The next day, sections were rinsed with 01 m PBST, incubated in

The next day, sections were rinsed with 0.1 m PBST, incubated in biotinylated horse anti-mouse IgG (1 : 200, Vector Laboratories, Burlingame, CA, USA) for1 h, and rinsed again with 0.1 m PBST. Tissue sections were then treated with solutions from the VECTASTAIN Elite ABC kit (Vector Laboratories) according to the supplier’s instructions for 30 min at room temperature followed by washes in 0.1 and 0.001 m PB. Immunoreactivity was detected using 3, 3′-diaminobenzidine (DAB; Sigma-Aldrich) at 25 mg/50mL in 0.1 m PB with 0.004% H2O2. Sections were thoroughly c-Met inhibitor rinsed with dH2O, dehydrated and then coverslipped. To determine the

number of BrdU-positive cells in the RMS, we first located the RMS by staining every tenth section throughout the left hemisphere with anti-BrdU, and then identified the single sagittal section within the 10-series that had the greatest representation of the RMS for analysis. The distribution of 1-h-labeled BrdU cells was highly localized in the RMS, which begins at the rostral tip of the lateral ventricle and terminates at the caudal end of the olfactory bulb (Fig. 1). The linear density of BrdU-positive cells per millimeter of RMS length was calculated from a single section that contained the most intact RMS exhibiting the stereotypical trajectory of proliferating cells en CP-868596 chemical structure route to the OB. BrdU-immunoreactive

cells in the RMS of this optimal section were counted under brightfield illumination and with the aid of a 20× objective (Zeiss 200M Axiovert inverted microscope equipped with Axiovision 4.6 software). RMS length was measured using NIH ImageJ (version 1.42) software. Linear density from 1 h BrdU labeling

was systematically determined for A/J, C57BL/6J and their RI strains and was expressed as mean ± SEM for each strain. Another counting approach adapted from Lee et al. (2003) was used in which we counted the number of BrdU-positive cells in every tenth immunostained section (80-μm intervals) throughout the entire medial to lateral extent of the RMS. The total number of labeled cells was calculated for 20 randomly selected animals and this value is highly Glycogen branching enzyme correlated with the linear density (R = 0.88; P < 0.0001; see Supplementary material Fig. S1), thus demonstrating the effectiveness of our single best-section quantification method. Animals used for analysis of BrdU-labeling in the RMS were also used to examine the proliferative activities in another neurogenic site, the subgranular zone (SGZ) of the hippocampal dentate gyrus. We quantified BrdU-positive cells in the SGZ, which is located at the interface between hilus and the granular layer of the dentate gyrus (DG), and this proliferative layer can be easily visualized by cresyl violet (CV) stain under a 40× objective (Kempermann et al., 2003).

In the current study, we set out to determine which personal, soc

In the current study, we set out to determine which personal, socioeconomic, treatment-related and disease-related characteristics were independently associated with reported difficulty taking antiretroviral therapy (ART) in those respondents who were taking ART at the time of completing the HIV Futures 6 survey. The HIV Futures 6 survey was an anonymous, self-complete, cross-sectional survey. The survey contained 189 items organized into eight sections: demographics; accommodation; health and treatments; services and communities; sex and relationships;

employment; recreational drug use; and finances. The survey was largely based on the HIV Futures 5 survey [26], which was see more in turn based on the four previous surveys PFT�� concentration [27–30]. The content of the survey was developed in consultation with a number of organizations and individuals in the HIV/AIDS sector. Survey respondents were recruited through community organizations and clinical settings, as

well as through online and paper-based advertisements in community organization and gay media within Australia. Previous survey respondents who indicated that they were interested in participating in future research projects were also approached. Any HIV-positive individual residing in Australia was eligible to complete the survey. Data were collected from October 2008 to April 2009. The HIV Futures 6 survey included two items that asked respondents about their aminophylline adherence to ART over the previous 2 days: ‘How many doses (dose times) of antiretroviral drugs did you miss yesterday?’ and ‘How many doses (dose times) of antiretroviral drugs did you miss the day before yesterday?’, with scores in the range 0–5 (a score of 5 representing ≥5 missed doses). The data from these survey items were highly skewed, with only 1.5% [13]

