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.     

虎杖苷对THP-1细胞增殖及凋亡的影响及其作用机制研究

目的探讨虎杖苷对急性单核细胞白血病细胞株THP-1增殖及凋亡的影响及可能的作用机制。方法以不同梯度浓度的虎杖苷处理THP-1细胞24 h、48 h，CCK-8法检测细胞增殖活力，并计算半数抑制浓度。取对数生长期的THP-1细胞，分为虎杖苷处理组（处理浓度为半数抑制浓度）和空白对照组（细胞中未施加虎杖苷溶液处理），培养48 h后，采用流式细胞术检测细胞凋亡及细胞周期；Western blot法检测PI3K、AKT、p-AKT、mTOR、p-mTOR、p70 S6K、p-p70 S6K蛋白的表达。结果虎杖苷可有效抑制THP-1细胞的增殖，48 h的半数抑制浓度为1 800 μmol/L。经1 800 μmol/L的虎杖苷溶液作用48 h后，THP-1细胞的凋亡率较空白对照组显著增加（P<0.05）；细胞周期出现G₀/G₁期至S期的阻滞，表现为G₀/G₁期的细胞比例较空白对照组明显上升，S期的细胞比例较空白对照组显著下降（P<0.05）；PI3K、AKT、p-AKT、mTOR、p-mTOR、p70 S6K、p-p70 S6K蛋白表达较空白对照组显著降低（P<0.05）。结论虎杖苷可有效抑制THP-1细胞的增殖，阻滞细胞周期并诱导细胞凋亡，其作用机制可能与PI3K/AKT/mTOR信号通路的抑制表达有关。     

胚胎脊髓移植加神经生长因子和尼莫地平对成年大鼠脊髓继发性损伤的影响

目的：用神经生长因子（NGF）和尼莫地平（ND）增强胚胎脊髓移植修复成年大鼠损伤脊髓的效果,缓解脊髓继发性损伤。方法：采用脊髓半切洞损伤模型,分为单纯胚胎脊髓移植组,移植加NGF组,移植加NGF和ND组,术后移植部位脊髓细胞内游离钙离子浓度,超氧化物歧化酶（SOD）,丙二醛（MDA）的变化,并比较各组死亡率,结果：移植加NGF组较单纯移植组,MDA明显下降,SOD显著升高,有统计学意义（P＜0．05）,但两组间细胞内游离钙离子浓度差别不显著（P＞0．05）,移植加NGF和ND组更有效地升高SOD浓度,降低钙离子浓度和MDA含量,与其它两组比较有显著性差异（P＜0．05）,移植加NGF和ND组的死亡率明显低于其它两组,有非常显著性差异（P＜0．01）,结论：NGF和ND能较好地改善继发性脊髓损伤,明显降低经胚胎脊髓移植术皇的成年大鼠死亡率,。。     

Total effective compliance of the vascular bed in essential hypertension

Total effective vascular compliance, hemodynamic parameters, cardiopulmonary (CPBV) and total blood volumes (TBV) were determined in 31 men, including nine normotensive controls and 22 permanent essential hypertensive patients. The effective compliance was calculated from the changes in central venous pressure recorded simultaneously with the changes in blood volume obtained after a rapid dextran infusion. In hypertensives, compliance was significantly reduced (1.55 +/- 0.6 vs 2.25 +/- 0.11 ml./mm. Hg/Kg. in controls) (P less than 0.001) and negatively correlated with blood pressure (P less than 0.01), cardiac index (P less than 0.01), and the CPBV/TBV ratio (P less than 0.01). These results suggest that venous compliance contributes to the control of cardiac output in essential hypertension.     

葡萄籽原花青素对牙龈上皮细胞炎症介质表达的影响

目的研究葡萄籽原花青素（GSPs）预处理对脂多糖（LPS）诱导的人牙龈上皮细胞（HGECs）炎症介质表达的影响。方法用含不同浓度GSPs（0、1、5、10、20、40、60、80、100 µg·mL⁻¹）培养液培养HGECs 6、12、24、48 h后，CCK-8检测细胞增殖活性。不同浓度GSPs（0、10、20、40 µg·mL⁻¹）处理HGECs 24 h后加入1.0 µg·mL⁻¹ LPS培养，酶联免疫吸附测定（ELISA）法检测促炎细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6及抗炎细胞因子IL-4、IL-10、转化生长因子（TGF-β）的表达水平，实时荧光定量聚合酶链反应（QRT-PCR）检测TNF-α、IL-1、IL-6、IL-4、IL-10和TGF-β mRNA表达水平。结果GSPs浓度为0~40 µg·mL⁻¹时细胞增殖无明显差异，且细胞增殖活性在24 h时最高。ELISA及QRT-PCR结果显示：与GSPs浓度为0 µg·mL⁻¹相比，GSPs浓度为10、20、40 µg·mL⁻¹时TNF-α、IL-1β和IL-6的表达降低（P<0.05），IL-4、IL-10和TGF-β的表达升高（P<0.05）。结论GSPs浓度在0~40 µg·mL⁻¹时对人HGECs增殖活性无明显影响，GSPs预处理HGECs能够抑制促炎因子的表达和促进抗炎因子的表达，对HGECs抵抗内毒素的刺激起到一定的预防作用。     

