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。     

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。     

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。     

Potentiating effect of disodium salt of 2,6-dimethyl-1,4-dihydropyridine-3,5-bis-carbonyl hydroxyacetic acid on the activity of various antitumor agents

The disodium salt of 2,6-dimethyl-1,4-dihydropyridine-3,5-bis-carbonyl hydroxyacetic acid (I) used in the mg/kg dose decreases the cyclophosphane toxicity in mice and potentiates the cytostatic activity of cyclophosphane, 5-fluorouracil and arabinosyl cytosine against leukemia P388, murine sarcoma 37 and Walker's carcinosarcoma. Administered alone I exhibits no antitumour activity. The potentiation of the antitumour effect of drugs appears independent of the administration schedule. Biochemical evidence indicates that I does not block DNA synthesis in leukemic cells in vitro, but significantly enhances the DNA-blocking effect of cyclophosphane in the same cells in vivo.     

Interactions of "ultra-low" doses of naltrexone and morphine in mature and young male and female rats

Sex and age influence morphine analgesia in humans and animals. Mature rats show greater morphine analgesia in males than in females. Ultra-low doses of naltrexone enhance morphine analgesia. In mature rats (18-22 weeks), naltrexone (0.002-2.0 mg/kg)-morphine (2 mg/kg) cotreatment enhanced morphine analgesia in females, an effect inversely related to naltrexone dose. Conversely, in mature male rats, naltrexone tended to decrease morphine analgesia with increasing dose. In young rats (8-10 weeks), morphine analgesia was unrelated to sex and in both sexes the naltrexone-morphine interaction was negligible. These data show that dose, age, and sex alter the naltrexone-morphine interaction in rats.     

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.     

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。     

HPPH光动力学治疗鼠G422脑胶质瘤的实验研究

目的: 通过对鼠G422脑胶质瘤脑及腋部皮下移植瘤模型HPPH光动力学治疗, 从肉眼、肿瘤生长曲线、病理、观察各剂量组疗效, 并与对照组及HpD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 mg/kg、0.3 mg/kg、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组自尾静脉推注入光敏剂, 24小时后以波长665 nm的半导体激光照射HPPH-PDT组和单665 nm激光照射组肿瘤, 功率密度200 mW/cm2, 每光斑照射17 min, 能量密度为204 J/cm2; 功率密度100 mW/cm2, 每光斑照射34min, 能量密度为204 J/cm2; 以波长630 nm的半导体激光照射HpD-PDT组及单630 nm激光照射组肿瘤, 功率密度200 mW/cm2, 每光斑照射20 min, 能量密度为240 J/cm2。肉眼观察肿瘤外形变化, 测量(治疗前、3、5、7、9 d)肿瘤体积, 于PDT后9 d处死鼠, 取肿瘤、肿瘤边缘、正常脑组织, 作病理检查。结果: 可见未经光动力治疗对照组肿瘤迅速生长,第9天体积平均长至治疗前的4.86～5.97倍, HPPH-PDT 0.3 mg/kg、0.45 mg/kg组与治疗前体积平均比是0.94及0.97倍,HPPH-PDT 0.15 mg/kg组是1.09倍、HpD-PDT组是1.6倍, 光动力学组肿瘤的生长速度明显低于对照组, P值＜0.05,有统计学差别, HPPH-PDT 各组优于HpD-PDT组。HPPH-PDT 0.3 mg/kg、0.45 mg/kg组抑瘤效果优于HPPH-PDT 0.15 mg/kg组、HpD-PDT组(P值＜0.05,有统计学差别)。HPPH-PDT 0.3 mg/kg、0.45 mg/kg组抑瘤效果相似。在同样能量密度时高功率密度组第9天疗效较低能量密度稍好,但无统计学差别。故由抑瘤效果层面分析HPPH-PDT对鼠G422脑胶质瘤有抑制作用, 并与HPPH剂量相关, 适宜的剂量为0.3 mg/kg; HPPH-PDT对鼠G422脑胶质瘤的抑瘤作用较HpD-PDT强。从病理观察鼠G422脑胶质瘤脑及皮下移植瘤各剂量HPPH-PDT组及HpD-PDT治疗组, 治疗9 d后仅个别标本肿瘤组织及细胞已消失, 大部分肿瘤组织明显变性坏死, 但深部仍有带活性肿瘤细胞, 与对照组成巢状生长大片活性肿瘤细胞有明显差别。且坏死程度, HPPH-PDT组明显优于HpD-PDT组, 0.3 mg/kg、0.45 mg/kgHPPH-PDT组优于0.15 mg/kg HPPH-PDT组, 0.3 mg/kg、0.45 mg/kg HPPH-PDT组两组程度相似, 故0.3mg/kg是较合适的HPPH-PDT光敏剂剂量。结论: 从抑瘤效果、病理分析, HPPH-PDT对鼠G422脑胶质瘤生长有抑制作用, 抑瘤效果与HPPH剂量有关, 适宜的剂量为0.3 mg/kg; HPPH-PDT对鼠G422脑胶质瘤抑瘤效果较HpD-PDT强。     

