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A, ER optimized at 23 cycles of PCR B, PR 23 cycles C, EgfR 26 cycles ; . Data are relative levels between cell lines for the same mRNA after normalization against actin mRNA expression. a As PR was undetectable in FASMCF, actual densitometry values for wild-type cells are shown. Peggy.coffey va.gov From the Editor. Welcome to the new year of the newsletter. In this issue we have included for you the citations for the VA speakers and the Centers of Excellence programs from the recent Consortium of MS Centers annual meeting. It is exciting to see how many VA members are participating in the annual meeting as well as collaborating outside the VA. The full abstract is available for you on the consortium website: mscare We plan on making some changes in the newsletter in the coming months. We will be including a series on Multiple Sclerosis topics. We will be including a literature review of recent MS literature in a different discipline each quarter, the first will be nursing MS literature in the October issue. We want to include your educational offerings so please send them to the editor with a contact name. We will also be listing offerings by the Centers of Excellence. Finally, we would like to include a review of web sites related to MS each quarter if anyone reading is a web guru and would like to write this please let the editor know. If you have ideas, comments, suggestions or would like to write let us know. Deborah Downey, NP deborah.downey va.gov. HOW CAN EDUCATION THROUGH ONE LAPTOP PER CHILD EMPOWER SCHOLARS, SIBLINGS, PARENTS AND TEACHERS? F 029 ; Ian G. Kennedy and Rex van Olst GEOBOOK: ENHANCING MOBILE LEARNING WITH GPS AND MULTIMEDIAL BOOK F 127 ; Claude Moulin and Andrea Piras ON DEVELOPING AND EVALUATING THE PERFORMANCE OF MOCLES: A MOBILE COLLABORATIVE E-LEARNING SPACE S 101 ; Ramli Kalamullah and Priwanto Radytya MOBILE PDA COMMUNICATION OF FINANCIAL ANALYSIS: LESSONS FOR LEARNING S 082 ; Scott D. Stewart. The use of bumetanide allowed us to accurately measure outward Na fluxes, stimulated by external Li [ Na: Li ; countertransport] . Fig. 1 shows this flux [V Na ; ] function of internal Na content. It can be seen that V Na ; is stimulated by Na ; i after a saturable function. Fig. 1 inset ; shows a Hanes plot of the data. The straight line obtained indicates that V Na ; is Michaelis-like function of Na ; i Hill coefficient 1 ; . The apparent dissociation constant for . ; internal Na KN was obtained from the intercept with the x axis and the maximal rate of Na efflux [V, Na ; ] was calculated from the intercept with the vertical axis Fig. 1, inset. Drugs Commonly Used for the Treatment of Chronic Heart Failure Excerpt-Table 2. ACC AHA Guidelines for the Evaluation and Management of Heart Failure ; Drug Initial Dose Titrate as tolerated up to maximum dose Maximum Dose ACE inhibitors Captopril * 6.25 mg 3 times daily 50 mg 3 times daily Enalapril * 2.5 mg twice daily 10 to 20 mg twice daily Lisinopril * 2.5 to 5.0 mg once daily 20 to 40 mg once daily Fosinopril 5 to 10 mg once daily 40 mg twice daily Quinapril 10 mg twice daily 40 mg twice daily Beta-receptor blockers Bisoprolol 1.25 mg once daily 10 mg once daily Carvedilol * 3.125 mg twice daily 25 mg twice daily; 50 mg twice daily for patients more than 85 kg Metoprolol succinate extended release 12.5 to 25 mg daily 200 mg once daily Loop diuretics * Bumetanide 0.5 to 1.0 mg once or twice daily Titrate to achieve dry weight up to 10 mg daily ; Furosemide 20 to 40 mg once or twice daily Titrate to achieve dry weight up to 400 mg daily ; Torsemide 10 to 20 mg once or twice daily Titrate to achieve dry weight up to 200 mg daily ; Digitalis glycosides Digoxin 0.125 to 0.25 mg once daily 0.125 to 0.25 mg once daily * UPMC Health Plan Preferred Drug as noted below. * Thiazide diuretics are not listed in this table but may be appropriate for patients with mild heart failure or associated hypertension, or as a second diuretic in patient's refractory to loop diuretics alone. * Carvedilol may be the BB of choice for African Americans. African American Heart Failure Trial ; . UPMC Health Plan Preferred Ace Inhibitors and ARBs ACEI ARB Captopril, Captopril HCTZ Diovan, Diovan HCT Enalapril, Enalapril HCTZ Avapro irbesartan ; , Avalide Lisinopril, Lisinopril HVTZ Quinapril, Quinaretic Patient Instructions Instruct patients to weigh themselves on the same scale at the same time each day and record the weights in a daily log. Instruct patients to take all medication as prescribed, even if symptom free. Instruct patients on the "warning signs" and how to respond.

