrotyrosine levels induced by LPS. Administration of L-NAME partially prevented these LPS-induced changes. On the other hand, in diabetic rats, administration of L-NIL only partially prevented the hemodynamic and biochemical changes, and increases in plasma nitrite and cerebral nitrotyrosine levels associated with LPS. Administration of L-NAME, however, had no effects on these LPS-induced changes in diabetic rats. There was a significant difference in nitrotyrosine levels between nondiabetic and diabetic rats in groups 2, 3, and 4 at 2 and 3 h after the treatment (at 3 h; nondiabetic--control, 4.6 +/- 0.4; LPS (i.v.), 8.9 +/- 1.0, LPS (i.v.) + L-NIL, 4.7 +/- 0.5; LPS (i.v.) + L-NAME, 7.1 +/- 0.9; diabetic--control, 5.5 +/- 0.4; LPS (i.v.), 13.6 +/- 1.2; LPS (i.v.) + L-NIL, 9.0 +/- 0.9; LPS (i.v.) + L-NAME, 13.0 +/- 1.0; densitometric units). Insulin therapy resulted in a decrease in iNOS activity (at 3 h: 1.0 +/- 0.5 fmol mg min), nitrotyrosine formation (at 3 h; 5.0 +/- 0.5, densitometric units), and mortality rates (30% at 6 h, 50% at 12 h) in the LPS (i.v.) + L-NIL group of diabetic rats. Selective iNOS inhibition in diabetic rats could not improve hemodynamic instability, chemical changes, iNOS activity, and nitrotyrosine formation during septic shock compared with the improvements observed in nondiabetic rats. Tight glucose control along with administration of L-NIL can result in more effective restoration of the biochemical changes of septicemia in diabetic rats. Thus, hyperglycemia may be one of the mechanisms related to the aggravation of endotoxin-induced shock.     

Effects of the K+ channel activators, RP 52891, cromakalim and diazoxide, on the plasma insulin level, plasma renin activity and blood pressure in rats

In normo- or hyperglycemic (i.v. infusion of 50 mg/kg/min glucose over 30 min) pithed rats, diazoxide (1 mg/kg/min i.v. over 20 min) significantly reduced plasma insulin content. By contrast, cromakalim, nicorandil or RP 52891 even at doses 40-fold higher than those producing the same hypotensive effect as diazoxide in intact anesthetized normotensive rats, failed to change insulin plasma levels. Glibenclamide (0.01-0.3 mg/kg i.v.) pretreatment antagonized dose-dependently the hypoinsulinemic activity of diazoxide with an i.v. ED50 value of 49 +/- 1 microgram/kg. In pithed rats, diazoxide increased markedly plasma renin activity. This effect was almost inhibited completely by 20 mg/kg i.v., but not at all by a 1-mg/kg i.v. dose of glibenclamide. In pentobarbital-anesthetized rats, diazoxide (0.5-2 mg/kg/min i.v. over 20 min) produced decreases in mean carotid artery blood pressure which were antagonized dose-dependently by glibenclamide (5-20 mg/kg i.v.). This sulfonylurea (20 mg/kg i.v.) also prevented the hypotensive effects of several i.v. administered K+ channel activators (cromakalim, RP 52891 and nicorandil) but not those of numerous hypotensive agents such as acetylcholine, adenosine, bradykinin, clonidine, histamine, salbutamol, dihydralazine, papaverine, platelet aggregating factor, nitroglycerin, nitroprusside, nitrendipine and diltiazem. Although glibenclamide lowered plasma glucose levels, its blocking activity vis-à-vis the hypotension evoked by cromakalim was not affected when its hypoglycemic effects were reversed with an i.v. injection of glucose.(ABSTRACT TRUNCATED AT 250 WORDS)     

