抗生素对肺、肝、肾和胰腺组织穿透能力及杀菌效力的实验研究

目的 测定头孢唑肟等７种抗生素对肺、肝、肾和胰腺组织的穿透能力,为临床选择用药提供参考。方法 小鼠灌服或静脉注射抗生素后在不同时间点采集血清、肺、肝、肾和胰腺组织标本,按微生物琼脂扩散法测定抗生素浓度。测定抗生素对６种常见病原菌的最小抑菌浓度（ＭＩＣ９０）。计算出抗生素对组织的穿透率（组织浓度／血清浓度）及在组织中的杀菌指数（组织浓度／ＭＩＣ９０）。结果 抗生素对肺、肝、肾和胰腺组织的穿透率分别是     

基于FDA不良事件报告系统的氯喹及羟氯喹不良反应分析与评价

目的：氯喹及羟氯喹是新型冠状病毒肺炎的推荐试用治疗药物,但存在较多安全性问题。研究利用FDA不良事件报告系统（FAERS）数据库挖掘和综合评价分析氯喹及羟氯喹相关事件,为新型冠状病毒肺炎患者提供安全用药信息。方法：从FAERS数据库中提取氯喹及羟氯喹相关不良事件个案报告,对患者基本信息、报告者信息、报告时间、常见不良事件等进行分析,采用比值比法（reporting odds ratio,ROR）和综合标准法（medicines and healthcare products regulatory agency,MHRA）两种比值失衡分析法检测氯喹及羟氯喹相关信号,进而通过病例分析和文献报道对ROR法和MHRA法均有检出的信号进行药品相关性评估分析。结果：2014年7月至2019年3月FAERS数据库中以氯喹和羟氯喹为主要和次要怀疑药物的初次上报报告分别为383例和11 169例,其中导致死亡的报告51例（13.3%）和310例（2.8%）,致死事件包括药物中毒、自杀、胎儿死亡、心脏骤停等。ROR法和MHRA法分别检出氯喹相关信号105个和100个,羟氯喹相关728个和650个。经筛选,相关的不良反应主要为心肌病、房室传导阻滞、视网膜病变、感音神经性耳聋、肌病、药物性精神病、转氨酶异常和溶血等。其中心肌病、房室传导阻滞、心室肥大、视神经萎缩、反射消失、肌无力综合征、血脂异常等和尖端扭转型室速、长QT综合征、限制性心肌病、颅神经损伤、低血糖等分别未在氯喹和羟氯喹说明书中提及。结论：在氯喹和羟氯喹的临床应用中,应关注心脏毒性、视网膜毒性和耳毒性等不良反应,并加强反射消失、肌无力综合征、血脂异常（氯喹）,及低血糖（羟氯喹）等新的不良反应信号的监测。     

槐定碱的抗肿瘤药理作用研究进展

体外实验发现槐定碱能浓度相关地抑制大肠癌LS174t细胞、SW620细胞、SW480细胞、HCT-116细胞,胃癌BGC823细胞、MGC-803细胞、SGC7901细胞、MKN45细胞、MKN28细胞,胰腺癌capan-1细胞,肝癌97H细胞、Bel细胞、HepG2细胞,食管癌EC109细胞,食管胃交界腺癌OE-19细胞、SK-GT2细胞,白血病K562细胞、HL60细胞,淋巴瘤U937细胞,骨髓瘤NS-1细胞,乳腺癌MCF-7细胞,卵巢癌PM-2细胞、SKVO3细胞,宫颈癌HeLa细胞,肺癌A549细胞、NCI细胞,DMS153细胞,黑素瘤A375细胞,舌鳞癌TCA8113细胞,神经胶质瘤U87细胞、U87MG细胞,前列腺癌PC3细胞增殖。整体实验发现槐定碱抑制SW480细胞、HCT-116细胞,白血病L1210细胞,肺癌Lewis细胞,肉瘤S180细胞、S37细胞、W256细胞、EAC细胞移植瘤在小鼠或大鼠体内生长。临床上槐定碱已被试用于治疗恶性滋养细胞肿瘤、消化道肿瘤、恶性淋巴瘤,有开发成抗肿瘤新药的潜力。     

