Comprehensive reviews on the use of thalidomide have been published and include efficacy and safety in relapsed MM. The rationale for using thalidomide was based on its antiangiogenic properties because, in MM, increased microvessel density has been inversely correlated to survival. However, thalidomide has multiple modes of action, including immunomodulatory effects. This initial experience generated a great enthusiasm, and a large number

of phase II trials were rapidly conducted. A systematic review of such 42 trials on >1600 patients confirm that the response rate is 29 % with an estimated 1-year overall survival (OS) of 60 %. The well-known teratogenicity of thalidomide is not a major concern CA3 in patients with MM because of patients age, but justifies careful informing of patients and programs to avoid drug exposure in women with childbearing potential. The major toxicities of thalidomide are fatigue, somnolence, constipation, and mostly peripheral neuropathy, which are related to the daily dosage and to treatment duration. The overall incidence of peripheral neuropathy is 30 % but may be higher if treatment is prolonged for >1 year. Because this complication

CX-5461 in vitro may be disabling and sometimes irreversible, patients should decrease the dose or stop the treatment if significant numbness occurs. After induction treatment, two to four cycles of combination therapies is followed by the maintenance therapy, which is continuous therapy with a single agent, with reasonable balance between maximum benefits and minimum toxicities [24] until the time of disease progression. Maintenance therapy for multiple

myeloma I GSK872 in vitro prefer disease control as a treatment goal, except in selected high-risk patients in whom an aggressive approach to achieving CR may be the only option to long-term survival (Fig. 5). The disease control approach involves targeting very good partial response selleck chemical (minimal residual disease) rather than CR as a goal by using limited, less intense therapy first and moving to more aggressive approaches as need arises (sequential approach): this allows patients to help determine the timing and number of transplants. Fig. 5 Strategy of myeloma treatment in our institute. We divided in four phases: initial therapy by two to four courses of BorDex/CyBorD/ or MPB >66 years old followed by PBSC-harvest. If the high risk patients, up-front PBSC-transplantation followed by Bor-maintenance. Otherwise, if the standard risks patients, maintenance-therapies may be the B-stages until progress disease. PD are defined as (1) above 10 % elevation of M-protein, (2) hypercalcemia, (3) anemia progress, (4) bone pain, (5) β2-MG elevation (6) additional chromosome ab. (7) BM myeloma cell elevation. After PD, problem-oriented PBSCT may be done with second maintenance with Lenalidomide Post-transplant consolidation/maintenance with novel agents can become an important step forward.

J Phys Chem B 2006, 110:8348–8356.CrossRef 5. Singh PK, Bisht G, Auluck K, Sivatheja M, Hofmann R, Singh KK, Mahapatra S: Performance and reliability study of single-layer and dual-layer platinum nanocrystal flash memory devices under NAND selleck compound operation. IEEE Trans Electron Devices 2010, 57:1829–1837.CrossRef 6. Kim H, Woo S, Kim H, Bang S,

Kim Y, Choi D, Jeon H: Pt nanocrystals embedded in remote plasma atomic-layer-deposition HfO2 for nonvolatile memory devices. Electrochem Solid-State Letters 2009, 12:H92.CrossRef 7. Novak S, Lee B, Yang X, Misra V: Platinum nanoparticles grown by atomic layer deposition for charge storage memory applications. J Electrochem Soc 2010, 157:H589-H592.CrossRef 8. Yeom D, Kang J, Lee M, Jang J, Yun J, Jeong DY, Yoon C, Koo J, Kim S: ZnO nanowire-based nano-floating gate memory with Pt nanocrystals embedded in Al2O3 gate oxides. Nanotechnology