蛋白酶抑制剂对内毒素致大鼠肾功能损害的保护作用

目的 探讨蛋白酶抑制剂对内毒素所致大鼠肾功能损伤的作用及其可能机制。方法 健康雄性Wistar大鼠32只，随机分为对照组（n=6），内毒素（LPS）组（n=10，静脉注射LPS5mg／kg），大剂量乌司他丁（UT）干预组（n=8，腹腔注射UT100kU／kg和LPS5mg／kg），小剂量UT干预组（n=8，腹腔注射UT50kU／kg和LPS5mg／kg）。给予LPS2h后用乌拉坦麻醉大鼠，测定动脉血气、血浆内皮素-1（ET-1）、乳酸、肌酐（Cr）水平；行肾组织病理学检查；穿刺膀胱取尿，测定N-乙酰氨基葡萄糖苷酶（NAG）。结果 LPS组动脉血pH值、动脉血氧分压（PaO2）、动脉血二氧化碳分压（PaO2）、剩余碱（BE）均明显低于对照组（P均〈0．01）；两个UT干预组动脉血pH值、PaO2、PaCO2和BE均明显高于LPS组（P〈0．05或P〈0．01）。LPS组血浆ET-1水平明显高于对照组（P〈0．01），两个UT干预组均明显低于LPS组（P均〈0．01），两个UT干预组之间差异无显著性（P〉0．05）。LPS组乳酸水平明显高于对照组（P〈0．001）；两个UT干预组均明显低于LPS组（P均〈0．01）；两个UT干预组间比较差异无显著性（P〉0．05）。LPS组血浆Cr及尿NAG均较对照组明显升高（P均〈0．01）；两个UT干预组血浆Cr及尿NAG水平均较LPS组明显降低（P均〈0．01），两个UT干预组间比较差异均无显著性（P均〉0．05）。肾脏病理检查可见LPS组肾小球大致正常，而肾小管上皮细胞空泡变性，部分上皮细胞崩解、脱落，管腔扩张，两个UT干预组肾小管病理变化均较LPS组减轻，不同剂量组间形态差异无显著性。结论 蛋白酶抑制剂UT能够减轻LPS所致的大鼠肾脏损伤。     

Hypotension during septic shock does not correlate with exhaled nitric oxide in anesthetized rat

Sepsis is characterized by hypotension, acidosis, and increased nitric oxide (NO) production. The role of NO in the development of sepsis-related hypotension is still unclear. The relationship among exhaled nitric oxide (ENO), arterial blood pressure (BP), and pH after administration of lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFalpha) was investigated in anesthetized rats. Forty-three adult male Sprague-Dawley rats were randomized into five groups: group 1 (C, n = 8) received normal saline; group 2 (LPS-I, n = 8) received Escherichia coli (LPS) 10 mg/kg intravenously (i.v.); group 3 (LPS-h, n = 10) received 100 mg/kg LPS i.v.; group 4 (n = 9) was treated with 100 mg/kg i.v. aminoguanidine (AG) 1 h after receiving 100 mg/kg i.v. LPS; group 5 (TNFalpha, n = 8) received 1 microg recombinant rat TNFalpha i.v.. ENO, BP, and pH were measured every 30 min for 4 h whereas arterial blood gases and pH were measured every hour. LPS administration induced a dose-related increase in ENO and a dose-related decrease in BP and pH. AG blocked the increase in ENO after LPS but had minimal effect on BP and pH. TNFalpha administration increased ENO without changing BP and pH. In LPS-treated rats, no significant correlation was found between ENO and BP (r2 = 0.13, P= ns). However, there was a significant correlation between pH and BP (r2 = 0.7, P < 0.01). Our results suggest that, in this animal model, ENO may not be a key mediator in the development of systemic hypotension during sepsis, while acidosis may significantly contribute to it.     

Opioid effects on lidocaine disposition and toxicity in mice

Morphine sulfate, 20 mg/kg, or equivalent doses of the opioids, meperidine and fentanyl, elevated plasma levels of lidocaine after i.v. administration of this antiarrhythmic drug. Plasma levels of the lidocaine metabolites, monoethylglycinexylidine and glycinexylidine, were reduced by opioids as lidocaine levels were elevated. The opioid antagonist, naloxone, 1 mg/kg, reversed the effects of morphine, 20 mg/kg, on lidocaine. After morphine, plasma levels of both lidocaine and indocyanine green were elevated, suggesting that the effect of morphine on lidocaine disposition was related to reduced hepatic blood flow. Morphine and meperidine increased lethality of i.v. lidocaine, as shown by marked reduction of LD50 by either opioid.     

