These results further strengthen the position from similar studies investigating CE effects on running or cycling performances lasting ~1 h that no ergogenic effects are exhibited when subjects consume a pre-activity meal. The discrepant findings from studies with fasted athletes highlights the impact pre-exercise feeding

protocols may have on the results of sport beverage studies and should be given consideration in future CE study design. References 1. Rollo I, Williams C: Influence of ingesting a carbohydrate-electrolyte solution before and during a 1-hr running performance test. Int J Sport Nutr Exerc Metabol click here 2009, 19:645–658. 2. Below PR, Mora-Rodriguez R, Gonzalez-Alonso J, Coyle EF: Fluid and carbohydrate ingestion independently improve performance during 1 h of intense exercise. Med Sci Sports Exerc 1995, 27:200–210.PubMed 3. Jeukendrup A, Brouns F, Wagenmakers AJ, Saris WH: Carbohydrate-electrolyte feedings improve 1 h time trial cycling performance. VX-809 cell line Int J Sports Med 1997, 18:125–129.PubMedCrossRef 4. Neufer PD, Costill DL, Flynn MG, Kirwan JP, Mitchell JB, Houmard J: Improvements in exercise performance: effects of carbohydrate feedings and diet. J Appl Physiol 1987, 62:983–988.PubMed

5. Ball TC, Headley SA, Vanderburgh PM, Smith JC: Periodic carbohydrate replacement during 50 min of high-intensity cycling improves subsequent sprint performance. Int J Sport Nutr 1995, 5:151–158.PubMed 6. El-Sayed MS, Balmer J, Rattu AJ: Carbohydrate ingestion improves endurance performance during

a 1 h simulated cycling time trial. J Sports OSBPL9 Sci 1997, 15:223–230.PubMedCrossRef 7. Millard-Stafford M, Rosskopf LB, Snow TK, Hinson BT: Water versus carbohydrate-electrolyte ingestion before and during a 15-km run in the heat. Int J Sport Nutr 1997, 7:26–38.PubMed 8. Carter J, Jeukendrup AE, Mundel T, Jones DA: Carbohydrate supplementation improves moderate and high-intensity exercise in the heat. Pflugers Arch 2003, 446:211–219.PubMed 9. Rollo I, Williams C, Nevill M: Influence of ingesting versus mouth rinsing a carbohydrate solution during a 1-h run. Med Sci Sports Exerc 2011, 43:468–475.PubMed 10. Anantaraman R, Carmines AA, Gaesser GA, Weltman A: Effects of carbohydrate supplementation on performance during 1 hour of high-intensity exercise. Int J Sports Med 1995, 16:461–465.PubMedCrossRef 11. Rollo I, Williams C: Influence of ingesting a carbohydrate-electrolyte solution before and during a 1-hr running performance test. Int J Sport Nutr Exerc Metab 2009, 19:645–658.PubMed 12. Welsh RS, Davis JM, Burke JR, Williams HG: Carbohydrates and physical/mental performance during intermittent exercise to fatigue. Med Sci Sports Exerc 2002, 34:723–731.PubMedCrossRef 13.

The low contact Opaganib angle (high wettability), presence of oxygen in the surface layer, and rough surface of the substrate are prerequisites for successful VSMC adhesion. Thus, the difference in the number of proliferated cells between annealed and relaxed samples can be attributed to the different elemental compositions of the surface layer and resulting different wettability. From Figure 4A,B, it is evident that the cell proliferation on the other samples, sputtered

for longer times, is very low. Sputtering for longer times (100 and 200 s), which leads to the formation of homogenous and continuous metal coverage, has a negative effect on cell interaction from the long-term point of view. The above results are illustrated on the photographs of the adhered (first day from seeding) and proliferated (seventh day from seeding) cells on the relaxed and annealed samples (Figure 5). The cells cultivated for 24 h are equally distributed on the surface. The cells on the samples that are as-sputtered for 20 s and those on subsequently annealed samples start spreading, and their adhesion increases; however, the cells on the samples sputtered for 200 s and coated completely with

silver stay small and round shaped. After 7 days from the seeding, the cells on the samples sputtered for 20 s are numerous and evenly distributed over the sample surface. The cell proliferation on the samples sputtered this website ADP ribosylation factor for 200 s is much worse. In the case of the as-sputtered layer, the silver forms homogenous coverage, completely shading the original polymer surface. After annealing of the thicker Ag layer, a dramatic coalescence of silver into distinctive hummock-like structures takes place, the latter being high enough to prevent a contact between polymer substrate and adhered cells. Figure 5 Photographs of adhered and proliferated VSMCs.