Enhanced antitumor action of 5-fluorouracil when used in combination with 4-methylmercaptopyrazolo[3,4-d]pyrimidine 1-nucleoside

Mice BDF1 with L 1210 or mice BALB/c with plasmacytoma MOPS-406 after pretreatment with ineffective doses of 1-beta-D-ribofuranosyl-4-methylmercaptopyrazolo(3,4-d)pyramidin e (25 to 100 mg/kg per 5 days) were treated with 5-fluorouracil at the optimal dose 100 mg per day. This combination produced a 1.5-2-fold or 2 to 4 fold enhancement of the antitumour effect of 5-fluorouracil without simultaneous increase of lethal toxicity.     

新型四酰胺基铝酞菁的制备及其在体光动力抗癌活性研究

为寻求在红光区具有良好光动力治疗（PDT）抗癌活性的新型四取代铝酞菁光敏剂，以4-硝基邻苯二甲酸为原料，用苯酐尿素法合成了四氨基铝酞菁（TAAIPc）、四乙酰胺基铝酞菁（TAcAAIPc）、四丙酰胺基铝酞菁（TPrAAIPc）和四丁酰胺基铝酞菁（TBuAAIPc）。表征了所得产物的结构，测试了其荧光光谱和急性毒性；并在输出波长532nm下测定了其光动力抗癌活性。结果表明，所得的酰胺基取代系列铝酞菁对小鼠无明显毒性。当注射剂量为20mg／kg时，上述四种铝酞菁光敏剂对小鼠S180实体瘤的抑瘤率分别为44．96％，45．87％．45．62％和48．65％，差别不明显。加大剂量至40mg／kg时，抑瘤率依次为39．16％，42．81％，40．56％和51．82％。在此剂量下，四丁酰胺基铝酞菁表现出较高的光动力治疗抗癌活性。     

Effects of (+/-)-idazoxan alone and in combination with L-DOPA methyl ester in MPTP-induced hemiparkinsonian monkeys

The effects of a combination of the alpha2-adrenergic receptor antagonist (+/-)-idazoxan with L-DOPA methyl ester were examined in three of four female adult monkeys (Macaca nemestrina) rendered hemiparkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). (+/-)-Idazoxan (0.16, 0.63, and 1.0 mg/kg) was given i.m. 10 min before L-DOPA methyl ester (12.5 mg/kg). (+/-)-Idazoxan reduced the maximum peak of contralateral circling elicited during the first hour following injection of L-DOPA methyl ester, but prolonged the duration of the circling response up to 50% (p < 0.05). The data support a role for alpha2-adrenergic receptor mechanisms in modulating the effects of L-DOPA on nigrostriatal dopamine function in the MPTP monkey model of hemiparkinsonism.     

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).     

Implantation and activation of high concentrations of boron in Germanium

There is renewed interest in the development of Ge-based devices. Implantation and dopant activation are critical process steps for future Ge devices fabrication. Boron is a common p-type dopant, which remarkably is active immediately after implantation in Ge at low doses. This paper examines the effect of increasing dose (i.e., 5/spl times/10/sup 13/-5/spl times/10/sup 16/ cm/sup -2/) and subsequent annealing (400/spl deg/C-800/spl deg/C for 3 h in nitrogen) on activation and diffusion of boron in Ge. Secondary ion mass spectrometry (SIMS), spreading resistance profiling (SRP), high resolution X-ray diffraction (HRXRD), Rutherford backscattering spectrometry (RBS), and nuclear reaction analysis (NRA) are used to characterize the implants before and after annealing. It is found that very high fractions of the boron dose (/spl sim/5%-55%) can be incorporated substitutionally immediately after implantation leading to very high hole concentrations, /spl ges/2/spl times/10/sup 20/ cm/sup -3/, deduced from SRP. Small increases in activation after annealing are observed, however, 100% activation is not indicated by either SRP or NRA. Negligible diffusion after annealing at either 400/spl deg/C or 600/spl deg/C for 3 h was, furthermore, observed.     

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.     