卡巴胆碱对肠缺血-再灌注大鼠血浆肿瘤坏死因子-α和白介素-10含量的影响

目的：研究拟胆碱药卡巴胆碱对肠缺血－再灌注大鼠血浆肿瘤坏死因子－α（TNF－α）、白介素－10（IL－10）和皮质醇含量的影响及其意义。方法：成年雄性Wistar大鼠，戊巴比妥钠腹腔麻醉，用动脉夹阻断肠系膜上动脉血流(SMAO），1h后松夹恢复灌流。随机数字表法将大量分为预防、治疗和对照3组，预防组和治疗组分别在夹闭后30min和再灌注后30min肌肉注射卡巴胆碱（0.1mg/kg)，对照组注射等量生理盐水。各组分别于未夹闭前（0h)和夹闭后1h,2.5h和6h测定血浆中TNF－α、IL－10和皮质醇含量。结果：大鼠缺血－再灌注损伤后，血浆TNF－α、IL－10和皮质醇含量均明显升高。肌肉注射卡巴胆碱后，治疗组及预防组血浆TNF－α含量在各时间点均明显低于对照组（P均＜0．01），同时预防组TNF－α含量在1h和6h点低于治疗组（P均＜0．05）；3组动物之间血浆IL－10和皮质醇含量在夹闭后各时间点均无明显差异。结论：卡巴胆碱能抑制肠缺血－再灌注大鼠体内促炎细胞因子的产生，而对抗炎细胞因子的释放影响轻微，有助于减轻缺血－再灌注损伤的全身性炎症反应。     

Endogenous opiate peptides may limit norepinephrine release during hemorrhage

The involvement of the sympathetic nervous system in the cardiovascular response to hemorrhage and subsequent opiate receptor blockade was studied in conscious rabbits. Plasma catecholamines were measured by high-pressure liquid chromatography to indirectly assess sympathetic activity. Arterial blood samples were drawn at four times during the experiment: 1) before hemorrhage; 2) after a 15% blood loss; 3) after mean arterial blood pressure decreased to less than 40 mm Hg; and 4) 2 min after an i.v. injection of naloxone (3 mg/kg) or saline. Rapid removal of 15% of the total blood volume (approximately equal to 8 ml/kg) increased heart rate and plasma norepinephrine. Plasma epinephrine and blood pressure remained at control levels. Further hemorrhage (approximately equal to 16 ml/kg) produced a sudden decrease in blood pressure and a large increase in plasma epinephrine. Plasma norepinephrine was not significantly different from the previous sample. Subsequent injection of naloxone significantly increased plasma norepinephrine and blood pressure compared to the saline-treated group. Plasma epinephrine was similar in the two groups. These studies suggest that naloxone may exert its pressor effect during hemorrhagic hypotension in the conscious rabbit by blocking a naturally occurring, opiate peptide-mediated inhibition of norepinephrine release. The results are consistent with a peptidergic limit on sympathetic activity being responsible for the decrease in blood pressure seen during acute hemorrhage.     

心肺复苏后血浆可溶性选择素及基质金属蛋白酶-9测定的临床意义

目的探讨心肺复苏(CPR)后是否会出现血浆可溶性P-选择素(sP-选择素)、E-选择素(sE-选择素)及基质金属蛋白酶-9(MMP-9)增高,并评价其临床意义.方法对CPR后存活≥48 h的82例患者于CPR后次日取血标本测定血浆sP-选择素、sE-选择素及MMP-9;按是否发生全身炎症反应综合征(SIRS)及脓毒症而进行分组;并选择65例非危重病患者作为对照.结果 CPR后SIRS发生率为68.3%(56/82例),SIRS组患者血浆sP-选择素水平明显高于非SIRS组患者及对照组(P均<0.01), SIRS组与非SIRS组血浆Se-选择素和MMP-9水平虽无明显差异(P>0.05),但却均高于对照组(P均<0.01).CPR后1周内43.9%(36/82例)的患者发展为脓毒症,脓毒症组患者血浆sP-选择素水平明显高于无脓毒症组患者(P<0.05),两组血浆sE-选择素和MMP-9水平无明显差异(P>0.05).CPR后死亡患者的血浆sE-选择素和MMP-9水平显著高于存活患者(P均<0.01),但两组的血浆sP-选择素水平无明显差异(P<0.05).结论 SIRS是CPR后一种常见的非特异性反应,对预后几乎无明显影响;血浆sP-选择素水平可能帮助识别脓毒症高危患者,而血浆sE-选择素和MMP-9水平可能有助于CPR后不良预后的判断.     

