lec3gauss+elimination

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FDA批准仿制安理申治疗阿尔茨海默病相关的痴呆症状

（自北京大学医药管理国际研究中心主办医药管理信息动态，海沙尔江译）摘
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参考文献
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Solutionsofsimultaneousequations：联立方程组的解

Solutions of simultaneous equationsThe HELM notes use Cramer’s rule to solve systems of linear equations but that method is compu-tationally very ineﬃcient,with many repeated subcalculations.The technique presented here-Gauss elimination-usually is a lot faster,especially for large systems.Consider the simultaneous equationsx+y=52x+3y=13Then y=5−x and so,2x+3(5−x)=132x+15−3x=13−x=13−15=−2Therefore x=2and y=5−2=3.However,this approach becomes very messy when we have three or more variables.And,even worse, you can easily“lose”information and get the wrong answer.Here is the sort of thing that can go wrong: Consider the system of equations2x+y+3z=12x+2y+5z=4x+y+z=1x+2y+2z=3It might be natural to take Equ2minus Equ1and then Equ4minus Equ3to give the two equationsy+2z=3y+z=2Solving these equations gives y=1and z=1.Plugging this back into theﬁrst equation gives2x= 1−y−z=1−1−3and hencex=−3 2 .Is this OK?NO!-these values,x=−32,y=1,z=1don’t satisfy the third equation.So,what has gone wrong?The problem is that we have not kept all the information from all4equations.So,we need a method that reliably ensures that we don’t lose information.We use a method known as Gaussian elimination.Gaussian eliminationWe are given a system of equationsax+by+cz+···=dex+fy+gz+···=k···Here a,b,c,d,e,···are constants and x,y,z,···are unknowns that we want to solve for.At each step of the procedure we are allowed to do one of the following3operations:(a)Add multiples of one equation to the others(b)swop two equations(c)multiply an equation by a(nonzero)number.and then,crucially,Write down all the resulting equations.This last step is a little tedious but it does stop errors like the one we had above.In doing this you can always reduce the system to Echelon Form,where each equation starts to the right of the one above,followed perhaps by several equations of the form0=0.ax+by+cz+···=df y+g z+···=kmz+nw+···=p······Note that it is possible to get an equation of the form0=−1or similar rubbish(that means that the system of equations is inconsistent-there’s no solution).At this stage,we can easily solve the system by back substitution where we start from the bottom equation and work upwards.There are3things that can happen:•You have an equation of the form0=−1.In this case there is No Solution.2•You have as many(nonzero)equations as unknowns.In this case you will have a Unique Solution which you can pretty much write down(see the examples below).•You have fewer equations than unknowns.In this case you have Inﬁnitely Many Solutions.I will explain below how youﬁnd them all.Lets try this with the system we had before:2x+y+3z=12x+2y+5z=4x+y+z=1x+2y+2z=3Since I don’t like fractions,I am going toﬁrst swop theﬁrst and fourth equation:x+2y+2z=32x+2y+5z=4x+y+z=12x+y+3z=1Now subtract twice Row1from the Rows2and4and subtract one copy of row one from Row3to give:x+2y+2z=3−2y+z=−2−y−z=−2−3y−z=−5Now using the second equation to eliminate the y’s from the last2equations gives:x+2y+2z=3−2y+z=−2z=−1−32z=−2−52And,ﬁnally taking equation4minus5/3times equation3givesx+2y+2z=3−2y+z=−2z=−1−320=−13So,the last equation is impossible and explains why there is No solution.Let’s do this with a few more examples.First,consider the system of equationsx+2y+3z=14x+5y+6z=12x+5y+7z=1Before going through the Gaussian elimination,I am going to introduce some convenient notation.We shall use the shorthand notation R1,R2,...to represent rows1,2,...and write for example R4−R1as shorthand for“Replace Row4by Row4minus Row1.”Secondly,we only need the numbers1,2,...,7,1 so we will write down the Augmented matrix for the system;this consists of all the numbers,with a vertical line in place of the equals sign.Here,though it is very important to put in a zero if some variable does not occur.This gives:1231 4561 2571Proceed by eliminating x from the second and third equations using row operation(a).123145612571R2−4R1R3−2R1∼12310−3−6−3011−1.Next we divide row2by(-3)to produce:12310−3−6−3011−1−13R2∼12310121011−1.Finally,we get12310121011−1R3−R2∼1231012100−1−2Reverting to a system of equations we see thatx+4y+2z=3y+2z=1−z=−2Solving from the bottom up this givesz=2y=−1−z=−3x=1−2y−3z=1+6−6=1The next thing I should explain is what to do when you end up with fewer equations than unknowns in echelon form.For example,one might have:x+y+z+w=2z+3w=5In this case,if I add in two equations y=27and w=34(or any other numbers)then I would have a system of equations in echelon form with the same number of equations as unknowns,and I could solve uniquely.So,we do something similar.The rule is:•If you are in echelon form and have fewer equations than unknowns,for each variable that does not appear at the beginning of an equation,put that equation equal to an arbitrary constant and then solve(uniquely)for the others.So,in our example this givesw=az=5−3w=5−3ay=bx=2−y−z−w=2−b−(5−3a)−a=−3−b+2aLets do one more example:−2x+z+w=−3x+y+z+w=2x+y−2z−2w=5−3x+y+4z+4w=−5We write in echelon form then swop rows one and two to get:−2011−31111211−2−25−3144−5∼11112−2011−311−2−25−3144−5Now keep doing row operations to get11112−2011−311−2−25−3144−5R2+2R1R3−R1r4+3R1∼111120233100−3−3304771111120233100−3−3304771R4−2R2∼111120233100−3−330011−1111120233100−3−330011−1R4+13R3∼111120233100−3−3300000Thus,we have the systemx+y+z+w=22y+3z+3w=1−3z−3w=3So,we can put w equal to an arbitrary number,as w does not appear at the beginning of any of these equations.Thus,we get solutionsw=cz=−1−w=−1−c2y=1−3(−1−c)−3c or y=2x=2−y−z−w=1.Finally,let’s do an example from networks.Consider the following ﬂow network510−−−−→•A x −−−−→•B 10−−−−→wy20−−−−→•D z −−−−→•C 5←−−−−30You are asked to ﬁnd the possible ﬂows x,y,z,w .The rule is that the ﬂow into any node has to be the same as the ﬂow out.Thus from the 4nodes we get the equations:A 15=x +w B :10+y =xorx −y =10C :y +z =30−5=25D :20+w =zorz −w =20I will leave the details to you but upon reducing to echelon form this gives the equationsx +w=15x −y =10y+z =25z−w=20with solutions:w =c,z =20+c,y =5−c,x =15−c.If you think about it,it is reasonable that you have an inﬁnite number of solutions,since one can increase the ﬂow around the middle circuit without causing a problem.Finally,for an application to electrical circuits,please read the HELM notes “Engineering Example 3”on Page 9of the notes “8.3:Solution by Gaussian Elimination.”The rule,here,is Kirchhoﬀ’s Law which says that the voltage drop around any circuit is exactly zero.Also,the drop across a resistor of x Ohms is xi ,where i is the current (note that this is not the square root of minus one—it is the notation they use in Electrical engineering...)Now you will be able to follow those explanations on those HELM notes.Other techniquesThere are (at least)two other techniques that also work for some systems.Theﬁrst is Cramer’s Rule This is described in the HELM notes and is quite good for a system of 3equations in3unknowns that has a solution.However for bigger systems it is Very Very slow.For systems that have inﬁnitely many solutions it does not work.So I strongly advise you not to use it. The second amounts toﬁnding the“inverse of the coeﬃcient matrix”(the words will be deﬁned next week).Once again,it is quite good for a system of3equations in3unknowns that has a solution. However for bigger systems it is Very Very slow.For systems that have inﬁnitely many solutions it does not work.So I strongly advise you not to use it.。

