Design and Synthesis of 4-Heteroaryl 1,2,3,4-Tetrahydroisoquinolines as Triple Reuptake Inhibitors

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Identification of coffee components that stimulate dopamine release from pheochromocytoma cells (PC-12)

Coffee and caffeine are known to affect the limbic system, but data on the influence of coffee and coffee constituents on neurotransmitter release is limited. We investigated dopamine release and Ca(2+)-mobilization in pheochromocytoma cells (PC-12 cells) after stimulation with two lyophilized coffee beverages prepared from either Coffea arabica (AR) or Coffea canephora var. robusta (RB) beans and constituents thereof. Both coffee lyophilizates showed effects in dilutions between 1:100 and 1:10,000. To identify the active coffee compound, coffee constituents were tested in beverage and plasma representative concentrations. Caffeine, trigonelline, N-methylpyridinium, chlorogenic acid, catechol, pyrogallol and 5-hydroxytryptamides increased calcium signaling and dopamine release, although with different efficacies. While N-methylpyridinium stimulated the Ca(2+)-mobilization most potently (EC(200): 0.14±0.29μM), treatment of the cells with pyrogallol (EC(200): 48±14nM) or 5-hydroxytryptamides (EC(200): 10±3nM) lead to the most pronounced effect on dopamine release. In contrast, no effect was seen for the reconstituted biomimetic mixture. We therefore conclude that each of the coffee constituents tested stimulated the dopamine release in PC-12 cells. Since no effect was found for their biomimetic mixture, we hypothesize other coffee constituents being responsible for the dopamine release demonstrated for AR and RB coffee brews.     

Spectrometric Smartphone-Based System for Ibuprofen Quantification in Commercial Dosage Tablets

A rapid and portable analytical methodology has been developed for ibuprofen (IBU) quantification in commercial dosage tablets using a spectrometric smartphone-based system. The analytical methodology employs point-of-use approaches both for sample preparation and detection, demonstrating its potential utility for portable quality control of pharmaceutical products. In this work, IBU is dissolved in methanol and then treated with a Co(II) aqueous solution, forming a blue complex which is extractable by dispersive liquid-liquid microextraction. Then, the sample’s absorption spectrum is directly measured by a spectrometric smartphone-based system using cartridge made of polyoxymethylene for solvent compatibility. The main experimental factors affecting the dispersive liquid-liquid microextraction of Co-IBU complex were optimized using a multivariate analysis. Under optimized conditions, a working range between 20 and 80 μg mL^?1 was obtained with a correlation coefficient of 0.996 for 5 calibration points. The limit of detection and limit of quantification obtained were 4 and 12 μg mL^?1, respectively. The performance of the proposed methodology was evaluated in commercial tablet dosage forms, and the results demonstrate the ability of the method to determine IBU in samples representative of those used in real-world quality control applications. Recovery values between 97% and 105% were obtained, which are comparable to those obtained via standard titrimetric methodology.     

Xylocain (Lidocaine, Lignocaine), its discovery and Gordh's contribution to its clinical use

Hans v. Euler, while investigating how genes and enzymes were chemically related in some chlorofylldefective mutants of barley, isolated gramme, an indole. Erdtman synthetized isogramine and found it to have weak anesthetic properties. He then together with Löfgren synthetized other amino-amides, but no one of them could compete with the existing local anesthetics of the ester-type, derivatives of para-aminobenzoic acid, e.g. procaine. Later Löfgren and Lundqvist followed up these studies and found an amid compound lidocaine (2-dimethylaminoacet2, 6-xylidide). Lidocaine represented such a significant advance over procaine in clinical tests preformed by T. Gordh that it was introduced for clinical use. It has now during a half century been the standard local anesthetic drug. All local anesthetics are neurotoxic in high enough doses. Xylocain ®, however, has had an excellent record of safety. Only during the last years have there been reports on possible toxic irritation and damage by Xylocain used for spinal anesthesia. The aetiology is still not clear. In this connection two early observations by Gordh and his coworkers are discussed.     

三种检查方法对乳腺疾病的诊断价值

目的探讨三算子扫描仪、多普勒彩色超声及钼靶X线摄影对乳腺疾病的诊断价值。方法对578例经手术和病理检查证实的乳腺良、恶性疾病患者术前均采用三算子扫描、彩超及X线进行诊断。结果对于乳腺增生性疾病、乳腺癌三种检查方法诊断符合率在87.61%～91.91%之间,三者间无统计学意义（P〉0.05）;对于乳腺良性肿瘤的诊断符合率彩超优于X线（P〈0.05）。对于≤35岁乳腺癌的诊断符合率三算子、彩超均优于X线（P〈0.05）,对于35～50岁乳腺癌三者之间无差别（P〉0.05）,对于≥50岁乳腺癌X线明显优于三算子、彩超（P〈0.05）。对于肿块〈2 cm的乳腺癌诊断符合率三算子、彩超优于X线（P〈0.05）,而对于无肿块仅伴有恶性钙化征象的诊断符合率X线明显优于三算子（P〈0.05）。结论三种检查方法对乳腺良、恶性疾病都有较高的诊断价值,且对于乳腺癌的诊断具有互补性。X线适合50岁以上以及有恶性钙化灶的患者,彩超适合于各种类型的乳房,可弥补X线的不足,三算子对乳腺疾病的敏感性、准确性与彩超相当。     

