Buddhism Assignment Example | Topics and Well Written Essays - 750 words

Buddhism - Assignment Example Moreover, the tradition accepts suffering as a component of human life (BBC). The four noble truths laid out by the Buddha enable believers to overcome obstacles that hinder them from understanding their real nature. Buddhism lays its foundation on the four truths. They are also rare among other religions in the world and focus on strengthening the faith of the believers rather than their warrior acts. Buddhists never use four noble truths to justify the warrior culture or any form of military actions and exploitations. The four truths ascribed to Buddhism are herein mentioned: Life is suffering: this is the first noble truth in Buddhism. It argues that the existence of the human nature is painful. In addition, suffering does not end with death due to the cyclic nature of life. Believers should focus on strengthening their faith and promoting peaceful coexistence between themselves as well as with nature rather than lament on the painful situations they encounter in life. There is a source of suffering: the second noble truth expounds on the cause of suffering among humans. It explains that suffering results from individual clinging and craving. In addition, suffering has links with human ignorance of reality. The desire held by people to satisfy their immediate interests is the main source of suffering in life (BBC). Individuals can overcome craving: the third noble truth establishes the cure for suffering among believers. The truth argues that a person can end his/her suffering by overcoming the need to satisfy their personal desires selfishly. Once an individual overcomes selfish craving, they enter into a state alluded to as Nirvana and that their suffering diminishes. In this state, an individual attains perfect happiness and peace as is the case of heaven. In Buddhism, it is the highest achievable state. The fourth noble truth provides believers with a criterion for overcoming selfish cravings. The process involves eight steps, which

Time Value of Money Essay Example for Free

Time Value of Money Essay Time value of money is useful in making informed business decisions. For example the net present value method can be used to help decide the best alternative among multiple alternative uses of a firm or personal financial resources. By discounting various alternatives to their present value one can compare the alternatives. Time value of money can also answer such questions as what ones investment will be worth at a certain point of time in the future, assuming a certain interest rate. Time value of money can also be used to compute such useful information as car, mortgage and other loan payments. Another use of time value of money in accounting is reporting of certain long-term assets and liabilities. Time value of money is based on the principle of compound interest. Each time there is a compounding period the new principal is increased by the interest from the previous period. Converting Before Using the Tables When using the tables, you may need to convert if, for example, in a lump sum situation there are more than one compounding periods in a year. Or you may need to convert (to monthly compounding) if, for example, you are working with an annuity situation involving a car loan that involves monthly rather than annual periodic payments. You often need to convert whether it is a lump sum or an annuity situation. Do the following conversions before using the tables. See some of the examples which follow these notes. For semi-annual compounding [or for deposits every six months in an annuity], take the annual interest rate and divide it by 2. Take the number of years and multiply by 2. For quarterly compounding [or for quarterly deposits in an annuity] take the annual interest rate and divide it by 4. Take the number of years and multiply by 4. For monthly compounding [or for monthly deposits in an annuity] take the annual interest rate and divide it by 12. Take the number of years and multiply by 12. Lump Sum Amounts Future Value of $1 = Present Value X Future Value of $1 Table Factor Present Value of $1= Future Value X Present Value of $1 Table Factor Use the $1 table when you are dealing only with a lump sum amount. (However when you have an annuity in the problem, do not use the lump sum table; instead use the annuity table. Use the annuity table even if you are looking for a lump sum, as shown in No. 4 which follows these notes.) Notice that there are four variables with lump sum situations: Present Value, Future Value, Interest Rate, and Period. You need to know three out of the four to figure out an unknown. You saw above how to compute Present Value and Future Value. Now suppose you want to find the interest rate. Present Value Approach: PV / FV = computed PV Table factor Go to the PV table. Where the table factor and periods intersect is the interest rate. Use this same approach to figure the number of periods when you know the interest rate and PV and FV. Annuities An annuity means a series of equal periodic deposits, or rents which can be either payments or receipts; they are made at equal periodic intervals. Use the annuity tables when you are dealing with equal periodic payments or receipts at equal periodic intervals. Use Ordinary Annuity table for payments made at the end of the period. Use Annuity Due table for payments made at the beginning of the period. Future Value of an Annuity = Annuity Deposit X Future Amount of an Annuity Table factor. Present Value of an Annuity = Annuity Deposit X PV of Annuity Table Factor Note the Annuity Deposit may be either a payment or receipt. Now say you wish to find the amount of the deposit, which could be either a periodic payment like a car or mortgage payment, or a periodic receipt such winnings from the lottery or more realistically monthly withdrawls of cash during retirement. Rent or Payment/Receipt = PV / PV of annuity table factor or Rent or Payment/Receipt = FV / FV of annuity table factor You cannot just use either of the PV or FV approaches. Use the PV approach if PV is the given information. You would have to use the FV approach if FV is the given information. Often you use the present value approach though. For example if you are buying a car and want to figure out the car payments, the current price of the car is Present Value. It is assumed to be the cash-equivalent price. A Few Practice Problems 1. You want to know how much you should deposit in the bank each month in order to have $10,000 in four years. What type of problem is this? A. present value of an annuity B. present value of an amount C. future value of an annuity D. future value of an amount The correct answer is C. First you know this is an annuity because it involves equal periodic payments to the bank at equal intervals. You know it is future value because you are asked to find what future amount your annuity will grow to. Even though it is growing to a single amount, be sure to note that you are looking for the future value of an ANNUITY. 2. You want to know how much you should deposit in the bank now in order to have $10,000 in four years. What type of problem is this? A. present value of an annuity B. present value of an amount C. future value of an annuity D. future value of an amount The correct answer is B. 3. Someone will pay you $10,000 in four years. You want to know how much it is worth to you now, assuming a certain interest rate. What kind of problem is this? A. present value of an annuity B. present value of an amount C. future value of an annuity D. future value of an amount The correct answer is B. 4. What single amount do you have to deposit in the bank now in order to be able to withraw $200 a month for the next five years? What kind of a problem is this? A. present value of an annuity B. present value of an amount C. future value of an annuity D. future value of an amount The answer is A. Even though a single amount will be deposited, it is still an annuity problem. Hint: any time a problem involves equal periodic payments, use an annuity table. 5. When you were born your parents set up a trust fund designed to accumulate $88,000 by the time you are 50 years old. You are 34 years old today. If you negotiate getting the money today, what will you get? Assume an 8% interest rate and annual compounding. First realize you are looking for present value. Today and now are hints you want present value. Next realize you need to subtract your current age for 50 years to get the number of years, which would be 16 years in this problem. So PV = FV X PV table factor for 8% and 16 years 25,687 = 88,000 X .2919 6. You are very rich and will be retired soon. You want to take out $416,000 every six months for 6 years. You can get a 6% interest rate. How much do you need to deposit in the bank today to make this happen? You are looking for the Present Value of an annuity , since you want the amount to deposit TODAY, and you will be withdrawing equal periodic payments. So use the annuity table even though you are putting a lump sum in the bank. PV annuity = Deposit X PV annuity factor ( 3%, 12 semi-annual periods) = 416,000 X 9.9540 = 4,140,864, the amount you need to deposit today. 7. Trego County wants to raise $4,000,000 to finance the construction of a new high school. The school board wants to make semiannual payments to repay the loan over the next 15 years. What will be the amount of the payments assuming the interest rate of 10%?