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Abraxane see Paclitaxel Protein-bound Particles for Injectable Suspension ; * Alfentanil Hydrochloride Alfenta ; 500 mcg 5 ml 2.290 Allopurinol Sodium Aloprim ; ICD-9's 274.9 or 790.6 plus 500 mg SDV the ICD-9 for the neoplasm. Need name of chemotherapy agent causing the elevation of uric acid and a statement as to why patient can not tolerate oral form of the drug. Amikacin Sulfate Amikin ; 50 mg Amino Acid Amino Acid Arginine Hydrochloride R-Gene 10 ; Ascorbic Acid see Vitamin C - Not Covered By Carrier ; * Atenolol Tenormin ; ICD-9's 401.0 - 429.9 Atropine Sulfate Edrophonium Chloride Azacitidine Vidaza ; Covered for Myelodysplastic Syndrome ICD-9 238.7 Aztreonam Azactam ; * Bacitracin Bacim ; Bretylium Tosylate Bretylol ; Brevibloc See Esmolol Hydrochloride ; Bumetanide Bumex ; Bupivacaine Hcl, 0.25%, 2 ml Considered Part of Procedure ; Bupivacaine Hcl, 0.50%, 2 ml Considered Part of Procedure ; 2 ml 2 0.140 0.260 mg ml 10 mg 1 mg 500 mg 50, 000 U 5 mg 0.25 mg 0.800 1.388 4.037 ml 1000 ml 300 ml 409.387. Conserved in all eukaryotes. The first sordarin was isolated from the fungus Sordaria areneosa [50]. Experimental sordarin compounds have been reported to be efficacious in the treatment of candidiasis, aspergillosis, coccidioidomycosis, histoplasmosis, and pneumocystosis [51-55]. The use of C-11-hydroxysordarins Fig. 7A ; as antifungal agents is reported in [56]. Despite the high degree of sequence homology of EF2s from diverse eukaryotes, the described compounds specifically interact with fungal EF2s resulting in selective inhibition of protein synthesis in these organisms [57]. The sordarins described have a broad spectrum of antifungal activity, including important pathogenic fungi such as Candida spp., dimorphic fungi, C. neoformans, and filamentous moulds. The patent also details the use of a sordarin compound with a second antifungal. A second application also from Merck describes a sordarin derived from the basic formulae depicted in figure 7A by fermentation Fig. 7B ; with improved efficacy to diverse fungal species [58]. A drawback not mentioned in these disclosures is that the t1 2 of sordarins in several animal species has been shown to be very short, indicating that high and repeated dosing may be required. Nevertheless, the high specificity of these compounds for fungal EF2, the apparent lack of significant toxicity, and the relative ease with which new sordarin variants can be synthesized suggests that these drugs could be extremely useful therapeutics. Novel 6, 7-disubstituted-5, 8-quinolinedione compounds Fig. 8 ; are proposed as antifungal drugs in [59]. These compounds function as antimetabolites of coenzyme Q to inhibit mitochondrial coenzyme-Q dependent succinoxidase and electron transport in Saccharomyces cerevisiae [60]. MIC data for 20 synthesized 6, 7-disubstituted-5, 8quinolinedione derivatives showed that amount of drug required to inhibit growth of Candida spp. and C. neoformans was less than or similar to fluconazole and ketoconazole in vitro . Some of this data has been published elsewhere [61, 62]. In a rat model of candidemia, a synthesized quinolinedione significantly prolonged survival compared to an equivalent dose of ketoconazole. No toxicity data is provided. Compounds that inhibit microbial NAD synthetase Fig. 9 ; are described in [63]. These compounds have diverse uses, including the capacity to inhibit or kill fungi by reducing or eliminating microbial production of NAD. The compounds are comprised of two aryl moieties joined by a suitable linker. Though details are not provided, the report claims that the compounds are highly effective against fungal pathogens, while having only moderate toxicity in mammals. Antifungal Proteins Antifungal proteins that are analogues of the radish seed antifungal protein 2 [Rs-AFP2] are detailed in [64]. The amino acid sequence of Rs-AFP2 is QKLCQRPSGT WSGVCGNNNA CKNQCIRLEK ARHGSCNYVF PAHK CICYFP C, and the mutants identified are 80% homologous. The patent details the generation of the mutants and provides some microbiological data using plant fungal pathogens. The authors state that these peptides can also be effective as food preservatives and as therapeutics for humans. The vector and buspirone.