Development and Validation of a Liquid Chromatogra

J. Chem. Chem. Eng. 5 (2011) 1-6.Development and Validation of a LiquidChromatography–Tandem Mass Spectrometry Method for Determination of Artemisinin in Rat PlasmaElhassan Gamal1,2, Yuen Kah1, Wong Jiawoei1, Chitneni Mallikarjun1,3, Al-Dahli Samer1, Khan Jiyauddin1 and Javed Qureshi31. School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia2. Local Pharmaceutical Manufacturing Department, General Pharmacy Directorate, MOH, 11111, Khartoum-Sudan3. School of Pharmacy and Health Sciences, International Medical University, 5700, Kula Lumpur, MalaysiaReceived: September 03, 2010 / Accepted: October 11, 2010 / Published: January 10, 2011.Abstract: Artemisinin is a potent anti-malarial drug isolated from traditional Chinese medicinal herb, Artemisia annua. The objective of this study was to develop and validate a sensitive and specific LC-MS/MS method for the determination of artemisinin in rat plasma using amlodipine as Internal Standard. The method consist of a simple liquid-liquid extraction with methyl tertiary butyl ether (MTBE) with subsequent evaporation of the supernatant to dryness followed by the analysis of the reconstituted sample by LC-MS/MS with a Z-spray atmospheric pressure ionization (API) interface in the positive ion-multiple reaction monitoring mode to monitor precursor→product ions of m/z 282.70→m/z 209.0 for artemisinin and m/z 408.9→m/z 237.0 for amlodipine respectively. The method was linear (0.999) over the concentration range of 7.8–2000 ng/mL in rat plasma. The intra and inter-day accuracy were measured to be within 94-104.2% and precision (CV) were all less than 5%. The extraction recovery means for internal standard and all the artemisinin concentrations used were between 82-85%.Key words: Artemisinin, LC-MS/MS, amlodipine, plasma, accuracy and precision.1. IntroductionArtemsinin is the name given to the active principle of qinghaosu, an extract of the Chinese medicinal plant qinghaosu or green Artemisia (Artemisinin annua L.) which has been used for many years centuries in Chinese traditional medicine for treatment of fever and malaria [1]. In 1972, Chinese researchers isolated artemisinin from Artemisia annua L. sweet wormwood) and its structure was elucidate in 1979 as show in Fig. 1.The determination of artemisinin and its derivatives in biological matrices have previously been characterized using several analytical techniques suchCorresponding author: Gamal Osman Elhassan Ph.D., research field: pharmaceutical technology. E-mail: ******************.as LC, HPLC, GC-MS etc [3-8]. However, some of these methods suffer from few drawbacks. In particulars, interference with endogenous constituents in the plasma at the absorption wave length of the derivatized compounds may render these techniques unsatisfactory and few of them lacked the required sensitivity to be used for measurement of drugFig. 1 The chemical structure of artemisinin [2].ll Rights Reserved.Development and Validation of a Liquid Chromatography–Tandem Mass Spectrometry Method forDetermination of Artemisinin in Rat Plasma2concentration in blood sample obtained from clinical investigation [9].To increase the specificity and sensitivity of HPLC-UV method, some workers combined it with a mass spectrometry (MS) and the total system is described as LC-MS technique [10, 11]. The development of LC-tandem mass spectrometry (LC-MS/MS) has made a more specific and sensitive analysis of artemisinin and its derivatives possible [12, 13]. The objective of this study was to develop a sensitive and specific LC-MS/MS method for the determination of artemisinin in rat plasma by simple liquid-liquid extraction procedure.2. Materials and Methods2.1 MaterialsArtemisinin was purchased from Kunming Pharmaceutical Corporation (Kunming, China). Amlodipine was obtained from Sigma Chemical (Louis, USA). Acetonitrile (ACN), formic acid and methyl tertiary butyl ether (MTBE) were purchased from J.T Baker (USA).3. Methods3.1 Instrumentation and ConditionsThe instrumentation comprised of Quattro-micro tandem mass spectrometer with Z-spray atomospheric pressure ionization (API) source (Micromass, Manchester, UK) using electrospray ionization (ESI) operated at positive mode. Chromatography was performed on an Alliance 2,695 separation module (Waters, M.A, USA). The delivery system consisted of an autosampler and a column heater. The chromatographic separation was obtained using an X Terra MS C8 encapped (5 μm) (150 × 2.1 mm) analytical column (Water, USA).3.2 Sample PreparationA 250 μL aliquot of plasma was pipetted into a screw-capped culture tube, followed by 100 μL of internal standard solution (50 ng/mL). To each tube, 5 mL (MTBE) extraction solvent was then added and the mixture was vortexed for 2.5 minutes followed by centrifuging for 15 minutes at 3,500 rpm. The upper layer was transferred to a reactive vial and dried under nitrogen flow at 40 °C. The residue was then reconstituted with 250 