A Supermolecular Photosensitizer with Excellent Anticancer Performance in Photodynamic Therapy

A supermolecular photosensitizer with excellent anticancer behavior when used for photodynamic therapy (PDT) is fabricated by the incorporation of zinc phthalocyanines (ZnPc) into the gallery of a layered double hydroxide (LDH). The composite material possesses uniform particle size (hydrodynamic diameter ～120 nm), and the host–guest and guest–guest interactions result in a high dispersion of ZnPc in a monomeric state in the interlayer region of the LDH matrix, with high singlet oxygen production efficiency. In vitro tests performed with HepG2 cells reveal a satisfactory PDT effectiveness of the ZnPc(1.5%)/LDH composite photosensitizer: a cellular damage as high as 85.7% is achieved with a rather low dosage of ZnPc (10 μg/mL). An extraordinarily high specific efficacy is demonstrated (31.59 μg^?1 (J/cm²)^?1), which is over 185.5% enhancement compared with the previously reported photosensitizers under similar test conditions. Furthermore, an in vivo study of the ZnPc(1.5%)/LDH demonstrates excellent PDT performance with an ultra‐low dose (0.3 mg/kg) and a low optical fluence rate (54 J/cm²). In addition, the ZnPc/LDH photosensitizer displays high stability, good biocompatibility, and low cytotoxicity, which would guarantee its practical application. Therefore, this work provides a facile approach for design and fabrication of inorganic–organic supermolecular materials with greatly enhanced anticancer behavior.     

Increased body resistance to the toxic action of cyclophosphane through the use of short-term hypoxic hypoxia

Experiments were carried out on 535 SHK albino male mice weighing 24.0 +/- 4.0 g to study the modifying effect of gas hypoxic mixture containing 10.0 +/- 1.0% O2 and 90.0 +/- 1.0% N2 (GHM-10) on cyclophosphane toxicity after intraperitoneal injection of 800, 1000, 1200, 1400, 1600, 1800, and 2000 mg/kg. Before the injection, the animals were kept in a hypoxic medium for 30 min, which reduced mortality rate. It is found that human organism can endure GHM-10 quite well.     

局部注射不同浓度骨保护素对大鼠正畸牙移动影响的研究

目的：研究局部注射不同浓度骨保护素对大鼠牙齿移动的影响。方法：选用10周龄雄性sD大鼠60只,分为实验组与对照组,实验组分0．5mg／kgOPG组和0．05mg／kgOPG组,每组20只。在右上颌第一磨牙施加40G左右力使其移向近中。在实验组和对照组大鼠右上颌第一磨牙腭侧粘骨膜下分别注入重组人骨保护素rhOPG—Fe和...     

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。     

Optimized acquisition time and image sampling for dynamic SPECT ofTl-201

With the recent development in scatter and attenuation correction algorithms, dynamic single photon emission computerized tomography (SPECT) can potentially yield physiological parameters, with tracers exhibiting suitable kinetics such as thallium-201 (Tl-201). A systematic way is proposed to investigate the minimum data acquisition times and sampling requirements for estimating physiological parameters with quantitative dynamic SPECT. Two different sampling schemes were investigated with Monte Carlo simulations: (1) Continuous data collection for total study duration ranging from 30-240 min. (2) Continuous data collection for first 10-45 min followed by a delayed study at approximately 3 h. Tissue time activity curves with realistic noise were generated from a mean plasma time activity curve and rate constants (K₁-k₄) derived from Tl-201 kinetic studies in 16 dogs. Full dynamic sampling schedules (DynSS) were compared to optimum sampling schedules (OSS). The authors found that OSS can reliably estimate the blood flow related K₁ and V_d comparable to DynSS. A 30-min continuous collection was sufficient if only K₁ was of interest. A split session schedule of a 30-min dynamic followed by a static study at 3 h allowed reliable estimation of both K₁ and V_d avoiding the need for a prolonged (>60-min) continuous dynamic acquisition. The methodology developed should also be applicable to optimizing sampling schedules for other SPECT tracers     

当归多糖抗衰老作用的实验研究

目的:观察不同剂量的当归多糖(ASP)对D-半乳糖致衰老小鼠模型是否具有抗衰老作用。方法:50只小鼠随机分为5组,一组为空白组,另4组用D-半乳糖致衰老。这4组分为模型组及三个不同剂量ASP组(100mg/kg、150mg/kg、200mg/kg)。ASP组每日各自灌胃不同剂量的ASP进行干预。测量小鼠脾脏指数,测定小鼠血清和脑组织SOD、MDA、GSH-PX含量及活性,测定小鼠脑细胞凋亡指数。结果:与模型组比较,ASP可拮抗脾脏的萎缩、增强血清和脑组织SOD活力、减少MDA含量、提高GSH-PX活性、降低脑细胞凋亡指数。结论:当归多糖有很好的抗衰老作用。