2008, 19:395204.CrossRef 9. Lee C, Meteer J, Narayanan V, Kan EC: Self-assembly of metal nanocrystals Geneticin datasheet on ultrathin oxide for nonvolatile memory applications. J Electron Mater 2005, 34:1–11.CrossRef 10. Li J, Liang XH, King DM, Jiang YB, Weimer AW: Quisinostat supplier Highly dispersed Pt nanoparticle catalyst prepared by atomic layer deposition. Appl Catal Environ 2010, 97:22–226. 11. Christensen ST, Elam JW, Rabuffetti FA, Ma Q, Weigand SJ, Lee B, Seifert S, Stair PC, Poeppelmeier KR, Hersam MC, Bedzyk MJ: Controlled growth of platinum nanoparticles on strontium titanate nanocubes by atomic layer deposition. Small 2009, 5:750–757.CrossRef 12. Hsu IJ, Hansgen DA, McCandless BE, Willis BG, Chen JG: Atomic layer deposition of Pt on tungsten monocarbide (WC) for the oxygen reduction reaction. J Phys Chem C 2011, 115:3709–3715.CrossRef Buspirone HCl 13. Farmer DB, Gordon RG: High density Ru nanocrystal deposition for nonvolatile memory applications. J Appl Phys 2007, 101:124503.CrossRef 14. Lim SH, Joo KH, Park JH, Lee SW, Sohn WH, Lee C, Choi GH, Yeo IS, Chung UI, Moon JT, Ryu BI: Nonvolatile MOSFET memory based on high density WN nanocrystal layer

fabricated by novel PNL (pulsed nucleation layer) method. In Symposium on VLSI Technol. Digest of Technical Papers: June 14–16 2005. New York: IEEE; 2005:190–191. 15. Maikap S, Wang TY, Tzeng PJ, Lin CH, Lee LS, Yang JR, Tsai MJ: Charge storage characteristics of atomic layer deposited RuOx nanocrystals. Appl Phys Lett 2007, 90:253108.CrossRef 16. Zhang M, Chen W, Ding SJ, Wang XP, Zhang W, Wang LK: Investigation of atomic-layer-deposited ruthenium nanocrystal growth on SiO2 and Al2O3 films. J Vac Sci Technol A 2007,25(4):775–780.CrossRef 17. Gou HY, Ding SJ, Huang Y, Sun QQ, Zhang W, Wang PF, Chen Z: Nonvolatile metal–oxide–semiconductor capacitors with Ru-RuOx composite nanodots embedded in atomic-layer-deposited Al2O3 films. J Electron Mater 2010,39(8):1343–1350.CrossRef 18.

10A). Average OD630 nm measurements of the crystal violet extracts, which are see more directly related to biofilm mass, were 0.204 ± 0.003, 0.137 ± 0.006, and 0.194 ± 0.003 for the wild-type, sur7Δ null mutant, and SUR7 complemented strains, click here respectively (p < 0.0001). Examination of the biofilm by scanning electron microscopy demonstrated a sparse biofilm architecture compared to control strain DAY185 (Fig. 10B). Figure 10 Analysis of C. albicans sur7 Δ biofilm formation. (A) Biofilm mass was assayed by staining the biofilm formed with Crystal Violet [45]. Data analyzed consisted of 14 replicates and statistical significance was determined by ANOVA (p-value < 0.0001), indicated on the figure with

an asterisk (*). (B) The structure and morphology of the biofilm formed by the sur7Δ null mutant strain and wild-type strain DAY185 was examined by scanning electron microscopy. Size bars indicate 20 μm. Next, in order to determine if the reduced biofilm mass of the

sur7Δ mutant is related to decreased attachment of the biofilm, we quantified the amount of planktonic cells in the biofilm www.selleckchem.com/products/a-769662.html wash of each strain. Compared to the control strains, there were significantly fewer planktonic cells (colony forming units) present in the biofilm formed by the sur7Δ null mutant (p < 0.0001; data not shown). These results are therefore consistent with the previous adhesion studies. Thus, reduced attachment of cells does not account for the lesser biofilm mass of the sur7Δ null mutant. Furthermore, as there is only a minor delay or impairment in filamentation in this growth selleck chemicals llc medium, it appears that the defect in biofilm formation is most likely due to a defect in cell wall or plasma membrane structure related to the absence of SUR7. The C. albicans sur7Δ mutant is defective in macrophage killing Lastly, we sought to determine the effect of the loss-of-function of SUR7 on the ability of C. albicans to kill macrophage cells. At early time points (1 and 5 hours co-incubation), the number of live macrophage cells co-incubated with the sur7Δ null mutant was similar

