Reduction of Nitric Oxide with L–/Vc–Monomethyl Arginine in lnterleukin–2 and Anti–CD3 Monoclonal Antibody Combination Therapy

We evaluated nitric oxide induction in antitumor therapy consisting of anti–CD3 monoclonal antibody (anti–CD3) and interleukin–2 (IL–2), then determined the effect of nitric oxide reduction with L–N^G–monomethyl arginine (LNMA) on the therapeutic methods. Female C57BL/6 mice, MCA102 (a non immunogenic, NK–resistant murine fibrosarcoma cell line), and 145–2C11 (hamster anti–murine–CD3 mAb) were utilized in an experimental hepatic metastasis model developed by injecting a tumor cell suspension into the spleen of mice. A marked increase in serum NO₂^–+ NO₁ was observed at 19 hours after anti–CD3 (10 μ, IV) and additional IL–2 administrations (40times10¹ U, twice, If) induced a further increase. The NO₂, + NO_3- elevation in spot urine in the combination therapy was not suppressed with LNMA at a dose of 100 μg/h but was significantly lowered at 300 μg/h. The efficacy of the anti–CD3 + IL–2 therapy was not diminished by LNMA administration either at 100 μg/h or at 300 μg/h.     

4－甲氧基－2－巯基－N－氧化吡啶钠的抗肿瘤及免疫抑制作用

４－个甲氧基－２－巯基－Ｎ－氧化吡啶钠（４－甲氧基巯氧吡啶钠，ＳｏｄｉｕｍＭｅｔｈｏｘｙｐｙｒｉｄｉｎｅｔｈｉｏｎｅ，ＳＭＰＴ）在试管内０．０１ｍｇ·Ｌ－１可抑制多种传代人癌细胞林，抑制细胞有丝分裂和损害细胞膜相结构，单用对动物移植性肿瘤无效，但明显增强氟脲嘧啶对小鼠Ｓ１８０的抑癌作用。使胸腺和脾脏重量明显减轻，抑制ＳＲＢＣ诱导的小鼠血清溶血素反应，抑制ＤＮＣＢ诱导的豚鼠皮肤迟发型超敏反应，抑制ＰＨＡ诱导的大鼠３Ｈ－ＴｄＲ参入的淋巴细胞转化。与２－巯基－Ｎ－氧化吡啶钠（巯氧吡啶钠，ＳｏｄｉｕｍＰｙｒｉｄｉｎｅｔｈｉｏｎｅ．ＳＰＴ）比较，小鼠ＬＤ５０（ｉｐ）增大，而试管内抑瘤的ＩＣ５０相近。     

Cavernous sinus involvement in recurrent Nelson's syndrome

Summary Two cases of meningiomas, which are considered to have been caused by the preceding irradiation, are reported. In both cases, the cytokinetic study of the tumour using bromodeoxyuridine (BrdU) was performed. The percent of the tumour cells in the S phase of the cell cycle was less than 1% in both cases. The low labelling indices might suggest a relatively slow growing potential of these tumours, though the radiation-induced meningiomas were reported as being rapidly growing and malignant.     

Antihepatotoxic Effects of chlorogenic acid from Anthocephalus cadamba

In the present study, chlorogenic acid (CGA) isolated from Anthocephalus cadamba was screened for hepatoprotective activity by in vitro and in vivo assay methods using carbon tetrachloride (CCl₄) as a model of liver injury. Intraperitoneal administration of CGA to mice at a dose of 100 mg/kg body weight for 8 days caused significant reversal in lipid peroxidation, enzymatic leakage, cytochrome P450 (Cyt P450) inactivation and produced enhancement of cellular antioxidant defence in CCl₄-intoxicated mice, revealing that the antioxidative action of CGA is responsible for its liver protective activity. CGA exhibited a better therapeutic protective action than silymarin (SM), in CCl₄-administered mice.     

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 2: Ring-Substituted Derivatives

A range of 18 derivatives of flavone-8-acetic acid (FAA) with substituents on the 2-phenyl group have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. There was no clear-cut relationship between in vitro and in vivo activity but the activity in each situation was found to be very sensitive to the precise substitution pattern with closely related isomers giving widely different activities. Some of the compounds, notably 10b,cj , and r , were active in vivo and these require further studies in order to evaluate their potential for development.     