of those respondents currently taking ART indicating any nonadherence in the previous 2 days. As a result, we needed to use a proxy variable to assess factors associated with nonadherence to cART. We considered using two other survey items: (i) self-reported most recent viral load (detectable vs. undetectable) and (ii) self-reported difficulty taking ART (‘Do you experience any difficulties in taking antiretroviral drugs?’; yes/no responses). The viral load variable was also fairly skewed, with only 48 respondents currently taking ART (5.5%) reporting a detectable viral load. Hence, we chose to use self-reported difficulty taking ART as our outcome variable. This variable was found to be highly associated with both self-reported adherence (Fisher’s exact test; P=0.001) and respondents’ most recent viral load test result (detectable vs. undetectable viral load; χ2-test; P=0.018), and was therefore deemed to be a suitable proxy variable for investigating factors associated with poor adherence to ART.

, 2008; Yang et al, 2009; Zaparoli et al, 2009; Bernardi et al

, 2008; Yang et al., 2009; Zaparoli et al., 2009; Bernardi et al., 2011). The relation here found, and the fact that these widely different stresses and growth conditions all had much the same down-regulating effect on the transcription of cp, suggest that the regulation of cp was most likely not caused directly by the particular factor tested, but was a more general response www.selleckchem.com/products/PLX-4720.html to the growth level of the fungus. This hypothesis is supported by the similarity of the 3D structure of CP to expansins (de Oliveira et al., 2011), proteins mainly found in plants where they have various roles in growth and in developmental processes involving cell wall modifications (McQueen-Mason & Cosgrove, 1994;

Cosgrove et al., 2002; Li et al., 2003; Choi et al., 2006). A small number of expansin-like proteins has also been found in fungi (Saloheimo et al., 2002; Bouzarelou et al., 2008; Brotman et al., 2008; Chen et al., 2010; Wang et al., 2010; Quiroz-Castañeda et al., 2011). Expansins cause cell wall loosening and cellulose disruption even though they do not have any cellulose-hydrolytic activity. Like expansins, CP is localized in the cell

CHIR-99021 concentration wall, has a double-ψβ-barrel fold, lacks lytic activity and has the ability to bind oligosaccharides. Moreover, the residues involved in carbohydrate binding are conserved among the members of the CP family, suggesting that the biological function of these proteins could be related to polysaccharide binding (de Oliveira et al., 2011). In conclusion, our results strengthen the functional similarity between CP and expansins and allow us to propose the involvement of CP in the remodelling and enlargement of the Dichloromethane dehalogenase cell wall that occur during hyphal growth and in the formation and differentiation process of chlamydospores. The work was supported by the Ministero Italiano dell’Università e della Ricerca Scientifica, Progetti di

Ricerca di Interesse Nazionale 2007 to A.S. “
“Salmonella enterica serovar Enteritidis is a major cause of human gastrointestinal disease, infection being due in large part to consumption of contaminated eggs. The lipopolysaccharide (LPS) of Salmonella is known to play a role in colonisation of the host and survival in hostile conditions including egg albumen. We investigated the contribution of LPS O-antigen length to colonisation of the reproductive tract of laying hens, contamination of eggs and survival in albumen. We show that expression of very-long O-antigen is essential for contamination of eggs, probably as a consequence of enhanced reproductive tract colonisation and survival in the forming egg. “
“Phosphorothioate modification of DNA and the corresponding DNA degradation (Dnd) phenotype that occurs during gel electrophoresis are caused by dnd genes. Although widely distributed among Bacteria and Archaea, dnd genes have been found in only very few, taxonomically unrelated, bacterial species so far.

The reason why they showed no activity against the two Coleoptera

The reason why they showed no activity against the two Coleoptera insects is still to be elucidated but could be due to target modification, inadequate insect sources, or the variability of Vip1–Vip2 binary toxins. However, our novel binary toxins Vip1Ac1 and Vip2Ae3 showed toxic activity to A. gossypii.