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Strata are removed from the analysis, abundance of S. iserti is negatively correlated with both Acropora rubble and distance from the eastern tip of the island. This relationship explains 51 % of the variation in abundance r2 0.512, p 0.028 ; . Spansoma aurofrenatum showed no correlation between microhabitat characteristics and abundance among sites Table 4 ; . S. viride abundance was correlated with the percent cover of Porites and Acropora rubble, but the correlation with Porites was positive when it was expected to be negative. If Porites is removed from the analysis, there is a non-significant relationship between distance from the eastern end of the island and S. viride abundance r2 0.254, p 0.08 ; . Likewise, the abundance of S. iserti was correlated with Porites, Porites rubble, and distance from the eastern tip of the island, but the correlations with Porites and Porites rubble were in the opposite direction from that expected by the analysis of small spatial scale microhabitat use. Four species showed positive correlations between abundance and total live coral cover Porites + Montastrea + live coral ; Table 5 ; . These species were Spari and busulfan.
Similar to that of DMA n 4, Table 1 ; , but displayed a lower minimally effective droplet concentration 100 M [554 ng] ; , n 4, Table 1 ; . The similarity of the effects of BIIB723 at 1 mM 5.34 g; 4.5 0.5 mm Hg ; and 3 mM 16.0 g; 4.9 1.7 mm Hg ; and the similar reductions produced by all three NHE-1 inhibitors at 3 mM suggest that a maximal IOP reduction was achieved of 4.1 to 5.0 mm Hg. We were unable to increase the delivered droplet concentration without substantially increasing the DMSO level, thereby triggering a vehicle-induced change in IOP. Carbonic anhydrase inhibition reduces the rate of production of H and HCO3 , which in turn must slow the rate of delivery of H and HCO3 to all cell sites, including the antiports. We have already reported that inhibiting carbonic anhydrase with intraperitoneal acetazolamide lowers mouse IOP by 11.9 1.3 mm Hg ; .16 We have now found that topical application of dorzolamide also reduces IOP, albeit to a lesser extent at the droplet concentration applied Table 1 ; . We also tested the effects of amiloride which inhibits NHE-1 antiports at a potency 1 to 2 orders of magnitude lower than the amiloride analogues DMA and EIPA.11 Consistent with this information, amiloride itself exerted no significant effect on mouse IOP at a droplet concentration of 1 mM 2.30 g, n 7, data not shown ; . To reach a 10-mM concentration, it was necessary to solubilize amiloride in 30% DMSO. After pretreatment with vehicle containing 30% DMSO, subsequent application of 10 mM amiloride in the same concentration of vehicle did not alter that IOP IOP 1.0 0.7 mm Hg, n 4, P 0.2 ; . Thus, at a concentration 10 times higher than EIPA's minimal effective concentration, amiloride had no effect, consistent with the known ratio of the potency of these inhibitors 3.9: 0.07 M, or 56 ; when applied to PE cells.11 In contrast to the IOP reductions triggered by the three selective inhibitors of the NHE-1 antiport at droplet concentrations of 0.1 to 3 mM Table 1 ; , blockage of the Na -K -2Cl symport with droplet concentrations of 0.1 to 10 mM 364 ng to 36.4 g ; bumetanide had no significant effect on IOP Fig. 2, Table 1.

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Department of Astronomy, Odessa National University, T.G.Shevchenko park, UA 65014, Odessa, Ukraine, il-a mail.od.ua Crimean Astrophysical Observatory, UA 98409 Nauchny, Ukraine University Observatory, Chungbuk National University, 361 763, Cheongju, Korea Institute for Basic Science Research, Chungbuk National University, 360?63, Korea Bohyunsan Optical Astronomy Observatory, Jancheon P.O.Box 1, Youngcheon, Kyungbuk 770-820 , Korea and butorphanol. We therefore examine here the novel possibility that 5HT modulates chloride homeostasis during the quiescent intervals. The effects of blocking the inward ; chloride cotransport with bumetanide Russell, 2000 ; were compared with the effects of 5HT and its antagonists, behaviorally by video analyses and during fictive swimming by whole-cell and gramicidin-perforated patch recordings. We show that bumetanide mimics the effects of serotonergic antagonists and opposes the effects of 5HT, behaviorally by introducing long quiescent intervals and cellularly by suppressing evoked chloride-mediated responses in isolation or during fictive swimming. We suggest that, early during development, 5HT regulates chloride homeostasis during the rest intervals to offset long periods of quiescence, which are commonly observed in other excitable developing networks. Thus, 5HT modulation allows the locomotor neuronal network to express a more mature, sustained activity pattern. Frusemide, bumetanide and ethacrynic acid Mechanisms of action The loop or high ceiling diuretics are potent, short acting natriuretics which inhibit sodium reabsorption in the medullary portion of ascending limb of the loop of Henl by blocking the sodium-potassium-chloride Na + K + 2Cl- ; cotransporter. This leads to the excretion of 30% of the filtered sodium, as the sodium concentration in the distal nephron is increased; moreover, the sodium concentration in the renal medullary interstitium and peritubular capillaries is decreased, impairing the concentrating ability of the countercurrent multiplier mechanism. The co-dependent reabsorption of calcium and magnesium are inhibited. Potassium and hydrogen ion exchange for sodium in the distal convoluted tubule is increased. Loop diuretics also increase and redistribute renal blood flow and have a systemic venodilatory effect. Pharmacokinetics Loop diuretics are acidic compounds pKa 3.5-3.8 ; administered orally or intravenously, either as a bolus or by continuous infusion. Frusemide furosemide in US texts ; has an oral bioavailability varying from 10 to 100%; the others are more completely and predictably absorbed orally. They are 95% protein bound and have an elimination half-life of only one to two hours. Frusemide is 50% excreted unchanged and 50% metabolized in the kidney, bumetanide is metabolized in the liver and, ethacrynic acid in both the liver and the kidneys. The loop diuretics reach their site of action by active transport by the probenecid-sensitive mechanism in the proximal convoluted tubule. This system is impaired in the presence of renal failure, necessitating large increases in dosage. Large doses are also required in the nephrotic syndrome to attain adequate tubular concentrations of free drug. Acute tolerance to the diuretic effects of frusemide has been reported. Chronic tolerance may develop as a result of hypertrophy of the distal nephron, increasing sodium reabsorption which can be counteracted by increasing the dose, the recumbent posture or coadministration of a thiazide and byetta.

