人参三醇组甙对雄性大鼠阿片肽与免疫功能的辐射防护作用

采用５ＧｙＸ射线全身照射雄性大鼠模型，大鼠于照射前２４ｈ及照射后，每天腹腔注射５ｍｇ／０．２ｍｌ人参三醇组甙，共注射１４ｄ，观察人参三醇组甙对其阿片肽与免疫功能的辐射防护作用。结果表明，照射组下丘脑阿片肽含量及胸腺和脾脏免疫参数均降低；而在照射加人参组下丘脑阿片肽组水平，所有的免疫参数虽降低但却高于照射组。结果提示，人参三醇组甙可减轻下丘脑网片肽含量及含量接近对照胸腺和脾脏免疫参数的降低，具有辐射防护作用。     

Lipidic membranes are potential "catalysts" in the ligand activity of the multifunctional pentapeptide neokyotorphin

Neokyotorphin (NKT) is a multifunctional pentapeptide that is involved in biological functions as diverse as analgesia, antihibernatic regulation and proliferation stimulus of tumour cells. The interaction of neokyotorphin with cell membranes is potentially important to all these multiple biological processes since receptor-mediated processes are thought to be involved in neokyotorphin action. Sargent and Schwyzer proposed in their "membrane catalysis" model that ligands interact with membrane lipids in order to adopt the necessary conformation for cell receptors. We have used fluorescence techniques to study the depth, orientation and extent of incorporation of NKT with model membrane systems (lipidic vesicles). The roles of lipid charge, membrane phase and sterol presence were investigated. The phenolic ring of tyrosine is located in a shallow position in membranes. The extent of partition is less in gel crystalline membranes than in liquid crystalline membranes. Addition of cholesterol causes a reorientation of the tyrosine ring at the interface of lipidic bilayers. Lipidic membranes meet all the conditions required for acting as potential "catalysts" in the ligand activity of the multifunctional pentapeptide NKT, because they modulate the exposure and orientation of the phenolic ring, which is most likely involved in docking to receptors.     

Preparation of wheat gluten hydrolysates with high opioid activity

The opioid activity of wheat gluten hydrolysates (WGHs) prepared with several proteases was investigated in vitro by the contraction of guinea pig ileum (GPI), and WGHs with high opioid activity were further obtained through desalting and ultrafiltration (UF). The opioid activity varied with different wheat gluten hydrolysates. AWGH (WGH prepared with Alcalase), PPWGH (WGH prepared with Pepsin followed by Pancreatin) and PWGH (WGH prepared with pepsin) had relatively stronger inhibitory effects on the contraction of GPI with IC₅₀ values of 1.21 ± 0.25, 1.29 ± 0.38 and 1.57 ± 0.21 mg protein/ml, respectively. Subsequently, AWGH and PPWGH were desalted using cation exchange resin and anion exchange resin, with high nitrogen recovery (88.51 and 89.28%, respectively) and high desalting ratio (84.67 and 85.20%). The resultant hydrolysates were further fractionated by UF performed with a 3 kDa molecular weight cut-off membrane. Compared with AWGH and PPWGH, the 3 kDa-permeates have higher opioid activities with high protein content above 90% and low ash content about 1.5%. The molecular weight distributions of the two 3 kDa-permeates were concentrated below 2,000 Da.     

实时直接分析-高分辨质谱法快速筛查凉茶中非法添加的21种解热镇痛类药物

目的 建立一种实时直接分析离子源（direct analysis in real time, DART）结合四极杆/静电轨道离子阱高分辨质谱法（Q-Exactive Orbitrap）快速筛查凉茶中非法添加的21种解热镇痛类化学药物。方法 样品经50%甲醇水超声提取,过0.22μm微孔滤膜后,用DART-MS/MS测定。DART离子源的样品传输速度为0.2 mm/s,离子化温度为400 ℃,栅极电压为300 V,扫描模式为正模式。结果 在全扫描模式下测定目标化合物的一级精密质量数,与理论精密质量数相比,相对质量偏差小于1.65 ppm,可实现精准定性;同时建立了21种解热镇痛类药物的二级质谱信息库,进一步提高定性准确性。该方法筛查限范围为1.00~200 μg/kg,满足筛查要求。结论 该方法具有分析速度快,精准定性,无需冗长色谱分离过程,环境友好等优势,可作为凉茶中21种解热镇痛类非法添加化学药物的高通量筛查和精准定性检测方法。     

Effects of Non-Opioid Analgesics on the Cell Membrane of Skin and Gastrointestinal Cancers

Skin and gastrointestinal cancer cells are the target of research by many scientists due to the increasing morbidity and mortality rates around the world. New indications for drugs used in various conditions are being discovered. Non-opioid analgesics are worth noting as very popular, widely available, relatively cheap medications. They also have the ability to modulate the membrane components of tumor cells. The aim of this review is to analyze the impact of diclofenac, ibuprofen, naproxen, acetylsalicylic acid and paracetamol on skin and gastrointestinal cancers cell membrane. These drugs may affect the membrane through topical application, at the in vitro and in vivo level after oral or parenteral administration. They can lead to up- or downregulated expression of receptors, transporters and other molecules associated with plasma membrane. Medications may also alter the lipid bilayer composition of membrane, resulting in changes in its integrity and fluidity. Described modulations can cause the visualization of cancer cells, enhanced response of the immune system and the initiation of cell death. The outcome of this is inhibition of progression or reduction of tumor mass and supports chemotherapy. In conclusion, non-opioid analgesics may be used in the future as adjunctive therapy for the treatment of these cancers.     

Development and Preliminary Experience with an Ease of Extractability Rating System for Prescription Opioids

Abstract

One important factor in the abuse potential of an opioid product is the ease with which active drug can be extracted. There are currently no standards for testing or reporting extractability. This article describes the development of an Extractability Rating System for use by the pharmaceutical industry and regulators. Despite several limitations, this effort serves as a call for standardized testing and reporting so that products can be accurately rated, and should help establish goals for drug developers who wish to develop “abuse-resistant” opioid products.     

Development and preliminary experience with an ease of extractability rating system for prescription opioids

One important factor in the abuse potential of an opioid product is the ease with which active drug can be extracted. There are currently no standards for testing or reporting extractability. This article describes the development of an Extractability Rating System for use by the pharmaceutical industry and regulators. Despite several limitations, this effort serves as a call for standardized testing and reporting so that products can be accurately rated, and should help establish goals for drug developers who wish to develop “abuse-resistant” opioid products.     

吸入性甲氧氟烷的临床应用及研究进展

甲氧氟烷作为氟化烃类麻醉剂，在麻醉剂量下可能会导致肾功能损害等严重的不良反应，但其亚麻醉剂量下产生的镇痛作用安全性好，耐受性高，是短期急性镇痛的治疗选择。本文从甲氧氟烷的药代动力学、临床有效性、不良反应及临床应用四方面进行叙述，探讨了甲氧氟烷作为镇痛剂在临床应用的可及性。甲氧氟烷作为吸入性镇痛剂使用方便，无需通过静脉给药即可为患者提供紧急镇痛，是门急诊紧急镇痛的良好选择。