Modification by L-NAME of codeine induced analgesia: possible role of nitric oxide

Objectives were to investigate the effect of nonselective nitric oxide synthase (NOS) inhibitor, L-NAME on codeine-induced analgesia and to see the role of NO in its antinociceptive effect. Also, to see if L-NAME can potentiate the antinociceptive response of sub-effective dose of codeine and to explore if opioid receptors have some role to play in L-NAME effects. Mice were injected with selected doses of codeine or other selected agents intraperitoneally and the latency to hot plate was recorded at zero, 15, 30, and 60 min of the treatments. The antinociceptive response of codeine (10 mg/kg, i.p.) was studied in comparison to those of the NOS inhibitor, L-NAME, and of nitric oxide donor, sodium nitroprusside (SNP). Assessment of nitrates and nitrites (NOx) in the sera of treated mice were also made. Codeine (20 mg/kg dose), induced analgesia significantly and dose dependently only after 15 min. L-NAME at 20, 40, and 80 mg/kg dose levels significantly changed the nonanalgesic effect of codeine (10 mg/kg) to highly significant analgesia. The effect of L-NAME 40 mg/kg was significantly higher than the other two doses and was almost equal to that of the higher dose of codeine. Naloxone itself did not show any intrinsic effect but almost abolished the L-NAME-codeine induced analgesia. Similarly, SNP (1 mg/kg) reversed the decrease in reaction time by L-NAME-codeine to its control values, significantly. Pretreatment with L-NAME rendered the nonanalgesic dose of codeine significantly analgesic almost in an equal potency to the high dose of codeine alone and indicate that the NO modulatory effect on the opioid analgesic codeine is probably, at least in part, through opioid receptors.     

The effects of flumazenil on the antinociceptive actions of morphine in rats

The 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazol[1,5-a][1,4]benzodiazepine-3-carboxylic acid ethyl ester (Flumazenil)-morphine interaction on analgesia (acute pain model, tail-flick test) was tested after intraperitoneal (IP) and intrathecal (IT) routes of administration in female rats. Analgesia was enhanced by the concurrent administration of Flumazenil with morphine (IP), in a dose-related way. Flumazenil alone (IP) did not produce analgesia. In contrast, morphine analgesia was not enhanced by Flumazenil by the IT route. These data demonstrate that Flumazenil enhances morphine-mediated antinociception by mechanisms that are likely to involve benzodiazepine receptors at sites other than the spinal cord.     

The relation of sex, age, and weight of mice to microwave radiation sensitivity.

It is of interest to determine whether the weanling mouse, the sexually mature mouse, or the aged mouse of both sexes are similarly sensitive to microwave radiation. This study included 114 male and female mice irradiated to death with 2450 MHZ microwave radiation at 7.5 watts forward power, a minimum of 14 mice being used for any single set of variables. Weanling mice of 1 month of age are fully developed with respect to most organ systems except the reproductive. Two month old mice are sexually and otherwise mature, fully capable of survival and reproduction. The age mice of both sexes were ex-breeders which had been used for constant litter production for at least 12 months, and had waning reproductive potential. They were therefore about 14 months of age. It was found that the male mice on the average weighed more than the females (least difference at weaning) and both showed considerable weight increase with age; that weanling males irradiated to death absorbed slightly more radiant energy than did the weanling females, but they were also slightly heavier; that time to death under constant exposure from the beam increased with age for both sexes, indicating increasing microwave resistance with age and/or weight; that the mean absorbed dose at death did not show significant differences related to age or weight within the same sex; that the males showed slight increase in radio-tolerance with age and/or weight as measured by the absorbed dose at death when compared with the females which showed a decline in radio-tolerance with age and/or weight; that in all cases sex seemed to be somewhat more important than did age or weight in determining the lethal absorbed dose at death; and that it took longer longer for the older mice to die due probably to the fact that the rate of absorption of radiation was slower with their increased weight. It is the absorbed dose in joules per gram that is biologically significant and the data shows that the mean absorbed dose to death within either sex shows no significant difference with respect to age or weight, but that the difference between the sexes are significant, particularly among the aged ex-breeders.     