氧化苦参碱防治高血糖、高血脂症及其并发症的药理作用及机制研究进展

氧化苦参碱可防治高糖、高脂引起的心血管并发症，脂肪肝并发症，糖尿病视网膜病变，糖尿病肾病以及肺、骨并发症。氧化苦参碱防治这些并发症的药理机制可能归因于：降血糖、调血脂及抗氧化作用，从源头上减少了氧化型低密度脂蛋白和糖基化终末产物的生成；抗氧化、抗炎和细胞保护作用可保护肝脏，促进肝糖原合成，在脂质转运、氧化和合成3个环节改善脂质代谢紊乱，产生降血糖、调血脂作用，也可保护受累的心血管系统、肾脏、肝脏、视网膜、肺和骨等其他器官，减轻胰岛素抵抗，提高胰岛素敏感性。因此氧化苦参碱有望开发为治疗代谢综合征的药物。     

A review of anti-inflammatory,antioxidant, and immunomodulatory effects of Allium cepa and its main constituents

ContextAllium cepa L. (Liliaceae), known as onion, is consumed throughout the world. Onion and its derivatives including saponins, aglycones, quercetin, cepaenes, flavonoids, organosulfurs, and phenolic compounds, showed various pharmacological properties and therapeutic effects.ObjectiveAnti-inflammatory, antioxidant, and immunomodulatory effects of A. cepa and its main constituents, along with the underlying molecular mechanisms are presented.MethodsDatabases including, Web of Knowledge, Medline/PubMed, Scopus, and Google Scholar were checked for articles published between 1996 and the end of July 2020, using the key-words Allium cepa, quercetin, anti-inflammatory, antioxidant and immunomodulatory.ResultsA. cepa and its constituents mainly quercetin showed anti-inflammatory effects mediated via reduction of total and differential WBC counts, inhibition of chemotaxis of polymorphonuclear leukocytes, COX, and LOX pathways and prevented formation of leukotrienes and thromboxanes, prostaglandin E2 (PGE2) as onVCAM-1, NF-κB, MARK,d STAT-1, JNK, p38 and osteoclastogenesis. A. cepa and its derivatives showed antioxidant effect by decreasing lipid peroxidation, NAD(P)H, MDA, NO, LPO and eNOS but enhancing antioxidants such as SOD, CAT, GSH, GPx, GSPO, TrxR, SDH, GST and GR activities and thiol level. Immunomodulatory effects of the plant and quercetin was also shown by reduction of Th2 cytokines, IL-4, IL-5, and IL-13 as well as IL-6, IL-8, IL-10, IL-1β and TNF-α and IgE levels, but increased CD4 cells, IFN-γ level and IFN-γ/IL4 ratio (Th1/Th2 balance).ConclusionsThe effect of onion and its constituents on oxidative stress, inflammatory and immune system were shown indicating their therapeutic value in treatment of various diseases associated with oxidative stress, inflammation, and immune-dysregulation.     

Hexavalent chromium is cytotoxic and genotoxic to hawksbill sea turtle cells

Sea turtles are a charismatic and ancient ocean species and can serve as key indicators for ocean ecosystems, including coral reefs and sea grass beds as well as coastal beaches. Genotoxicity studies in the species are absent, limiting our understanding of the impact of environmental toxicants on sea turtles. Hexavalent chromium (Cr(VI)) is a ubiquitous environmental problem worldwide, and recent studies show it is a global marine pollutant of concern. Thus, we evaluated the cytotoxicity and genotoxicity of soluble and particulate Cr(VI) in hawksbill sea turtle cells. Particulate Cr(VI) was both cytotoxic and genotoxic to sea turtle cells. Concentrations of 0.1, 0.5, 1, and 5 μg/cm² lead chromate induced 108, 79, 54, and 7% relative survival, respectively. Additionally, concentrations of 0, 0.1, 0.5, 1, and 5 μg/cm² lead chromate induced damage in 4, 10, 15, 26, and 36% of cells and caused 4, 11, 17, 30, and 56 chromosome aberrations in 100 metaphases, respectively. For soluble Cr, concentrations of 0.25, 0.5, 1, 2.5, and 5 μM sodium chromate induced 84, 69, 46, 25, and 3% relative survival, respectively. Sodium chromate induced 3, 9, 9, 14, 21, and 29% of metaphases with damage, and caused 3, 10, 10, 16, 26, and 39 damaged chromosomes in 100 metaphases at concentrations of 0, 0.25, 0.5, 1, 2.5, and 5 μM sodium chromate, respectively. These data suggest that Cr(VI) may be a concern for hawksbill sea turtles and sea turtles in general.     