Antimitotic Prodrugs Advantages And Disadvantages

Antimitotic Prodrugs Advantages And Disadvantages Abstract The intricate prodrug therapy has made possible the synthesis and identification of novel drug discovery that have significant structural modifications or intermediate derivatives which may facilitated and enhanced therapeutic parameter during in vitro and in vivo studies. Along with improved target delivery of prodrugs provides the capability to not only overcome certain limitation of antimitotic drugs, but to increases the chances to undergo clinical phase trial studies to get in to action. Development of these new prodrugs as improved alternatives gone through from significant challenges; nevertheless these potential therapies also use to analysed and give suggestion about their further development by clinical studies. Introduction Cancer is diseases in which the bodys cells become abnormal and split without control. Cancer cells may show aggression nearby tissues. They may spread through the bloodstream and lymphatic system to other parts of the body. [1, 2, 3]. Now the days there are mainly three types of treatments are in use surgery, radiation and chemotherapy. Among these, surgery and radiotherapy are to be employed for specific treating are and chemotherapy employed during the systemic treatment of metastases in local as well as regional cancer cells. Chemotherapeutic drugs can be divided in to alkylating agents, antimetabolites plant alkaloids (antimitotics), topoisomerase inhibitors, and other antitumor agents. All of these drugs affect the cell division or DNA synthesis and translation, and function in other ways. The proliferation rate is the play the key role in for the effects of these drugs thus; they are not much selective of tumours. Chemotherapy is treatment with drugs that kill cancer cells and make them less active. It is the treatment of disease by chemicals, especially by killing micro-organisms or cancerous cells. In popular usage, it refers to antineoplastic drugs used to treat cancer or the combination of these drugs into cytotoxic standardized treatment regimen. In its non-oncological use, the term may also refer to antibiotics, long time use of chemotherapy consequences natural cell deaths in the treatments of tumour [4]. Sometime these agents produce remission and re-growth which result in proliferation of cancer cells along with resistance of drugs. Although, intense researches have been conducted in the field of cancer, there are some pioneering ideas need to come in this field to decrease toxicities, physicochemical properties and therapeutic index [5]. The use of prodrug is generally established as a strategy to improve the physicochemical, biopharmaceutical or pharmacokinetic properties of pharmacologically potent agents, and thereby increase the develop ability and usefulness of a potential drug [6,7]. The aim of the prodrug establishment is to improve (i) physicochemical properties like solubility, chemical stability, taste and odour etc. (ii) selectivity; (iii) pharmacokinetic and pharmacodynamic problems and (iv) therapeutic index. Thus; by these improvements, we can overcome the formulations challenges of the drugs [8, 9]. The most of the antimitotic prodrugs developed with conjugating prodrug molecules to low to high molecular weight molecules like sugars, enzymes, vitamins, antibodies, polymers and nanoparticals. These are the carriers which transport prodrug in to tumour and drug release with conjugating the drug to the carrier through a spacer that include particular point which make the specific targeting of the drug. These carriers are very complicated in the structure and demand very hard work to make carries linked prodrugs. Hetrogenecity, biodistribution, expression of multidrug resistance, interstitial pressure and amount of the drug reaching to the target site, are the problems which make the task more difficult. Along with that targeting properties will preserved or not with structural changes are major problems in the formulation of carrier liked prodrug molecules. Here I provide an overview of recent developments in targeted antimitotic prodrug and conjugate design. These are examples which, illustrating the salient features of different targeting strategies. I have focused on prodrug and conjugate examples in priclinical trials or advanced preclinical studies with advantages and disadvantages associated to each strategy are also discussed. Antimitotics In the process of mitosis eukaryotic cell isolate the chromosome in its cell nucleus into two the same sets which are divided in two nuclei. In cancer the single cell start converts from normal cell to cancerous cells by the process of mitosis. The mitosis inhibitors contain certain different cancer drugs. They are different in mechanism of action from the other classes of cancer drugs [12]. They mainly interfere with cell proliferation of cell rather than alter DNA structure and function. Mitosis includes DNA replication which divides the cells in to two new cells. Spindle fibers separate newly replicates chromosomes and convert them in to two forming cells. The fibres which are produce microtubules which fix with the replicated chromosomes. Now chromosomes pull one of this copy to each side of the cell which includes spindle fibers, without that cell cannot divide. Antimitotics inhibit this earlier uncertain spindle function during cell cycle. Spindle fibers form of long chains of smaller subunit of tubuline protein. In the process of polymerisation tubuline subunits can add to microtubule. Some types of antimitotics stop the process of forming of tubuline monomers which inhibits the microtubule. In this process they arrest movement of chromosomes as well as spindle tubule [13]. Examples of mitotic inhibitors include Taxanes, paclitaxel (Taxol) and docetaxel (Taxotere), Epothilones like ixabepilone (Ixempra), and Vinca alkaloids: vinblastine (Velban), vincristine (Oncovin), and vinorelbine (Navelbine), estramustine (Emcyt) and Colchicines. Vinca alkaloids and colchicines are those who have more over same mechanism of action. Vinblastine inhibiting the formation spindle fibers which are responsible for position of chromosome and the separation of the chromosomes during anaphase. It also inhibits the formation of microtubules which are responsible for the formation of cell division. Vinca alkaloids have many side effects like others [14]. Vincristine also binds to the tubuline monomers and arrests the formation of spindle microtubules. As result of this, it blocks the movements of chromosome during cell division. Speficity is the major problem