葡萄糖酸钙、维生素K1联合奥美拉唑与单独给予奥美拉唑治疗消化道出血的疗效及安全性比较

目的探讨葡萄糖酸钙、维生素K1联合奥美拉唑与单独给予奥美拉唑治疗消化道出血的疗效及安全性比较。方法回顾分析我院收治的180例消化道出血患者,随机分为对照组和观察组,每组90例。对照组单独给予奥美拉唑,观察组给予萄糖酸钙、维生素K1联合奥美拉唑,观察两组患者的临床疗效及安全性比较。结果治疗后观察组患者的总有效率为97.78%明显高于对照组的90.00%(χ2=4.74,P<0.05);各临床症状的缓解时间均显著短于对照组(P<0.05);两组均无严重的不良反应发生,观察组患者的不良反应发生率低于对照组,但两组无显著性差异(P>0.05)。结论应用葡萄糖酸钙、维生素K1联合奥美拉唑治疗消化道出血疗效显著,能更好的发挥止血作用,且不良反应少、发生率低,适宜临床广泛应用。     

健宝灵颗粒配合葡萄糖酸锌治疗小儿厌食症疗效观察

目的:观察健宝灵颗粒配合葡萄糖酸锌治疗小儿厌食症的临床疗效。方法:将我院2010年1月～12月儿科门诊及急诊就诊的76例小儿厌食症患儿随机分为两组,对照组指导家属合理喂养、纠正挑食和偏食,并给予口服多酶片,1～3岁者1片/次,2次/d,4～8岁2片/次,2次/d。治疗组在对照组治疗基础上,口服葡萄糖酸锌片,1～3岁1片/次(70 mg),2次/d,4～8岁1.5片/次,2次/d,并口服健宝灵颗粒,1～5岁1袋/次,2次/d,6～8岁1袋/次,3次/d。口服药物包括多酶片、葡萄糖酸锌片、健宝灵颗粒均服用2周为1个疗程,1个月服1疗程,连用3个月。结果:治疗组总有效率86.8%,对照组总有效率63.2%,两组比较差异有统计学意义(P<0.05);治疗组6个月体重增加(1.15±0.13)kg,对照组增加(1.04±0.11)kg,两组比较差异有统计学意义(P<0.01);治疗组6个月内呼吸道及消化道感染次数(1.89±0.80)次,对照组(2.32±0.84)次,两组比较差异有统计学意义(P<0.05)。结论:健宝灵颗粒配合葡萄糖酸锌治疗小儿厌食症简单方便、疗效可靠,并能提高患儿免疫力、减少感染性疾病的发生。     

黄芪注射液、葡萄糖酸锌联合佐治小儿病毒性心肌炎的临床观察

目的:观察黄芪注射液、葡萄糖酸锌联合佐治小儿病毒性心肌炎的临床疗效.方法:102例患者随机分成两组,对照组44例,治疗组58例.两组均予常规休息、抗感染、营养心肌、对症支持等综合治疗;治疗组在此常规综合治疗的基础上加用黄芪注射液与葡萄糖酸锌颗粒冲剂.结果:治疗组总有效率91.38%,对照组72.73%,两组差异有统计学意义(P＜0.05).结论:黄芪注射液、葡萄糖酸锌联合治疗小儿病毒性心肌炎疗效显著,值得临床应用.     

Interactions of the antimicrobial peptide Ac‐FRWWHR‐NH2 with model membrane systems and bacterial cells

Abstract: The acetylated and amidated hexapeptide FRWWHR (combi‐2), previously identified by combinatorial chemistry methods, shows strong antimicrobial activity. The binding of the peptide to 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐[(phospho‐rac‐(1‐glycerol)] (POPG) and 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine (POPC) vesicles was studied using fluorescence spectroscopy and isothermal titration calorimetry (ITC). Differential scanning calorimetry (DSC) with dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) multilamellar vesicles was performed to determine changes in the lipid phase behaviour upon binding the peptide. Two‐dimensional proton nuclear magnetic resonance (NMR) spectroscopy, to solve the bound peptide structure, was performed in the presence of dodecylphosphatidylcholine (DPC) and sodium dodecyl sulphate (SDS) micelles. The fluorescence, ITC and DSC studies indicate that the peptide interacts preferentially with lipid vesicles containing negatively charged head groups. Conformational information determined using NMR indicate that the combi‐2 peptide adopts a coiled amphipathic conformation when bound to SDS and DPC micelles. Leakage assays indicate that the peptide is not very efficient at causing leakage from calcein‐filled large unilamellar vesicles comprised of POPG/POPC (1 : 1). The rapid passage of either the fluorescent‐tagged peptides combi‐2 or the previously studied peptide Ac‐RRWWRF‐NH₂ (combi‐1) into Escherichia coli and Staphylococcus aureus suggests that instead of membrane disruption, the main bactericidal site of action of these peptides might be located inside bacteria.     

