实体肿瘤药物输运与给药方式的集中参数模型及实验研究

目的研究不同给药方式对实体肿瘤抗癌药物疗效的影响,并通过动物实验验证。方法分别建立体内药代动力学和肿瘤内药物输运的集中参数模型,模拟单次快速注射和等时间间隔三次快速注射时肿瘤间质组织药物浓度Ct随时间的变化。实验小鼠分为两组,分别进行抗癌药羟基喜树碱(HCPT)单次快速注射和等时间间隔3次快速注射,观察其肿瘤内药物平均浓度。对数值模拟结果和动物实验结果进行比较。结果数值模拟结果显示,对于相同总量药物,等量等间隔的三次给药,肿瘤间质组织药物浓度Ct高于单次给药。动物实验的实测结果相同。结论3次给药的效果显著优于单次给药。集中参数模型基本能够定量反映不同给药方式的效果。     

兔激素性股骨头坏死的血液流变学改变

目的　探讨血液流变学指标在激素性股骨头坏死过程中的变化规律及其作用。方法　20只兔随机分成2组，每组10只。A组（激素性股骨头坏死动物模型组）：间隔24h耳缘静脉内2次注射大肠杆菌内毒素，每次40μg/kg，注射内毒素后注射醋酸泼尼松龙20mg/kg。B组（正常对照组）。两组分别在注射后24h、72h、7d、14d 及21d，进行血浆黏度、全血黏度、血小板计数及血脂测定，21d取股骨头和肝脏行病理组织学观察。结果　A组用药后24h血浆黏度、全血黏度升高，血脂升高(P<0.01)血小板计数减少(P<0.01)，用药后72h、7d、14d 及21d，持续异常，与B组相比差异显著。A组21d时病理切片见股骨头骨细胞和肝细胞变性、坏死。结论　在激素性股骨头坏死动物模型中，血液流变学指标异常在引起血栓前状态，形成血栓导致骨坏死过程中可能发挥了重要作用。     

Long-term evaluation of usefulness of skin and incremental challenge tests in patients with history of adverse reaction to local anesthetics

A variety of adverse reactions to local anesthetics has been described, some of which are thought to be allergic. Different protocols of prick and intradermal skin tests as well as subcutaneous challenge tests are used to select a local anesthetic which can safely be used. Their long-term effectiveness has not yet been assessed. Twenty-eight patients with a history of adverse reaction to local anesthetics were evaluated over a 3-year period. Loss of consciousness occurred in eight patients, skin reaction in nine, and vagal symptoms in eight. Various reactions were recorded in the remaining three patients. Rapid spontaneous recovery was the rule, suggesting that immediate allergic reaction and, in particular, anaphylactic reaction were unlikely. Investigation allowed the selection of a tolerated anesthetic in all cases. Reexposure occurred in 19 patients 16–50 months after evaluation and 6.8 ± 5.5 years after the first reaction. No patient presented a second reaction. In conclusion, adverse reactions to local anesthetics seem to be, in most cases, not allergic in nature. Evaluation protocols are effective in selecting an agent susceptible to tolerance, but are time consuming. However, they probably contribute to an important reassurance effect that is likely to increase tolerance to subsequent local anesthetic administration. Simplification of the protocols and better patient selection are proposed.     

幼儿攻击性行为游戏矫正的倒返设计研究

目的：探讨幼儿集体游戏用于矫正幼儿攻击性行为的效果。方法：采用倒返实验，对三名被试进行了游戏矫正。结果：三名被试在实验的基线阶段有明显的攻击性行为，游戏介入后攻击性行为明显减少，游戏取消后攻击性行为再度增加，游戏再次介入后，攻击性行为再次明显减少；方差检验的结果表明，被试在基线阶段的攻击性行为与游戏矫正后的攻击性行为差异极显著。结论：运用自然的幼儿集体游戏可以矫正幼儿的攻击性行为。     

The effects of amrinone and glucagon on verapamil-induced cardiovascular toxicity in anaesthetized rats

The goal of this study was to compare the effects of glucagon and amrinone on mean arterial pressure (MAP) and heart rate, when used alone and in combination, in an anaesthetized rat model of verapamil toxicity. Rats were anaesthetized and the carotid artery was cannulated for MAP and heart rate measurements. Jugular and femoral veins were cannulated for drug administration. After verapamil infusion (15 mg/kg/h), control animals were given normal saline solution and the other groups received amrinone (0.1 or 0.2 mg/kg/min), glucagon (0.3 mg/kg bolus followed by 0.1 or 0.2 mg/kg/min infusion), glucagon plus amrinone (0.1 mg/kg/min and 0.1 mg/kg/min respectively) or glucagon plus amrinone (0.2 mg/kg/min and 0.1 mg/kg/min respectively). Glucagon (0.2 mg/kg/min) significantly increased MAP when compared to the control group ( P  < 0.01). The combination of glucagon and amrinone did not produce a synergistic effect for the recovery of MAP. Furthermore, this combination masked the positive effects of glucagon (0.2 mg/kg/min) on MAP.Glucagon (0.2 mg/kg/min) increased the heart rates compared with those of the control group ( P  < 0.05). Additionally, amrinone (0.1 mg/kg/min) plus glucagon (0.1 mg/kg/min) increased the heart rates ( P  < 0.05). Finally, glucagon dose dependently recovered MAP. While amrinone depressed MAP in combination with glucagon, it did not alter the positive chronotropic effect of high dose glucagon.     