μL of mobile phase and 20 μL was injected into the LC-MS/MS system.3.3 Assay ValidationCalibration curve at a concentration range of 7.8–2,000 ng/mL were constructed by spiking blank human plasma with a known amount of artemisinin. Plasma sample spiked with artemisinin at these concentrations 7.8, 62.5, 250, 2,000 ng/mL were used to determine the within and between-day accuracy and precision. For within-day accuracy and precision, replicates analysis (n = 6) for each concentration were performed in a single day. For between-day evaluation, analysis was carried out with a single sample of each concentration daily over 6 days, with calibration curve constructed on each day of analysis. The extraction recovery of artemisinin was estimated by comparing the peak height obtained after extraction of the samples from plasma with that of aqueous artemisinin solution of the corresponding concentration.4. Results and DiscussionBoth electrospray (TIS) and atmospheric pressure chemical ionisation (APCI) methods have been reported previously for the quantification of artemisinin derivatives in biological fluids [11, 12, 14-16]. According to the previously reported methods TIS was found to be superior to APCI for the quantification of artesunate and dihydroartemisinin (DHA) mainly because of improved linearity [16]. Therefore in this method electrospray ionization was used. When artemisinin and amlodipine were injected directly into the mass spectrometer along with mobile phase in the positive mode, the protonated molecules of artemisinin and amlodipine were set as precursorll Rights Reserved.Development and Validation of a Liquid Chromatography–Tandem Mass Spectrometry Method forDetermination of Artemisinin in Rat Plasma3(a)(b)Fig. 2 (a) Positive-ionization electrospray mass spectra of precursor ion for artemisinin; (b) Positive-ionization electrospray mass spectra of product ion for artemisinin.ions with m/z of 282.7 and 408.7, respectively. The product ion that gave the highest intensity was m/z of 209.0 for artemisinin and 237.7 for amlodipine. Fig 2(a) shows the spectra precursor ion, 2(b) production for artemisinin.Artemisinin and amlodipine have retention time of approximately 6.9 and 1.65 minutes, respectively (Fig.3). The peak was well resolved and free from interference from endogenous compounds in rat plasma (Fig. 4).ll Rights Reserved.Development and Validation of a Liquid Chromatography–Tandem Mass Spectrometry Method forDetermination of Artemisinin in Rat Plasma4Fig. 3 Plasma spiked with 500 ng/ml artemisinin and amlodipine 50 ng/mL.Fig. 4 Chromatograms for analysis of artemisinin in plasma (Rat blank plasma).Calibration curve was linear over the entire range of calibration curves with a mean correlation coefficient greater than 0.9995 (Fig. 5).The limit of quantification (LOQ) of the assay method was 7.8 ng/mL being the lowest concentration used to construct the calibration curve whereas the limit of detection (LOD) was 3.9 ng/mL at a signal to noise ratio of 3. The validation data demonstrated a good precision, accuracy and recovery. The extraction recovery means for internal standard and all artemisinin concentrations used were 75-85% (Table 1). The within-day and between-day accuracy and precision values are given in Table 2.Neither artemisinin nor the internal standard producedll Rights Reserved.Development and Validation of a Liquid Chromatography–Tandem Mass Spectrometry Method forDetermination of Artemisinin in Rat Plasma5Fig. 5 Mean calibration curve of artemisinin (ng/mL).Table 1 Extraction recovery.Concentration (ng/mL) Mean recovery (%) CV (%)7.81 75.081.5062.50 82.161.94250.00 82.03 2.072000.00 85.23 1.48Table 2 Within-day and between-day precision andaccuracy.Added (ng/mL)Within-day Between-day Accuracy (%) C.V (%) Accuracy (%) C.V (%)7.81 96.00 4.60 104.11 2.30 62.50 98.10 1.60 94.10 2.20 250.00 98.10 1.50 98.10 1.60 2000.00 96.10 2.50 97.10 1.80any detectable carry-over after three injections of upper limit of quantification. Blank rat plasma showed no interference with artemisinin. Interfering signals from blank plasma contributed less than 20% of the artemisinin signal at LOQ. There was no interference of artemisinin on the internal standard or vice versa. A small enhancement for artemisinin and the internal standard could be detected when references in neat injection solvent were compared with references in extracted blank biological matrix. The normalized matrix effects (artemisinin/internal standard) were close to 1 with a low variation in accordance with international guidelines. Post-column infusion experiments confirmed the absence of regions with severe matrix effects (i.e., no sharp drops or increases in the response) for blank human plasma extracted with the developed method.Xing et al. used artmether as an internal standard for the analysis of artemisinin [17]while for the analysis of artemisinin derivatives; artemisinin was used as internal standard [14]. In the present study amlodipine