Photographs of VSMCs adhered (first day) and proliferated (seventh day) on Ag-coated PTFE with different deposition times (20 and 200 s) for as-sputtered and annealed samples. Conclusions The properties of silver layers sputtered on PTFE for different times and their changes under annealing were studied by different methods. The biocompatibility of the samples prepared under different conditions was examined in vitro experiments with vascular smooth muscle cells. Relations between physicochemical properties of silver layers and their biocompatibility were found. Coating with silver leads to an increase of surface wettability, which is further affected by oxidized structures adsorbed by the sample surface. With the increasing thickness of the silver layer, an increase of the oxygen concentration is also observed which is explained by high affinity of silver to oxygen and oxidized structures.

The method of xenograft tumor volume measurement, radiation and reagent administration are described in Methods section. The tumor volumes in the ABT-737 plus radiation Poziotinib research buy group were significant smaller than those in the DMSO plus radiation group (P < 0.01). However, the growth curves of the tumors in the DMSO group, the DMSO plus radiation group and the ABT-737 group were very similar. In this study, six mice per group were used. Points, mean volumes; bars, SD. Discussion Fractionated radiation (FR) is used often in radiotherapy treatment to facilitate the recovery of normal tissues,

while the repair of cancer cells is generally less efficient between fractions. However, the acquired radioresistance of cancer

cells is thought to occur during the repopulation of the tumor during the long-term FR [19]. The proliferating cancer cells that repopulate the tumor may be different subpopulation with a different genotype that confers radioresistance. Cancer cells with acquired radioresistance many survive during radiotherapy and lead to additional cancer recurrence Ceritinib nmr after radiation therapy, thus limiting the effectiveness of radiation therapy. Therefore, to promote better outcomes for patients undergoing radiotherapy, an effective strategy may be to target the cells acquired radioresistance. In the present study, the MDA-MB-231R cells were obtained after fractionated radiation with total dose of 50 Gy and were cultured without radiation for the next 10 passages. The radioresistance

of MDA-MB-231R cell line was determined using a colony-forming assay. The results of Western blot analysis showed that the anti-apoptotic proteins Bcl-2 and Bcl-xL Fossariinae were overexpressed in the MDA-MB-231R cells that had acquired radioresistance. RT-PCR analysis confirmed that the expression of the anti-apototic genes Bcl-2 and Bcl-xL were upregulated in the radioresistant MDA-MB-231R cells and overexpressed compared with their parental cell line. The overexpression of anti-apoptotic proteins in the Bcl-2 family is frequently observed in many different tumor types and has been associated with resistance to radiotherapy [20, 21]. However, the molecular mechanism underlying the acquired radioresistance of cancer cells remains unclear. Several mechanisms are thought to contribute to the acquired radioresistance, including mutated p53 [22], amplification of DNA repair genes [23], overexpression of the cell-cycle regulator protein, cyclin D1 [19] and activation of pro-survival oncogenes such as EGFR [24]. The overexpression of Bcl-2 and Bcl-xL in the MDA-MB-231R cells indicated that these anti-apoptotic proteins play an important role in the acquisition of radioresistance. The expression of anti-apoptotic proteins is closely related to the radiosensitivity of cancer cells, and targeting these proteins could be an effective method to overcome radioresistance. An et al.

0 Fig. 3 Change from baseline in serum levels of a IL-6, b TNF-alpha, c IFN-gamma, and d hs-CRP following IV zoledronic acid infusion in a subset of 96 patients receiving treatment with placebo (plac), acetaminophen (acet), or fluvastatin (fluv). Measurements were taken at baseline and at 24 and 72 h post-infusion. hs-CRP highly sensitive C-reactive protein, IFN interferon, IL interleukin, TNF tumor necrosis factor Inflammatory biomarker changes were weakly correlated with changes

in body temperature and VAS scores. IL-6, IFN-gamma, and hs-CRP levels were generally higher in patients with a major increase in symptom severity (with the exception of severe headaches). However, some asymptomatic patients also experienced biomarker elevations. The use of acetaminophen appeared to attenuate increases in IL-6 and IFN-gamma levels at 24 h in this treatment group compared with those reported for the placebo and fluvastatin learn more groups (Fig. 3a, c). Safety In safety evaluations, post-dose symptoms were not counted as AEs, since they were collected in patient diaries as secondary outcomes. The most common Vemurafenib clinical trial AEs were musculoskeletal and connective tissue disorders, general disorders and administration site conditions, and gastrointestinal disorders. AEs occurred at comparable rates across treatment groups. There were no deaths in the study. Five (0.6%) patients reported six serious