褪黑激素对严重烧伤早期肾功能损害的保护作用

目的观察褪黑激素（MLT）对严重烧伤大鼠肾组织氧化应激损伤和肾功能不全的保护作用及机制。方法将70只SD大鼠随机分为假手术组（10只）、烫伤组（用背部浸入沸水中30S造成30％总体表面积Ⅲ度烫伤模型，30只）和MLT治疗组（伤后立即腹腔注射MLT 10mg／kg，每12h补充注射1次，30只）。检测各组伤后6、24和72h肾组织丙二醛（MDA）和还原型谷胱甘肽（GSH）含量、血浆肌酐（BCr）及尿素氮（BUN）水平，以及伤后6h肾组织谷胱甘肽过氧化物酶（GSH-Px）和髓过氧化物酶（MPO）活性。结果烫伤后各时间点肾组织MDA水平明显升高，而GSH含量则显著下降，二者变化均以伤后6h最明显（P均〈0．01）。BCr及BUN水平在烧伤后6h达高峰（P均〈0．01），然后呈进行性下降。单次MLT治疗使伤后6h肾组织MDA水平降低27．8％（P〈0．01），使GSH含量提高44．4％（P〈0．05），并抑制BCr及BUN水平（P〈0．05和P〈0．01）。连续注射MLT对以上各指标均无明显影响。此外，MLT使烧伤后6h肾组织MPO水平降低30．2％（P〈0．05），但对GSH-Px活性无明显影响。结论30％Ⅲ度烫伤可导致大鼠肾脏发生明显的氧化应激损伤（伤后72h内）及急性肾功能不全（伤后24h内），单次MLT治疗对二者均具有一定的保护作用，可能与MLT具有强大的自由基清除能力及抑制中性粒细胞聚集有关。     

Comparison of urethane/chloralose and pentobarbitone anaesthesia for examining effects of bacterial lipopolysaccharide in mice

Although anaesthetics are widely used to alleviate stress in endotoxaemic animals, these drugs themselves may interfere with the effects of lipopolysaccharide (LPS). The effects of LPS on serum glucose, biochemical markers of hepatic, renal and pancreatic exocrine function, and lung myeloperoxidase (MPO) activity were compared using anaesthesia with either urethane/chloralose or pentobarbitone. Groups of 10-13 of C57B1/6 mice (22.3 +/- 0.18 g) were treated with 40 mg/kg LPS or the same volume of saline (10 mL/kg, i.p.) at time 0, Animals were anaesthetized either with urethane (1000 mg/kg) and chloralose (50 mg/kg) or with pentobarbitone (90 mg/kg, i.p.) after 2 h and blood and lung samples obtained after 6 h. In pentobarbitone-anaesthetized mice, LPS caused hypoglycaemia and increased serum levels of alanine aminotransferase (ALT), lipase and creatinine suggesting damage/dysfunction of liver, exocrine pancreas and kidney respectively. Lung tissue MPO activity, an indicator of neutrophil infiltration, was also increased. Urethane/chloralose-treated mice demonstrated hypoglycaemia and enhanced serum levels of ALT and creatinine in response to LPS, but failed to show LPS-induced increases in serum lipase and lung MPO activity. It is concluded that while pentobarbitone may be successfully used in experimental models of endotoxaemia in mice, anaesthesia with urethane and chloralose may protect mice against LPS-mediated damage/dysfunction in the exocrine pancreas and in the lung, and therefore, is not recommended in studies on endotoxaemic mice.     