with vincristine because it also affects the healthy cells with cancer cells during cell division. Vindesine is another Vinca alkaloid who binds to the microtubules. It has target specificity problem which makes them less potent [15]. Texel is natural antimitotic drug and different in mechanism of action from Vinca alkaloids. Paclitaxal and docetaxel are the two important analogues . Paclitaxel inhibits microtubuline assembly rather than monomers. It binds to microtubules and prevent this breakdown because these two processes, polymerisation and breakdown, both are requiring for movement of replicated chromosomes. The prevention of chromosomes breakdown inhibits them to move to opposite direction of dividing cells. Reduction in bone marrow function which may result in anaemia, blood in stools or black stools, fast or irregular heart beat, are common side effects associated with paclitaxel [16]. Docetaxel has same mechanism of action as paclitaxel but if the drug is give with combination it will cause major side effects than paclitaxel [17]. Epothilones is microtubule function inhibitor. It binds to beta-tubuline subunit on microtubules and preventing polymerization during cell division and eventually causes cell death. Mainly peripheral neuropathy, mylosuppersion with white blood cells and hypersensitivity reactions are the side effects which cause by Epothilo nes [18]. Colchicines are antimitotics which have same mechanism of action as Vinca alkaloids. It also binds to tubuline and inhibits polymerization of microtubules. Tubuline availability is necessary for mitosis process and colchicines are inhibiting these tubules as spindle poison. Cancer cell have nature to proliferate most and this make them more susceptible to Colchicines drugs [19]. These are natural anitimitotics and their analogues. Their mechanism of action is mainly on tubuline and sometime called antitubuline agents. But they have their own challenges like insolubility, bioavability, pharmacokinetic and pharmacodynemics, and toxicities problems. Tubuline plays a key role in their effects to bind mitosis but to overcome these challenges, proteins which are involve in the mitosis, are founded. They are presently under process to develop the capacity of clinical efficacy that those drugs have established [20]. Present scenario in antimitotics drug development (Specific druggable protein targets) The targeted proteins with specific function of new generation of anti mitotics are identified with molecularly targeted drug discovery. These new agents play important role in the unique way to provide the significant effects, which take beyond the certain limitations of drugs as well as extend the scope of their clinical efficacy of current antitubuline drugs. Although, they are facing some considerable challenges, but molecular mechanism of action of mitotic-checkpoint plays important role in mitosis [21]. Antitubuline drugs have complex chemical structure and are complicated to isolate and synthesised from their natural sources. Neurotoxicity and insolubities are the major problems with Vinca alkaloids and Taxanes. They also interfere in function of microtubules in axons, which provoke the neuronal vesicle motility. The non-structural components of mitosis as potential drug targets are one of the solution for therapy. They have unique effects in morphological stages during the mi tosis which is bring mitotic Kinesins, Aurora kinases and polo-like kinases (PLKs), as druggable protein target classes [22]. Targeting these proteins is well known as mitotics kinesin, kinesin spindle protein (KSP) are requires for the proliferation from prophase to prometaphase and Centromeric protein E (CENPE) is required during prometaphase to metaphase and also have effects in mitotic checkpoint [23, 24]. These protein targets are only finds in dividing cells so non-dividing cells are not effected. This showed that, this kind of target inhibition have potential and improved therapeutic index compare to tubuline target anti mitotic drugs. Although, proteins inhibitors might not enough effects on both the mitotic spindle and cytoskeleton but they have some significant role out side the mitosis. Moreover, to support these new agents, the role played by them in the mitosis, cause target inhibition to be connected with tumour growth inhibition. By the using pharmacodynemic marker, significant effective dose during drug development founded. These doses were affected instead of maximally tolerated dose, might also caused improved therapeutics index. The mechanism of action of these agents by which they inhibits tumour cells undergo cell death was not properly defined but they have many positive effects on these proteins. Activation of caspace 3 (significant effectors) has been identified in studies of protein target drugs, along with that mitotic catastrophe has also been founded [25, 26, 27]. Actually, catastrophe is cell death occurs from metaphase of mitosis against the drugs that produce DNA damage because of in this stage the caspace 2 is involved rather than caspase 3 which produces many morphological and therapeutic aspects of cell death. On the other hand, mitotic check point as effectors of cell death against protein inhibitors was contentious. It was suggested that KSP inhibitors needed mitotic checkpoint. In contrast to that, role of checkpoint studies involved that; this signalling might cause cell death with mitotic damage [28, 29, 30]. This mechanism might supported by Aurora B inhibitors [31]. Eventually, the mechanism of action of these new protein inhibitors became more understandable that, they are more involved in killing cell by unique mechanism but also, different genetic alterations, which may produce during cancer, play the important role during inhibition by these agents. Although, this studies is unfinished so its hard to get these new agent in action because they needed further more researches. KSP Inhibitors: Ispinesib was first KSP inhibitor and studied in clinic to check the therapeutic effects. Small molecules of KSP ATPase were targeting by this drug but it was not involved in effecting ATP and ADP. In terms of specificity, it was 40,000 times more selective as compare to other kinesins. Firstly it was studied intravenously and results founded that during different number of days, the cumulative dose delivery was same and dose limiting toxicity on both occasion was neutropenia as well as haematopoietic lineages, along with that nausea, vomiting and diarrhoea also observed. Raise in the dose also increases the amounts of phosphor-histones-H3 in tumour which involved inhibition of proliferation