was found to be suitable because it could be separated chromatographically, ionized and fragmented under the conditions that optimized the intensity of artemisinin peak (Fig. 3).The analysis of artemisinin and its derivatives with mass spectrometry are most often performed with a different mode of ionization. Xing et al. used ESI inletin the positive ion-multiple reaction monitoring mode which relatively producing a higher sensitivity than in the SIM mode. Therefore, the mass spectrometry was operated at positive ion-MRM mode.4. ConclusionThe LC-MS/MS method described in this work is suitable for the determination of artemisinin in plasma. The assay procedure is simple with a relatively shortll Rights Reserved.Development and Validation of a Liquid Chromatography–Tandem Mass Spectrometry Method forDetermination of Artemisinin in Rat Plasma6retention time allowing sufficient sample to beprocessed to be applied to pharmacokinetic and bioavailability studies of artemisinin. The accuracy and precision of the assay method, as well as the recovery of extraction procedure were found to be satisfactory.References[1] D.L. Klayman, Qinghasou (Artemisinin): An antimalaria drug from China, Science 228 (1985) 1049-1055.[2] X.D. Luo, C.C. Shen, The chemistry, pharmacology andclinical applications of Qinghaosu (artemisinin) and it’sderivatives, Med. Res. Rev. 7 (1987) 29-52.[3] K.T. Batty, M. Ashton, K.F. Llett, G . Edwards, T.M. Davis,Selective high-performance liquid chromatography ofartesunate and α-and β-dihydroartemisinin in patients withfalciparum malaria, J. Chromatog. B 677 (2-3) (1996)345-350.[4] J. Karbwang, K. Na-Bangchang, P. Molunto, V . Banmairuroi, Determination of artemisinin and its majormetabolite, dihydroartemisinin, in plasma usinghigh-performance liquid chromatography withelectrochemical detector, J. Chromatog. B 7 (1-2) (1997)259-265.[5] K.L. Chan, K.H. Yuen, H. Takayanki, S. Jinandasa, K.K. Peh, Polymorphism of artemisinin from Artemisia annua,Phytochemistry 46 (7) (1997) 1209-1214.[6] G .Q. Li, T.O. Peggins, L.L. Fleckenstein, K. Masonic,M.H. Heiffles, T.G . Brewer, The pharmacokinetics andbiovailability of dihydroartemisinin, arteether, artemether,artesunic acid and artelinic acid in rats, J. Pharm.Pharmacol 5 (1998) 173-182.[7] B.A. Avery, K.K. Venkatesh, M.A. Avery, Rapid determination of artemisinin and related analogues usinghigh-perfomance liquid chromatography and anevaporative light scattering detector, J. Chromat. B 730 (1)(1999) 71-80.[8] S.S. Mohamed, S.A. Khalid, S.A. Ward, T.S.M. Wan,H.P.O. Tang, M. Zheng, R.K. Haynes, G . Edwards,Simultaneous determination of artemether and its majormetabolite dihydroartemisinin in plasma by gaschromatography-mass spectrometry-selected ionmonitoring, J. Chromat. B 731(1999) 251-260.[9] K.T. Batty, M. Ashton, K.F. Llett, G . Edward, T.M. Davis,The pharmacokinetics of artemisinin (ART) and artesunate (ARTS) in healthy volunteers, Am J. Trop Med. Hyg. 58(2) (1998) 125-126.[10] C. Souppart, N. Gouducheau, N. Sandenan, F. Richard,Development and validation of a high-performance liquid chromatography-mass spectrometry assay for the determination of artemisinin and its metabolite dihydraartemisinin in human plasma, J. Chromat. B 774(2002) 195-203.[11] H. Naik, D.J. Murry, L.E. Kirsch, L. Fleckenstein,Development and validation of high-performance liquid chromatography-mass spectroscopy assay for determination of artesunate and dihydrroartemisinin in human plasma, J. Chromat. B 816 (1-2) (2005) 233-242. [12] J. Xing, H. Yan, S. Zhang, G . Ren, Y . Gao, A high-performance liquid chromatography/tandem mass spectrometry method for the determination of artemisinin in rat plasma, Rapid Commun in Mass Spectro. 20 (9) (2006) 1463-1468. [13] J. Xing, H.X. Yan, R.L. Wang, L.F. Zhang, S.Q. Zhang,Liquid chromatography-tandem mass spectrometry assay for the quantitation of β-dihydroartemisinin in rat plasma, J. Chromat. B 852 (1-2) (2007) 202-207. [14] M. Rajanikanth, K.P. Madhusudanan, R.C. Gupta, An HPLC-MS method for simultaneous estimation of alpha, beta-arteether and its metabolite dihydroartemisinin, in rat plasma for application to pharmacokinetic study, J Biomed. Chromat. 17 (7) (2003) 440-446. [15] Y . Gu, Q. Li, M.V . Elendez, P. Weina, Comparison of HPLC with electrochemical detection and LC–MS/for the separation and validation of artesunate and dihydroartemisinin in animal and human plasma, J. Chromatogr B 867 (2008) 213-218. [16] W. Hanpithakpong, B. Kamanikom, A.M. Dondorp, P.Singhasivanon, N.J. White, N.P. Day, N. Lindegardh, A liquid chromatographic-tandem mass spectrometric method for determination of artesunate and its metabolite dihydroartemisinin in human plasma, J. Chromatogr. B 876 (2008) 61-68. [17] Y . Xing, H. Yan, S. Zhang, G . Ren, Y . Gao, A high-performance liquid chromatography/tandem mass spectrometry method for the determination of artemisinin rat plasma, Rapid Communication in Mass Spectrometry 20 (9) (2006) 1463-1468.ll Rights Reserved.。