茶色素及维生素E对冠心病患者血浆vWF、0xLDL水平的影响

目的：本文观察了65例冠心病（CHD）患者口服茶色素及维生素E（VitE)后血浆血管性假血友病因子（vWF)和氧化型低密度脂蛋白（oxLDL)的改变，并探讨其改变的临床意义。方法：65例确诊为冠心病患者随机给予口服茶色素（375mg/d)、VitE(100mg/d)和安慰剂（粒／天），时间8周。采用酶标法测定血浆vWF和oxLDL。结果：服药前3组CHD患者血浆vWF和oxLDL水平高于正常对照组（P＜0．01）；与服药前相比，服药4周后，茶色素组、VitE组病人的血浆vWF和oxLDL水平下降（P＜0．05）；服药8周时，血浆oxLDL水平在茶色素组和VitE组患者均可见进一步下降（P＜0．01），而血浆vWF水平则有所不同，茶色素组进一步下降（P＜0．01），VitE组病人未见进一步下降，与服药4周时相当（P＜0．05）；服药前茶色素组、VitE组及安慰剂组3组患者的血浆vWF和oxLDL水平无统计学差异（P＞0．05）。结论：CHD患者存在内皮功能不全和动脉血栓形成倾向，茶色素和VitE具有改善内皮功能不全、抑制动脉血栓形成和抑制LDL氧化作用，因而对阻止动脉粥样硬化（AS）的进一步发展可能得到有益作用。     

Effects of TRH and high-dose corticosteroid therapy on evoked potentials,and tissue Na+, K+ and water content in experimental spinal injury

The therapeutic effects of continuous infusion of thyrotropin-releasing hormone (TRH) and methylprednisolone (MP) in experimental spinal cord injury were studied in Swiss albino rats. Thirty rats received a 53-g clip-compression injury on the cord at T1, then were allocated randomly and blindly to one of three treatment groups (ten animals in each): (1) control; received equal volumes of saline solution; (2) MP; received 30 mg/kg methylprednisolone i.v. 1 h after trauma, followed by infusion of 5.4 mg/kg/per hour i.v. for 3 h; (3) TRH; received 2 mg/kg TRH i.v. 1 h after trauma, followed by infusion of 1 mg/kg/per hour i.v. for 3 h. MP and TRH treatments significantly improved somatosensory-evoked potentials (SEPs;P<0.001). Both treatments significantly reduced water content, decreased Na⁺ content and increased the K⁺ content of the cord segment that included the centre of the impact (P<0.01). Our data provide evidence for the beneficial effects of high-dose corticosteroid and TRH in promoting electrophysiological recovery and preserving spinal cord tissue following experimental injury.     

艾司洛尔和芬太尼对高血压患者气管插管循环反应影响的研究

目的 :比较艾司洛尔和芬太尼对高血压患者气管插管时循环和儿茶酚胺反应的影响。方法 :将 6 0例美国麻醉医师协会 (ASA)分级标准 ～ 级且行气管插管全麻手术的高血压患者随机分为 4组 ,分别于插管前静脉注射生理盐水 (A组 )、 2 m g/ kg艾司洛尔 (B组 )、2 μg/ kg芬太尼 (C组 )和 2 mg/ kg艾司洛尔 +2 μg/ kg芬太尼 (D组 )。静脉给咪唑安定、阿曲库胺和异丙酚诱导插管。测定插管前后收缩压 (SAP)、舒张压 (DAP)、心率 (HR)、心率收缩压乘积 (RPP)及血浆去甲肾上腺素 (NA)和肾上腺素 (A)浓度。结果 :气管插管后 1min和3min,A组患者 SAP、DAP、HR、RPP、NA和 A均非常显著高于基础水平 (P<0 .0 5或 P <0 .0 1) ,B组患者NA和 C组患者 SAP插管后均明显升高 (P均 <0 .0 5 ) ,D组患者气管插管后 SAP、DAP、HR和 NA、A水平与基础值比较无明显差异 (P均 >0 .0 5 )。结论 :高血压患者气管插管有明显循环和应激反应 ,2 mg/ kg艾司洛尔或 2 μg/ kg芬太尼预处理仅能部分减少插管反应 ,联合应用 2 mg/ kg艾司洛尔和 2 μg/ kg芬太尼能完全抑制高血压患者插管时的循环和儿茶酚胺反应。     