Simultaneous extraction and quantitation of fentanyl and norfentanyl from primate plasma with LC/MS detection

The quantitation of both fentanyl and its desalkyl metabolite, norfentanyl, in plasma using LC/MS has not been previously described. The detection and quantitation of fentanyl and norfentanyl was achieved using LC/MS detection. The liquid-liquid extraction used toluene as the organic phase. Chromatography was carried out using a Zirchrom-PBD (50 mm x 2.1 mm, 3 microm) column with a mobile phase of acetonitrile-ammonium acetate (10 mM), citrate (0.1 mM, pH 4.4) (45:55, v/v) with a flow rate of 0.3 ml/min. Mass spectroscopy detection was performed using ESI in the positive mode. The LOQ for fentanyl was 25 pg/ml and norfentanyl was 50 pg/ml. For the concentrations of 75, 250, and 750 pg/ml, respectively, fentanyl had inter-day precisions of 6.6, 7.2, and 6.6% with accuracies of 4.0, 5.1, and 5.1% and intra-day precisions of 1.6, 1.9, and 1.9% with accuracies of 11.6, 9.4, and 8.4%, and norfentanyl had inter-day precisions of 7.4, 0.3, and 0.7% with accuracies of 9.1, 8.8, and 12.3% and intra-day precisions of 5.3, 1.4, and 0.1% with accuracies of 10.9, 8.9, and 12.8%. The recoveries of fentanyl were 85, 92, and 75% and of norfentanyl were 40, 49, and 46% at the 75, 250, and 750 pg/ml concentrations, respectively.     

Inhaled anesthetic agents.

PURPOSE: The pharmacology, bioavailability and pharmacokinetics, indications, clinical efficacy, adverse effects and toxicities, and dosage and administration of the inhaled anesthetics are reviewed. SUMMARY: The inhaled anesthetics include desflurane, enflurane, halothane, isoflurane, and sevoflurane and are thought to enhance inhibitory postsynaptic channel activity and inhibit excitatory synaptic activity. The mechanism of action of inhaled anesthetics has not been completely defined. A number of factors can influence the pharmacokinetics of inhaled anesthetics, including solubility in blood, cardiac output, tissue equilibration, extent of tissue perfusion, metabolism, and age. All of the available inhaled anesthetics are effective for inducing or maintaining anesthesia or both. Most clinical trials of inhaled anesthetics have evaluated differences in induction and emergence from anesthesia by comparing (1) times to loss of reflex, extubation, and response to verbal commands; orientation to time and place; and ability to sit up without assistance, (2) need for post-surgical analgesia, and (3) time to discharge as measures of efficacy. Adverse effects and toxicities of the inhaled anesthetics include nephrotoxicity, hepatotoxicity, cardiac arrhythmias, neurotoxicity, postoperative nausea and vomiting, respiratory depression and irritation, malignant hyperthermia, and postanesthesia agitation. Safety issues surrounding these gases include occupational exposure and intraoperative fires within the delivery systems used with inhaled anesthetics. Drugs used for anesthesia during surgery can account for 5-13% of a hospital's drug budget. CONCLUSION: The inhaled anesthetics have been shown to be both safe and effective in inducing and maintaining anesthesia. These agents differ in potency, adverse-effect profile, and cost. Newer anesthetic gases, such as sevoflurane and desflurane, appear to have more favorable physico-chemical properties. These factors, as well as patient characteristics and duration and type of procedure, must be considered when selecting an inhaled anesthetic.     

Effects of methotrexate and cyclophosphamide on polyamine levels in various tissues of rats

The effects of methotrexate (MTX) and cyclophosphamide (CYP) on body weight, organ weight, and the concentration of putrescine, spermidine, and spermine in 14 different tissues were measured in rats that had been given these compounds for 5 consecutive days. These three polyamines in both the thymus and spleen of rats treated with MTX and CYP showed a statistically significant decrease. Further, putrescine in the seminal vesicles, kidney, liver, and small intestine of MTX-treated rats, and in the prostate, seminal vesicles, kidney, heart, liver, small intestine, and lung of CYP-treated rats, spermidine in the prostate, seminal vesicles, testis, thymus, spleen, kidney, heart, small intestine, and skeletal muscle of CYP-treated rats, and spermine in the prostate, seminal vesicles, kidney, heart, small intestine, and stomach of CYP-treated rats showed statistically significant decreases. Recognition of the significance of polyamine levels and attention to their response in anti-cancer drug therapy may have clinical implications.     