Lec3

Roles of Social Science
• Analyze the frequently observed phenomena and explain the reason. NE serves as a powerful tool. • Predict what will happen in the future. Although it is usually difficult to make a one-shot prediction, NE may succeed to predict the stable situation after some (long) history of adjustment processes.
Dominance
• Let x and y be feasible strategies for player i. Then strategy x is strictly dominated by y if the following is satisfied:
si S i u i ( x, si ) u i ( y , si )
Which factor serves as a main reason to achieve Nash equilibrium depends on situations.
1. Rationality
• Players can reach Nash equilibrium only by rational reasoning in some games, e.g., Prisoners’ dilemma. • However, rationality alone is often insufficient to lead to NE. (see Battle of the sexes, Hawk-Dove game, etc.) • A common (and correct) belief about future actions combined with rationality is enough to achieve NE. 2 and 3 help players to share a correct belief.

思尔明

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思尔明安慰剂
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显著提高认知功能全面改善临床症状
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思尔明经典文献
老年性痴呆多中心随机双盲研究(意大利) 老年性痴呆多中心随机双盲研究(意大利) 多发梗塞性痴呆多中心随机双盲研究(德国) 多发梗塞性痴呆多中心随机双盲研究(德国) 血管性痴呆前瞻性双盲多中心研究(中国) 血管性痴呆前瞻性双盲多中心研究(中国)

第一代: 第一代:麦角胺治疗血管性头痛第二代:二氢麦角碱,改善脑功能主要为扩血管作用, 第二代 : 二氢麦角碱, 改善脑功能主要为扩血管作用, 有一定的促进脑代谢作用第三代:新一代麦角类药物－思尔明,通过对传统麦角类第三代:新一代麦角类药物－药物改造, 药物改造,使其改善脑功能的作用更趋完善
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显著提高认知功能全面改善临床症状
三重完善作用机制
增强脑动脉流量增强脑动脉血氧浓度
改善脑循环
显著提高认知功能全面改善临床症状
显著提高认知功能
全面改善临床症状
急、慢性血管性或代谢性脑功能不全
慢性大脑功能不全(轻度认知功能障碍,MCI; 慢性大脑功能不全(轻度认知功能障碍,MCI; 血管性认知功能障碍,VCI) 性认知功能障碍,VCI) 老年型痴呆(阿茨海默氏病,AD) 老年型痴呆(阿茨海默氏病,AD) 血管性痴呆(多发梗塞性痴呆,MID) 血管性痴呆(多发梗塞性痴呆,MID) 脑血管疾病后遗症
全面改善临床症状
1989年由意大利进口, 1989年由意大利进口,原名脑通®,是国内第一个上市的脑功能改年由意大利进口善药物 2000年更名为思尔明并重新上市, 2000年更名为思尔明®,并重新上市,成为辉瑞公司旗下品牌 2005年 2005年4月泰凌成为思尔明®中国总代理