口服ALA在皮肤及肿瘤中的代谢

目的 :探求ALA口服在皮肤及皮肤肿瘤中的代谢 ,寻求皮肤肿瘤光敏诊断最佳的ALA口服剂量及时间。方法 :口服不同剂量的ALA(2 0mg/kg、4 0mg/kg、6 0mg/kg、80mg/kg、10 0mg/kg) ,不同时间 (1小时、2小时、4小时、6小时、8小时、10小时、12小时、2 4小时、4 8小时 )以激光诱导荧光OMA检测系统测定肿瘤及左股部皮肤荧光 ,并经数据处理 ,寻求皮肤肿瘤与正常皮肤荧光相对值相差最大的合适的ALA口服剂量及诊断时间。结果 :脉宽 2 0或 30A皮肤肿瘤荧光值总和与组织荧光值总和之比除以正常皮肤荧光值与组织荧光值总和之比在口服ALA6 0mg/kg ,服ALA后 6 - 8小时时比值最大。结论 :从以上数据分析口服ALA作皮肤肿瘤OMA荧光光谱分析剂量以 6 0mg/kg ,服ALA后 6 - 8小时作荧光光谱分析较合适 ,计算相对值在峰值宽度 2 0 - 30A面积均可。     

槐定碱对心力衰竭大鼠心肌细胞钙诱导钙释放的影响

目的:研究槐定碱对心力衰竭大鼠心肌细胞钙诱导钙释放的影响。方法:结扎大鼠冠状动脉左前降支制备心力衰竭模型,随机分为假手术组、心力衰竭组、槐定碱5 mg/kg、10 mg/kg和20 mg/kg剂量组。4周后酶解法分离各组大鼠心室肌细胞,采用膜片钳和激光扫描共聚焦显微镜同步实时记录系统记录心肌细胞的L-型钙电流(ICa.L)及胞浆内的钙瞬变。结果:心力衰竭组大鼠心肌细胞的ICa.L、钙火花发生率及钙瞬变峰值明显低于假手术组;槐定碱中剂量和高剂量组大鼠心肌细胞的ICa.L、钙火花发生率及钙瞬变峰值明显高于心力衰竭组;槐定碱低剂量组与心力衰竭组相比差异不显著。结论:一定浓度的槐定碱对改善心力衰竭大鼠心肌细胞钙诱导钙释放功能具有重要的作用。     

口服ALA联合HPD在鼠脑肿瘤中的代谢

目的:探求ALA口服联合小剂量HPD注射在鼠脑组织及脑肿瘤中的代谢,寻求静脉注射小剂量HPD联合口服ALA脑肿瘤光敏诊断及治疗的最佳的ALA口服剂量及时间。方法:鼠单纯静脉注射1.25mg/kg、口服不同剂量的ALA(20mg/kg、40mg/kg、60mg/kg),及二者联合,及在不同时间(用药前、用药后1小时、2小时、4小时、6小时、8小时、10小时、12小时、24小时、48小时),以激光诱导荧光OMA检测系统测定脑肿瘤及正常脑组织荧光,并与未用药健康鼠脑组织,及未用药脑肿瘤鼠脑组织作对比,并经数据处理,寻求脑肿瘤与正常脑组织荧光相对值相差最大的合适的ALA口服剂量及诊断时间。结果:单纯用1.25mg/kg的HPD在用药后8小时脑肿瘤组织与正常脑组织630nm除以610荧光峰相对值之比值最大,单纯用口服ALA20mg/kg在口服后8小时比值最大,单纯口服ALAALA40-60mg/kg,比值4-6小时比值最大。静脉注射1.25mg/kg的HPD合并口服ALA20mg/kg(简称M20组)在用药后8小时比值最大,合并口服ALA40-60mg/kg组(简称M40、M60组)比值4-6小时比值最大。结论:静脉注射HPD1.25mg/kg合并口服ALA20mg/kg(简称M20组),该小剂量使用光敏剂同样能达到光敏诊断及治疗目的。鼠在用药后8小时作光敏诊断及光动力学治疗最合适,而人在用药后24小时是最佳的光敏诊断及治疗的最佳时间。     