Changes in dermatological characteristics of skin caused by electroluminescent infrared heating lamp in healthy Korean men

We examined the changes in skin conditions before and after the application of electroluminescent infrared heating lamp to the body regions of healthy Korean men. We assessed the differences in sebum, moisture, pores, wrinkles, pigmentation, and elasticity of the skin in the forearm, back, and shin regions. A total of 30 healthy men in their 20s were enrolled. We used a Skin Diagnosis Meter for skin state measurements. Statistical differences were found between the pre- and post-measurement values in the moisture, wrinkles, pigmentation, and elasticity of skin. In the correlation analysis results, moisture and wrinkle, moisture and elasticity, pore and pigmentation, and wrinkle and elasticity were positively correlated, respectively. However, moisture and pore, moisture and pigmentation, pore and wrinkle, pore and elasticity, wrinkle and pigmentation, and pigmentation and elasticity were negatively correlated, respectively. These results suggest that the change in skin condition is associated with external stimulants. The effect of infrared radiation on the various skin conditions may differ depending on the part of the body.     

Food processing: a century of change

In 1900, the population was beset with poverty, and infectious and deficiency diseases were common. The first half of the century was blighted by world wars, economic depression and post-war austerity. Nevertheless, a combination of enlightened social policy and the application of medical, nutritional and food science, resulted in substantial improvements in health, such that, by 1950, many hitherto common infectious diseases were under control, and the diet was generally nutritionally adequate. The second half of the century saw increasing economic prosperity, and unprecedented social and scientific advances. The impact on food processing was manifold: nascent technologies such as freezing and chilling were increasingly exploited, and the consumer became the major focus of a food industry that became more sophisticated, embracing automation, computerisation and new developments in, for example, drying, heat processing, controlled and modified atmosphere packaging, ingredients and quality assurance. By 1999, this had led to an industry which provided foods that were not only safe, nutritious and palatable, but which were also increasingly convenient and healthy.     

Bioaccumulation and depuration of ethylene glycol by crayfish (procambarus spp.)

Crayfish were exposed to 50, 200, or 1000 μg/mL ethylene glycol (EG) daily for 61 days, and were subsequently transferred to clean water for a 67-day decontamination phase. During uptake and loss, samples were analyzed for EG in gills, muscle, gastrointestinal tract, and hepatopancreas. An open one-compartment mathematical model described the uptake and loss phases data. Uptake was dependent upon the aqueous concentration of EG. Crayfish did not concentrate EG above the water concentration. Bioaccumulation factors for the selected tissues at 61 days of exposure to 50, 200, and 1000 μg/mL EG, respectively were as follows: 0.40, 0.21, and 0.21 for gills; 0.48, 0.21, and 0.21 for muscle; 0.61, 0.42, and 0.27 for gastrointestinal tract; and 0.60, 0.33, and 0.22 for hepatopancreas. Time to equilibrium was 5,4,5, and 4 days for gills, muscle, gastrointestinal tract, and hepatopancreas, respectively, at 50 μg/mL aqueous concentration; 5, 4, 6, and 4 days, respectively, at 200 μg/mL aqueous concentration; and 7, 5, 7, and 5 days, respectively, at 1000 μg/mL aqueous concentration. Crayfish eliminated the accumulated EG within 5 days for animals exposed to 50 μg/mL EG and 6 days for those exposed to 200 and 1000 μg/mL EG. © 1993 John Wiley & Sons, Inc.     