to the numbers found when co-incubated with either DAY185 or the SUR7 complemented strain (>1,000 macrophages per field; data not shown). After 24 hours of co-incubation, significantly more macrophages per field remained when co-incubated with the sur7Δ null mutant (841 ± 87) than either of the control strains (5 ± 2 and 3 ± 1 for wild-type and SUR7 complemented strains, respectively) (Fig. 11A and 11B p < 0.0001). These results indicate that C. albicans SUR7 is required for in vitro macrophage killing. Figure 11 In vitro test of virulence using the macrophage killing assay. Macrophages were seeded onto a glass slide and subsequently co-incubated with C. albicans strains at a multiplicity of infection of 2. (A) Live macrophage cells from four fields per strain tested were counted and the averages were compared using ANOVA.

Nuevo, M., Meierhenrich, U. J., Muoz-Caro, G. M., Dartois, E., d’Hendecourt, L., Deboffle, D., Auger, G., Blanot, D., Bredehoft, J. H., Nahon, L., (2006) The effects of circularly polarized light on amino acid enantiomers produced by the UV irradiation of interstellar ice analogs, Astron. Astrophys., 457:741–751. Nuevo, M., Meierhenrich, U. J., d’Hendecourt, L., Muoz-Caro, G. M., Dartois, E., Deboffle, D., Thiemann, W. H.-P., Bredehoft, J.-H., Nahon, L., (2007) Enantiomeric separation of

complex organic molecules produced from irradiation of interstellar/circumstellar ice analogs, Adv. Space Res., 39, 400–404. Pizzarello, S., Cronin, J. R., (2000) Geochem. Cosmo. Acta, Non-racemic amino acids in the Murray and Murchison meteorites, 64:329–338. Pizzarello, S., Zolensky, M., Turk, K. A., (2003) Geochem. Cosmo. Acta, Nonracemic isovaline in the

Murchison selleck chemicals meteorite: Chiral distribution and mineral association, 67:1589–1595. Reisse, J., Cronin, J., in: Bordeaux, P. U. d. (Ed.), Les traces du vivant, Presses Universitaires de Bordeaux, Bordeaux 2003, pp. 82–113. E-mail: Louis.​DHendecourt@ias.​u-psud.​fr The Salt-Induced Peptide Formation Reaction as Possible Origin of Biohomochirality Daniel Fitz, Bernd M. Rode Division of Theoretical Chemistry; Institute of General, Inorganic and Theoretical Chemistry; University of Innsbruck The Salt-Induced Peptide Formation see more (SIPF) Reaction has been shown to yield considerable amounts of di- and oligopeptides from amino acids in aqueous solution under assumed

prebiotic conditions just with the help of sodium chloride and Cu(II) ions. Strikingly, a few amino acids, especially alanine (Plankensteiner, et al. 2004) and valine (Plankensteiner, et al. 2005), show better reactivity when present in their L-form compared to their D-enantiomers, suggesting that this reaction might have played a keyrole in the origin of biohomochirality. This PI3K inhibitor drugs behaviour may be explained by the geometry of the active, peptide-forming /www.selleck.co.jp/products/MG132.html species. Under the reaction conditions a central copper ion forms a complex containing two amino acids and one choride ligand in a distorted square ‘plane’. This distortion gives rise to central chirality at the copper ion, which, because of its relatively high atomic number, can now provide considerably high parity-violating energy differences (PVEDs, caused by parity violation in weak interactions) between a complex containing L-amino acids and its D-analogue. Ab initio geometry calculations of such active complexes show that the out-of-plane distortion of the ligands is more pronounced for amino acids showing an enantiomeric preference for the L-form than for those which do not (Fitz, et al. 2007).