Interactions between tetraethylammonium and methohexitone at the chick neuromuscular junction: Experiments with the moving fluid electrode technique

The effect of methohexitone on the depolarization and contracture responses produced by tetraethylammonium (TEA), acetylcholine (ACh) and repetitive indirect stimulation were investigated, using the moving fluid electrode technique, in the chick biventer cervicis (BVC) nerve muscle preparation. TEA (4.8 × 10^?4?4.8 × 10^?2 M) produced contracture and depolarization responses which were concn-dependent. These responses were potentiated by methohexitone (8.8 × 10^?5 M). The mean ED₅₀S for the contracture responses in the control Krebs solution and with methohexitone were (mean ± S.E.M.) 6.5 ± 0.03 × 10^?3 M and 1.3 ± 0.04 × 10^?3 M (N = 6) respectively. The mean ED₅₀S for the depolarizations were (mean ± S.E.M.) 5.9 ± 0.1 × 10^?3 and 1.5 ± 0.06 × 10^?3 M (N = 6) respectively. ACh (5.5 × 10^?6?1.1 × 10^?2 M) produced contracture and depolarization responses which were concn-dependent. These responses were reduced by methohexitone (8.8 × 10^?5 M). The mean ED₅₀S for the contracture responses in the control Krebs solution and with methohexitone were (mean ± S.E.M. 2.4 ± 0.21 × 10^?4 and 2.3 ± 0.1 × 10^?3 M (N = 6) respectively. The mean (± S.E.M.) ED₅₀S for the depolarizations were 8.4 ± 0.33 × 10^?4 and 3.7 ± 0.14 × 10^?3 M (N = 6), respectively. Repetitive indirect stimulation, at 1–20 Hz, produced contraction and depolarization responses which were frequency-dependent. These responses were slightly potentiated by methohexitone (8.8 × 10^?5 M). The mean (± S.E.M.) frequency₅₀S for the contractions produced in the control Krebs solution and with methohexitone were 9.2 ± 0.1 and 8.5 ± 0.2 Hz (N = 6) respectively. The mean frequency₅₀S for the depolarizations were (mean ± S.E.M.) 7.2 ± 0.1 and 5.8 ± 0.19 Hz (N = 6) respectively. It is concluded that TEA may have a direct post-synaptic action, in addition to releasing ACh from the presynaptic nerve terminals. TEA produces more contracture tension than does ACh for a given level of membrane depolarization. Methohexitone, non-competitively, reduces the responses produced by applied ACh whereas it potentiates those produced by TEA and repetitive nerve stimulation.     

Molecular Docking and Interactions of Pueraria Tuberosa with Vascular Endothelial Growth Factor Receptors

Pueraria tuberosa is known for its therapeutic potentials in cardiovascular disorders, but its effect in angiogenesis has not been studied so far. In this study, a computational approach has been applied to elucidate the role of the phytochemicals in inhibition of angiogenesis through modulation of vascular endothelial growth factor receptors: Vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2, major factors responsible for angiogenesis. Metabolite structures retrieved from PubChem and KNApSAcK – 3D databases, were docked using AutoDock4.2 tool. Hydrogen bond and molecular docking, absorption, distribution, metabolism and excretion and toxicity predictions were carried out using UCSF Chimera, LigPlot⁺ and PreADMET server, respectively. From the docking analysis, it was observed that puerarone and tuberostan had significant binding affinity for the intracellular kinase domain of vascular endothelial growth factor receptors-1 and vascular endothelial growth factor receptor-2 respectively. It is important to mention that both the phytochemicals shared similar interaction profile as that of standard inhibitors of vascular endothelial growth factor receptors. Also, both puerarone and tuberostan interacted with Lys861/Lys868 (adenosine 5’-triphosphate binding site of vascular endothelial growth factor receptors-1/vascular endothelial growth factor receptors-2), thus providing a clue that they may enforce their inhibitory effect by blocking the adenosine 5’-triphosphate binding domain of vascular endothelial growth factor receptors. Moreover, these molecules exhibited good drug-likeness, absorption, distribution, metabolism and excretion properties without any carcinogenic and toxic effects. The interaction pattern of the puerarone and tuberostan may provide a hint for a novel drug design for vascular endothelial growth factor tyrosine kinase receptors with better specificity to treat angiogenic disorders.     