含对乙酰氨基酚的感冒药及柴芩清宁胶囊单次给药对小鼠肝毒性“量-时-毒”关系研究

目的研究对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片及柴芩清宁胶囊单次给药致小鼠肝毒性的“时-毒”“量-毒”关系。方法在肝毒性“时-毒”关系研究中,昆明种小鼠随机分为对照组、对乙酰氨基酚片组、复方氨酚烷胺片组、美扑伪麻片组、柴芩清宁胶囊组,各给药组根据给药后取血时间随机分为给药后1、2、4、8、12、24、48、72、96 h 9个亚组,3种西药给药剂量均为425.98 mg/kg（以对乙酰氨基酚水平换算）,柴芩清宁胶囊给药剂量为3 680.50 mg/kg;在肝毒性“量-毒”关系研究中,昆明种小鼠随机分为对照组,对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片、柴芩清宁胶囊高,中,低剂量组,3种西药高、中、低剂量分别为266.24、425.98、681.57 mg/kg,柴芩清宁胶囊高、中、低剂量分别为1 437.70、2 300.31、3 680.50 mg/kg,每组10只,雌雄各半,于给药后12 h取血。给药后观察动物一般状况;在相应时间点取血及脏器,检测血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和碱性磷酸酶（ALP）水平,计算肝脏、脾脏和胸腺脏器系数。结果与对照组比较,单次ig柴芩清宁胶囊1 437.70~3 680.50 mg/kg后,小鼠一般状况、血清ALT、AST、ALP水平和脏器系数均无明显变化。与对照组比较,单次ig对乙酰氨基酚片、复方氨酚烷胺片、美扑伪麻片425.98 mg/kg后,随给药后时间延长,小鼠出现怠动、毛色不华等毒性症状,12 h最为明显,24~72 h消失;血清ALT、AST和ALP水平不同程度增加,均在给药后12 h达到高峰,毒性持续时间分别约达72、24和24 h;肝脏、脾脏、胸腺脏器系数均无明显变化。与对照组比较,单次ig 3种西药266.24 mg/kg后,小鼠一般状况、血清ALT、AST、ALP和脏器系数均无明显变化;3种西药425.98和681.57mg/kg剂量组血清ALT、AST和ALP水平显著升高,且呈剂量相关性;681.57 mg/kg剂量可导致肝脏脏器系数明显升高,脾脏、胸腺脏器系数无明显变化。结论单次ig柴芩清宁胶囊3 680.50 mg/kg对小鼠不造成肝损害;大剂量对乙酰氨基酚片、复方氨酚烷胺片和美扑伪麻片均可对小鼠造成一定的急性肝损伤,且肝损伤均呈现一定的“时-毒”和“量-毒”关系。     

A review of the new antifungals: posaconazole, micafungin, and anidulafungin

This column reviews 3 new systemic antifungal agents (posaconazole, micafungin, and anidulafungin) from the standpoint of dermatology. Posaconazole, approved to treat invasive Aspergillus and Candida infections, is available in an oral suspension and resembles fluconazole, but seems to have a broader spectrum of activity. Posaconazole is effective against yeasts and molds and could be effective in treating rare fungal infections involving Zygomycetes, Mucor necrotizing fasciitis, rhinocerebral mucormycosis, some Fusarium species, Penicillium, Histoplasma, Blastomyces, Coccidioides, Paracoccidioides, and sporotrichosis, chromoblastomycosis, mycetoma, and phaeohyphomycosis, including Scedosporium apiospermum and Exophiala, Alternaria, and Bipolaris species. Posaconazole may abate onychomycosis and dermatophytes, but clinical trial data is lacking. Micafungin and anidulafungin are echinocandins like caspofungin and are useful salvage therapy for invasive aspergillosis and candidiasis. The exciting new agents have extended the armamentarium against antifungal pathogens, but have yet to find their place in the dermatologic practice.     

Influence of pentobarbital and chloralose anesthesia on quinidine-induced effects on atrial refractoriness and heart rate in the dog.