Inhibiting effect of thymogen on the development of tumors of the esophagus and forestomach induced by N-nitrososarcosine ethyl ester in rats

Immunostimulating synthetic peptide thymogen being an analog of the thymus polypeptide drug thymalin was studied for its effect on carcinogenesis of the esophagus and forestomach in male rats. Rats received N-nitrososarcosine ethyl ester (NSEE) per os in the daily dose of 100 mg/kg of body weight during 8 weeks. After cessation of the carcinogen administration rats were treated with thymogen (the daily dose of 10 micrograms per rat) or immune-inactive polypeptide drug pulmolin from the alveolar tissue of lung (the daily dose of 0.5 mg per rat) during the following 32 weeks. Animals were killed 40 weeks after the experiment beginning. NSEE induced the esophagus and forestomach tumours, mainly papillomas and rarely carcinomas, practically in all rats, more than 5 tumours per rat, on the average. Thymogen decreased the tumour incidence by 12% and made tumour multiplicity 1.7 times as low. Pulmolin did not influence development of these tumours.     

Transzygotic carcinogenic effect of nitrosoethylurea in rats

The results of two experiments on the transzygotic transfer of the nitrosoethylurea (NEU) carcinogenic effect are presented. In the first experiment female rats received 60 mg/kg b. w. of NEU at 16, 18 and 20th day of the pregnancy. Their F1 descendants developed multiple tumours of the nervous system after a short latency (up to 40 weeks). The rats of F2, F3, F4 and F5 generations which were not in a direct contact with NEU developed a statistically higher incidence of tumours occurring spontaneously (those of mammary gland, pituitary, and haematopoietic tissue). However, the incidence of nervous system tumours was at the level of controls. In the second experiment male rats received 80 mg/kg b. w. of NEU and then were mated with untreated females. The incidence of the nervous system tumours in the descendants of treated males was somewhat higher than in the controls. The manifestations and mechanisms of the transzygotic effect are discussed.     

Mechanisms of the origination of hypersegmented (hyperdiploid) neutrophils in rats as affected by cyclophosphamide

Feulgen cytophotometry has revealed tetraploid DNA content in some hypersegmented mature granulocytes in rat peripheral blood after two weeks of daily injections of cyclophosphamide (20 mg/kg of body weight). In bone marrow of rats which were given the preparation for 7 days myeloblasts, promyelocytes and myelocytes are blocked in G2 phase of the mitotic cycle. About 50% of metamyelocytes, bands and segmented granulocytes are also tetraploid. Thus cyclophosphamide has induced tetraploid hypersegmented neutrophils in rats as a result of maturation of G2 blocked proliferative pool granulocytes.     

Effect of khingamin on the development of SV40 virus-induced and transplantable tumors in hamsters

Chloroquine was administered to 2-month hamsters inoculated at birth with an oncogenic virus SV-40 which was injected daily in a dose of 30 mg/kg for a month. Chloroquine-treated animals showed a statistically significant (6 weeks) shorter latent period of tumour development. The drug exerted no effect neither on the rate and incidence of transplantable E-1 test tumours or on the phenomenon of resistance in experiments on 4-6-month hamsters under its multiple administration in doses close to maximum tolerated ones (40 mg/kg).     