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Pathogens of Infectious Diseases A. Gram-positive bacteria 22. 10 3 mol l 1, vanadate did not affect Vbl but significantly depolarized Vte; within 5 min, a steady state was reached. 10 4 mol l 1 vanadate had no significant effect on Vte. The depolarizing effect of 10 3 mol l 1 vanadate on Vte suggested the inhibition of an electrogenic transport system for theoretical considerations, see also Weltens et al. 1992 ; . Therefore, it was of interest to examine the effects of vanadate on the Ba2 + induced hyperpolarization of Vbl. A typical example is shown in Fig. 3C. Vanadate caused a depolarization i.e. a reduction of the Ba2 + -induced hyperpolarization ; of Vbl within 5 min. The effect was statistically significant Table 3A ; . The effects of vanadate on electrical potentials were not easily reversible within the experimental period i.e. approximately 15 min wash-out ; . K + -selective measurements Since 10 3 mol l 1 vanadate did not affect Vbl in the absence of Ba2 + within 5 min, a drastic effect on [K + was not expected. This was verified in 51 mmol l 1 [K ]bl. Examples of intracellular and luminal measurements are given in Fig. 3D, E. The addition of 10 3 mol l 1 vanadate did not cause significant changes in Vbl or [K + ]i. In the lumen of another tubule, the reversible response of Vte and [K + ]l decrease in [K + ]bl in control conditions was first confirmed. Upon administation of 10 3 mol l 1 vanadate, Vte began to decrease within the first minute; after 6 min, Vte had decreased by 18 mV. Within the same period, [K + ]l was not affected. The experimental data are summarized in Table 3B. There was no significant effect on [K + and [K + ]l. A similar lack of effect on [K + and [K + ]l was observed not shown ; in 5 mmol l 1 [K ]bl. Effects of bumetanide Fluid secretion experiments The loop diuretic bumetanide inhibits K + Cl and Na + K 2Cl cotransport systems see Ellory and Hall, 1988 ; . A concentration of 10 5 mol l 1 is usually sufficient for maximal inhibition of the Na + K 2Cl cotransporter, but much higher concentrations are generally needed to affect the K + Cl cotransporter see Ellory and Hall, 1988; Palfrey and O'Donnell, 1992 ; . Bumetanide was tested in 5, 51 and 113 mmol l 1 [K ]bl. In 51 mmol l 1 [K ]bl, 10 4 mol l 1 bumetanide significantly diminished fluid secretion rate; the application of 10 3 mol l 1 almost completely abolished it Fig. 4A, Table 2B ; . Only at 10 4 mol l 1 was the effect reversible. In the lower [K + ]bl 5 mmol l 1 ; , bumetanide reversibly inhibited fluid secretion when applied at 10 5 mol l 1. The inhibitory effect of 10 4 mol l 1 bumetanide was more pronounced and the fluid secretion did not recover within the 30 min wash-out period Fig. 4B, Table 2B ; . In the high-K + , Na + -free solution, in contrast, bumetanide 10 4 mol l 1 ; had no significant effect Fig. 4C, Table 2B ; . Electrical potential measurements Since bumetanide 10 4 mol l 1 ; diminished the fluid secretion rate in 51 and 5 mmol l 1 [K ]bl, electrophysiological effects were tested in these bath solutions. As is shown in Fig. 4D, in 51 mmol l 1 [K ]bl, Vte remained constant after the addition of 10 4 mol l 1 bumetanide; in 5 mmol l 1 [K ]bl, Vte was 4 mV higher than the control and campral.

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