By Ishaq Lat, PharmD Chair, Membership Committee ; and Chris Scott, PharmD Chair-elect, Membership Committee ; The Membership Committee is in the process of identifying interested members for the Mentor and Mentee M&M ; Program. This year we are looking to build on the initial success of the program by matching more members. The M&M Program is designed to provide critical care pharmacists with guidance in their professional growth and is open to all members. The program serves an important role within the CPP section by offering participants a means to attain counsel and support through interaction that fosters excellence in clinical practice, research, teaching, and SCCM CPP involvement. Based on a brief demographic request form and or stated preference, an interested individual will be matched with a mentor from a pool of volunteers. PGY-2 program directors are encouraged to inform their residents in training of this opportunity as they progress in their career paths. If you are interested in serving as either a mentor or mentee, please email Ishaq Lat, PharmD, at ishaq.lat uchospitals or Chris Scott, PharmD, at cmscott purdue.
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Central neuronal system pathology. In multiple sclerosis MS ; the mechanism of demyelination may involve the cooperation of the immune system and free radical generating system of oligodendrocytes. Since myelin is enriched with iron, thus, demyelination will expose iron and supply the necessary substrates for iron catalyzed hydroxyl radical attack, which leads to various lipid peroxidation products including isoprostanes.57, 58 Greco et al59 in 1999 proved that lipid peroxidation occurs in MS brain in vivo. They measured CSF -epi-PGF2 in subjects with definite MS, and found that the level of CSF -epi-PGF2 was 3 times higher than in patients with other noninflammatory neurological diseases, or in nonneurological patients undergoing subdural anesthesia.59 It is worth mentioning that increased level of lipid peroxidation in MS patients occurs also at the erythrocyte level.60 In addition glutathione peroxidase activity was found decreased in MS patients.61, 62 A more recent study showed a significant reduction in plasma and lymphocytes ubiquinone, plasma vitamin E, and erythrocyte glutathione peroxidase. In MS patients, blood antioxidant deficiency was associated with significantly higher levels of plasma polyunsaturated fatty acids. They concluded that the blood of patients with MS shows signs of significant oxidative stress. They also suggested, the possibility of counteracting it by antioxidant administration plus an appropriate diet.63 But there is controversy regarding levels of glutathione peroxidase. A more recent study conducted on MS patients in the active phase by using antibody-based enzyme immuno-assay on serum samples, showed increased levels of glutathione peroxidase in the active phase compared to those in non active phase of MS and controls.64 They suggested that these enzymes reflect the activity of the defense of MS. In addition, iron metabolism plays a role in the pathogenesis of MS, Zeman et al65 demonstrated a lower level of transferrin among relapsing remitting, secondary progressive and primary progressive MS.65 A recent study conducted in Boston, United States of America found no association between intake of fruits and vegetables and risk of MS. They concluded that use of vitamin C, vitamin E and multivitamin supplements were unrelated to risk of MS. 66 In conclusion, it is quite clear that there is considerable evidence to support a role for oxidative stress as a pathological cause in a number of neurodegenerative disorders. Free radicals may be part of a cascade, which characterizes neuronal cell death and may provide a biochemical tool by which the pathological process can be inhibited. More studies on the action of ROS and their sources may lead to a better understanding of the basis of neurodegenerative diseases and to the development of appropriate therapeutic agents.