The effects of pentobarbital and chloralose on the atrial effective refractory period (AERP), atrial and ventricular rates, and mean blood pressure and also on the effects of quinidine on the same parameters were investigated in dogs with chronic atrioventricular block and implanted atrial pacing electrodes. Pentobarbital (30 mg/kg) increased the AERP by up to 12%, atrial and ventricular rates by 39 and 40%, respectively, and after initial lowering (48%) it increased the mean blood pressure (46%). Chloralose (100 mg/kg) increased the AERP (less than 30 min) by up to 7%, the atrial rate by 49%, the ventricular rate (less than 5 min) by 18%, and the mean blood pressure by 47%. In conscious dogs, quinidine at cumulative doses of 2, 4, and 8 mg/kg, i.e., at plasma levels between 2.7 +/- 0.6 and 6.3 +/- 1.3 micrograms/ml, increased the AERP by up to 21, 28, and 46%, the atrial rate by 49, 65, and 72%, and the ventricular rate (less than or equal to 5 min) by 17, 14, and 14%, and lowered the mean blood pressure by 19, 33, and 43%, respectively. Pentobarbital increased the quinidine-induced lengthening of the AERP by up to 10, 21, and 25 ms, respectively, and reduced the corresponding atrial (38, 53, and 67 beats/min) and ventricular (4, 4, and 5 beats/min) chronotropic effects. In contrast, chloralose reduced the quinidine-induced lengthening of the AERP (5, 12, and 22 ms, respectively), but did not modify the corresponding atrial and ventricular chronotropic effects. Neither pentobarbital nor chloralose altered quinidine plasma levels or the hypotensive effects of this drug.(ABSTRACT TRUNCATED AT 250 WORDS)     

松叶提取物对“过食膏粱厚味”型高尿酸血症大鼠尿酸生成排泄、肝功能及血脂水平的影响

目的 研究松叶提取物对“过食膏粱厚味”型高尿酸血症大鼠尿酸生成排泄、肝功能及血脂水平的影响。方法 将60只♂SD大鼠,随机分为正常对照组、模型对照组、别嘌醇（0.01 g·kg^-1）阳性对照组、松叶提取物3个剂量组（10.0,5.0,2.5 g·kg^-1）,每组10只。除正常对照组给予等体积蒸馏水,其余各组每天上午灌胃给予脂肪乳剂造模,下午灌胃给药,连续9周。观察大鼠一般行为学、摄食量、体质量,分别检测大鼠血清SUA、SCR、BUN、ALT、AST、TC、LDL-c含量;收集24 h尿液,记录UV,检测大鼠尿UUA、UCR含量,计算24 h UUA、FEUA、CUr、CCr,末次给药后测定血清和肝脏XOD、ADA、HGPRT活性。结果 模型对照组大鼠体质量明显降低,血清SUA、SCR、BUN、ALT、TC、LDL-c水平以及血清和肝组织XOD、ADA活性显著升高,肝组织HGPRT活性显著降低,同时UUA、UCR、UV、24 h UUA、FEUA、CUr、CCr显著降低。松叶提取物能显著降低高尿酸血症大鼠血清SUA、SCR、BUN、ALT、TC、LDL-c水平,降低血清和肝组织XOD、ADA活性,升高肝组织HGPRT活性,并且升高UUA、UCR、UV、24 h UUA、FEUA、CUr、CCr。结论 松叶提取物能有效降低HUA大鼠尿酸的生成并促进其排泄,且具有保肝、调血脂的功能。     

Characterization of age-related changes in body weight and organ weights from birth to adolescence in humans.

The pharmacokinetics and tissue dose of chemicals may differ among individuals of a population, particularly between adults and children. The adult-children differences in pharmacokinetics arise from age-related changes in the physiological, biochemical, and physicochemical determinants of uptake and disposition of chemicals. The objectives of this study were to review the published literature to assemble data on the human body weight and organ weights as a function of age (specifically between birth and 18 yr old) and to analyze these data, in order to develop regression equations for calculating body weight and organ weights of children using age as the dependent function. The specific organs/tissues for which the data on age-related weight were obtained and analyzed include blood, adipose tissues, liver, lungs, brains, heart, kidneys, spleen, the reproductive organs (male: prostate gland, seminal vesicle, testes, and epididymis; female: ovaries, uterus, and uterine tubes), glands (adrenal, pituitary, thymus, pancreas, and thyroid), bone marrow (total and red), intestinal tract, stomach, muscle, skin (epidermis and dermis), and skeleton. In both male and female children, the sum of these organs is systematically lower than the body weight, and this discrepancy may be resolved with the additional availability and consideration of data on hypodermis weight. The equations and data on body weight and organ weights presented in this article should be useful for constructing age-specific, physiologically based pharmacokinetic models for children.     