HPPH光敏剂不同时段在颅内外肿瘤、正常脑及皮肤组织间的代谢分布

目的:观察静脉注射不同剂量HPPH光敏剂后不同时段透过血脑屏障在颅内外肿瘤与正常脑组织、皮肤间的代谢分布,并确定静脉注射HPPH光敏剂后在脑胶质瘤高浓度聚集与正常组织大部份排出相差距离最大的时间段,为光敏诊断、光动力治疗提供最佳时间及剂量。方法:建立鼠G422脑胶质瘤、腋部皮下移植瘤模型,设立注射HPPH 0.15mg/kg组、HPPH 0.3mg/kg组、HPPH 0.45mg/kg组、以荧光图像早期癌诊断仪测定注药前、注药后(4、8、12、18、24、32、48h)肿瘤及正常脑组织、皮肤、口腔及眼粘膜的荧光峰值,选择在肿瘤中有较高的HPPH浓度,正常脑组织及皮肤大部分已排出的最大距离值,以确定HPPHPDT,HPPH注药后最佳的诊断、治疗时间及剂量。结果:从鼠G422脑胶质瘤、腋部皮下移植瘤模型注HPPH 0.15mg/kg组、HPPH 0.3mg/kg组、HPPH 0.45mg/kg组、以荧光图像早期癌诊断仪测定注药前、注药后(4、8、12、18、24、32、48h)不同时间脑肿瘤、腋部皮下肿瘤、正常脑、正常皮肤、口腔及眼粘膜的荧光峰值看,HPPH在注药后12～24h时正常组织荧光峰已较低,而肿瘤尚有较高的荧光峰,二者的距离也较大,是作荧光诊断及光动力学治疗的较佳时间,HPPH 0.3mg/kg、HPPH 0.45mg/kg组峰值平均值接近,并稍高于HPPH 0.15mg/kg组,故HPPH注药0.3mg/kg、注药后12～24h是作鼠G422脑胶质瘤肿瘤光敏诊断及光动力学治疗的较佳剂量及时间,三组注药后口腔及眼粘膜的荧光峰值均较高,且48h仍有较高的浓度,应注意口、眼在HPPH-PDT后对光的防护。皮肤48h时荧光峰较低,可减少皮肤避光时间。结论:通过荧光图像早期癌诊断仪测定静脉注射HPPH在肿瘤及正常组织中的代谢,确定HPPH能作光敏诊断及光动力学治疗,注药0.3mg/kg、注药后12～24h是较佳的光敏诊断及光动力学治疗的剂量及时间。     

口服ALA在脑组织及脑肿瘤中的代谢

目的:探求ALA口服在脑组织及脑肿瘤中的代谢,寻求脑肿瘤光敏诊断最佳的ALA口服剂量及时间。方法:口服不同剂量的ALA(20mg/kg、40mg/kg、60mg/kg、80mg/kg),不同时间(1小时、2小时、4小时、6小时、8小时、10小时、12小时、24小时、48小时)以激光诱导荧光OMA检测系统测定脑肿瘤、正常脑组织及左股部皮肤荧光,并经数据处理,寻求脑肿瘤、正常脑组织与正常皮肤荧光相对值相差最大的合适的ALA口服剂量及诊断时间。结果:脑肿瘤荧光峰值除以组织荧光峰值与正常脑组织荧光峰值除以组织荧光峰值之比,及在ALA40~60mg/kg,服ALA后2~8小时时比值最大。结论:从实验数据分析口服ALA作脑肿瘤OMA荧光光谱分析剂量以40~60mg/kg,服ALA后2~8小时作荧光光谱分析较合适。     

Antineoplastic and toxic effects of blastolysin in the treatment of spontaneous mammary cancer in dogs

The anticancer activity and toxicity of blastolysin were studied in 13 dogs with mammary cancer using two different schedules. The agent was given 5 times in a dose of 2.5-10 mg/kg with a 72 h interval (the first schedule) and 10 times in a dose of 0.4-1.7 mg/kg in 24 h (the second schedule). The first schedule exhibited the highest anticancer effect with the least toxicity. Blastolysin was found to depress erythropoiesis.     