Transradial artery approach in STEMI patients reperfused early and late by either primary PCI or pharmaco-invasive approach

The purpose of the study was to investigate the safety and efficacy of transradial artery approach (TRA) in STEMI patients who reperfused early (≤3 h from symptoms onset) or late (>3 h from symptoms onset) by either PPCI or pharmaco-invasive strategy (PI), thrombolysis followed by CA. Therefore, a total 143 STEMI patients (who were presented within 12 h from symptoms onset or 12–24 h with an evidence of ongoing ischemia or suffered from an acute STEMI were randomized for either PI or PPCI. Eighty-two patients were assigned to PI arm while the rest assigned were to PPCI arm. Patients who were taken to a non-PCI capable hospital received streptokinase and were then transferred to our Hospital for CA. TRA was used in the catheterization laboratory for all patients. Each arm was divided according to reperfusion time into early and late subgroups. A primary endpoint was death, shock, congestive heart failure, or reinfarction up to 30 days. There was a non-significant difference regarding LVEF in both arms. Myocardium wall preservation was significant in the early PI arm (P = 0.023). TIMI flow had no discrepancy between both arms (P = 0.569). Mean procedural and fluoroscopic time were 35.1 ± 6.1 and 6.3 ± 0.9 min. There were no reported entry site complications. There was no difference in primary endpoint complications (P = 0.326) considering the different times of patients’ reperfusion (early; P = 0.696 vs. late; P = 0.424). In conclusion, it is safe and effective to use TRA in STEMI patients who reperfused by either early or late PPCI or PI. We recommend PI for STEMI patients with delay presentation if PPCI is not available.     

Identification and measurement of rat eosinophil phospholipase D. Its activity on schistosomula phospholipids

A sensitive assay, using [¹⁴C]lecithin as a substrate, has been developed for the measurement of phospholipase activity in rat peritoneal polymorphonuclear leukocytes. Cell extracts were found to contain a phospholipase D activity and indirect evidence suggested that eosinophils are responsible for the cleavage of lecithin. Intact peritoneal cells were also able to hydrolyze exogenous [¹⁴C]lecithin in vitro. When [³H]choline-labeled schistosomula were used as targets in antibody-dependent cytotoxicity experiments, the radioactivity of lecithin decreased more rapidly in a complete cytotoxicity system than in controls, suggesting that hydrolysis of schitosomula phosholipids occured during the killing process.     

自制简易弹力止血装置在经桡动脉行冠状动脉介入治疗术后的应用

[目的]探讨自制简易弹力止血装置在经桡动脉行冠状动脉介入治疗术后的应用效果。[方法]将我院2017年5月—2017年7月接受经皮桡动脉冠状动脉介入治疗的170例病人设为对照组,将2017年8月—2017年10月接受经皮桡动脉冠状动脉介入治疗的172例病人设为观察组。对照组使用3M自粘弹力绷带包扎桡动脉穿刺点,观察组使用自制的简易弹力止血装置压迫桡动脉穿刺点。评价干预期间两组病人血肿、皮下出血、张力性水疱、手部肿胀、渗血发生情况。[结果]与对照组相比,观察组病人皮下出血、手部肿胀、渗血发生率均较低(P<0.05)。[结论]在经桡动脉行冠状动脉介入治疗术后病人中使用自制简易弹力止血装置,可以减少病人术后皮下出血、手部肿胀、渗血的发生。     

Inhibition by trichloroethylene and 1,1,2-trichloro-1,2,2-trifluoroethane of taurocholate uptake into basolateral rat liver plasma membrane vesicles

It has previously been shown that trichloroethylene (TRI) and 1,1,2-trichloro-1,2,2-tri-fluoroethane (FC 113) interfere with the transport of bile acids by isolated human and rat hepatocytes in a dose-dependent and reversible manner. This finding may explain the rise in serum bile acids (SBA) following exposure to these chemicals. However, the effect of these compounds on the transport of bile acids across the cellular membrane in the absence of confounding variables, such as interference by intracellular metabolism, binding to cytosolic proteins and intracellular conjugation, has not been investigated. Accordingly, in vitro effects of TRI and FC 113 on uptake of [³H]taurocholate (TC) into purified basolateral (blLPM) and canalicular (cLPM) rat liver plasma membrane vesicles were examined by a rapid filtration technique. Both TRI and FC 113 caused a dose-dependent inhibition of TC uptake into blLPM vesicles at an approximate concentration of 3 m and 72 μ , respectively. Initial rates of TC uptake in the presence of TRI and FC 113 were significantly inhibited by 69 and 61%, respectively (P< 0.05). In contrast, these chemicals had no effect on TC uptake into cLPM vesicles. This confirms studies in intact cells where these solvents were found to inhibit the uptake of bile acids by hepatocytes rather than interfere with the process of efflux. In conclusion, and consistent with the previous findings, the data suggest that the mechanism of TRI and FC 113-induced elevation of SBA may, in part, be due to selective inhibition of bile acid transport by the parent compounds at the basolateral domain of the hepatocyte plasma membrane.