牙龈卟啉单胞菌上调钙结合蛋白1促进牙龈上皮细胞增殖

目的探究钙结合蛋白1在牙龈卟啉单胞菌（P. gingivalis）影响牙龈上皮细胞增殖和凋亡中的作用。方法P. gingivalis感染CA9-22细胞，在感染24 h后，采用实时荧光定量聚合酶链反应、免疫印迹法和免疫荧光法检测钙结合蛋白1（CALB1）的表达。通过RNA干扰法抑制CALB1表达，BrdU分析检测细胞增殖，Caspase 3活性测定检测细胞凋亡，免疫印迹法检测MDM2和p53的表达。结果P. gingivalis感染促进CA9-22细胞中CALB1的表达，并且CALB1的表达具有感染复数依赖性。CALB1促进CA9-22细胞增殖，上调细胞内MDM2的表达，同时抑制p53的表达。下调CALB1表达不影响P. gingivalis感染对CA9-22凋亡的抑制作用。结论P. gingivalis感染可通过上调CALB1表达促进CA9-22细胞增殖，其机制可能与影响MDM2-p53有关。     

Identification and potential role of PSD-95 in Schwann cells

Postsynaptic density-95 (PSD-95) is one of neuronal nitric oxide synthase (nNOS)-anchoring proteins and plays an important role in specifying the sites of reaction of nitric oxide (NO) in the nervous system. The present study aims to investigate the presence of PSD-95 in rat Schwann cells (SCs) and the association of PSD-95 and nNOS with serum-induced SCs proliferation. The expression of both molecules downregulated significantly after 48 h of serum deprivation, and increased gradually to the peak at 12 h, ultimately returned to the control level at 48 h after serum stimulation. The association of PSD-95 with nNOS was observed in Ki67 and BrdU-positive SCs. The selective nNOS inhibitor arrested the cell cycle progress and decreased the proliferating cell nuclear antigen (PCNA) levels. These findings suggested that PSD-95 and nNOS may collectively participate in the proliferation of SCs, providing further evidence for the role of NO during peripheral nerve regeneration.     

Endoplasmic reticulum chaperone gp96 in macrophages is essential for protective immunity during Gram‐negative pneumonia

Klebsiella pneumoniae is among the most common Gram‐negative bacteria that cause pneumonia. Gp96 is an endoplasmic reticulum chaperone that is essential for the trafficking and function of Toll‐like receptors (TLRs) and integrins. To determine the role of gp96 in myeloid cells in host defence during Klebsiella pneumonia, mice homozygous for the conditional Hsp90b1 allele encoding gp96 were crossed with mice expressing Cre‐recombinase under control of the LysM promoter to generate LysMcre‐Hsp90b1‐flox mice. LysMcre‐Hsp90b1‐flox mice showed absence of gp96 protein in macrophages and partial depletion in monocytes and granulocytes. This was accompanied by almost complete absence of TLR2 and TLR4 on macrophages. Likewise, integrin subunits CD11b and CD18 were not detectable on macrophages, while being only slightly reduced on monocytes and granulocytes. Gp96‐deficient macrophages did not release pro‐inflammatory cytokines in response to Klebsiella and displayed reduced phagocytic capacity independent of CD18. LysMcre‐Hsp90b1‐flox mice were highly vulnerable to lower airway infection induced by K. pneumoniae, as reflected by enhanced bacterial growth and a higher mortality rate. The early inflammatory response in Hsp90b1‐flox mice was characterized by strongly impaired recruitment of granulocytes into the lungs, accompanied by attenuated production of pro‐inflammatory cytokines, while the inflammatory response during late‐stage pneumonia was not dependent on the presence of gp96. Blocking CD18 did not reproduce the impaired host defence of LysMcre‐Hsp90b1‐flox mice during Klebsiella pneumonia. These data indicate that macrophage gp96 is essential for protective immunity during Gram‐negative pneumonia by regulating TLR expression. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.