Δ9-Tetrahydrocannabinol and the extrapyramidal system

The behavioural effects of stereotypy and catalepsy by ⁹-Tetrahydrocannabinol (⁹-THC) in the rat were estimated and the possible involvement of the basal ganglia in these behaviours was studied using brain lesion techniques. In addition, the interactions of ⁹-THC with a dopaminergic (amphetamine) and a cholinergic stimulant (RS-86) were evaluated using the above methods.The excitatory effects of ⁹-THC alone, i.e., circling, sniffing, and head movements, were of low intensity and short duration and they were not significantly affected by lesions in the basal ganglia. On the other hand, ⁹-THC was found to depress behaviour, including catalepsy and atonic muscular prostration, the former being markedly potentiated, while prostration was unaffected by such lesions.⁹-THC was also found to potentiate cholinergic-induced catalepsy, extrapyramidal lesions causing further potentiation.Amphetamine-induced circling, sniffing, and gnawing emerged as a triad of related behaviour fragments. This was altermated by pallidal lesions and ⁹-THC treatment, the combination of the two being additive. The potentiation by ⁹-THC of amphetamine-induced rhythmic head and body movements was unaffected by pallidal lesions and so could be mediated by another brain area.The hypothesis is proposed that ⁹-THC exerts its cataleptogenic and some of its amphetamine interaction effects by reducing dopaminergic transmission in the basal ganglia.     

Vergleich veränderter Bewußtseinszustände unter den Halluzinogenen (−)-Δ9-trans-Tetrahydrocannabinol (Δ9-THC) und N,N-Dimethyltryptamin (DMT)

Zusammenfassung Die Untersuchung vergleicht unter Verwendung zweier Placebo-Kontrollgruppen veränderte Bewußtseinszustände, die unter den Halluzinogenen (–)⁹-trans-Tetrahydrocannabinol (⁹-THC) und N,N-Dimethyltryptamin (DMT) auftreten. 24 Probanden erhielten 250g ⁹-THC p.o. pro kg Körpergewicht, und 26 Probänden wurde 250g DMT pro Körpergewicht i.m. appliziert. Die Placebogruppe bestand aus insgesamt 24 Probanden. Die Effekte wurden retrospektiv mit einem Fragebogen erfaßt, dessen Items nach inhaltlichen und testtheoretischen Gesichtspunkten zu den folgenden 8 Skalen zusammengefaßt wurden: Optische Sinnestäuschungen, akustische Sinnestäuschungen, Konzentrations- und Gedächtnisstörungen, Derealisationserscheinungen, Depersonalisationserscheinungen, Leiberlebensveränderungen, euphorisches Zustandsbild und dysphorisches Zustandsbild.In allen acht Syndromen unterschieden sich die beiden Halluzinogene signifikant von Placebo. Zwischen den Halluzinogenen konnte jedoch keine signifikante Differenz nachgewiesen werden. In der Skala optische Sinnestäuschungen zeigte sich als Tendenz, daß DMT hier eine stärkere Wirkung als ⁹-THC entfaltet.Methodische Probleme des Vergleichs verschiedener Halluzinogene werden diskutiert.     

Stimulant actions of Δ 9-Tetrahydrocannabinol in mice

⁹-Tetrahydrocannabinol (THC) augments the locomotor activity produced by methamphetamine (0.5 mg/kg) in aggregated mice. THC-induced augmentation was dose related and lasted for a two-hour period. Maximal effective dosage of THC was 15 mg/kg with higher dosages of 30 and 60 mg/kg producing a decrease from maximum in locomotor activity. THC, 15 mg/kg, also increases locomotor activity among aggregated animals treated with saline. However, the increase was much less than the methamphetamine augmentation. In similar studies using isolated mice THC produced only a dose-related decrease in locomotor activity among both methamphetamine-treated and saline-treated animals. THC, 60 mg/kg, had no effect on methamphetamine-induced lethality in aggregated mice. However, at 15 mg/kg, THC significantly enhanced the lethality of methamphetamine. THC did not after methamphetamine lethality in isolated mice. Distribution studies using ¹⁴C-methamphetamine indicated that neither THC nor isolation of animals affected tissue concentration or disappearance of ¹⁴C material. Previously reported synergistic interaction between amphetamine and THC is related to aggregation of the animals rather than drug treatment. Since THC at low doses can stimulate motor activity in saline-treated animals, amphetamine may act only to amplify the behavioral activity produced by low doses of THC.     