三巯三嗪三钠成分 -回复

三巯三嗪三钠成分-回复三巯三嗪三钠是一种常用的药物组合。

它由三种药物组成，分别是三巯嗪、三巯异酮和三钠盐。

在医疗领域中，三巯三嗪三钠通常用于治疗精神疾病，如精神分裂症和情感障碍等。

首先我们来了解一下三巯嗪。

三巯嗪属于抗精神病药物的一种，它可以通过调节多巴胺受体的活性来缓解精神症状。

多巴胺是一种神经递质，与情绪调节和认知功能密切相关。

三巯嗪可以减少多巴胺的释放，并减少多巴胺受体的活性，从而改善患者的思维、情绪和行为问题。

第二种成分是三巯异酮，它也是一种抗精神病药物。

三巯异酮通过调节神经递质的平衡来发挥作用。

具体而言，它可以阻断多巴胺受体，并减少多巴胺的释放，从而减少多巴胺引起的精神症状。

此外，三巯异酮还可以影响神经递质谷氨酸和γ-氨基丁酸（GABA），这些都是与情绪和认知功能密切相关的神经递质。

最后一种成分是三钠盐，它是一种使用广泛的药物添加剂，具有缓冲作用。

在三巯三嗪三钠中，三钠盐的主要作用是调节pH值，以保持药物的稳定性和安全性。

三巯三嗪三钠的使用主要是基于其对多巴胺和其他神经递质的影响，从而减少精神症状。

这种药物组合通常用于精神分裂症的治疗。

精神分裂症是一种严重的精神障碍，患者可能出现幻觉、妄想、混乱思维和消极症状等。

三巯三嗪三钠可以帮助减轻这些症状，并提高患者的生活质量。

然而，三巯三嗪三钠也有一些不良反应和潜在的风险。

常见的不良反应包括嗜睡、头晕、口干和便秘等。

长期使用还可能出现代谢病变，如体重增加、血脂异常和糖代谢紊乱等。

此外，三巯三嗪三钠还与一些严重的不良反应相关，如心律失常和恶性综合征等。

因此，在使用三巯三嗪三钠之前，医生需要仔细评估患者的病情和风险，并提供个体化的治疗方案。

总结起来，三巯三嗪三钠是一种治疗精神疾病的常用药物组合。

它由三巯嗪、三巯异酮和三钠盐组成，通过调节神经递质的活性来减轻精神症状。

尽管三巯三嗪三钠在临床上被广泛使用，但它也有一些不良反应和风险。

因此，在使用此药物之前，必须进行详细的医学评估，并提供个体化的治疗方案，以确保患者的安全和疗效。

格雷厄姆LEC 安全评价法

格雷厄姆LEC 安全评价法格雷厄姆(BenjaminGraham,1894-1976)评价法是一种简单易行的评价操作人员在具有潜在危险性环境中作业时的危险性、危害性的半定量评价方法。

格雷厄姆评价法，是用与系统风险有关的三种因素指标值的乘积来评价操作人员伤亡风险大小，这三种因素分别是：L（事故发生的可能性）、E（人员暴露于危险环境中的频繁程度）和C （一旦发生事故可能造成的后果）。

给三种因素的不同等级分别确定不同的分值，再以三个分值的乘积D 来评价作业条件危险性的大小，即：D=L×E×C 风险分值D=LEC。

D值越大，说明该系统危险性大，需要增加安全措施，或改变发生事故的可能性,或减少人体暴露于危险环境中的频繁程度，或减轻事故损失，直至调整到允许范围内。

量化分值标准对这3种方面分别进行客观的科学计算，得到准确的数据，是相当繁琐的过程。

为了简化评价过程，采取半定量计值法。

即根据以往的经验和估计，分别对这3方面划分不同的等级，并赋值。

具体如下：事故发生的可能性（L）分数值事故发生的可能性10 完全可以预料 6 相当可能3 可能，但不经常 1 可能性小，0.5 完全意外很不可能0.2 可以设想极不可能0.1 实际不可能暴露于危险环境的频繁程度（E）分数值暴露于危险环境的频繁程度10 连续暴露 6 每天工作时间内暴露3 每周一次或偶然暴露 2 每月一次暴露1每年几次暴露0.5 非常罕见暴露发生事故产生的后果（C）分数值发生事故产生的后果100 10 人以上死亡40 3～9 人死亡15 1～2 人死亡7 严重3 重大 1 伤残风险（D）分析风险D=LEC 就可以计算作业的危险程度，并判断评价危险性的大小。

其中的关键还是如何确定各个分值，以及对乘积值的分析、评价和利用。

D值危险程度>320 极其危险，不能继续作业160-320 高度危险，要立即整改70-160 显著危险，需要整改20-70 一般危险，需要注意<20 稍有危险，可以接受根据经验，总分在20 以下是被认为低危险的，这样的危险比日常生活中骑自行车去上班还要安全些；如果危险分值到达70～160 之间，那就有显著的危险性，需要及时整改；如果危险分值在160～320 之间，那么这是一种必须立即采取措施进行整改的高度危险环境；分值在320 以上的高分值表示环境非常危险，应立即停止生产直到环境得到改善为止。