He－Ne激光照射、免疫抑制剂及二者配合应用对大鼠全胰十二指肠移植的影响

以Ａｌｌｏｘａｎ糖尿病模型大鼠作为受体，健康雄性大鼠为供体，行全胰十二指肠移植术，观察了Ｈｅ－Ｎｅ激光照射、免疫抑制剂及二者配合应用抗移植排斥反应的作用效果。结果表明，日剂量为３９．７２Ｊ／ｃｍ２的Ｈｅ－Ｎｅ激光照射，可推迟排斥反应的发生时间、降低排斥反应的发生程度及延长大鼠全胰十二指肠移植物的存活时间。激光照射与８－５－３ｍｇ／ｋｇ／ｄａｘ的硫唑嘌呤（Ａｚａ）配合应用，具有相加的效果，上述作用更为显著，且与环孢霉素Ａ（ＣｓＡ）的作用效果接近。     

雄附散对抗博莱霉素诱导的大鼠肺间质纤维化的作用机制

目的探讨雄附散对大鼠肺间质纤维化干预的机制。方法将70只SD大鼠随机分为正常组,假手术组,模型组,醋酸泼尼松组（5．6mg／kg）,雄附散高、中、低剂量组（1．4g／kg、0．7g／kg、0．35g／kg）。各组大鼠于造模后第2天开始连续4周灌胃（is）,给予生理盐水（0．014L／kg）或相应药物（0．014L／kg）,28d后取右中肺组织进行HE染色和Masson染色及MDA含量、SOD和GSH-PX活性测定。结果HE染色和Masson染色均提示雄附散高剂量组肺组织无明显形态学改变,肺组织中SOD和GSH-PX酶活性明显高于其他各组（P〈0．01）,MDA含量明显低于各药物干预组（P〈0．01）。结论雄附散可能通过提高受损组织中抗氧化酶活性水平来对抗肺组织纤维化过程。     

Characteristics of the carcinogenic action of methyl(acetoxymethyl)nitrosamine and DNA repair in rats of different ages

A pattern of DNA methylation and carcinogenesis has been studied in young (3 month-old) and old (14 month-old) female rats following a single intravenous injection (13 mg/kg) of methyl(acetoxymethyl)nitrosamine (DMN-OAc). The incidence of various tumours as well as the incidence of tumours in some peculiar sites were found to be similar in young and old DMN-OAc-treated rats. The life time of old rats was less than that in young animals; the average period of tumour detection was also shorter in old rats. In both young and old animals the highest concentrations of methylated purines were found in lung and kidney DNA. However, the level of DNA methylation in old rats was higher than in corresponding tissues of young animals. Efficiency of O6-meG repair in methylated template DNA was found to be the highest in liver extracts of 1- and 12-month-old rats. Further, by the age of 2 years, the activity of O6-meGT decreased. The findings suggest that different age periods could be characterized by different efficiency of DNA alkylation, synthesis and repair.     

姜黄素对大鼠角膜碱烧伤的作用

目的:探讨不同浓度姜黄素在大鼠角膜碱烧伤中的作用。方法:建立SD大鼠角膜碱烧伤模型,大鼠分为4组(第1至4组),对照组(第1组)只给予羧甲基纤维素钠,第2,3,4组分别给予100mg/kg BW2、00mg/kg BW及400mg/kg BW姜黄素。在碱烧伤后第3,7,14d用硫代巴比土酸(TBA)法测丙二醛(MDA)含量,化学比色法检测角膜超氧化物歧化酶(SOD)活力。结果:第1,2组之间和第3,4组之间的SOD,MDA无统计学意义。第1,2组与第3,4组相比,后者SOD活力明显增加,MDA含量显著减少。结论:姜黄素对大鼠角膜碱烧伤具有保护作用且与姜黄素浓度有关。     

苯那普利对糖尿病大鼠肾小球基底膜负电荷位点的影响

目的：探讨血管紧张素转换酶抑制剂苯那普利（benezapril）对糖尿病大鼠肾小球基底膜负电荷位点的影响。方法：链脲佐菌素（STZ）腹腔注射诱发大鼠糖尿病模型，苯那普利灌胃，2周、12周取肾脏皮质组织，采用组织化电镜的方法，定量分析肾小球基底膜负电荷位点的变化。结果：糖尿病模型组大鼠肾小球基底膜的负电荷位点较对照组显著减少，苯那普利治疗组的肾小球基底膜负电荷位点较糖尿病模型组显著增多，与对照组相似。结论：苯那利对实验性糖尿病大鼠肾小球基底膜的负电荷位点有保护作用。     