层粘连蛋白、基质金属蛋白酶-9在卵巢粘液性肿瘤中的表达及其意义

目的 :探讨层粘连蛋白 (LN)、基质金属蛋白酶 9(MMP 9)在卵巢粘液性肿瘤中的表达以及与临床病理因素和预后的关系。方法 :应用免疫组织化学方法检测 43例卵巢粘液性肿瘤LN、MMP 9的表达情况。结果 :LN、MMP 9的表达 ,在卵巢粘液性肿瘤从良性、交界性到恶性发展中 ,LN的表达级别和MMP 9的表达阳性率逐渐增高 ;LN的表达程度与卵巢粘液性囊腺癌的组织学分级有关 (P =0 0 0 0 ) ;MMP 9的表达与卵巢粘液性囊腺癌的组织学分级 (P =0 0 48)、FIGO分期 (P =0 0 47)、术后复发和死亡 (P =0 0 30 )有关。在卵巢粘液性囊腺癌中 ,LN的表达程度在MMP 9阳性组与MMP 9阴性组之间差异有显著性 (P =0 0 0 8) ,并呈正相关。结论 :LN、MMP 9在卵巢粘液性肿瘤的浸润转移中起重要作用 ,是卵巢粘液性肿瘤的恶性指标之一 ,可望作为交界性粘液性囊腺瘤及粘液性囊腺癌的诊断和分级的客观指标 ;MMP 9可协助临床估计预后。     

血管紧张素Ⅱ和氯沙坦对大鼠小动脉平滑肌细胞的基质金属蛋白酶2和9表达的影响

目的　为研究血管紧张素Ⅱ导致血管重构的机制是否与其影响平滑肌细胞的基质金属蛋白酶 2和 9的表达及活性有关。方法　应用RT PCR、Westernblot、明胶酶谱分析等方法观察不同浓度的血管紧张素Ⅱ对体外培养的大鼠肠系膜小动脉平滑肌细胞的金属蛋白酶 2和 9的表达及活性的影响。结果　高浓度的血管紧张素Ⅱ作用VSMC 48h时 ,可以诱导金属蛋白酶 2和 9的表达及活性增加。不同浓度影响程度不同 ,1× 10 - 8mol·L- 1和 1× 10 - 7mol·L- 1的血管紧张素Ⅱ影响最强。 1× 10 - 6 mol·L- 1氯沙坦可以部分阻断血管紧张素Ⅱ对金属蛋白酶 2和 9的诱导作用。结论　血管紧张素Ⅱ可以诱导小动脉VSMC的金属蛋白酶 2和 9的表达及活性增加 ;AT1受体参与介导此过程     

骨巨细胞瘤MMP-9、血管内皮生长因子表达及其意义

[目的]探讨骨巨细胞瘤MMP-9、VEGF的表达及其意义.[方法]采用免疫组化法检测82例骨巨细胞瘤标本MMP-9、VEGF、PCNA、CD34表达,分析其与骨巨细胞瘤临床病理特性的关系.[结果]MMP-9、VEGF的阳性表达率分别为65.85%、57.32%.复发与未复发组间、转移与未转移组间VEGF、MMP-9的表达差异有显著性(P＜0.05).多因素Logistic回归分析显示VEGF、MMP-9及手术方式对复发有显著影响(P＜0.05).[结论]MMP-9、VEGF的表达与骨巨细胞瘤的血管生成、细胞增殖、转移及复发有关,可作为判定骨巨细胞瘤复发潜能、指导临床治疗的参考指标.     

大肠癌细胞侵袭转移的PKC调节机制研究

目的　探讨蛋白激酶C(PKC)对大肠癌细胞侵袭转移的调节机制。方法　采用羊膜侵袭培养系统和明胶酶谱分析的方法 ,研究PKC激活剂佛波酯PMA ,对人大肠癌细胞株HT 2 9体外侵袭作用的影响及PKC抑制剂staurosporine(SP)对PMA的拮抗作用 ,研究这种体外的侵袭作用与细胞分泌 72kD的基质金属蛋白酶MMP 2和 92kD的基质金属蛋白酶MMP 9的关系。结果　PMA可显著增强HT 2 9细胞的侵袭性 ,与对照组相比 ,有显著性差异 (P <0 .0 1) ,而SP则可拮抗PMA的这种诱导作用。PMA还可增加HT 2 9细胞分泌MMP 2和MMP 9,而SP则可拮抗PMA的这种诱导作用 ,抑制MMP 2和MMP 9的分泌。结论　PKC可调节大肠癌细胞侵袭转移 ,PKC的激活可诱导大肠癌细胞侵袭性增强和增加MMP 2和MMP 9的分泌 ,PKC的抑制可促进大肠癌细胞侵袭性降低和减少MMP 2和MMP 9的分泌。MMP 2和MMP 9的分泌与肿瘤细胞侵袭性有密切关系 ,PKC可能通过调节MMP 2、MMP 9的分泌来影响肿瘤细胞侵袭和转移特性的     

Sequential production and activation of matrix-metalloproteinase-9 (MMP-9) with breast cancer progression

The degradation of the basement membrane by matrix-metalloproteinase(MMP) and serine protease is a critical pointin tumor invasion and metastasis. We measured theactivity of MMP-9 from 28 normal, 12 benignand 126 breast cancer tissues using gelatin zymographywith an image analysis system. ProMMP-9 was expressedin 17.5% of the cancer patients compared to2.5% in 40 non-cancerous tissues (p=0.014).The mature form of MMP-9 (82 kD) wasexpressed only in T2–T4 stages. During the earlyphase of breast cancer (DCIS and T1 stage)progression, only production of proMMP-9 increased. However, asthe cancer grew or invaded skin (T2–T4), orwith lymphovascular permeation, both production and activation ofMMP-9 increased. In conclusion, proMMP-9 production was themain cause of increased MMP-9 activity during theearly phase, while both production and activation increasedin the late phase of breast cancer.