Synthesis and Structure Elucidation of 5-Aminomethinimino-3-methyl-4-isoxazolecarboxylic Acid Phenylamides and Their Immunological Activity

A series of 5-aminomethinimino-3-methyl-4-isoxazolecarboxylic acid phenylamides 4 has been prepared by condensation of 5-amino-3-methyl-4-isoxazolecarboxylic acid phenylamides 1 with trichloroacetic aldehyde. Alcoholysis of trichloro derivatives 2 gave 5-alkoxymethine derivatives 3 which, on reaction with an appropriate amine, formed the corresponding compounds 4 . The compounds obtained were evaluated for their immunological activity. The properties of three compounds, described in this report, permitted inhibition of the immune response in all possible ways: diminishing both types of immune response ( 4d ), humoral immune response ( 4a ), or cellular immune response ( 4c ). Preparation 4d is comparable in its effectiveness to CsA, so it may be potentially used as an agent for prolongation of the function of transplanted organs. Two other compounds may potentially be used in cases where only one type the immune response is required for combating pathogen invasion.     

N-ω-Carbethoxypentyl-4-quinolones: A New Class of Leukotriene Biosynthesis Inhibitors

6-[(4-Quinolinyl)oxy]hexanoic acids and the corresponding esters were designed and synthesized as inhibitors of the production of arachidonic acid metabolites. The inhibitory activities were assayed in vitro by evaluation of serum leukotriene B₄ and thromboxane B₂ production. While all 6-[(4-quinolinyl)oxy]hexanoic acids and their esters proved to be inactive, the N-alkyl-4-quinolones, obtained as by-products in their synthesis, were found to be a new class of leukotriene biosynthesis inhibitors.     

巨噬细胞杀伤白色念珠菌作用的探讨

本研究经杀菌试验和免疫后保护力试验探讨小鼠巨噬细胞在抗白色念珠菌感染中的作用,结果表明白色念珠菌酵母形体对巨噬细胞杀伤作用的抵抗力及对小鼠的毒力均较菌丝形体强。小鼠体内不同部位巨噬细胞杀伤白色念珠菌的作用不同,脾脏巨噬细胞作用大于腹腔残存巨噬细胞。经白色念珠菌活菌静脉免疫后脾巨噬细胞杀白色念珠菌作用增强,但其对再感染的抵抗力不增强。     

成人原发性肾病综合征血容量与肾素,醛固酮,心钠素的关系

探讨成人原发性肾病综合征(NS)血容量与肾素、醛固酮及心钠素的关系。方法 应用~(113)mInCl标记转铁蛋白稀释法测定血容量,放免法测定血浆激素水平。对水肿期NS28例、正常26例及其中NS缓解期随访18例进行检测。结果 (1)水肿期NS血容量与正常组无差别,血浆肾素活性(PRA)、血管紧张素Ⅱ(ATⅡ)、醛固酮(Ald)、心钠素(ANP)水平均较正常组高,白蛋白、各激素水平与血容量无显著相关;(2)缓解期与水肿期比较,总的血容量无差异,Ald、ANP显著降低,PRA、ATⅡ则无明显差异;(3)Ald与24小时尿排钠(UNaV)显著负相关。结论 Ald和ANP是NS钠排泄的主要调节因子。     

Neurotensin injected into the nucleus accumbens blocks the psychostimulant effects of cocaine but does not attenuate cocaine self-administration in the rat

The neuropeptide neurotensin (NT) has been shown to modulate mesolimbic dopaminergic activity. Neurotensin injected into the VTA produces motor stimulation and release of dopamine in the nucleus accumbens. In contrast, when neurotensin is administered into the nucleus accumbens, it produces neuroleptic-like effects such as attenuation of the locomotor activity elicited by psychostimulants. In the present study, the hypothesis that neurotensin injected into the nucleus accumbens might modulate the psychostimulant and reinforcing actions of cocaine was tested. In experiment one, rats were trained to self-administer cocaine intravenously on an FR5 schedule of reinforcement. Following the establishment of baseline responding, rats were implanted with bilateral cannulae in the nucleus accumbens. One week later, rats were injected into the nucleus accumbens with various doses of neurotensin (4.2, 8.4 and 16.7 μg, total doses bilaterally) immediately prior to the self-administration session. No significant effects were found with any of the doses of neurotensin tested on the self-administration of cocaine. However, in experiment 2, neurotensin at doses of 4.2 and 16.7 μg injected into the nucleus accumbens significantly reduced the locomotor activation induced by an acute injection of cocaine (15 mg/kg i.p.) and a dose of 16.7 μg attenuated the locomotor activation induced by amphetamine (0.75 mg/kg i.p.). Thus, neurotensin in the nucleus accumbens appears to specifically modulate the acute locomotor activating properties of cocaine but not cocaine self-administration. Different mechanisms by which NT interacts with dopamine in the nucleus accumbens may provide a means of selectively altering psychostimulant motor actions without affecting psychostimulant reinforcement.