The effect of ferromagnet particles on the growth of Walker carcinosarcoma 256 in Wistar rats

The intravenous injection of ferromagnetic particles (FMP) was studied for its effect on the growth of Walker 256 carcinosarcoma in Wistar rats. The injection of FMP in a dose of 750 mg/kg increased the organism resistance to the tumour development against a background of phagocytic reaction activation in neutrophils. The injection of FMP in a dose up to 2 g/kg inhibited the phagocytic reactions of neutrophils and accelerated the tumour growth. The data obtained evidence that depending on the FMP dose the total reactivity of the organism may either increase or decrease, thus changing, respectively, its resistance to the development of the tumour process.     

HPPH光动力学治疗鼠G422脑胶质瘤诱导肿瘤细胞凋亡的实验观察

目的:通过对鼠G422脑胶质瘤脑及腋部皮下移植瘤模型的HPPH光动力学治疗,从电镜、FCM测定细胞凋亡率,观察各剂量组疗效,并与对照组及HpD-PDT作对比,寻找HPPH-PDT治疗鼠G422脑胶质瘤合适的HPPH剂量。方法:建立鼠G422脑胶质瘤脑及腋部皮下移植瘤模型,设立空白对照组、单注射HPPH 0.45 mg/kg组、单注射HpD组、单665 nm激光照射组、单630 nm激光照射组、HPPH-PDT各组(0.15、0.3、0.45 mg/kg组)、HpD-PDT 5 mg/kg组。单注射HPPH组、HPPH-PDT组和单注射HpD组、HpD-PDT组自尾静脉注入光敏剂,24 h后以波长665 nm的半导体激光照射HPPH-PDT组和单665 nm激光组肿瘤,功率密度200 mW/cm~2,每光斑照射17 min,能量密度为204 J/cm~2;以波长630 nm的半导体激光照射HpD-PDT组及单630nm激光照射组肿瘤,功率密度200 mW/cm~2,每光斑照射20 min,能量密度为240 J/cm~2。于PDT后9 d处死鼠,取肿瘤、肿瘤边缘、正常脑组织,作电镜、FCM细胞凋亡检查。结果:以流式细胞仪及电镜观察肿瘤细胞凋亡,显示鼠G422脑胶质瘤脑及皮下移植瘤HPPH-PDT各剂量组、HpD-PDT组与空白、单注药和单照光三组对照组比较,肿瘤细胞凋亡率明显升高,P<0.01,差别有统计学意义。HPPH-PDT各组细胞凋亡率高于HpD-PDT组,0.3 mg/kg、0.45 mg/kgHPPH-PDT组的细胞凋亡率明显高于0.15 mg/kgHPPH-PDT组,HpD-PDT组,P<0.01,差别有统计学意义,0.45 mg/kg HPPH-PDT组细胞凋亡率稍高于0.3 mg/kgHPPH-PDT组,P>0.05,差别无统计学意义。故HPPH0.3 mg/kg是适宜的HPPH-PDT光敏剂剂量。HPPH-PDT0.3 mg/kg组和HpD-PDT组比较,肿瘤细胞凋亡率明显升高,P<0.01,差别有统计学意义。故由肿瘤细胞凋亡率和电镜分析,HPPH-PDT能诱导鼠G422脑胶质瘤细胞凋亡,凋亡率与HPPH剂量相关,适宜的剂量为0.3 mg/kg;HPPH-PDT诱导鼠G422脑胶质瘤细胞凋亡的作用较HpD-PDT强。结论:从电镜、FCM观察HPPH-PDT对鼠G422脑胶质瘤生长有抑制作用,能诱导肿瘤细胞凋亡及死亡。凋亡率与HPPH剂量有关,适宜的剂量为0.3 mg/kg;HPPH-PDT诱导鼠G422脑胶质瘤细胞凋亡的作用较HpD-PDT强。