These data confirmed the validity of microarray to quantify changes in bacterial transcript levels. While the heat-induced upregulation of ctsR and hrCA may seem paradoxical in view of their previously described repressor activities [13, 18] that should down-regulate the transcription of other HSP genes belonging to their respective operons, other parameters may be involved to explain this paradox. First, it has been shown that the CtsR repressor needs ClpC protein to be active [18], and that high temperature may lead to accumulation of conformationally inactive CtsR in the absence of

the chaperone co-factor [18]. Second, the global regulatory impact of ClpP protease on S. aureus virulence and stress responses also affects the regulation of genes of both the CtsR- and HrcA-controlled regulons [15]. Finally, significant heat shock-induced Histone Methyltransferase inhibitor alterations in energy supplies, which may influence the availability of intracellular Selleck Epacadostat ATP levels required for Clp ATPases activities, might also have an impact on the transcriptional control of both CtsR- and HrcA operons. Finally, to find out whether the presence of a fully functional

SigB operon was required for heat-shock transcriptomic responses of HrcA- or/and CtsR-regulated HSP components, we also assayed by qRT-PCR the changes of HSP transcript levels in strain ISPU, a derivative of S. aureus strain ISP794 that was genetically restored with a complete rsbU + operon. The 16-fold increase in transcript levels of the SigB-regulated gene asp23 confirmed RsbU restoration in the strongly pigmented strain ISPU compared to its non-pigmented RsbU-negative parent ISP794 (data not shown). Additional file 3 shows that heat-induced transcript levels in strain ISPU were either equivalent or <2-fold Meloxicam higher than those recorded in the

RsbU-defective parental strain ISP794. Thus, a fully functional SigB operon was not required for induction of heat-shock regulons HrcA and CtsR. In contrast to those heat-induced gene activities, serine protease HtrA-like (htrA) and trigger factor (tig) coding genes, as well as several other genes coding for Clp ATPases (clpL, clpQ, clpX, clpY) were not at all induced by up-shift to either 43°C or 48°C (Additional file 2), in agreement with previous observations [17, 18]. Finally genes coding for in situ repair mechanisms of Emricasan order damaged amino acid residues, such as those belonging to either the methionine sulfoxide reductase complex or the peptidyl-prolyl cis-trans isomerase protein PrsA [11, 36], were only marginally up-regulated by temperature up-shifts at 43°C or 48°C (Additional file 2). Impact of heat stress on S. aureus growth and survival Evaluation of S. aureus outcome following temperature up-shifts at 43°C or 48°C was performed by several assays. Both optical density measurements at OD540 and viable counts indicated that S. aureus cultures were in late-log phase during heat shock.

Certain E. coli clones with specific virulence factors

are involved in extraintestinal infections the so called extraintestinal pathoghenic E. coli (ExPEC), and these bacteria often cause both urinary tract infections and septicemia. Furthermore, specific E. coli are involved in childhood diarrhea, (enteropathogenic E. coli), tourist diarrhea (enterotoxigenic E. coli), and recently, bloody diarrhea associated with hemolytic uremic syndrome (verotoxin-producing E. coli). In the 1970′s, it was found that hemolytic E. coli were linked to active UC, although it was believed that the hemolytic E. coli were innocent bystanders, and their presence in the colon was assisted by the inflammation but did not cause it [6]. On the other hand, it has been shown that apathogenic E. coli prevents relapse of UC just as well as mesalazine [7]. Furthermore, E. coli has been linked to CD, since an abundance of specific adherent-invasive E. coli was found in resected ileum from patients find more with CD, compared to non inflamed ileum resected due to other causes [8, 9]. Very recently, it was demonstrated by ribosomal intergenic spacer analysis that enterobacteriaceae are more abundant in tissue samples from patients with IBD compared to controls, and after culture, specific phylogenetic groups of E. coli were found to be more frequent among learn more patients with UC and CD [10]. Moreover, it has been shown that E. coli are very predominant