of tumour cells with dose. As consequence, the pharmacodynamic activities also increased. In earlier, the renal cell, hepatocellular and colorectal cancers are not responding to anti tubuline agents, but this KSP inhibitor extend the time duration of stability for more than 6 months. This agent a lso needed following treatments of natural anti tubuline agents [32]. The next KSP ATPase inhibitor is same to Ispinesib, and during clinical evaluation it came from the chemical synthesis [33]. It has more efficacious than first one. During the studies it is connected with dose limiting toxicities that is neutropenia and hyperbilirubinaemia [34, 35]. For cholangiocarcinoma, it gives some positive effect and two more cancers extend as stable diseases for more than six months. Third potent KSP inhibitor is MK-0731. It is more selective about more than 20,000 fold and associated with increased activity of hepatic transaminases and neutropenia [36]. Finally, clinical experience of KSP inhibitors showed that these agents associated with common dose limiting toxicities like neutropenia, increased activity of hepatic transaminases which are also observed with tubulin inhibitors. Although, some of toxicities like alopecia, mucositis and neuropathy, are not often seen. Nausea and vomiting have seen uncommonly with these protein targeting inhibitors. AURORA and PLK inhibitors One of the potent drug called as VX-680 also know as MK0457 as ATP competitive inhibits Aurora A, B and C to inhibit the cell differentiation in cell culture [37]. Its mechanism of action is to inhibit the FMS-related tyrosine kinase 3 and imatinib-resistant mutants forms of Abelson tyrosine (ABL) kinase. Imatinib and dasatinib are the resistant to those agents. During the studies, cancer cell from different patients, were tested against intravenous infusions. As results, neutropenia was mostly observed dose limiting toxicity and when the dose increased the some pharmacodynemic effects in skin was also observed. To evaluate that, phospho-histone-H3, Ki67 (antigen) and cycline B1 expressions are being checked before and after these studies. In the skin biopsies, there was no strong evidence observed, which showed the mitotic arrest or decrease in cell proliferation in the skin, during clinical studies. There was strong proof about the effects on cell proliferation which are haematopoi etic, but it was not case with skin biopsies. Mitotic inhibition, aneuploidy, was expected from the pan-Aurora but only delay in the mitotic progression observed during studies. Moreover, these agents inhibit the Aurora B and decrease the PHH3 levels when other anti-mitotic agent increases this biomarker. To overcome this limitation, the assays procedures developed which are capable to find out the decrease in the level of PHH3. Skin was not responding to these drugs. Extended stable disease for more than 6 months observed [21]. Another ATP-competitive Aurora B inhibitor is AZD1152 with significant IC50 cellular proliferation. This inhibitor evaluated in two schedules. In the both schedules, neutropenia observed as dose limiting toxicity for intravenous infusion. Moreover, next assessments reached in phase I and II studies for cancer like leukaemia [38]. BI 2536 is first ATP-competitive inhibitor of PLK1. There were three different partitions to evaluate this small molecule inhibitor. Every partition was evaluated by intravenous infusion and as result of that, same toxicity and dose delivery were obtained. Thrombocytopenia and neitropaenia were major dose limiting toxicities in every partition [39]. The second ATP non-competitive inhibitor of PLK1 is ON 01910. It may support PLK, to bind the substrates. It is currently under trail for two different doses because it has low potency to FLT1 and platelet derived growth factor receptor (PDGFR). Increased activity of hepatic enzymes, anaemia, leucopoenia and gastrointestinal symptoms, are the adverse effects with this inhibitor [40]. All over, neutropaenia without significant neuropathy was major dose limiting toxicity with these inhibitors. Challenges and Developments in New Antimtotic Drugs Although, these novel antimitotic drugs have very significant role in inhibition of mitosis, they are facing many problems during their developments. Their appropriate ways, potential to reduce toxicities, activities, safety profile, and efficacy are some promising questions are yet to be solved. These agents have reduced risk of neurotoxicity, which is proved in clinic, but they also have dose limiting toxicities like neutropenia with relative sparing of the other haematopoietic lineages. So it will be difficult to tell yet that they have potential [41]. Another challenge was that, there was no clear perceptive between inhibition of respective mitotic target and cell death. Because they have mechanism of action is to arrest mitosis but whether this mitosis arrest initiate by activating by mitotic checkpoint or it is followed by mitotic slippage for further cell death. To identify the patients who are best responding to these agents is also a challenge in developments in theses agents. In addition to that, during clinical development, it is difficult to develop surrogate tissue to check the pharmacodynemic responses of these drugs because targets of these agent, was absent in most of them [42]. Along with pharmacodynemic effects, duration of such effect both is also crucial determinants for apoptosis. Therapeutic window can be calculated by evaluation of tumour markers at maximum tolerated dose (MTD) or below the MTD if possible but this might be achieved by incorporation of serial tumour biopsies was uniquely challenging. In addition to, which schedules would be sufficiently discover pharmacodynemic and pharmacokinetic data was difficult [43]. Considerable steps have already come in to view, to overcome these limitations and evade toxic side effects, produced by these agents. Such steps make two different types of practices; they are prodrugs and drug targeting methods. During these practices both methods led to increase some of biochemical properties along with pharmacokinetic and pharmacodynemic effects. Prodrug Prodrugs are chemically modified versions of pharmacologically active agents that must undergo transformation in vivo to release the active drug. The prodrug is administered in an inactive or significantly less active form. The use of prodrugs is generally established as a strategy to improve the physicochemical, biopharma-ceutical or pharmacokinetic properties of pharmacologically potent agents, and thereby increase the develop ability and usefulness of a potential drug [6]. Antimitotic Prodrugs which are in Use or Developing The following are the antimitotic prodrugs which try to develop to overcome these limitation associated with specific antimitotic drugs like Vinca alkaloids, Texans, Cochicines and phodopyllotoxins. A) Hydrolytically Activated Paclitaxel Prodrug Paclitaxel is well using in diseases like ovarian cancer, breast cancer and lung cancer but it has limitation like low water solubility, less effective, drug resistance and some effects. At high dose it produces hypersensitive reactions, hematologic toxicity, and neurotoxicity. It also limited by granulocyte colony-stimulating factors dependent neutropenia. It has dose dependent neurotoxicity expressed by loss of sensation [44]. Adapt from [44] By masking position7 hydroxyl group of paclitaxel with hydrophilic side chain (*) and resulted 7-(2, 3-dihydroxypropyl carbonoxy) paclitaxel is biologically inert and is activated at low pH conditions by hydrolytic cleavage of the carbamate linkage, obtaining active paclitaxel, dihydroxy propanol, and CO2 [44]. Following are the results obtained by analysing paclitaxel prodrug. Figure, (A) Figure, (B) Table 1, Figure A and Figure B, Adapt from [44]. Table 1 is hydrolytic activation of paclitaxel prodrug in vivo, indicating decrease in prodrug and increase in active drug. Figure (A), for conversion to active paclitaxel in vivo, indicating peak plasma concentrations were observed at 3 hours for paclitaxel prodrug (P1) and at 6 hours for active paclitaxel (P2), for 1 patient. Figure (B), for activation of paclitaxel in vivo, demonstrates the slow-release mechanism in vivo, for 5 pateints [44]. B) First enzymatically activated Taxotere Prodrugs Designed for ADEPT (Antibody Directed Enzyme Prodrug Therapy) and PMT (Prodrug Mono Therapy) Paclitaxel and its semi synthetic analogue docetaxel is essential drugs in the treatment of cancer as antimitotic drugs. There is slight difference between them is substitution at 3- nitrogen on the side chain and the 10-posititon of the taxoid core. They have high potency to solid tumour but they have number of undesirable side effects and poorer water solubility and also with detergent they initiate hypersensitivity reaction on body. These drugs delivery have evaluated on enzymatic hydrolysis in ADEPT (Antibody Directed Enzyme Prodrug Therapy) and PMT (Prodrug Mono Therapy).The two docetaxel prodrugs in figure A have synthesised with glucuronic moiety is linked to a double spacer. Para hydroxyl bezyle alcohol connected to diamer tether through a carbamate linkage in this spacer. This complex was shown to be more potent and labrets drugs in the presence of ÃŽÂ ²-Dglucuronidase enzyme in ADPET and PMT therapy [45]. Figure A, structure of scheme 2 and scheme 3 (Prodrug 4), scheme 2 and scheme 4 (Prodrug 5) and Prodrug 3 Adapt from [45] Following are the results by the comparison of these two drugs. Both of prodrugs have 24 hr-run of stability and there was no release from the prodrug during this time. Table 1 showed that these two prodrugs have compatible IC 50 values for the ADEPT and PMT strategy. Figure A and figure B showed that, during HPLC detection, prodrug level decreased until finished and spacer and parent drug, docetaxel, reached at area of stability [45]. Table 1, measured for L1210 cell lines were (HPLC): Prodrug, Scheme 2 and scheme 3 : 4.86 uM Docetaxel : 14. 4 uM Spacer: 75.3uM Prodrug, Scheme 2 and scheme 4: 2.69 uM Spacer:45.8uM Figure A, Comparison of the disappearance of the three prodrugs. Figure B, Enzymatic cleavage of prodrug 5 Figure 2, Scheme 2 and Scheme 4. Table 1, Figure A and Figure B adapt from [45]. C) Zyn-Linked colchicines: Controlled-release lipophilic prodrugs With enhanced antitumor efficacy Zyn-linked drug have rapid binding property to cell membrane. These Zyn-linkers prolong their binding and preservation in tissues, make sense to produce Zyn-linkers conjugates those who have better local delivery of therapeutics. Colchicine has chosen for these studies because this drug and its analogues are still under examination. Five Zyn linked colchicine analogues with either cleavable hydrazone or imine bonds, have synthesised and evaluated their stability ,cytotoxicity and antitumour activity [46]. Fig.1. Structures of colchicine and modifications to form the analogues for Zyn-Linking are shown. Fig. 2.Structures of the Zyn-Linkers modified for attachment of the colchicine analogues. Fig.3. Structures of Zyn-Linker conjugates are shown with the bonds subject to hydrolysis indicated by an arrow: (a) hydrazones conjugates linked at the B-ring of the colchincine moiety, (b) imine conjugate, and (c) hydrazones conjugate linked at the A ring of the colchicine moiety. Figure 1, 2 and 3, adapt from [46] Following are the results for their relationship among different properties. Table 1 Table2 Table3 Table 1, 2 and 3, adapt from [46] Table 1 showed that, ZYN 162 and PKH 158 at pH 7.2, are two potential products and out of them one is expected and one is unidentified products. Table 2 showed that, 80% to less than 1%, was range of therapeutic and unhydrolysed conjugated, was inactive. Zyn-linkers had no antimitotic activity; on the other hand, drug or Zyn-linked drugs were active. Table 3 showed that, with 4-formayl group thiocolchicine have reduced their toxicities and enhanced therapeutic activity [46]. D) Preparation, characterization, cytotoxicity and pharmacokinetics Of liposome containing water-soluble prodrugs of paclitaxel Paclitaxel have antimitotic effect against the various cancers like breast cancer, ovarian cancer, head and neck cancers. Due to its aqueous insolubility, it was dissolving in the mixture of 50 % Ethanol and 50 % Cremopher EL (caster oil). Neurotoxicity and hypersensitivity are side effects of this Cremopher. So to reduce this side effect and to enhance the drug entrapment in liposome with better aqueous solubility, three prodrugs and prodrugs liposome formulations have synthesised and evaluated their pharmacokinetic parameter, stability and antitumor activity with parent drug [47]. Following are the results obtained during comparison in stability, cytitoxicity and pharmacokinetic property of drug, prodrugs and their prodrug liposome. 1) Stability Table1 Table 2 Figure 1, 2 and 3, Table 1 and 2, adapt from [47] Figure 2 and 3 showed that, by the changing the property like diameter, membrane fluidity and charge, liposome containing 2-mPEG-paclitaxel composed of PC-PG-CHOL 9:1:5 showed better stability more than 2 months and good entrapment ability. Table 1 and 2 showed that, in vitro cytotoxic effects of liposome containing compound 3 and 4 on two cell line, HT-29 and MeWo, maintained, but rapidly hydrolysed and giving free parent drugs, while liposome loaded paclitaxel-2succinyl had more resistance to hydrolysed. 