哪些药物可以治疗阿尔茨海默病

如对您有帮助，可购买打赏，谢谢
生活常识分享哪些药物可以治疗阿尔茨海默病
导语：阿尔茨海默病是一种老年性疾病，多发病与60岁以上的老人，也是老年痴呆。

当出现阿尔茨海默病以后患者的记忆力会下降的严重，，慢慢的健忘直
阿尔茨海默病是一种老年性疾病，多发病与60岁以上的老人，也是老年痴呆。

当出现阿尔茨海默病以后患者的记忆力会下降的严重，，慢慢的健忘直到什么都请不起来，甚至连亲人都记不得，目前阿尔茨海默病的治疗是不容易的，只有通过药物和物理治疗才能减轻阿尔茨海默病的发病。

一、胆碱能药物
1 多奈哌齐(donepezil)
商品名为安理申，为选择性非竞争性可逆的第二代ache抑制剂，属于苄基哌啶类化合物，选择性很强，在脑组织内作用最敏感的区域是皮质和海马回，因此可极大地减轻胆碱能缺乏导致的学习功能缺陷，还能增加整个脑血流量;减轻淀粉样蛋白的神经毒性作用;减轻自由基导致的神经变性。

2 利斯的明(rivastigmine)
商品名为艾斯能，是非竞争性氨基甲酸类胆碱酯酶抑制剂，也是丁酰胆碱酯酶抑制剂。

给药后0.5 h～2 h达最大血药浓度，t1/2为2 h，但在脑组织内对胆碱酯酶的抑制作用可达9 h。

能选择性的抑制大脑皮质和海马的ache，对于皮质小脑通路和纹状体通路的影响较小，可避免抑制呼吸中枢和产生锥体外系症状。

该药不依赖肝细胞色素p450酶系代谢，极少发生药物互相作用，未见肝脏毒性报道。

艾斯能不仅可改善轻中度ad患者的临床表现，而且对晚期重症ad疗效更显著。

3 加兰他敏(galantamine)
为第二代可逆性竞争性ache抑制剂，又是烟碱受体调节剂，具有。

用于抑郁和应激障碍的嗪酮和二嗪酮V3抑制剂[发明专利]

专利名称：用于抑郁和应激障碍的嗪酮和二嗪酮V3抑制剂专利类型：发明专利
发明人：J·J·莱图尔诺,何国勤,M·J·奥尔迈耶,P·乔基尔,C·M·里维埃罗
申请号：CN200680023720.3
申请日：20060607
公开号：CN101212969A
公开日：
20080702
专利内容由知识产权出版社提供
摘要：公开了可用于治疗抑郁、应激和其它障碍的取代吡啶、嘧啶、吡嗪、吡啶酮、嘧啶酮、吡嗪酮和苯乙酰胺。

所述化合物具有右式。

申请人：药典公司
地址：美国新泽西
国籍：US
代理机构：中国国际贸易促进委员会专利商标事务所
代理人：张敏
更多信息请下载全文后查看。

脑白质疏松症课件

临床表现
· 智力及认知功能的障碍 · 下肢功能的障碍 · 皮质功能减退的非特异性表现
智力及认知功能的障碍
· 内侧边缘环路、基底边缘环路和防御边缘环路是与记忆情绪行为等智能活动有关的边缘环路，这三种环路联系纤维分布在脑室系统周围，当脑室系统周围的白质病变导致以上环路联系纤维中断，或导致皮质-皮质连接损伤时，即会出现智力及认知功能障碍。
下肢功能的障碍
· 常表现为步行缓慢步基增宽步幅小步行能力下降和轻微平衡障碍等这与脑室系统周围支配下肢的特异性上下行纤维受损有关，也可能与中枢传导时间延长，感觉信息和姿势反射整合障碍有关。
皮质功能减退的非特异性表现
·如头晕头痛等，可能与患者伴有高血压病糖尿病高脂血症等原发病有关。
病理表现
3级为不规则延伸至深部白质。
诊断与鉴别诊断
·依据对称分布的脑白质病变，合并脑萎缩， LA诊断并不困难。但应于以下疾病相鉴别：
多发性硬化：病因尚不明确，可能与病毒感染或自身免疫有关，发病以20 —35岁的中青年，女性多见，急性期病灶可有强化。病灶与侧脑室壁常呈垂直排列，与脑室周围白质内的小血管走行一致。与其鉴别要结合病史及发病年龄。
A7
syivian M2
horizontal M1
缺血
内，
终末
岭区，
糖尿
病变关联表现
·LA患者多伴有前后循环血管的异常，主要表现为管壁粗细不均，常呈串珠样改变多处或局限性狭窄远端分支减少等，可同时累及前后循环血管。这些脑血管的异常改变可引起远端供血区域的低灌注，从而导致白质缺血损伤，促使LA的发生。
LA的MR分级诊断
MR的Fazekas量表(最低0分，最高6分)
· 在Flair上评定脑室周围高信号和深部白质高信号，总分可通过概括两个部分的分数来获得。