AEs (one [hypokalemia] in the placebo group, two [syncope and pleuritic pain] in the acetaminophen group, and three [convulsion, pyrexia, and uveitis] in the fluvastatin group). Ten (1.3%) patients withdrew from the study due to AEs (three in the placebo group, three in the acetaminophen group, and four in the fluvastatin group). There were no notable differences between treatment groups in serious AEs or treatment withdrawals. No clinically significant

between-group differences were observed in laboratory values MRIP or vital signs. Discussion Transient post-dose symptoms are the most frequently reported AEs following ZOL infusions in postmenopausal women [1]. These symptoms are believed to be caused by the accumulation of IPP as a result of FPP blockade in the mevalonate pathway, a key step in the inhibition of bone resorption by ZOL [10]. Statins block an earlier stage of this pathway and do not lead to IPP accumulation. In vitro, pretreatment of peripheral blood mononuclear cells with a statin followed by exposure of the cells to a bisphosphonate prevents the bisphosphonate-induced release of inflammatory cytokines including TNF-alpha and IFN-gamma [12]. In this trial, we evaluated the efficacy of acetaminophen and fluvastatin in preventing or reducing post-dose symptoms following administration of a single infusion of ZOL in bisphosphonate-naive postmenopausal women with low bone mass.

J Gerontol Ser A Biol Sci Med Sci 53:B369–379 32. Gordon T, Hegedus J, Tam SL (2004) Adaptive and maladaptive motor axonal sprouting in aging and motoneuron disease. Neurol Res 26:174–185PubMed 33. Florini BAY 73-4506 clinical trial JR, Ewton DZ, Falen SL, Van Wyk JJ (1986) Biphasic concentration dependency of stimulation of myoblast differentiation

by somatomedins. Am J Physiol 250:C771–778PubMed 34. Goldspink G, Yang SY (2004) The splicing of the IGF-I gene to yield different muscle growth factors. Adv Genet 52:23–49PubMed 35. Musaro A, McCullagh K, Paul A, Houghton L, Dobrowolny G, Molinaro M, Barton ER, Sweeney HL, Rosenthal N (2001) Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle. Nat Genet 27:195–200PubMed 36. Petrella JK,

Kim JS, Cross JM, Kosek DJ, Bamman MM (2006) Efficacy of myonuclear addition may explain differential myofiber growth among resistance-trained young and older men and women. Am J Physiol Endocrinol Metab 291:E937–946PubMed 37. Firth SM, Baxter RC (2002) Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev 23:824–854PubMed 38. Messi ML, Delbono O (2003) Target-derived trophic effect on skeletal muscle innervation in senescent mice. J Neurosci 23:1351–1359PubMed 39. Schertzer JD, van der Poel C, Shavlakadze T, Grounds MD, Lynch GS (2008) Muscle-specific overexpression of IGF-I improves E–C coupling in skeletal muscle fibers from dystrophic mdx mice. Am J Physiol Cell Physiol 294:C161–168PubMed 40. Rasmussen BB, Fujita S, Wolfe RR, Mittendorfer B, Roy M, Rowe VL, Volpi E (2006) Insulin resistance

Lumacaftor order of muscle protein Calpain metabolism in aging. FASEB J 20:768–769PubMed 41. Kandarian SC, Jackman RW (2006) Intracellular signaling during skeletal muscle atrophy. Muscle Nerve 33:155–165PubMed 42. Reid MB (2005) Response of the ubiquitin–proteasome pathway to changes in muscle activity. Am J Physiol Regul Integr Comp Physiol 288:R1423–1431PubMed 43. Giresi PG, Stevenson EJ, Theilhaber J, Koncarevic A, Parkington J, Fielding RA, Kandarian SC (2005) Identification of a molecular signature of sarcopenia. Physiol Genomics 21:253–263PubMed 44. Leeuwenburgh C (2003) Role of apoptosis in sarcopenia. J Gerontol Ser A Biol Sci Med Sci 58:999–1001 45. Hiona A, Leeuwenburgh C (2008) The role of mitochondrial DNA mutations in aging and sarcopenia: implications for the mitochondrial vicious cycle theory of aging. Exp Gerontol 43:24–33PubMed 46. Dirks AJ, Hofer T, Marzetti E, Pahor M, Leeuwenburgh C (2006) Mitochondrial DNA mutations, energy metabolism and apoptosis in aging muscle. Ageing Res Rev 5:179–195PubMed 47. Herbst A, Pak JW, McKenzie D, Bua E, Bassiouni M, Aiken JM (2007) Accumulation of mitochondrial DNA deletion mutations in aged muscle fibers: evidence for a causal role in muscle fiber loss. J Gerontol Ser A Biol Sci Med Sci 62:235–245 48.