in inflamed mucosa of patients with UC, and that these strains based on 16 S rRNA PCR are “”active”" and overrepresented in comparison with the microbiota of healthy controls, who generally had a higher biodiversity of the active microbiota [11]. In addition, an exuberant inflammatory response to E. coli has been demonstrated among patients with UC [12]. The aim of our study was to characterize possible differences in phylogenetic group, serotype, ExPEC

genes and virulence between E. coli isolated from patients with active IBD, patients with inactive disease and healthy controls, as well as to examine whether multilocus HDAC inhibitor sequence typing (MLST) could further Ribonuclease T1 distinguish between these E. coli. MLST is considered the most stable and appropriate of currently available molecular typing techniques for long term epidemiology and for the identification of bacterial lineages that have an increased propensity to cause disease [13]. Results Fecal samples were collected from 18 patients with IBD with present or past involvement of the left side of the colon and from 10 healthy controls. In both patients and controls, a sigmoidoscopy was performed. Ten patients were found to have a non-inflamed mucosa, whereas 8 had clear inflammation in the sigmoid colon. More detailed characteristics of patients are presented in Table 1. A total of 26 E. coli strains were isolated from study subjects. From 3 patients and 1 control, no E. coli could be isolated. From one patient with active IBD and one patient with inactive IBD two different E.

A likely explanation for these

differences could be that check details rep-PCR analysis embraces the entire bacterial chromosome, whereas the main signals reported in MALDI-TOF MS are generated from ribosomal proteins alone [18, 13]. Since we studied a small number of strains, we can’t draw firm conclusions about the correlation between automated rep-PCR and MALDI-TOF for molecular typing of Ochrobactrum anthropi. However, both methods have demonstrated a similar sensitivity in discriminating the variability among the strains studied. Although strict comparison between PFGE and MALDI-TOF was problematic, due to the different methods involved (i.e., protein profiling for MALDI-TOF dendrogram and genetic profiling for PFGE), the tests showed a similar separation between the CZ1552 strain and the other strains. Although the results obtained by the two techniques were similar, on the whole, MALDI-TOF results were obtained much more rapidly, within a few minutes. MALDI-TOF is not only much easier and less-time consuming than PFGE, it also requires a limited amount of bacterial colonies and allows comparison at all times with the universal database. Semi-automated rep-PCR appeared to be more discriminative than PFGE in typing the 23

O. anthropi strains isolated during this hospital outbreak. Both rep-PCR and MALDI-TOF MS yielded four clusters and a common ancestor, while PFGE showed the same CP673451 ic50 PFGE profile in 22 isolates. In PFGE, strain CZ1552 was the odd one out, whereas rep-PCR identified strain CZ1424 as being different. These strains

were found to be genetically unrelated to each other. The marker used for the rep-PCR analysis (the region between the noncoding repetitive sequences in bacterial genomes) is less genetically Captisol order stable than the one used for PFGE (the target sequence of the SpeI restriction Amisulpride enzyme). Hence, the variability shown by rep-PCR is likely to represent changes in the same clone that could not be detected by PFGE [19]. Rep-PCR analysis is a technique aimed at defining clonal relationships, and its ease of use and faster turnaround time as compared to PFGE makes it a rapid method of screening outbreaks of O. anthropi and therefore allows timely implementation of control measures. Conclusions In conclusion, rep-PCR and MALDI-TOF MS appear to be extremely useful for evaluation of clonal relationships between isolates. The different marker (genomic vs. proteomic) evaluated, as well as the completely different techniques used increase the reliability with which isolate similarity or diversity may be assessed during a hospital outbreak. In addition, we believe that advances in the molecular typing of Ochrobactrum anthropi would facilitate the study on the epidemiology, prevention and control of the infections caused by this pathogen. References 1.