孕烯醇酮唾液酸苷对β-淀粉样蛋白致神经元损伤的保护

孕烯醇酮唾液酸苷对β-淀粉样蛋白致神经元损伤的保护张勤;周斌;李文姬;李绍顺;姜远英;殷明
【期刊名称】《第二军医大学学报》
【年(卷),期】2001(22)1
【总页数】2页(P93-94)
【关键词】孕烯醇酮;演粉样β蛋白;神经元损伤;唾液酸苷;早老性痴呆
【作者】张勤;周斌;李文姬;李绍顺;姜远英;殷明
【作者单位】第二军医大学药学院药理学教研室
【正文语种】中文
【中图分类】R749.160.5;R971
【相关文献】
1.神经活性甾体别孕烯醇酮对脑皮质神经元损伤的保护作用 [J], 李贤慧;张新昌;王刚;刘海玲;夏时海
2.脱氢表雄酮唾液酸苷对A β25-35致海马神经元损伤作用研究 [J], 张勤;周斌;程明和;李绍顺;殷明
3.蝇蕈醇对β-淀粉样蛋白(25-35)致海马神经元损伤的保护作用 [J], 王澎伟;梁庆成;吴云
4.五味子酮对β淀粉样蛋白所致神经元应激损伤的保护作用 [J], 朱嘉琦;拓西平;陈海生;吕建勇;贾丽艳;周俊
5.孕烯醇酮唾液酸苷对小鼠记忆障碍的改善作用 [J], 周斌;张勤;赵早瑞;李文姬;李绍顺;姜远英;殷明
因版权原因，仅展示原文概要，查看原文内容请购买。

姜黄素对三氯化铝致老年性痴呆模型大鼠的作用

姜黄素对三氯化铝致老年性痴呆模型大鼠的作用
戴晓莉; 马玉奎
【期刊名称】《《食品与药品》》
【年(卷),期】2011(13)4
【摘要】目的研究姜黄素对三氯化铝所致痴呆模型大鼠学习记忆能力和海马内β-淀粉样前体蛋白(β-APP)阳性神经元的影响,以期探讨姜黄素抗老年性痴呆的作用机制。

方法用三氯化铝致老年性痴呆模型大鼠为实验对象,以其学习记忆能力、背海马和齿状回内β-APP阳性神经元的数量为指标,全面考察姜黄素抗老年性痴呆的作用。

结果姜黄素(0.1,0.3,1.0 g?kg-1?d-1,ig),能明显对抗老年性痴呆模型大鼠学习记忆能力的下降,抑制背海马和齿状回内β-APP阳性神经元的生成。

结论姜黄素对三氯化铝所致的老年性痴呆有明显的改善作用。

【总页数】3页(P257-259)
【作者】戴晓莉; 马玉奎
【作者单位】山东省医药工业研究所山东济南 250100
【正文语种】中文
【中图分类】R965
【相关文献】
1.姜黄素对三氯化铝致老年性痴呆模型大鼠的作用 [J], 戴晓莉;马玉奎
2.长春西汀对三氯化铝致痴呆模型大鼠的疗效 [J], 杨东娜;王瑾
3.知母皂苷对三氯化铝致老年性痴呆模型大鼠的作用 [J], 马玉奎;李莉;刘国宾
4.芹菜甲素对三氯化铝致老年性痴呆模型大鼠的干预作用 [J], 马玉奎;渠广民;徐丽;张桂英
5.姜黄素对三氯化铝所致大鼠神经损伤的保护效应 [J], 杨芳;谷薇薇
因版权原因，仅展示原文概要，查看原文内容请购买。

具有三个年龄阶段的单种群自食模型(英文)

具有三个年龄阶段的单种群自食模型(英文)
高淑京
【期刊名称】《生物数学学报》
【年(卷),期】2005(20)4
【摘要】建立并研究了两个具有三个年龄阶段的单种群自食模型．这篇文章的主要目的是研究时滞对种群生长的作用．对于没有时滞的的模型,我们利用Liapunov函数,得到了系统平衡点全局渐近稳定的充分条件;而具有时滞的的模型,我们得到,随着时滞r增加,当系数满足一定条件时,正平衡点的稳定性可以改变有限次,最后变成不稳定;否则,时滞模型的正平衡点的稳定性不改变．
【总页数】7页(P385-391)
【关键词】阶段结构;自食;时滞;全局渐近稳定
【作者】高淑京
【作者单位】大连理工大学应用数学系
【正文语种】中文
【中图分类】O175.1
【相关文献】
1.具三个年龄阶段的自食单种群系统的定性分析 [J], 邢铁军;杜明银;王生丽
2.具有阶段结构的自食单种群模型的稳定性 [J], 高淑京
3.具有三个年龄阶段单种群自食阻滞模型 [J], 麻作军;李相锋
4.具有3阶段结构的自食单种群征税模型 [J], 曾夏萍;高建国
5.污染环境下具有脉冲输入环境毒素的单种群模型的灭绝阈值研究(英文) [J], 焦建军;陈兰荪
因版权原因，仅展示原文概要，查看原文内容请购买。