An additional

document [see Additional file 2] compares the contrast-weighted sensitivity of SML to the six other resists cited in the ‘Background’ section. Figure 3 Comparison of SML and PMMA contrast curves. Both SML (triangles) and PMMA (circles) were exposed at 30 keV and developed for 20 s in MIBK/IPA (1:3) (filled symbols) and IPA/water (7:3) (open BMN 673 ic50 symbols). Figure 4 Comparison of SML contrast and contrast-weighted sensitivity for various developers. The contrast (circles) and contrast-weighted sensitivity (triangles) have been arranged in increasing clearance dose. The contrast-weighted sensitivity has units of dose (μC/cm2). Based on the analysis of contrast curves, IPA/water (7:3) was selected as the preferred developer for fabricating www.selleckchem.com/products/gsk1120212-jtp-74057.html dense, high-AR gratings. Similar to PMMA, both IPA and water alone are poor or non-developers for SML resist but are effective in

combination. The usage of ultrasonic agitation during development was chosen to help promote the dissolution of SML fragments as inspired by Yasin’s work [21]. Since resist fragments tend to coil in poor solvents and exhibit a smaller radius of gyration, ultrasonic agitation may be expected to promote the rapid removal of these fragments, enabling a narrower grating trench [21]. As described in the ‘Methods’ section, a brief rinse in low-surface-tension fluid was used to reduce the probability of pattern collapse. The surface tension of pentane (approximately AMP deaminase 16 dyn/cm) and hexane (approximately 18 dyn/cm) is at least four times less than that of water (approximately 73 dyn/cm). Figure 5 presents top-view grating micrographs of 70-nm-pitch SML gratings in a 300- to 330-nm-thick resist showing the effect of increasing line dose. The line width increases from 25 nm at 550 pC/cm (Figure 5a) to 32 nm at 750 pC/cm (Figure 5b) and to 40 nm at 950 pC/cm (Figure 5c) just prior to pattern collapse. Observing the top-view grating micrographs, clearance cannot be conclusively ascertained; however, this question is explored through cross-sectional micrographs ahead. Based on the observations from Figure 5, it is estimated

that as low as 25-nm resolution with SML is readily achievable without resolution enhancement techniques. Furthermore, the gratings show low line edge roughness. The resolution limits (with thinner resists) were not explicitly pursued as this work focused on maximizing the AR, pattern density, and sensitivity by co-optimizing the exposure and development conditions. Given that the proximity effect appears to be of minor importance, if at all (see Figure 1a), the results in Figure 5 are representative of the resist performance even without clearance and can be employed to co-optimize the resist thickness and process conditions if so desired. Figure 5 Micrographs of 70-nm-pitch gratings patterned by 30 keV on 300- to 330-nm-thick SML.

Six kinds of chemotherapeutic drugs and verapamil in culture solution The six kinds of chemotherapeutic agents were Cisdiaminodichloro-platinum (DDP), vindesin (VDS), 5-Fluorouracil (5-Fu), Hydroxycamptothecine (HCP), Mitomycin C (MMC), and Adriamycin

(ADM), being cell cycle nonspecific agents, e.g. alkylating agents and anti-tumor antibiotics, and cell cycle specific agents, e.g. antimetabolites. The 6 kinds of chemotherapeutic agents were prepared respectively LY2606368 price with 1640 culture solution to form 2-folds of peak plasma concentration (2× PPC) for use. When the solution was used for assay, added 100 μl culture solution which containing equal amount of cells with another 100 μl of the above stock solution, so the concentration of the chemotherapeutic