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71 ; BOEHRINGER INGELHEIM PHARMACEUTICALS, INC. [US US]; 900 Ridgebury Road, Ridgefield, CT 06877 US ; . 72 ; BETAGERI, Rajashehar; 62 Redwood Drive, Bethel, CT 06801 US ; . BREITFELDER, Steffen; 93 Park Avenue, #1305, Danbury, CT 06810 US ; . CIRILLO, Pier, F.; 180 Washington Road, Woodbury, CT 06798 US ; . GILMORE, Thomas, A.; 160 Christian Road, Middlebury, CT 06762 US ; . HICKEY, Eugene, R.; 5 Woodbury Drive, Danbury, CT 06811 US ; . KIRRANE, Thomas, M.; 61 Davis Street, Danbury, CT 06810 US ; . MORIAK, Monica, H.; 20 Boulevard Drive, Danbury, CT 06810 US ; . MOSS, Neil; 199 Barlow Mountain Road, Ridgefield, CT 06877 US ; . PATEL, Usha, R.; 20 Dairy Farm Drive, Brookfield, CT 06804 US ; . PROUDFOOT, John, R.; 40 Currituck Road, Newtown, CT 06470 US ; . REGAN, John, R.; 287 Rockingstone Avenue, Larchmont, NY 10538 US ; . SHARMA, Rajiv; 37 Midrocks Road, Ridgefield, CT 06877 US ; . SUN, Sanxing; 3821 Padanaram Avenue, Danbury, CT 06811 US ; . SWINAMER, Alan, D.; Apt. 36, 151 Shelter Rock Road, Danbury, CT 06810 US ; . TAKAHASHI, Hidenori; 68 Ehmer Drive, LaGrangeville, NY 12540 US ; . 74 ; RAYMOND, Robert et al. etc.; Boehringer Ingelheim Pharmaceuticals, Inc., P.O. Box 368, 900 Ridgebury Road, Ridgefield, CT 06877 US ; . 81 ; ZA; EP AT BE CH and azmacort.
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Were subjected to either Western blotting Fig. 3A ; or immunoprecipitation-Western blotting Fig. 3B ; . The wild-type AR and AR mutants were expressed to similar levels, and the relative abundance of p300 was similar between samples in transfected cells Fig. 3A ; . In three separate immunoprecipitation-Western blot assays increased amounts of ARK630Q or ARK630T were associated with p300 compared with wild-type AR Fig. 3C ; . Conversely, a tiny nonpolar substitution, ARK630A, showed reduced binding of p300 Fig. 3D ; , consistent with a role for an acetylation-induced increase in polarity and or hydrophobicity in docking to bromodomain coactivators. We examined whether direct acetylation of recombinant AR could alter the affinity for p300 in pull-down experiments. In the presence of p300 and acetylcoenzyme A, the AR fusion protein 624-676 is efficiently acetylated 7 ; . Under the same conditions, a semiquantitative GST pull-down experiment was conducted in the presence and absence of acetyl-coenzyme A Fig. 3E ; . p300 bound the AR fragment in the pull-down, and the association of p300 with the unacetylated AR was disrupted above 0.6 M salt. p300 binding with acetylated AR held up under more stringent salt washing conditions, suggesting that AR acetylation enhances p300 binding Fig. 3E, lane 2 versus 5 ; . To consider the alternative possibility, that in the presence of AR, acetyl-coenzyme A may enhance acetylation of p300 and thereby regulate AR binding and function, we conducted in vitro acetylation experiments with the AR fusion protein and assessed the autoacetylation of p300 Fig. 3F ; . The addition of AR peptide did not increase p300 autoacetylation, suggesting that augmentation of p300 acetylation did not independently contribute to increasing the binding of p300 to the AR. p300 overexpression enhanced activity of both the unliganded Fig. 3G ; and liganded wild-type AR Fig. 3H ; . The AR acetylation site mutants were activated relatively more by p300 either in the absence 9- to 10-fold ; Fig. 3G ; or in the presence 4.5-fold ; of ligand Fig. 3H ; . Since p300 may serve as a platform to recruit AR coactivators, we examined the role of the AR acetylation site mimic in regulating AR coactivation by ARA55, ARA70, SRC1a, TIP60, and Ubc-9 34 ; . Each of the AR coactivators augmented activity of the liganded AR mutants more than wild-type AR Table 1 ; . AR acetylation site regulates corepressor binding and function. The repression function of several unliganded NR, mediated by N-CoR SMRT nuclear receptor corepressor silencing mediator for retinoid and thyroid hormone receptors ; , involves recruitment of HDACs, TBL1, or basal transcriptional components TFIIB, TAFII32, TAFI70 ; 5, 8, 11, ; . Furthermore, the AR binds to HDAC1 in the liver in vivo 5, 8, 11, ; . AR-deficient 293T cells transfected with wild-type AR and the AR mutants showed similar levels of AR and HDAC1 expression by Western blotting Fig. 4A, lanes 1 to 3 ; Saturating AR immunoprecipitation with subsequent Western blotting for the AR and HDAC1 showed that HDAC1 binding to the AR mutants was reduced by 60 to 85% Fig. 4B ; . The specific HDAC inhibitor TSA induced wild-type AR activity with MMTV-Luc 1.8-fold at 5 nM and 5.2-fold at 10 nM ; Fig. 4C ; consistent with the binding of HDAC1 to the AR. In contrast, the AR acetylation site mutants were not activated by TSA at 5 nM and conveyed reduced TSA induction at 10 nM Fig. 4C ; P 0.05, n 9 and bactroban, for example, avappro weight loss.