Interactions of hepatotoxic agents with proteins and subcellular structures

Two proteins with high affinity for amatoxins have been characterized in calf thymus nucleic, the RNA-polymerase II (or B) and a 100 K protein of unknown function. Most of the toxic effects of amatoxins are based on the inhibited synthesis of mRNA. The 100 K protein may be involved in functions of cytokinesis as suggested by experiments with PtK1 cells and a fluorescent labelled amatoxin. The molecular toxicity of phallotoxins can be understood in terms of their affinity for actin. By interaction with rabbit muscle actin the concentration of action monomers is decreased. In hepatocytes, the phallotoxins change the structure of the microfilamentous web.     

Interactions of paralytic shellfish toxins with xenobiotic-metabolizing and antioxidant enzymes in rodents.

Paralytic shellfish toxins (PSTs) are neurotoxins known to block voltage-gated sodium channels in intoxicated animals and humans. Their metabolism in mammalian systems and their effects on other receptors are not as well understood. In this study, we investigated the in vitro metabolism of two classes of PSTs, gonyautoxin 2/3 (GTX2/3) and C1/2 toxins (C1/2), using rat and mouse liver enzyme preparations. We also analyzed the effects of these toxins on several antioxidant and xenobiotic-metabolizing enzymes in mice. These toxins were selected for their prevalence in the coastal waters of Southern China. When the toxins were incubated with liver preparations containing Phase I and Phase II xenobiotic metabolizing enzymes and appropriate co-factors, no transformation of the toxins was detectable. When mice were given sub-lethal doses of GTX2/3, a loss of activity was observed in hepatic ethoxyresorufin-O-deethylase, penthoxyresorufin-O-deethylase, glutathione peroxidase and superoxide dismutase, but not in glutathione S-transferase, catalase and glutathione reductase. Exposure to the same mouse units of C1/2 caused only a slight reduction in the activity of penthoxyresorufin-O-deethylase and glutathione peroxidase. Our results indicated that these toxins may not be metabolized readily in mammals and that they may cause adverse effects other than sodium channel blocking.     

X‐ray Crystallographic and Fluorometric Analysis of the Interactions of Rhein to Human Serum Albumin

To investigate the interactions between natural drugs and human serum albumin (HSA), we performed fluorescence spectroscopy and X‐ray crystallography to gain insight into binding mechanism and behaviour of rhein to HSA. Our fluorescence results demonstrated that rhein strongly binds with HSA, and other compounds may affect binding affinity of rhein to different extent. Structural analysis revealed that rhein binds to the IIA subdomain of HSA. The carboxylate group of rhein forms hydrogen bonds with Arg218 and Lys199, as well as a salt bond with Arg222. Hydroxyl group (4) of rhein forms a hydrogen bond with His242, and hydroxyl group (5) of rhein forms a hydrogen bond with Arg257. Oxygen atom (7) of rhein forms a hydrogen bond with Arg222, and oxygen atom (6) of rhein forms a hydrogen bond with H₂O. Furthermore, hydroxyl group (4) of rhein also forms a hydrogen bond with H₂O. Our results reveal the biochemical and structural characteristics of the interaction between rhein and HSA, providing guidance for future development of rhein‐based compounds and a drug–HSA delivery system.     

Synthesis,characterization, and in vitro effect of the Cu(II) complex with niflumic acid and 3‐picoline on paraoxanase‐I

Niflumic acid is used to treat inflammatory rheumatoid diseases, pain, and fever. The present study reports the experimental, spectroscopic, thermal, structural analyses, and biological activities of this complex. The nonsteroidal anti‐inflammatory drug niflumic acid, 3‐picoline, and copper(II) chloride were utilized to synthesize a new complex: [Cu₂Cl ₂(nif) ₂(3‐pic) ₄]. The crystal structure of [Cu ₂Cl ₂(nif) ₂(3‐pic) ₄] was determined by X‐ray crystallography. The complex crystallizes in the triclinic space group P‐1 and each Cu(II) center displayed six‐coordinated distorted octahedral geometry. Two Cu(II) centers are connected by a chloro‐bridge to form the binuclear metal core. Finally, the in vitro effects of the synthesized new complex and free niflumic acid were evaluated on the human serum paraoxonase 1 enzyme. At low doses, both the new complex and free niflumic acid showed very good inhibition activity with different inhibition mechanisms. In addition, the results showed that the new complex has more inhibition activity than free niflumic acid.     