This is probably the second report of Vip1 and Vip2 binary toxins exhibiting toxicity against Homoptera. Moreover, Carfilzomib in vitro our novel Vip1Ac1 and Vip2Ae3 binary toxins show higher toxicity to A. gossypii than the previously reported Vip1A (BR) and Vip2A (BR) binary toxin (Sattar et al., 2008). The reason why the two binary toxins show toxicity to the same target pest may be due to high homology in amino acid sequence with the membrane-binding proteins of Vip1Ac1 and Vip1A (BR). Despite this similarity, there are differences between the Vip2Ae3 and Vip2A (BR) given that their LC50 for A. gossypii is distinct. Co-expression ITF2357 mw proteins showed toxicity to A. gossypii, while single-expression protein had no activity. This difference in bioassay results between co-expression and single-expression proteins is an indication that the mode of action of the two active units for binary toxin is different. Similar to earlier reports (Shi et al., 2006),

Vip1Ac1 and Vip2Ae3 binary toxin identified in our work showed no toxicity against Lepidoptera and Diptera insects. The identification system of novel vip1-type genes that included PCR–RFLP and SON-PCR is reliable for identification of novel vip1 genes. The identification

of Vip1Ac1 and Vip2Ae3 provides an alternative source of Vips useful to infer resistance to crops against insect pests. Moreover, the discovery of binary toxin of Vip1Ac1 and Vip2Ae3 may be useful for biological control to avoid insect resistance. We thank Dr Yiu-kwok Chan for correcting Ketotifen the manuscript. This study was supported by Chinese Major Project to Create New Crop Varieties Using Gene Transfer Technology (No. 2008ZX08001-001) for transgenic research, the Ministry of Agriculture of China (No. 2008ZX08009-003). “
“The effect of Lactobacillus plantarum genomic DNA on lipopolysaccharide (LPS)-induced mitogen-activated protein kinase (MAPK) activation, nuclear factor-kappa B activation, and the expressions of tumor necrosis factor-alpha, interleukin-1 receptor-associated kinase M, and the pattern recognition receptor were examined. Pretreatment of p-gDNA inhibited the phosphorylation of MAPKs and nuclear factor-kappa B, and also inhibited LPS-induced TNF-α production in response to subsequent LPS stimulation. L. plantarum genomic DNA-mediated inhibition of signaling pathway and tumor necrosis factor-alpha was accompanied by the suppression of toll-like receptor (TLR) 2, TLR4, and TLR9 and the induction of interleukin-1 receptor-associated kinase M, a negative regulator of TLR.

We assessed the production of OMVs from K pneumoniae ATCC 13883

We assessed the production of OMVs from K. pneumoniae ATCC 13883 during in vitro culture. Bacteria were cultured in LB broth, and OMVs were purified from culture supernatants. TEM analysis showed that K. pneumoniae-derived vesicles were spherical bilayered structures with diameters of 20–200 nm (Fig. 1a). No bacteria or protein contaminants were observed. The small-sized OMVs with diameters of approximately 20–30 nm were commonly observed, whereas relatively

large-sized vesicles with diameters of > 50 nm were less commonly observed. This result suggests that K. pneumoniae produces and secretes OMVs into the extracellular milieu during in vitro culture. Klebsiella pneumoniae OMVs were subjected to SDS-PAGE. Many protein bands were identified in the K. pneumoniae OMVs, but the protein profiles were different between OMVs and whole-cell lysates (Fig. 1b), selleck products suggesting the absence of bacterial contaminants. Proteomic analysis was conducted to identify proteins in the OMVs from K. pneumoniae ATCC 13883. We identified