Figure 3 Effect of metabolic inhibitors and anoxia on AThTP levels in BL21 cells. The bacteria were grown overnight in LB medium and transferred to minimal medium in the absence

or the presence of O2 (replaced by N2), KCN (1 mM) or iodoacetate (1 mM) (20 min, 37°C) either in the absence of substrates or in the presence of 10 mM D-glucose or 10 mM L-lactate. (**, p < 0.01; *, p < 0.05: two-way ANOVA followed by the Dunnett test for comparisons with the respective control. (Means ± SD, n = 4) Figure 4 Effect of KCN on AThTP levels in BL21 cells. The bacteria (BL 21 strain) were grown overnight in LB medium, and transferred #Selleck Stattic randurls[1|1|,|CHEM1|]# to M9 minimal medium and incubated at 37°C in the presence of 10 mM L-lactate. After 60 min, 1 mM KCN was added. (Means ± SD for 3 experiments) Uncoupling of oxidative phosphorylation in the presence of a substrate induces a rapid accumulation of AThTP The most dramatic effect on AThTP levels was obtained in the presence of the uncoupler CCCP, which

induced a rapid appearance of AThTP. E. coli cells (BL21 strain) were incubated for 20 min in the presence of glucose (10 mM) and increasing concentrations of CCCP (Figure 5A). The amount of AThTP increased with increasing concentrations of CCCP. This increase was paralleled by a stimulation of O2 consumption (Figure 5B). Progressive increase in CCCP concentration also led to an increased lag before the growth resumed (Figure 5C). The recovery of growth in the presence of low (< 10 μM) concentration Mannose-binding protein-associated serine protease of CCCP may be related to development by the bacteria of mechanisms

Selleck BLZ945 of CCCP ejection [19]. In any event, the recovery was only partial in the presence of 5 or 10 μM CCCP and completely blocked at higher concentrations. These results suggest that the collapse of Δp favors the appearance of AThTP. Figure 5 Dose-dependent effects of CCCP on AThTP content, respiration and growth of E. coli. (A) The bacteria (BL21 strain) were transferred to minimal M9 medium containing 10 mM D-glucose and the indicated CCCP concentrations. After 20 min (37°C, 250 rpm), the intracellular AThTP concentration was determined by HPLC. (B) Effect of CCCP on the respiratory ratio Γ (O2 consumption in the presence of CCCP over the O2 consumption in the absence of CCCP) measured in the presence of 10 mM glucose at 37°C by polarographic recording of O2 consumption. (C) Growth curves of the bacteria in the presence various concentrations of CCCP. (Means ± SD, n = 3) A low energy charge is not sufficient to trigger AThTP accumulation Our results indicate that carbon starvation is a robust trigger of AThTP accumulation in E. coli cells, whatever the strain used (see Table 2). However, AThTP can also be produced in the presence of a carbon source when metabolic inhibitors are present, suggesting that AThTP production is linked to metabolic inhibition and/or energy stress rather than the absence of an extracellular carbon source.

However, the MLST data indicated different STs due to changes in the nucleotide sequences of the analyzed housekeeping genes; see more these data are consistent with the findings of Poh et al. [46]. In addition, the VREF isolates within clusters II-B1 and IV displayed identical PFGE and MLST profiles, in agreement with other authors [22, 33]. Nevertheless, pulsotypes from different wards showed similar multidrug resistance profiles, possibly due to horizontal genetic transference between these isolates. MLST is an important tool

for studying the molecular epidemiology of outbreaks of E. faecium and microbial population biology [44]. MLST analysis of VREF clinical isolates revealed four STs: ST203, ST412, ST612 and ST757. As previously reported, clonal complex 17 harbors various STs that have been involved in hospital outbreaks. Our results