Copper(I) (Pseudo)Halide Complexes with Neocuproine and Aminomethylphosphines Derived from Morpholine and Thiomorpholine – In Vitro Cytotoxic and Antimicrobial Activity and the Interactions with DNA and Serum Albumins

Herein, a series of CuI or CuNCS complexes with neocuproine (2,9‐dimethyl‐1,10‐phenanthroline: dmp) and two tris(aminomethyl)phosphines derived from morpholine (P(CH₂N(CH₂CH₂)₂O)₃) or thiomorpholine (P(CH₂N(CH₂CH₂)₂S)₃) were tested as cytotoxic agents in vitro towards mouse colon carcinoma (CT26) and human lung adenocarcinoma (A549). The studies showed that the complexes exhibit potential antitumor properties, displayed by IC₅₀ values below 10 μm towards the tested cell lines, in the case of 4‐h incubation time with the examined compounds. Moreover, a high antimicrobial activity of all the complexes was observed against Staphylococcus aureus and Candida albicans with minimal inhibitory concentrations equal to 1–2 μg/mL. To gain insight into the molecular mechanism of biological activity of the complexes, we investigated also their interactions with plasmid DNA (pUC18) and the human and bovine serum albumins. Gel electrophoresis experiments demonstrated that all the compounds were comparably efficient in DNA degradation process; however, luminescence quenching showed surprising dependence on the interactions strength of the used compounds with the albumins. Apart from exceptionally effective [CuI(dmp)P(CH₂N(CH₂CH₂)₂O)₃], the complexes with P(CH₂N(CH₂CH₂)₂O)₃ quenched more strongly luminescence of bovine serum albumin, while the complexes with P(CH₂N(CH₂CH₂)₂S)₃ were more active in the quenching of human serum albumin luminescence.     

Interactions of peroxynitrite with uric acid in the presence of ascorbate and thiols: implications for uncoupling endothelial nitric oxide synthase

It has been suggested that uric acid acts as a peroxynitrite scavenger although it may also stimulate lipid peroxidation. To gain insight into how uric acid may act as an antioxidant, we used electron spin resonance to study the reaction of uric acid and plasma antioxidants with ONOO-. Peroxynitrite reacted with typical plasma concentrations of urate 16-fold faster than with ascorbate and 3-fold faster than cysteine. Xanthine but not other purine-analogs also reacted with peroxynitrite. The reaction between ONOO- and urate produced a carbon-centered free radical, which was inhibited by either ascorbate or cysteine. Moreover, scavenging of ONOO- by urate was significantly increased in the presence of ascorbate and cysteine. An important effect of ONOO- is oxidation of tetrahydrobiopterin, leading to uncoupling of nitric oxide synthase. The protection of eNOS function by urate, ascorbate and thiols in ONOO(-)-treated bovine aortic endothelial cells (BAECs) was, therefore, investigated by measuring superoxide and NO using the spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine (CMH) and the NO-spin trap Fe[DETC]2. Peroxynitrite increased superoxide and decreased NO production by eNOS indicating eNOS uncoupling. Urate partially prevented this effect of ONOO- while treatment of BAECs with the combination of either urate with ascorbate or urate with cysteine completely prevented eNOS uncoupling caused by ONOO-. We conclude that the reducing and acidic properties of urate are important in effective scavenging of peroxynitrite and that cysteine and ascorbate markedly augment urate's antioxidant effect by reducing urate-derived radicals.     

Interactions of formulation excipients with proteins in solution and in the dried state

A variety of excipients are used to stabilize proteins, suppress protein aggregation, reduce surface adsorption, or to simply provide physiological osmolality. The stabilizers encompass a wide variety of molecules including sugars, salts, polymers, surfactants, and amino acids, in particular arginine. The effects of these excipients on protein stability in solution are mainly caused by their interaction with the protein and the container surface, and most importantly with water. Some excipients stabilize proteins in solution by direct binding, while others use a number of fundamentally different mechanisms that involve indirect interactions. In the dry state, any effects that the excipients confer to proteins through their interactions with water are irrelevant, as water is no longer present. Rather, the excipients stabilize proteins through direct binding and their effects on the physical properties of the dried powder. This review will describe a number of mechanisms by which the excipients interact with proteins in solution and with various interfaces, and their effects on the physical properties of the dried protein structure, and explain how the various interaction forces are related to their observed effects on protein stability.     