159 proteins in the K. pneumoniae OMVs (Supporting Information, Table S1). The proteins identified in the K. pneumoniae Selleck Rapamycin OMVs were predicted to occur in the extracellular space (n = 13), outer membrane (n = 24), periplasmic space (n = 25), inner membrane (n = 13) and cytoplasm (n = 84). Of the proteins identified in the K. pneumoniae OMVs, the outer membrane protein X, murein lipoprotein, phage shock protein: Acetophenone activates phage shock-protein expression, putative uncharacterized protein ygdR and 30S ribosomal protein S20 were the most abundant among the proteins located in the

outer membrane, periplasmic space, inner membrane, extracellular space and cytoplasm, respectively. These results suggest that K. pneumoniae OMVs contain numerous proteins originating from inner membrane and cytoplasm as well as outer membrane and periplasmic space. OMVs are naturally secreted products of Gram-negative bacteria, and OMV production appears to be a conserved process among Gram-negative bacteria (Beveridge, 1999; Kuehn & Kesty, 2005; Kulp & Kuehn, 2010). Additionally, Gram-positive bacteria such as Staphylococcus aureus and Bacillus anthracis also produce membrane-derived vesicles (Lee et al., 2009; Rivera et al., 2010; Gurung et al., 2011). Deatherage et al. (2009) proposed the OMV biogenesis model in Salmonella typhimurium. During bacterial growth and division, localized reductions in the density of outer membrane–peptidoglycan and outer membrane–peptidoglycan–inner membrane associations result in the bulging and release of the outer membrane as OMVs. Based on this model, OMVs only reflect the outer membrane and periplasmic components. However, cytoplasmic and inner membrane proteins have been identified in OMVs from E. coli (Lee et al., 2008), H. pylori (Olofsson et al., 2010) and Acinetobacter baumannii (Kwon et al., 2009).

Through pregnancy, it is routine to monitor LFT tests at each ant

Through pregnancy, it is routine to monitor LFT tests at each antenatal clinic appointment as a marker for potential obstetric complications

(HELLP, pre-eclampsia, acute fatty liver, etc.), particularly in the final trimester. Finally, in those diagnosed late and not receiving HBV treatment incorporated into cART, LFT flares may be seen shortly after delivery, which in some relates to HBeAg seroconversion and reappearance or a marked increase in HBV DNA levels. Where acute infection is suspected, testing for anti-HBc IgM is recommended. Acute HBV is uncommon during pregnancy and each case needs to be managed with specialist advice. Data suggest that lamivudine as part of cART does not completely protect against the development of acute HBV infection, although it is unknown whether

this is also the case Selleck Ponatinib with tenofovir with or without lamivudine/emtricitabine. Although there is a theoretical risk of high HBV DNA levels and the linked association with increased risk of transmission combined with the potential for acute hepatitis and threat to maternal and fetal health, the presumption would be that this would be abrogated by the patient already being on cART incorporating tenofovir and either emtricitabine or lamivudine. Where the woman is not on ART, a tenofovir-based ART regimen this website should be commenced immediately. 6.1.3 Where pegylated interferon or adefovir is being used to treat HBV in a woman who does not yet require HIV treatment and who discovers she is pregnant, treatment should be stopped and switched to a tenofovir-based cART regimen. Grading: 1C If a woman on pegylated interferon becomes pregnant it should be discontinued and changed to a tenofovir-based cART regimen because of the anti-proliferative effect of the drug. Few data are available on the risk of congenital malformation with first-trimester exposure to the newer therapies telbivudine (FDA category B) and entecavir (FDA Category C). The outcome of the pregnancy should be reported to the Interferon Pregnancy and Antiretroviral Pregnancy Registries. 6.1.4 Since there is no evidence of any adverse effect on maternal or neonatal health if women become

pregnant while taking antiretroviral not therapy active against HBV, treatment should be continued. Grading: 1C For tenofovir, emtricitabine and lamivudine, APR [53] and the Development of Antiretroviral Therapy Study (DART) [190] have not identified any increased risk in prevalence or any specific pattern of anomaly, even when administered in the first trimester. Hence, when a patient becomes pregnant on an anti-HBV viral agent as part of their cART (tenofovir, lamivudine or emtricitabine), as for HIV management, cART should be continued as the potential risk to the fetus from drug exposure is outweighed by that of a hepatitis flare or liver disease progression if the drug(s) were to be discontinued in addition to HIV virological rebound and risk of MTCT.

