Research+Log+Page

[I saw that you tried to copy this over but ran into problems. The easiest way is to hit edit - then text editor and copy all the wikitext - then paste this in the text editor of the new page JCB]
 * Erica Frankel Log**
 * [You need to create a page called "Erica Frankel Log" - since we can't rename pages just copy this and paste it on the new page and I'll delete this one JCB]

November 29,2009 Just keeping track of more of the sites I have been using to find my information [|Cypher Stent] [|Boston Scientific] [|Abbott]  [|Sirolimus Eluting Stents] November 23, 2009 Starting to write my paper today and needed more sources about the general information of Sirolimus. Below are some links I have found. [|NIH Information] **[] [] November 10, 2009 I just started to look at PubMed and PubChem and have found a wealth of resources to use in my paper. I have been previously been looking strictly at chemistry resources, but have found that medicinal journals provide a great amount of knowledge with regards to sirolimus and it's applications, far more than I was even aware of. I still have to filter through many of the results I have found and will soon add the links to the papers I will most likely use.
 * [|FDA-immunosuppressive medications]

October 30, 2009 It was very hard to find resources with the same properties listed. Due to the complexity of the compound, finding resources that contained properties were fairly difficult. Properties of Sirolimus ** [|Cell Signal] MW: 914.19g/mol Formula: Formula:C 51 H 79 NO 13 MP: 173-187 °C Solubility:Not soluble in water, soluble in water, DMSO Appearance: white to off white powder State at room temp: solid [|LC Labs] MW: 914.17 g/mol Formula: C 51 H 79 NO 13 MP: 173-187 °C Solubility: not soluble in water, soluble in methanol and DMSO Appearance: White to off white powder Form at room temperature: solid [|Fermentek Biotechnology] MW: 914.2 g/mol Formula: C 51 H 79 NO 13 MP: 178°C-182°C Solubility: Soluble in DMSO, methanol Appearance: Off white to yellow powder State at room temperature: Solid [|AG Scientific] MW: 914.2g/mol Formula: C51H79NO13 MP: 183-185°C Solubility: Soluble in DMSO, methanol Appearance: yellow powder State at room temperature: Solid [|Chemical Book] MW: 914.19 g/mol Formula: C51H79NO13 MP: 183 - 184 °C Density: 1.18g/cm3 Solubility: Insoluble in water Appearance: white to off white powder State at room temperature: solid MW: 914.17186 (g/mol) Formula: C 51 H 79 NO 13 H-Bond Donor: 3 H-Bond Acceptor: 13 [|Wikipedia] MW : 914.172 g/mol Formula: C 51 H 79 NO 13 Half Life: 57-63 hours [|Chemspider] MW: 914.1719 g/mol Formula:C 51 H 79 NO 13 Density: 1.18g/cm3 H-Bond Donor: 3 H-Bond Acceptor:14
 * Other properties from different sources**
 * [|PubChem Link] **

October 17,2009 Summarization of Article =[Full Marks JCB]=

[]
Immunotherapy has come a long way in recent years with regards to organ transplants. Various immunosuppressants are now used in the treatment against t The rejection of organ transplants as well as decreasing any toxic side effects. The article reviews immunosuppressents which are on the market now or in clinical trials. Case studies and other clinical trial articles were searched using various key words. The manufactures of both MMF and rapamycin were contacted directly to gain any more revelent unpublished information. MMF is produced from a derivative of the Penicillin mold, and is shown to reduce the amount of transplant rejections. It targets the lymphocytes and inhibits the production of purine. The infection CMV was seen more so in patients receiving MMF after transplants than those whom took azathioprine. There were also increased cases of patients having gastrointestinal side effects because of treatment with MMF. The way in which MMF induces CMV infection includes the depletion of guanosine triphostphate in the lymphocytes, which in turn decreases the proliferation. In addition to CMV infection, MMF was seen to cause a type of herpes viral infection in patients having had renal and heart transplants. In those having had a heart or liver transplant, there were increased incidents of Hepititis B and C infections. The MMF had no effect on the severity of the Hepetitis infection itself. At concentrations lower than used to treat organ-tranplant patients, MMF is seen to be effective against HIV type 1. Using MMF in the treatment of HIV patients is being studied. Unlike the cases where CMV infection occured from treatment with MMF, no patients were seen to develop the P.Carinii infection. This is mainly due to MMF's ability to inhibit one of the monophosphate groups in the P.carinii. MMF is metabolized before treatment of the specific area of organ transplant. There was no difference in effectiveness in patients who were on dialysis compared to healthy patients. There was no clinical significance seen in healthy patients when MMF was administered along with acyclovir. There has been no reported interactions between MMF and other drugs including lactam antibiotics, antifungal agents, glycopeptides and other inhibitors. Rapamycin works by targeting mTOR, which inhibits the translation process of mRNA to DNA, needed for cell division. The cell cycle is halted because of this. Rapamycin has been used in conjunction with cyclosporine in an effort to reduce the amount of CMV infection cases. Herpes-zoster cases have also been seen in patients who have been treated with Rapamycin. Rapamycin has the ability to inhibit fungal activity in //in vitro// studies. There are a wide range of fungi which Rapamycin acts against. Because rapamycin is a substrate for cytochrome P-450 and P-glycoprotiens, metabolism rates may decrease causing the incidental increase in Rapamycin levels. Rapamycin is just one derivative of many macrolide antibiotics. The various derivatives inhibit different cytochrome and glycoprotein groups. Rifampin increases metabolism rates which have the ability to lower rapamycin levels in the body. Other azole antifungal agents also inhibit cytochrome P-3A4 which may increase the levels of Rapamycin. Because of this, it is important to monitor Rapamycin levels if these agents are used in conjuction. Everolimus is a derivative of Rapamycin with a shorter half-life. In cases where Everolimus was used in patients, only 3% contracted the CMV infection compared to those whom received MMF. Everolimus was also shown to have activity against the proliferation of tumors. Caustic and fatal infections were seen to arise in patients treated with earlier monoclonal antibodies. In order to prevent this, antibodies working against IL-2R should be used as an effective immunosuppressive treatment. Although basiliximab has not been seen to have any efficacy for immunosuppressive treatment in kidney transplant patients, it was shown to work against the proliferation of the CMV infection, Furthermore, patients treated with basiliximab showed to have lower rates of Herpes related virus after transplant. Basiliximab and the corresponding derivation daclizumab have not shown to have any effect on the HCV infection. There has been no documented information regarding whether basiliximab or daclizumab have any effect on the prevention of fungal activity. Immunosuppressive drugs are useful in treating major infections and preventing organ transplant rejection. In the future, immunosuppressive drugs may be able to treat infections at a highly specific location with minimal side effects.
 * The Impact of Novel Immunosuppressive Agents on Infections in Organ Transplant Recipients and the Interactions of These Agents with Antimicrobials**
 * Introduction**
 * Methods**
 * MMF**
 * Rapamycin**
 * Everolimus**
 * Monoclonal Antibodies**
 * Conclusions**