H NMR-based metabonomic study on the metabolic changes in the plasma of patients with functional dyspepsia and the effect of acupuncture

Functional dyspepsia (FD) is a common gastrointestinal disorder with multiple pathogenic mechanisms seen in clinical practice, and acupuncture may potentially be an alternative therapy for it. In order to investigate the biological effects of FD and the effect of acupuncture on metabolism, ¹H nuclear magnetic resonance (NMR)-based metabonomic techniques have been used to compare the plasma metabolic profiles of six female FD patients with those of six female healthy control subjects. Plasma metabolic profiles of FD patients treated by acupuncture at the Foot-Yangming Meridian were also collected and compared. Data obtained from NMR spectroscopy were subjected to principal components analysis (PCA). The results show that there are relatively higher levels of glucose, acetate, high-density lipoprotein (HDL), and phosphatidylcholine (PtdCho), and lower levels of lactate, leucine/isoleucine, N-acetyl glycoprotein (NAc), and low-density lipoprotein/very low-density lipoprotein (LDL/VLDL) in FD patients than in healthy controls. Acupuncture treatment of FD patients significantly changed the levels of leucine/isoleucine, lactate and glucose, and slightly changed lipids level towards those of the healthy controls, demonstrating its therapeutic effects on the relief of FD symptoms. Due to the limited number of subjects, the present work is just a proof-of-principle study and further researches with larger number of subjects are needed. Our work shows the potential of an NMR-based metabonomic approach in the study of biological effects of acupuncture.     

Interactions of intracerebroventricular pertussis toxin treatment with the ataxic and hypothermic effects of ethanol

Summary Pretreatment with pertussis toxin (0.5 and 1.0 g/animal, i. c. v., seven days prior to testing) reversed the reduction in locomotor activity in the holeboard test caused by administration of the alpha₂-adrenoceptor agonist, medetomidine (0.1 mg/kg, i. p.). Intrinsic behavioral effects of pertussis toxin treatment were also observed, these included a reduction in exploratory head-dipping and an increase in locomotor activity. These doses of pertussis toxin also reduced the ataxia induced by a 2.4 g/kg dose of ethanol. Pertussis toxin treated animals also exhibited a diminished hypothermic response to ethanol (2 g/kg), although the pertussis toxin treated animals had lower body temperatures prior to ethanol administration compared to sham treated animals. Neither the behavioral effect of pertussis holotoxin in the holeboard nor its effects on reversing medetomidine hypolocomotion or ethanol-induced ataxia were seen following administration of the binding oligomer of pertussis toxin which binds to the cell membrane but does not possess the enzymatically active subunit. These findings implicate mechanisms involving pertussis toxin sensitive G-proteins in modulating some behavioral and physiological effects of ethanol.     

Mycotoxin Interactions along the Gastrointestinal Tract: In Vitro Semi-Dynamic Digestion and Static Colonic Fermentation of a Contaminated Meal

Aflatoxin B1 (AFB1) and ochratoxin A (OTA) naturally co-occur in several foods, but no studies have followed the fate of mycotoxins’ interactions along the gastrointestinal tract using in vitro digestion models. This study used a novel semi-dynamic model that mimics gradual acidification and gastric emptying, coupled with a static colonic fermentation phase, in order to monitor mycotoxins’ bioaccessibility by the oral route. AFB1 and OTA bioaccessibility patterns differed in single or co-exposed scenarios. When co-exposed (MIX meal), AFB1 bioaccessibility at the intestinal level increased by ~16%, while OTA bioaccessibility decreased by ~20%. Additionally, a significant increase was observed in both intestinal cell viability and NO production. With regard to mycotoxin–probiotic interactions, the MIX meal showed a null effect on Lactobacillus and Bifidobacterium strain growth, while isolated AFB1 reduced bacterial growth parameters. These results were confirmed at phylum and family levels using a gut microbiota approach. After colonic fermentation, the fecal supernatant did not trigger the NF-kB activation pathway, indicating reduced toxicity of mycotoxins. In conclusion, if single exposed, AFB1 will have a significant impact on intestinal viability and probiotic growth, while OTA will mostly trigger NO production; in a co-exposure situation, both intestinal viability and inflammation will be affected, but the impact on probiotic growth will be neglected.     