2-PEG-paclitaxel also had ability to make difference in pharmacokinetic parameters as compare to free drug [47]. D) Synthesis and evaluation of water-soluble docetaxel prodrugs- Docetaxel esters of malic acid. Paclitaxel and docetaxel are semi synthetic analogues widely used for various cancers. But water solubility is major limitation for these drug and to come over from this limitation, at C20, C7 -or/and C10 position several research group introduced solubilising moieties [48]. Figure A Figure A, table 1 and table 2, adapt from [48] Figure A, table 1 and table 2 showed that, 20-DLmalyl docetaxel sodium salt 3a come out with excellent water solubility, more active than docetaxel in vitro and antitumor activity in vivo [48]. E) Synthesis of Water Soluble Prodrugs of the Cytotoxic Agent Combertastatin A4 Combertastatin A4 has structure similar to colchicine. It is an inhibitor of tubulin polymerisation to stop proliferation of cells. Although, this drug has potential for antimitotic activity, it is soluble in the few pharmaceutically accepted solvents. Synthesis of water soluble glycosides of combertastatin A4, have conducted by make modification by hydroxyl function. To increase the yield, they have reversed the components of the Witting reaction [49]. Adapt from [49] The ammonium salt have prepared and converted into potassium salt to make crystal form. This ammonium salt was more stable in buffer solution and degraded slowly in plasma at 37 C when incubated with acid phosphates and alkaline phosphatise [49]. F) Prodrugs of 40-Demethyl-4-deoxypodophyllotoxin: Synthesis and Evaluation of the Antitumor Activity 4-Deoxypodophyllotoxin (DPT) and 4-demethyl-4-deoxypodophyllotoxin (DDPT) have comparable in vitro potency against different cell lines but free hydroxyl group at 4 position in structure of DDPT loss its in vivo antitumor activity against BDF1/3LL model. Replacing this free group by bioreversible functionality might improve in vivo activity. For that series of prodrugs have synthesised and evaluated their cytotoxic and antitumor activities [50]. Following are the results obtained during studies. Adapt from [50]. Table showed that 10 and 11 derivatives were properly transferred in to parent drug 2 but weak in vivo activity and 6 derivative showed IR of 95% of antitumor activity. The carbamates and carbonates of two compounds, 6 and 9, showed potent antitumor activity, might be by intermolecular cyclic rearrangements of hydroxyl side chain. Moreover, amino acid prodrugs, 12 to 17, demonstrated better water solubility and potent antitumor activity [50]. Discussion Presently the antimitotics prodrugs are novel compounds and hold many promises and may have abilities to improve the drawbacks of anti tubuline or specific protein inhibitors, which are regulating the cell cycle, demonstrated by clinical data. With observations to clinical activity, it is too premature to tell for most of the agents in development. There are number of prodrugs have been developing and some have evaluated in laboratory. Antimitotic prodrugs may improve limitations of these drugs during in vitro and in vivo studies but there are still need more information about clinical phase trails by using number of patients, to these prodrugs. In particular, hydrolytically activated paclitaxel prodrug has decreases toxicity in vivo and produced better responses in patients with end stage in cancer. Serum half- life also dramatically increased with maximum plasma concentration, in vivo, but more studies require about responses in phase III trails, as it was evaluated in 10 patients. Moreover, information needed about, high concentration expose to tumour tissue for critical time, as significant G2M phase arrest is primary mechanism of action. First prodrugs of docetaxel have synthesised for the ADPET (Antibody Directed Enzyme Prodrug Therapy) and PMT (Prodrug Mono Therapy) strategies. Spacer have nitro group on the aromatic ring. In the hydrogenesis step it could be preserved which is not seen in the previous paclitaxel prodrugs. This nitro and amino groups containing prodrugs have expressed good kinetics and enzymatic hydrolysis in particular cell line, but more information needed about self immolative spacer for its effects on the paclitaxel on various cell lines. This issue need more clarification prior to clinical trails in malignancy models. Four conjugates of Zyn-linked colchicine have hydro linkage, imine bond in spacer arms, colchicines moiet

Charater of Sydney Carton in A Tale of Two Cities :: Tale Two Cities Essays

Charater of Sydney Carton in A Tale of Two Cities    Sydney Carton, one of the main characters of the book, A Tale of Two Cities, is a drunken lawyer who works with Stryver on the trial of Charles Darnay.he doesnt care about anything. At first this man seems as if he is a lazy, good for nothing, alcoholic. he tells Lucie Manette he doesn't believe that his life is worth anything and feels as if it is pointless to even live anymore. When you first meet him during the court scene it looks as if he just rolled out of bed and was dragged to the courtroom. This one man sat leaning back, with his torn gown half off him, his untidy wig put on just sat it had happened to light on his head after it's removal, his hands in his pockets, and his eyes on the ceiling as they had been all day. Something especially reckless in his demeanor not only gave him a disreputable look, but so diminished the strong resemblance he undoubtedly bore to the prisoner. However after he meets Lucie he falls madly in love for her. This marks a period of ch ange for Sydney Carton. But he then knows that Charles Darnay is going to be married to her. He sill believes that his life is worthless but it seems as if he's a bit more willing to work and to do things for other people.    Towards the middle of the book, A Tale of Two Cities, Carton professes his love for Lucie and he says For you, and for any dear to you, I would do anything. I would embrace any sacrifice for you and for those dear to you. And when you see your own bright beauty springing up anew at your feet, think now and then that there is a man who would give his life, to keep a life you love beside you. He means that he would do anything for her, because he loves her so very much. He tells Josh Barsad that he is going to marry miss Manette, but then he backs out of it.    At the very end of the novel you find out that Carton is about to go to the guillotine, but not for him.