agent was reduced by half, i.e. equal to 1× PPC which were DDP 10.0 mg/L, VDS 1.0 mg/L, 5-Fu 110 mg/L, HCP 5.0 mg/L, MMC 3.0 mg/L, and ADM 10.0 mg/L. Taking 0.2 mg/ml (200 mg/L) verapamil (VPL) (Shanghai Hefeng Pharmaceutical Co. Ltd. China. Verapamil hydrochloride Injection, 5 mg/2 ml) which was equal to 200 folds of the known 1× PPC (0.1 to 1.0 mg/L)[12], added VPL to A549 parental cells, A549 radioresistant cells, and MCF-7 vincristin resistant (MCF7/VCR) cells respectively without VX-765 research buy chemotherapeutic agents added for the observation of VPL on cell toxicity. Another group was the combined treatment of VPL and chemotherapeutic agent for MCF7/VCR cells. Drug sensitiveness experiment of monolayer cell One 96 well cell culture plate was used, with each group containing 4 wells and the experiment group having 20000 cells per well. The blank well had no cells added, but added with 200 μl culture solution. In the control group, 100 μl culture solution contained cells and another 100 μl culture solution without cell added. As to the ADM blank control group, 100 μl drug containing solution and 100 μl culture solution were added respectively. Urease MTT assay methods Testing cells added with chemotherapeutic drug were cultured for 48

hrs, and then added with 20 μl MTT (5 mg/ml) to every well. After 4 hrs the A value at 490 nm was measured with DG-3022A model enzyme-linked immunosorbent assay instrument (produced by Huadong Electronic Tube Factory, China) and the sensitivity experiment was performed. Evaluation of the therapeutic efficacy in MTT experiment Taking the 1× PPC for the standard in the drug sensitivity experiment, cell survival rate = (A value in the experimental group/A value in the control group) × 100%, and inhibition rate = 1 – cell survival rate. Standard for the evaluation of drug sensitivity was as followed, i.e. Sensitive: 100% > inhibition rate % > 70%; Relatively Sensitive: 70% > inhibition rate % > 20%; Insensitive: 20% > inhibition rate %> 0%.

calcd. for C15H10N2S: C, 71.97; H, 4.03; N, 11.19; S, 12.81. Found: C, 71.85; H, 3.97; N, 11.10; S, 12.77. 9-Fluoro-12(H)-quino[3,4-b][1,4]benzothiazine (4b) Yield 68 %; m.p.: 168–169 °C; 1H NMR (CD3OD, 500 MHz) δ (ppm): 6.64–6.68 (m, 1H, Harom), 6.70–6.75 (m, 1H, Harom), 6.87–6.91 (m, 1H, Harom), 7.44–7.49 (m, 1H, H-2), 7.56–7.61 (m, 1H, H-3), 7.73–7.76 (m, 1H, H-4), 8.01 (s, 1H, H-6), 8.05–8.09 (m, 1H, H-1); EI-MS m/z: 268 (M+, 100 %); Anal. calcd. for C15H9FN2S: C, 67.15; H, 3.38; N, 10.44; S, 11.95. Found: C, 67.09; H, 3.31; N, 10.40; S, 11.89. 9-Chloro-12(H)-quino[3,4-b][1,4]benzothiazine (4c) Yield 64 %; m.p.: 173–174 °C; 1H NMR (CD3OD, 500 MHz) δ (ppm): 6.88–6.91 (m, 2H, Harom), 7.02–7.05 (m, 1H, Harom), 7.55–7.60 (m, 1H, H-2), 7.68–7.73 (m, 1H, H-3), 7.78–7.82 (m, 1H, H-4), 8.12 (s, 1H, H-6), 8.17–8.20 Selleck CHIR 99021 (m, 1H, H-1); EI-MS m/z: 285 (M+, 100 %); Anal. calcd. for C15H9ClN2S: C, 63.27; H, 3.19; N, 9.84; S, 11.26. Found: C, 63.22; H, 3.15; N, 9.77; S, 11.23. 9-Bromo-12(H)-quino[3,4-b][1,4]benzothiazine (4d) Yield 54 %; m.p.: 96–98 °C; 1H NMR (CD3OD, 500 MHz) δ (ppm): 6.83–6.86 (m, 1H, Harom), 7.03–7.05 (m, 1H, Harom), 7.12–7.15 (m, 1H, Harom), 7.48–7.54 (m, 1H, H-2), 7.60–7.66 (m, 1H, H-3), 7.77–7.81 (m, 1H, H-4), 8.06 (s, 1H, Alvelestat in vitro H-6), 8.09–8.14 (m, 1H, H-1); EI-MS