基于网络药理学和分子对接技术探讨自拟“清瘟汤”治疗新型冠状病毒肺炎的机制

目的利用中药网络药理学和分子对接技术,探讨清瘟汤作用靶标与新型冠状病毒(SARS-CoV-2)之间的关联以及多成分、多靶标的治疗机制。方法通过建立化学成分、靶点,筛选主要活性成分和靶标,用Cytoscape软件构建和分析网络,使用String对靶标进行GO及KEGG功能富集分析,采用Autodock软件对“清瘟汤”(QWT)主要活性成分与SARS-CoV-2的3C类似蛋白酶(3CLpro)和血管紧张素转换酶2(ACE2)蛋白进行分子对接。结果QWT中共有172个活性成分涉及480个靶标,其中大多数中药归胃经、肺经和脾经,27个活性成分(琥珀酸、香豆素、γ-氨基丁酸、谷氨酰胺、槲皮素、山柰酚、脯氨酸、赖氨酸、木犀草素、色氨酸、L-缬氨酸、胆碱、芹菜素、β-谷固醇、苯丙氨酸、丙氨酸、水杨酸、DL-缬氨酸、羽扇豆酚、腺苷、谷氨酸、熊果酸、大黄素、异鼠李素、黄豆苷元、柠檬酸、阿魏酸)与靶标关系最密切;QWT关键靶点涉及CASP3,CYP1A1,JUN,TP53,HMOX1,ICAM1,FOS,PPARG,CXCR4,SRC,TYR,B2M,MMP9,RPS27A,PSMD3,NPEPPS,CNDP2,TNF,AKT1,APP,NPY1R,CTSS,PTGER3,GGCT,UBB,HLA-A,PTGS2,CXCL8,FUM,PSMC4等,重要靶标富集在感染性疾病、肺部疾病和免疫性疾病三大类疾病通路上,GO分类和KEGG通路富集主要调控抗炎、免疫、血管生成、钙通道等相关。分子对接结果显示,槲皮素、芹菜素、熊果酸、异鼠李素、羽扇豆酚与3CLpro和ACE2蛋白具有一定的亲和力。结论QWT中的活性化合物主要作用于CASP3,CYP1A1,JUN,TP53,HMOX1等靶点,其中有5种化合物可与SARS-CoV-2的2种主要蛋白进行分子对接,QWT总体通过调节多条信号通路,从而可能产生抗SARS-CoV-2作用。     

Synthesis of 3-cyano-6-methyl-4-pyridyl-2(1H)-pyridinethiones as well as 2-substituted 6-methyl-4-pyridyl-pyridine-3-carbonitriles and 3-carbonic acid amides, respectively, and testing their cardiovascular activity

By the base catalyzed reaction of our previously described 3-cyano-6-methyl-4-pyridyl-2(1H)-pyridinethiones 1 and 2, respectively, with branched and unbranched, respectively, alkyl, aralkyl-, alkinyl-, hydroxyalkyl-, ethoxycarbonyl- and carbamoylalkylhalides the new in 2-position substituted 6-methyl-4-pyridyl-pyridine-3-carbonitriles 15-30 were formed. By means of oxidation of the 2-methylthio-substituted pyridine-3-carbonitriles 3 and 4 with potassium periodate and potassium permanganate in diluted acetic acid, respectively, the sulfinyl compounds 5 and 6, respectively, and the sulfonyl compounds 7 and 8, respectively, were prepared. By heating of 3 and 4, respectively, with concentrated sulphuric acid the 2-methylthio-pyridine-3-carboxamides 9 and 10 were obtained. The oxidation of these compounds with potassium periodate and potassium permanganate, respectively, had yield the pyridines 11 and 12, respectively, as well as 13 and 14, respectively.     

齐墩果酸和熊果酸的神经精神药理作用研究进展

齐墩果酸和熊果酸同属五环三萜酸类化合物,它们又是同分异构体.药理作用几乎相同,都具有抗氧化、抗炎、免疫调节、抗肿瘤、抗微生物、保肝、抗糖尿病、调脂、减肥、抗动脉粥样硬化作用.综述齐墩果酸和熊果酸保护神经细胞、镇痛、抗焦虑、抗神经分裂症、抗抑郁、改善学习记忆等神经精神药理作用,为齐墩果酸和熊果酸防治老年痴呆、帕金森病和抑郁症的研发提供依据.