Ozzie Freedman Portrayed as a Hero Essay example -- essays research pa

Ozzie Freedman Portrayed as a Hero   Ã‚  Ã‚  Ã‚  Ã‚  A hero can be defined as one who inspires through manners and actions; who leads through personal example. Under this definition, the character Ozzie Freedman from Philip Roth’s â€Å"The Conversion of the Jews† (1959) can be classified as a hero. The sections of Discoveries: Fifty Stories of the Quest (Schechter & Semekis 1992): The Call, The Other, The Journey, Helpers and Guides, The Treasure, and Transformation, can be applied to the story about Ozzie to support it’s inclusion in this class, entitled â€Å"Myth of the Hero†.   Ã‚  Ã‚  Ã‚  Ã‚  The chapter on The Call describes that a hero may be â€Å"on the brink of a decisive change† (21) and they â€Å"perceive the danger of remaining where they are† (22). The hero must be â€Å"ready †¦ to leave [his] old, familiar [life] behind and move on to something new† (23). In â€Å"The Conversion of the Jews†, we see Ozzie questioning his faith and going against the Jewish teaching by believing that God could â€Å"let a woman have a baby without having intercourse† (384). He stood up to the rabbi in class and was prepared to defend his questioning and beliefs.   Ã‚  Ã‚  Ã‚  Ã‚  The Other is a character who embodies the exact opposite personality of the protagonist. According to Schechter & Semekis, the Other causes self-revelation in the protagonist, which his journey would not begin without. In Roth’s story, Itzie is Ozzie’s best friend, who does not question authority or his faith, quite the opposite of Ozzie. He gives Ozzie a hard time for always asking questions and speaking out in class. (‘â€Å"What do you open your mouth all the time for?†Ã¢â‚¬â„¢ (383)). Ozzie realizes he doesn’t want to be like Itzie and blindly accept the Jewish belief about Jesus. He defends his right to question something in order to seek validity, and says, ‘â€Å"Itz, I thought it over for a solid hour, and now I’m convinced God could do it.†Ã¢â‚¬â„¢   Ã‚  Ã‚  Ã‚  Ã‚  Discoveries describes The Journey as a portrayal of â€Å"how difficult the hero’s quest is† (8). In Roth’s story, Ozzie faces â€Å"external enemies, agents of conservatism or conformity that must be overcome† (Schechter & Semekis, 8). He is speaking out against the Jewish religion, saying that he believes God could impregnate a woman without her having intercourse. When he delivers this defiance to Rabbi Binder, he is... ...nbsp;  Ã‚  Ã‚  Ã‚  By applying the theory of the hero’s journey as found in Discoveries: Fifty Stories of the Quest and applying it to Roth’s â€Å"The Conversion of the Jews†, we see that the character Ozzie Freedman truly fits the title of a hero. Ozzie questions his religious beliefs and is not ashamed to bring forth his insight and seek answers and new ways of thinking. He winds up teaching his mentor a lesson in religion and sets out to have his message heard, despite the possibility of ridicule and even death. Once he realizes he has a different belief than the people of the Jewish religion, he understands his life will never be the same and that he cannot go back to the Jewish belief that God is not able to produce a child without intercourse. Ozzie gets his message across, that one should never be punished for his beliefs, and he is then born into a new day and a new life journey. Works Cited Roth, Philip. â€Å"The Conversion of the Jews.† Discoveries: Fifty Stories of the Quest. 2nd ed. Harold Schechter and Jonna Gormely Semekis. New York: Oxford, 1992. Schechter, Harold, and Jonna Gormely Semekis. Discoveries: Fifty Stories of the Quest. 2nd ed. New York: Oxford, 1992.

Ethics in Criminal Justice Professions Essay -- Criminal Justice Ethic

Criminal Justice professionals make decisions everyday and they have to be able to recognize when an issue involves ethical considerations. Therefore, in order to recognize these issues and make appropriate and correct decisions, it is important that the criminal justice professional study ethics. In order to make a good ethical decision the professional will have to have the ability to apply knowledge of ethics, know the ethical terminology and the concepts needed in making a good ethical decision. Criminal Justice professionals are in positions of power and exercise power and authority over others. Therefore, it is important for them to study ethics because they must be aware of the ethical standards needed in making critical decisions involving discretion, force, and due process. It is also a fact that criminal justice professionals who exercise power and authority over others can be tempted to abuse their powers. Police decisions can affect life, liberty, and property, and as guardians of the interests of the public, police must maintain high standards of integrity. Police discretion concerning how to act in a given situation can often lead to ethical misconduct (Banks 29). It is also important for criminal justice professionals to study ethics, as ethics is important in criminal justice policy making. These professionals are in a position to make choices and analyze options in order to make decisions that affects the lives of many people. Professionals who formulate policies should act ethically and they have to realize the ethical responsibility in making policies especially when it comes to punishment. These professionals need to know how unethical and ethical policy-making decisions differ in how it affects those ... ...f nothing and therefore ethics â€Å"cannot be taught,† but since 99.9 percent of business and criminal justice professionals have a conscience, it is possible to teach and learn ethics (Perry). Works Cited Banks, Cyndi. Criminal Justice Ethics: Theory and Practice. 3rd ed. Thousand Oaks: Sage, 2009. Print. Felkenes, George. "Ethics in the Graduate Criminal Justice Curriculum." Teaching Philosophy 10. (1987): 23-26. eBook. Mills, Karen. "Can Ethics be Taught?" Oct. 2010. Arizona Department of Transportation. 02 Dec. 2010 . Perry, David L. "Can Business Ethics Be Taught?" Mar. 1994. Teaching Business Ethics. 03 Dec. 2010. . Pollock, Joycelyn M. Ethical Dilemmas and Decisions in Criminal Justice. Belmont: Wadsworth, 2010. Print.