revealed two allelic profiles, ST203 and ST412, belonging to clonal complex 17 STs involved in hospital outbreaks. However, clonal complex 17 has been resolved into learn more two different subgroups, one of which harbors ST17 and ST18, while the second harbors ST78 [47]. ST17, ST18 and ST203 are the major groups in the genetic lineage of E. faecium; they are distributed worldwide and have been associated with outbreaks [18, 48]. ST412 was the most selleck screening library frequent sequence type found in the VREF isolates from HIMFG and was genetically linked to the ST78 lineage. Interestingly, ST412 has been identified worldwide and associated with outbreaks [49]. According to the eBURST analysis, ST612 showed characteristics of the STs belonging to the 18 lineage. ST757 has not been characterized within clonal complex 17. In addition, ST757 displayed resistance markers (ampicillin and quinolones), virulence genes (esp + and/or hyl +) and the purK1 allele; however, it has not been associated with

outbreaks. Nevertheless, this community of multidrug-resistant strains is able to infect humans and might contribute to the spreading of these bacteria in the hospital, highlighting the importance of molecular typing via MLST to identify STs involved in nosocomial outbreaks. Recently, it was shown that MLST analysis of typified E. faecium based on selected alleles may generate misleading results due to the recombination of five alleles (atpA, ddl, gdh, gyd and pstS). As only the purk and adk alleles are located in crotamiton regions where there is no predicted recombination, the results must be interpreted with care [50]. The genome of E. faecium is highly plastic due to the few existing barriers to the acquisition of foreign genetic elements [51, 52]. Recent studies have provided evidence of high levels of recombination through comparative genomics analyses [51–54]. Whole-genome sequencing platforms are superior to conventional typing methods, providing an excellent tool for determining phylogenies and regions of recombination and for accurately discriminating between outbreak- and non-outbreak-causing VREF isolates [50, 55].

aureus pulmonary infections [12]. In spite of its relevance, the behaviour of S. aureus in undernourished subjects has not been fully investigated. In this context, we used a PEM murine model to evaluate both, the susceptibility and the ability to mount a protective immunity against a MRSA with emphasis on lung selleck chemicals involvement. Results Alterations determined by undernutrition We initially characterized a model of dietary restriction by determining body weight, triglyceride seric levels and leucogram. Effects of two percentages (10 and 20%) of dietary

restriction were compared with parameters observed in a control group that received food ad libitum. Both levels of restriction determined a significant weight loss and decreased serum concentration of triglycerides (figure 1a and 1b, respectively). However, only RAD001 the group submitted to 20% of dietary restriction presented alterations compatible with secondary immunodeficiency as decreased lymphocyte number (figure 1c). Figure 1 Alterations determined

by undernutrition. BALB/c mice were submitted to two percentages of dietary restriction TNF-alpha inhibitor (10 and 20%) and evaluated in relation to weight loss (a), seric triglyceride concentration (b) and differential blood cell count (c). Results are expressed as mean ± SD of 5 animals per group (*p < 0.05) in relation to well nourished group. Effect of dietary restriction and immunization on bacterial load Twenty-four hours after intraperitoneal infection with 5 × 108 CFU/0.5 mL of S. aureus, all animals from the four experimental groups presented bacteria in the blood (figure 2a). Determination of CFU in the spleen did not show any significant difference among these groups

(figure 2b). However, differences were observed in lung analysis. Well nourished mice immunized with formolized S. aureus presented a significant reduction in CFU in this organ. Interestingly, this effect was not triggered in undernourished mice. An even increased amount of bacteria Unoprostone was present in undernourished immunized animals (figure 2b). A reduced amount of bacteria was also observed in the liver of well nourished mice that were previously immunized with S. aureus (figure 2c). Injection of Complete Freund’s Adjuvant alone did not reduce bacterial load (not shown). Figure 2 Effect of dietary restriction and immunization on bacterial load. BALB/c mice were submitted to dietary restriction (20%), immunized with the formolized bacteria and infected with 5 × 108 CFU/0.5 ml of S. aureus. The bacterial load was determined 24 hours later in the blood (a), spleen and lung (b) and liver (c). Results are expressed as mean ± SD of 5 animals per group (*p < 0.05) in relation to well nourished group. Lung histopathological analysis As expected the pulmonary parenchyma from well nourished and non infected mice showed a very well preserved alveolar structure without any inflammatory process (figure 3a).