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National Institutes of Health, Laboratory of Experimental Pathology; Senior Assistant Surgeon, Commissioned Corps. USPHS, 1961-1963. a. b. c. Tumor Metabolism Research Radiation Pathology Service Pathology for the Indian Health Service and baycol.
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Hepatitis C Virus HCV ; is considered to be an opportunistic infection among those with HIV, due to the relatively high co-infection rate of HIV and HCV. * Currently, no national funding infrastructure exists to provide treatment to those infected only with HCV, and state and local resources for such treatment vary greatly. Without HCV treatment programs, much of the burden for treating co-infected patients has fallen on ADAPs and other Ryan White programs. In June 2006, 25 of the 46 ADAPs responding covered treatment for HCV on their ADAP formularies, down one from 26 in 2005 see Appendix X ; . In 2005, NASTAD's ADAP Crisis Task Force negotiated an agreement with a pharmaceutical company to provide free full-course HCV treatments for up to 1, 500 clients in all ADAP programs. This agreement remains and has been renewed. Some states that take advantage of this program do not otherwise include HCV drugs on their formularies. It is important to note that beyond medications, treatment of HCV also requires considerable and costly tests that most ADAPs cannot afford to or do not ; cover, and HCV medication cannot be initiated without such testing. As a result, ADAPs that cover HCV medications have reported lower than expected utilization. Hepatitis A and B vaccines are recommended for those at high risk for HIV and people living with HIV. In June 2006, 21 ADAPs reported covering hepatitis A and B vaccines on their formularies see Appendix X ; . Some ADAPs are adding the A and B vaccines to their formularies because their clients are unable to secure the vaccine through other public health programs. For example, while some state health departments offer hepatitis A and B vaccines to adults at risk through their immunization program, persons living with HIV may not always be eligible. In an effort to provide these vaccinations to ADAP clients, NASTAD's ADAP Crisis Task Force negotiated an agreement for low-cost hepatitis A and B vaccines for rebate ADAPs. Direct purchase ADAPs are able to access HRSA's Prime Vendor Program to obtain vaccines at a significantly reduced price. It is hoped that the reduced price will allow more ADAPs to provide the A and B vaccines to their HIV positive clients.
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Access to services has been increased by providing additional outreach for maternal and child health activities, SC has increased the number of sites for growth monitoring from 7 to 27, for EPI from 7 to 12, and for antenatal care from 0 to 3. Health education is now available in the villages through the VHP, who provides talks to mothers groups 1-4 times a month. Environmental sanitation activities are under the responsibility of the HSA with the VHCs. The SC HSAs can take an active role in sanitation because they are responsible for a specific catchment population and they are based in the villages. The MOH has only 7 HSAs and 1 health assistant to cover the entire Chilipa area. Now, there are 48 VHCs and an additional 23 HSAs. Mothers' Grouns have given women in the villages a regular forum for discussing health issues and for receiving new messages about how to care for their children. Interviews with community members revealed that women now feel that they are capable of treating their children at home first for diarrhea and malaria. This saves them the time and money they would have spent to seek care at the health center 2 of the 3 health centers in Chilipa charge for services ; . Village Health Committees have been formed in all 48 villages, replacing the 16 moribund area health committees present before SC arrived. The VHCs still need to receive training, although village headmen have been oriented. These VHCs provide a structure for supporting the VHP, and for working with the HSA on village environmental activities, such as promoting latrines, baths, and dish racks, digging rubbish pits, and organizing activities for clearing the surroundings. The Roster: Described in more detail in Section E., the roster is a population-based listing of children under five and women of child bearing age that helps the VHPs identify high risk individuals needing services, This system, because it registers everyone, encourages equity and participation of all community members, by seeking out of those who are not using services as well as those who do. Access to Literacy has been increased by providing 