Patient Education

Psychosocial Factors and Patient Education 09 Oct 11 Zahava Ohana Homework Week Two (1) Give examples of psychosocial factors that affect the health care professional and the effect those factors could have on the patient education; Patient’s background. For example, that patient came from a background that does not believe on any medicines. They go to a â€Å"voodoo doctor† for some spiritual interventions and they are content on that. Because they are not too well educated or maybe it is their first time being seen in a medical treatment facility. This is will leave a lot of patience on the patient care professional and have way of approach how to convince that patient to be compliant by gathering more information on why this patient don’t believe in taking medications. (2) Give examples of psychosocial factors that affect the patient and the effect those factors could have on patient education; I only have an example of psychosocial factors that affect the patient and the effect those factors on patient education are his or her previous experiences. For example, this patient had been treated horribly on his past visit for PTSD. We know this kind of problem or disorder is very important. Especially to a military that were â€Å"blown up†. This type of patients needs extra assistance and a careful note taking. Guiding him to the right person and always reinforced by a good patient education. By showing them, you care and always ready for them. This will make his previous experiences is outdated†. Because, you took the time and showing the patient by explaining the necessary things that he will be going during his next visits. (3) Explain what is meant by personality styles and give examples of approaches that could be used to help the patient. Include self-perfection as a factor; This is the patients or individual lifetime fingerprint or history. Since childbirth, every human being is already being mold in types of personality styles. One is introvert or extrovert. One is made by thinking and the other is feeling. Example a Marine that has a high pain tolerance. When he presents himself at sickbay, he seems fine and not distressed. Because through his time he learned how to block the pain and keep going. This approach will be tough at times because he tell you the only reason he came to sickbay is my boss ordered me to seek medical help. This is so common in the military not showing the true self because the failure of not an option. A good subjective note will determine on how bad his injury is. After his medical examination a good concise and list of things on how to take medication he was prescribe, a physical therapy appointments that need to be present on all his appointments. In addition, informing his superiors regarding his conditions. (4) List the steps in adjustment to illness and how the patient copes with each of the steps; Denial is one of the steps in adjustments to illness. For instance, a patient was diagnosed with lung cancer. That patient will go to all the stages first will be denial, ‘this can’t be†, next will be anger, â€Å"why this happened to me now’, bargaining is next, â€Å"I will be a good person and hope this cancer goes away†, next is depression, that patient will stop caring and last one is acceptance, he is ready and understand why it happened. This step depends on how the patient will cope on this step. He can go straight acceptance. It is very hard to understand denials. Compensatory strategies for example a patient is so good in playing sports like basketball after an uneventful tragedy the patient was injured and ended up his basketball career. Nevertheless, his passion in basketball he ended using his talent by coaching young kids to be a good player. This is how he copes by helping and sharing all his ideas and skills on how to be the best and dominant individual in the court. (5) explain the health professional’s role in teaching the patient at different life stages; The health professional’s role in teaching at different life stages is very challenging and rewarding. It should be approach on patient’s level not at health professional. Patients are not taught all the fancy medical terminologies. However, we are taught these terminologies to apply it in our notes. The patient relays to you the problem and the health professional translate to our medical notes and convey it to the medical providers. It should not matter if we are dealing with a toddler or a geriatric. Because it how the health professional handles and delivers. All stages should be treated the same. Patient education will be taught or relay to the patient in trusting and clear instructions and always have a time of asking. Either the patient ask the health professional ask first the questions or you ask the question if there is a need of clarification. This is what I have been doing when I approach a patient. I get on my knees or sit right next to them. Asking the pertinent questions and before they leave the medical facility. I proudly and confident ask if they need some assistance in getting to their car or escorting them to their love ones and If the patient is able enough I explained to the patient all the important things along with their relatives. 6) define the role of the family in patient education; The role of the family in patient education plays a major part. As we all know family support systems is either good or bad. Sometimes, a decision of a family member can result to a life-altering event towards patient’s recovery or vice versa. This also includes their beliefs if they need to continue to support what the health professional instructions or just go with belief not seek further medical treatment because it is not their belief or they are fully convinced by the health professional’s patient education. Nevertheless, if a family supports and follows the instructions from the health professional it lessens our burden or task in hand. Because we have these supporting group that is willingly to assist you especially when saw your confidence, trust and motivation. (7) How might the family influence the compliance of the patient and what measures can the health care professional use in communication with the family; The family can influence the patient compliance in many ways. The eagerness of the family in helping their sick love ones to the path of recovery. Because the family believes the health professional’s explanation was clear and open of all question and suggestion. The best measure use in the communication is one on one with the patient’s family. Explaining to them all the procedures, what to expect after the procedures, the medications that will be prescribe to the patient and how to assist the patient in day-to-day task. Following it up by appointments and reminding them a day prior of the follow up appointments. Psychosocial factors and patient education will always come in hand to hand. It is how the health professional approach a patient in different stages. â€Å"Adaptable and overcome’. This is what I was been taught and learned when I was in military for 20 years. Always on the ready to any things that comes to you. References 1) Text: Falvo, Chapters 4 – 6 2) Module Two; Lecture Two 3) Eberle, C. (n. d. ) Illness behavior in the elderly. University of Nebraska Medical Center. Retrieved July 5, 2007, from http:// webmedia. unmc. edu/intmed/geriatrics/lectures/ill_behv2_03_files/outline. htm