NMDA receptor mediated dendritic plasticity in cortical cultures after oxygen-glucose deprivation

Dendrites and spines undergo dynamic changes in physiological and pathological conditions. Dendritic outgrowth has been observed in surviving neurons months after ischemia, which is associated with the functional compensation. It remains unclear how dendrites in surviving neurons are altered shortly after ischemia, which might reveal the mechanisms underlying neuronal survival. Using primary cortical cultures, we monitored the dendritic changes in individual neurons after oxygen-glucose deprivation (OGD). Two to four hours of OGD induced approximately 30–50% cell death in 24 h. However, the total dendritic length in surviving neurons was significantly increased after OGD with a peak at 6 h after re-oxygenation. The increase of dendritic length after OGD was mainly due to the sprouting rather than the extension of the dendrites. The dendritic outgrowth after 2 h of OGD was greater than that after 4 h of OGD. Application of NMDA receptor blocker MK-801 abolished OGD-induced dendritic outgrowth, whereas application of AMPA receptor antagonist CNQX had no significant effects. These results demonstrate a NMDA receptor-dependent dendritic plasticity shortly after OGD, which provides insights into the early response of surviving neurons after ischemia.     

长期生存癌症患者的述情障碍

目的：探讨长期生存癌症患者的述情障碍及其相关因素，方法：采用多伦多述情障碍量表及症状自评量表，对36例长期生存癌存患者测评，并与45例正常人进行对照比较，结果：（1）癌症组与对照组在SCL－90评价中无显著性差异（P＞0．05）。（2）癌症组TAS总分值明显高于对照组，其中以Ⅱ、Ⅲ、Ⅳ因子尤为明显（P＜0．05－0．01）。（3）Ⅰ因子与躯体化、焦虑、恐怖焦虑及精神病症呈显著性正相关（P＜0．05）。Ⅲ因子与强迫性，人际关系敏感，敌意及精神病症呈显著性负相关（P＜0．05）。Ⅳ因子与偏执化呈显著性负相关（P＜0．05）。结论：长期生存癌症患者虽然SCL－90测评可正常，但存在较明显的述情障碍。     

Influence of age on iminodipropionitrile-induced vestibular and neurobehavioral toxicities in rats

A direct association between aging and drug-induced dyskinesia has been reported by several investigators. Iminiodipropionitrile (IDPN), a prototype nitrile compound produces a motor syndrome in rodents, which resembles neuroleptic drug induced dyskinesia. In this investigation attempt has been made to study the effect of age on IDPN induced vestibular hair cell degeneration and resulting dyskinetic syndrome. Male Wistar rats aged 3, 6 and 12 weeks received IDPN in the doses of 0, 200 and 400 mg/kg, intraperitoneally for 3 consecutive days. IDPN-induced dyskinesia was assessed using a behavioral testing battery on days 3, 4, 5, 6, 7, 14, 21 and 28. The rats were sacrificed on day 28; temporal bones were excised for vestibular histopathology and sera were collected for measuring the indices of oxidative stress (glutathione and conjugated dienes). IDPN in the dose of 200 mg/kg produced dyskinesia in 12 weeks old rats, but failed to do so in 3 and 6 weeks old rats. The high dose of IDPN (400 mg/kg) caused dyskinesia in all age groups, however, its onset and severity were age-dependent. Older rats showed an early onset and significantly high incidence of dyskinesia as compared to younger rats. The susceptibility of rats to IDPN-induced behavioral deficits was proportional to oxidative stress and degeneration of sensory hair cells in the crista ampullaris.     

Piracetam peptide analog L-PGLU-D-Ala-NH2 maintains the plastic properties of synaptic transmission in long-lasting hippocampal slices

Brain Research Institute, All-Union Mental Health Research Center, Academy of Medical Sciences of the USSR. Research Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. V. Val'dman). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 12, pp. 602–604, December, 1990.     

Selected testicular enzymes as biochemical markers for procarbazine-induced testicular toxicity

Single doses of procarbazine (MIH) were injected IP at 0, 50, 100, 200, and 400 mg/kg body weight to CD-1 male mice. Activities of hyaluronidase, lactate dehydrogenase isoenzyme-X, and the dehydrogenases of sorbitol, -glycerophosphate, glucose-6-phosphate, malate, isocitrate, and glyceraldehyde-3-phosphate in the testes of the mice were determined and correlated with changes in spermatogenic cell types in seminiferous tubules. All enzyme activities were higher than controls or remained unchanged on days 10–20 after drug treatment. Activities of hyaluronidase, sorbitol dehydrogenase, and lactate dehydrogenase isoenzyme-X decreased significantly to below normal levels on day 30 after drug treatment for all doses, whereas those of the other five dehydrogenases remained significantly higher than controls. All enzyme activities approached control levels with the concomitant recovery of spermatogenesis by day 60 after drug treatment. Histological examination of seminiferous tubules revealed that premeiotic spermatocytes were significantly reduced on days 10–20 but reappeared on day 30 after MIH treatment (400 mg/kg). The postmeiotic spermatogenic cells were unaffected at the time of MIH treatment, but had disappeared completely on day 30 after drug treatment. MIH, at the highest dosage, selectively destroyed spermatogonia and premeiotic spermatocytes; however spermatozoa and elongated spermatides were unaffected. This study demonstrated that the cytotoxic effect of MIH on spermatogenesis could be evaluated via changes in testicular enzyme activities. The present studies demonstrated that hyaluronidase, sorbitol dehydrogenase, and lactate dehydrogenase isoenzyme-X could serve as useful biochemical markers for assessing testicular toxicity induced by drugs and chemicals.