m/z: 329 (M+, 100 %); Anal. calcd. for C15H9BrN2S: C, 54.73; H, 2.76; N, 8.51; S, 9.74. Found: C, 54.68; H, 2.73; N, 8.44; S, 9.71. 9-Methyl-12(H)-quino[3,4-b][1,4]benzothiazine (4e) Yield 83 %; m.p.: 202–203 °C; 1H NMR (CD3OD, 500 MHz) δ (ppm): 2.19 (s, 3H, CH3), 6.74–6.77 (m, 1H, Harom), 6.84–6.88 (m, 2H, Harom), 7.50–7.54 (m, 1H, H-2), Nintedanib (BIBF 1120) 7.61–7.65 (m, 1H, H-3), 7.78–7.81 (m, 1H, H-4), 8.09 (s, 1H, H-6), 8.14–8.18 (m, 1H, H-1); EI-MS m/z: 264 (M+, 100 %); Anal. calcd. for C16H12N2S:

C, 72.70; H, 4.58; N, 10.60; S, 12.13. Found: C, 72.61; H, 4.53; N, 10.53; S, 12.09. 11-Methyl-12(H)-quino[3,4-b][1,4]benzothiazine (4f) Yield 65 %; m.p.: 81–83 °C; 1H NMR (CD3OD, 500 MHz) δ (ppm): 2.36 (s, 3H, CH3), 6.77–6.84 (m, 2H, Harom), 6.90–6.95 (m, 1H, Harom), 7.50–7.55 (m, 1H, H-2), 7.59–7.64 (m, 1H, H-3), 7.70–7.82 (m, 1H, H-4), 7.98–8.03 (m, 1H, H-1), 8.13 (s, 1H, H-6); EI-MS m/z: 264 (M+, 100 %); Anal.

For both host cells the inhibitory effect on the percent infection was in the range of 0.5 to 5.0 μM. Surprisingly, NQ8 and NQ9 caused about a 2.5-fold

decrease of infection. For both host cells, the IC50 values after 48 h of treatment used to calculate the endocytic index are displayed in Table 3. NQ8 was the most active compound. Non-infected macrophages and HMCs treated with the compounds for 2 days were tested with the MTT assay to evaluate their toxicity to mammalian cells. For HMCs, the LC50 values were 8 μM for NQ1 and NQ12 and 10 μM for NQ8; NQ9 was the least toxic quinone with values higher than 10 μM. The LC50 was higher than 10 μM in macrophages for all four compounds. Table 3 IC 50 values (μM) of the naphthoquinones on intracellular Smoothened Agonist cell line BGB324 order amastigotes of T. cruzi Cpd HMC Macrophages NQ1 2.81 ± 0.43a,b 3.65 ± 0.71 NQ8 1.53 ± 0.11 1.49 ± 0.01 NQ9 2.48 ± 0.39 1.63 ± 0.18 NQ12 9.83 ± 2.64 2.51 ± 0.71 aThe IC50 was calculated for the endocytic index (number

of parasites/100 host cells) after two days of treatment. bMean ± standard deviation of at least three independent experiments. Ultrastructural analysis Transmission electron microscopy showed that treatment with the NQs induced important alterations in the mitochondrion of the epimastigotes, leading to swelling and the appearance of membranous structures in the organelle matrix (Figures 2, 3, 4 and 5). Autophagic features, such as atypical cytosolic membranous structures (Figures 3, 4, 5) and the appearance of endoplasmic reticulum surrounding reservosomes (Figures 2 and 5), were detected in treated parasites. The naphthoquinones PI-1840 also led to intense

cytosolic vacuolization (Figures 4 and 5), the formation of blebs in the flagellar region (Figures 2, 3 and 5) and the induction of loss of the electron-density of the cytosol (washed out aspect) (Figures 3 and 5). The scanning electron microscopy technique demonstrated no important morphological alterations in treated epimastigotes (data not shown). Figure 2 Transmission electron microscopy analysis of T. cruzi epimastigotes treated with NQ1. (A) Untreated epimastigote showing normal ultrastructural aspect and presenting typical morphologies of the mitochondrion (M), kinetoplast (K), flagellum (F), nucleus (N), Golgi (G), reservosome (R) and cytostome (Cy). (B-E) The concentration of 0.3 μM NQ1 led to swelling in the mitochondrion (*), the formation of abnormal cytosolic membranous structures (white arrowheads) and the appearance of endoplasmic reticulum surrounding reservosomes (white arrows). Blebs (thick black arrows) was formed in the flagellar membrane of treated parasites. Bars = 500 nm (A, B, E) and 200 nm (C, D). Figure 3 Transmission electron microscopy analysis of T. cruzi epimastigotes treated with NQ8. (A-D) Treatment with 0.

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