Clinical and biological effects of low doses of (3 amino-1 hydroxypropylidene)-1,1-bisphosphonate (APD) in Paget''s disease of bone

Abstract. At doses varying between 500 and 1500 mg/day, the disodium salt of (3 amino-1 hydroxypro-pylidene)-1,1-bisphosphonate (APD) has been shown to induce rapid and complete biochemical responses in Paget's disease of bone, but a short-lived and self-limited fever has been observed in 30–40% of patients. The present study is an open and unrandomized trial, performed to explore the use of lower doses of APD (250 and 50 mg/day) given for 6 months to fourteen patients suffering from Paget's disease of bone. Subjective clinical improvement and complete biochemical remission (as assessed by normalization of urinary hydroxyproline excretion and plasma alkaline phosphatase concentration) was observed in ten out of eleven patients given 250 mg/day, but fever did not occur. Thus, a significant decrease in urinary hydroxyproline excretion was noted as early as 15 days after the beginning of the treatment (from 4.5 to 1.3 μmol/l GF; P > 0.05) whereas plasma alkaline phosphatase concentration fell significantly only 1 month later (from 330 to 195 IU/ml; P > 0.05). Both mean (± SEM) urinary hydroxyproline excretion (0.98 ± 0.08 μmol/l GF) and plasma alkaline phosphatase concentration (70 ± 8 IU/ml) were in the normal range after 6 months of treatment. Plasma calcium and phosphorus concentration, urinary calcium excretion and TmP/GFR decreased whereas plasma immunoreactive parathyroid hormone concentration increased. These changes were statistically significant (P < 0.05) only transiently and disappeared at the time when bone formation (assessed by plasma alkaline phosphatase) returned to normal. An increase in total body retention of ⁴⁷Ca during the second month of treatment was documented in five patients (P < 0.05), compatible with a positive calcium balance. Plasma immunoreactive calcitonin did not change (P > 0.05). After 6 months of treatment at 50 mg/day, APD also induced significant decreases in urinary hydroxyproline excretion (from 4.23 to 1.73 μmol/l GF; P < 0.05) and plasma alkaline phosphatase concentration (from 360 to 162 IU/ml; P < 0.05) but biochemical remissions were not complete and these two variables were significantly higher than the corresponding values in the group of patients receiving 250 mg APD/day. Less marked changes were also noted in all the other variables measured. Biological and clinical tolerance was good in all the patients. It is concluded that 250 mg/day of APD is an effective dose schedule, capable of reducing to normal levels the indirect indices of bone turn-over, but in contrast with higher doses, without inducing fever.     

Dynorphin effects on plasma concentrations of anterior pituitary hormones in the nonhuman primate

The role of dynorphin-(1-13) and dynorphin-(1-10)-amide in the neuroendocrine control of primate anterior pituitary hormones was studied in nonrestrained, ovariectomized rhesus monkeys. The effects of these opioids on plasma concentrations of prolactin (PRL), luteinizing hormone (LH), follicle stimulating hormone (FSH) and thyrotropin (TSH), and interactions with naloxone are reported here. Intravenous administration of dynorphin-(1-13), 30 to 120 micrograms/kg, significantly increased plasma PRL levels 3- to 4-fold. These PRL increases occurred within 5 min and levels remained elevated for at least 60 min. Administration of naloxone (1.0 mg/kg i.v.) antagonized the rise in PRL levels. Dynorphin-(1-13) had no significant effect on plasma LH, FSH or TSH levels. Dynorphin-(1-10)-amide (30-120 micrograms/kg) increased plasma PRL levels 2- to 4-fold at 5 to 40 min after administration. Plasma LH levels were significantly depressed 100 to 120 min postdrug. Dynorphin-(1-10)-amide produced no change in plasma FSH or TSH levels. These results indicate that dynorphin is involved in the modulation of PRL and perhaps LH secretion, although not affecting TSH or FSH release.