October 15, 2009 Went on the Wyeth website, which is the producer of sirolimus, to get the drug facts. []

I searched on JSTOR to find some articles involving sirolimus/rapamycin's activity within the body. I found five articles that either use mice or humans and discuss the various affects rapamycin has. I exported the articles into my refworks account **[You need to put links to the DOIs of these articles - I can't access them this way JCB]**

1) Rapamycin Is Active against B-Precursor Leukemia in vitro and in vivo, an Effect That Is Modulated by IL-7-Mediated Signaling. [|Brown, Valerie I.]; [|Fang, Junjie]; [|Alcorn, Keith]; [|Barr, Rosalind]; [|Kim, Jenny M.]; [|Wasserman, Robert]; [|Grupp, Stephan A.] []

2) Targets for Cell Cycle Arrest by the Immunosuppressant Rapamycin in Yeast [|Heitman, Joseph]; [|Movva, N. Rao]; [|Hall, Michael N.][|Science], 1991, 253, 5022, 905-909, American Association for the Advancement of Science. [|Proc. Natl. Acad. Sci. U. S. A.], 2003, 100, 25, 15113-15118, National Academy of Sciences []

3) Invasive Aspergillosis in Mice Immunosuppressed with Cyclosporin A, Tacrolimus (FK506), or Sirolimus (Rapamycin) [|High, Kevin P.]; [|Washburn, Ronald G.][|J. Infect. Dis.], 1997, 175, 1, 222-225, The University of Chicago Press []

4) The Impact of Novel Immunosuppressive Agents on Infections in Organ Transplant Recipients and the Interactions of These Agents with Antimicrobials,[|Husain, Shahid]; [|Singh, Nina].[|Clinical Infectious Diseases], 2002, 35, 1, 53-61, The University of Chicago Press []

5) The Target of Rapamycin (TOR) Proteins. [|Raught, Brian]; [|Gingras, Anne-Claude]; [|Sonenberg, Nahum][|Proc. Natl. Acad. Sci. U. S. A.], 2001, 98, 13, 7037-7044, National Academy of Science []

Peggy Dominy's lecture was very informative. I have used many of her suggested references previously, such as Illiad and science direct. The most helpful part of her lecture was her introduction of RefWorks, which I will be using now to compile my bibliographies. It formats the references in the correct way, saving time.
 * October 8, 2009**

Went on scifinder today so start investigating topics of discussion, perhaps looking at patents will be the most efficient way of getting synthesis of rapamycin and any close derivatives. I found one patent on the synthesis of rapamycin, filed in 1999. U.S. 8 pp., Cont.-in-part of U.S. Ser. No. 926,251. Patent 1999 CODEN: USXXAM Wyeth is the owner of the drug; I will also research the topic rapamycin synthesis with Wyeth's name included in the search Tentative topics of discussion for paper: -Introduction to anti-inflammatory drugs -discovery history -Sirolimus (rapamycin) and its derivatives -Synthesis and production of rapamycin and corresponding derivatives -mechanism of synthesis -Use in medical devices, examples -Mechanism of action -associated biomolecules attacked -Any other uses for rapamycin -Conclusions -Perhaps a multimedia project showing slideshow of rapamycin's interaction with biomolecules in vitro Just searching around for alittle and thought wikipedia would be a go starting point. I will also look in Scifinder under "sirolimus" or "rapamycin"and see what I find there. http://en.wikipedia.org/wiki/Sirolimus
 * October 4, 2009**
 * http://jra.sagepub.com/cgi/content/abstract/10/2/91-**an article based on the comparison of sirolimus coated stent with another drug known as valsartan
 * October 3, 2009**
 * October 1, 2009**

I have still been thinking about what I would like to research for my final product. Having worked with medical devices on my past co-op, the theme is readily in my mind and seems to be of growing importance in the medical world. Specifically, studying the use of rapamycin in organ and tissue transplants. Furthermore, rapamycin is used in various stents to prevent inflammation in arteries after surgery. -Could go into detail of anti-inflammatory functions in the body as well as present the mechanism for which it works **[The mechanism of action would be excellent - you'll need to identify the biomolecules involved and some analogues JCB]** -Mention the different uses of the drug -Any derivatives of the drug that may perform similarly in vitro, also any differences
 * September 30, 2009**

September 24, 2009 First Class today. Went over syllabus and multimedia options for use in final project. I have no clue what to research for my project. I am thinking of looking at the application of older drugs for the use in medical devices.