20 literacy classes in the area with an additional 20 planned to start late 1995 ; . Although SC planned to train a total of 600 women altogether 2 sessions with 300 participants total in each ; , they have reached this level with the first class sessions. Demand for literacy was much higher than expected and originally over 1, 700 individuals enrolled. With drop-outs, the number of participants is now about 600 with two months left in the classes ; . Literacy helps women to better understand health messages, both because health messages are covered during the class, and because the women can read posters and pamphlets. Thus, literate women have more chance to benefit from CS services. It should be noted, however, that the changes in the Malawian political system over the last year have had a large impact on developing community participation in health activities. Although the political changes have allowed communities to be more verbal about what they want and what they are not happy with, the fall of the one-party state has also given self-help a bad name. During the previous regime, self-help was often a cover-up for forced labor. There is now an attitude that one should be paid for whatever one does, even for one's own community, and it is more difficult to get communities to participate. There is also a feeling that now that the government has changed, people in the rural areas should be getting more things from government and cardizem.
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The nonbiologicals that were approved in 2001 are often referred to as new molecular entities or NMEs. 4 of these 24 NMEs are already listed in the Shands at UF Formulary, despite the fact that 11 of these drugs were approved in the 4th quarter of the year. When the FDA reviews NMEs, they are classified as standard or priority. About 30% of the NMEs approved in 2001 were priority drugs ie, bimatoprost, caspofungin, fondaparinux, imatinib, tenofovir, travaprost, and zoledronic acid ; . Caspofungin, which was added in the Formulary in April 2001, is the 1st antifungal approved in the US in the category of echinocandins. There are limited published data on caspofungin, and the labeled indication is for the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies ie, amphotericin B, lipid formulations of amphotericin B, and or itraconazole ; . Caspofungin can only be used after the approval of the ID Service or in the Bone Marrow Transplant Unit.
Sale of the oral hygiene business to P&G, and the 59 million reversal of a provision for litigation with Bayer. In 2004, it included gains on divestment of 206 million, including the gain arising on the sale of Arixtra, Fraxiparine and associated assets. Operating Income As a result of the various factors described above, in particular the inclusion of Aventis in the scope of consolidation, our operating income amounted to 2, 888 million in 2005, compared to 2, 426 million in 2004. Financial Income and Expenses Net financial expense for 2005 was 245 million, compared to 115 million in 2004. In 2005, net financial expense mainly comprised the cost over 12 months ; of servicing the Aventis acquisition debt an expense of 444 million, compared to 165 million in 2004 ; , partly offset by gains on the disposal of several equity holdings in biotechnology companies amounting to 94 million. The 2005 figure also included the positive effect of the remeasurement of some financial instruments. Income Tax Expense Income tax expense came to 477 million, compared to 479 million in 2004. For additional information on our income taxes in 2005, see "-- Year Ended December 31, 2005 Compared with Pro Forma Year Ended December 31, 2004 Unaudited ; -- Income Tax Expense." Share of Profit Loss ; of Associates The share of profit loss of associates totaled 427 million compared to 409 million in 2004 ; . This line mainly comprises our share of after-tax profits from the territories managed by BMS under the Plavix and Avspro alliance 404 million in 2005, compared to 361 million in 2004 ; . The contribution from our 50% stake in Merial also recorded further growth. Minority Interests Minority interests made a negative contribution to net income of 335 million in 2005 compared to 255 million in 2004 ; . This includes the share of pre-tax profits paid over to BMS from territories managed by sanofiaventis 300 million in 2005, compared to 257 million in 2004 ; . Consolidated Net Income Loss ; As a result of the foregoing, we recorded consolidated net income of 2, 258 million in 2005, compared to 1, 986 million in 2004. The table below shows trends in consolidated net income by business segment between 2004 and 2005 and cardura.
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