Interactions with selected drug renal transporters and transporter-mediated cytotoxicity in antiviral agents from the group of acyclic nucleoside phosphonates

Members of acyclic nucleoside phosphonates (ANPs) possess antiviral and antiproliferative activities. However, several clinically important ANPs may cause renal injury, most likely due to their active accumulation in the renal tubular cells. The goal of this study was to investigate in vitro relationships between the affinity of several structurally related potent ANPs to selected human transporters and their cytotoxicity. SLC (solute carrier family) transporters (hOAT1, hOCT2, hCNT2, hCNT3) and ABC (ATP-binding cassette) transporters (MDR1, BCRP), which are typically expressed in the kidney, were included in the study. The transport and toxic parameters of the tested compounds were compared to those of two clinically approved ANPs, adefovir and tenofovir. Transport studies with transiently transfected cells were used as the main method in the experiments. Most of the ANPs studied showed the potency to interact with hOAT1. GS-9191, a double prodrug of PMEG, displayed an affinity for hOAT1 comparable with that of adefovir and tenofovir. No significant interaction of the tested ANPs with hOCT2, hCNT2 and hCNT3 was observed. Only GS-9191 was found to be a strong inhibitor for both MDR1 and BCRP. PMEO-DAPy showed the potency to interact with MDR1. Most of the tested substances caused a significant decrease in cellular viability in the cells transfected with hOAT1. Only with the exclusion of GS-9191, a relatively lipophilic compound, did the in vitro cytotoxicity of the ANPs closely correspond to their potential to interact with hOAT1. The increased cytotoxicity of the studied ANPs found in OAT1 transfected cells was effectively reduced by OAT inhibitors probenecid and quercetin. The higher cytotoxicity of the compounds with affinity to hOAT1 proved in the inhibitory experiments evidences that ANPs are not only inhibitors but also substrates of hOAT1. Any clear relationship between the potency of ANPs to inhibit the studied efflux transporters and their cytotoxicity was not demonstrated. In conclusion, the study documented that among the studied transporters hOAT1 seems to be the decisive determinant for renal handling in most of the tested ANPs. This transporter may also play an important role in the mechanism of their potential cytotoxic effects. These facts are in good accordance with previous findings in the clinically used ANPs.     

Interactions of partial LSD analogs with behavioral disrupting effects of LSD and DMT in the rat.

Adult male Holtzman rats were trained to barpress on a schedule whereby every fourth press earned a reward of 0.01 ml of sugar-sweetened milk (FR4). After an i.p. injection of LSD (0.1 mg/kg) or DMT (3.2 or 10 mg/kg) such barpressing is abolished completely and resumed, usually within an hour, at a rate near the preinjection control rate of pressing. It continues at a steady, uninterrupted pace until the animals are removed from the operant chamber one-half hour later. A series of N,N-diethylnipecotamide derivatives were synthesized and tested for their ability to modify the disruptive effect of these hallucinogens. N,N-diethylbutyramide (DBA) and 1-methyl-1,2,5,6-tetrahydropyridine-3-(N,N-diethylcarboxamide) (THPC) were also tested. Pretreatment with a single i.p. injection of any of these compounds (5--40 mg/kg) either had no effect on or else prolonged the duration of hallucinogen-induced cessation of barpressing.     

利拉鲁肽对缺氧和高糖状态下人脐静脉内皮细胞释放NO的影响及机制研究

摘 要 目的：观察利拉鲁肽对缺氧和高糖状态下人脐静脉内皮细胞释放一氧化氮NO）的影响,并探讨其可能机制。方法: 采用体外分离和培养的人脐静脉内皮细胞（HUVECs）建立缺氧和高糖模型,分别以利拉鲁肽、利拉鲁肽+exendin(9-39)孵育 HUVECs,通过MTT法测定各实验组细胞增殖活力、比色法测定乳酸脱氢酶(LDH )漏出量、硝酸还原酶法检测NO含量,以半定量RT PCR技术检测各组细胞内皮型一氧化氮合酶（eNOS）基因表达情况。结果: 利拉鲁肽能促进缺氧和高糖状态下HUVECs细胞增殖活力,减少LDH的漏出量,促进NO的释放和eNOS基因的表达(P＜0.05或P<0.01)。胰高血糖素样肽-1（GLP-）受体阻断药exendin(9-39)可以部分抑制利拉鲁肽的上述作用（P＜0.05）。结论:利拉鲁肽能够改善缺氧和高糖状态下人脐静脉内皮细胞的内皮功能,其机制可能与上调eNOS基因表达、促进NO分泌有关。