To our knowledge, this is the first study to investigate

To our knowledge, this is the first study to investigate

the effect of rhGH in HIV-infected patients both with and without HALS. The lipolytic effect of rhGH appeared to be present in patients with and without HALS. The difference between groups in indices of abdominal fat accumulation was the result of an improvement in the GH group and a deterioration in the placebo group. This was particularly the case for patients suffering from HALS, indicating a deterioration of fat distribution over time in these patients. No such change took place in the patients without HALS. Indices of fat atrophy in the extremities did not show the same tendency. Although fasting plasma glucose increased significantly (0.4 mM) in the GH group compared with the placebo group, it is important to note that indices of beta-cell function (2-h post-challenge glucose level) and insulin resistance (HOMA-IR) did not change in any of the study groups. Screening Library in vivo The frequency of patients with IGT did not change over the course of the study in either the placebo or the GH group, and did not differ between groups at baseline or week 40. In patients who had a mildly impaired glucose tolerance at baseline, fasting glucose

levels did not deteriorate selleck kinase inhibitor more with rhGH treatment. The chosen dose of rhGH can probably be considered safe with respect to glucose metabolism in this group of patients, although the slight increase in plasma glucose indicates that parallel monitoring of glucose metabolism is warranted. Other cardiovascular risk factors, such as lipid levels and blood pressure, did not change during the course of the study. The HIV-infected patients enrolled in the present study are probably representative of the morphological and metabolic problems in the general HIV-infected population by not merely reflecting the group DOK2 of patients with HALS, which could probably benefit the most from rhGH treatment. Thus, we may have underestimated the morphological changes that occur in patients more seriously

affected by fat redistribution. Lo et al. [15] investigated one-selected group of HIV-infected patients with both relative GH deficiency and HALS, and reported that as many as a third of HIV-infected patients with HALS have a relative GH deficiency. We have previously shown that HIV-infected patients with HALS probably compensate for impairments in GH secretion by increasing the GH sensitivity of GH target tissues [13]. It is unknown whether GH sensitivity in relatively GH-deficient patients is increased, and whether those patients could possibly benefit even more from rhGH treatment. The complex dynamics in the GH/IGF-I axis of HIV-infected patients impedes comparison with data from the present study. However, it is possible that we underestimated the effect of rhGH in patients with HALS and relative GH deficiency. There are several limitations to the present study.

To our knowledge, this is the first study to investigate

To our knowledge, this is the first study to investigate

the effect of rhGH in HIV-infected patients both with and without HALS. The lipolytic effect of rhGH appeared to be present in patients with and without HALS. The difference between groups in indices of abdominal fat accumulation was the result of an improvement in the GH group and a deterioration in the placebo group. This was particularly the case for patients suffering from HALS, indicating a deterioration of fat distribution over time in these patients. No such change took place in the patients without HALS. Indices of fat atrophy in the extremities did not show the same tendency. Although fasting plasma glucose increased significantly (0.4 mM) in the GH group compared with the placebo group, it is important to note that indices of beta-cell function (2-h post-challenge glucose level) and insulin resistance (HOMA-IR) did not change in any of the study groups. Doxorubicin concentration The frequency of patients with IGT did not change over the course of the study in either the placebo or the GH group, and did not differ between groups at baseline or week 40. In patients who had a mildly impaired glucose tolerance at baseline, fasting glucose

levels did not deteriorate Selleck ALK inhibitor more with rhGH treatment. The chosen dose of rhGH can probably be considered safe with respect to glucose metabolism in this group of patients, although the slight increase in plasma glucose indicates that parallel monitoring of glucose metabolism is warranted. Other cardiovascular risk factors, such as lipid levels and blood pressure, did not change during the course of the study. The HIV-infected patients enrolled in the present study are probably representative of the morphological and metabolic problems in the general HIV-infected population by not merely reflecting the group Adenosine triphosphate of patients with HALS, which could probably benefit the most from rhGH treatment. Thus, we may have underestimated the morphological changes that occur in patients more seriously

affected by fat redistribution. Lo et al. [15] investigated one-selected group of HIV-infected patients with both relative GH deficiency and HALS, and reported that as many as a third of HIV-infected patients with HALS have a relative GH deficiency. We have previously shown that HIV-infected patients with HALS probably compensate for impairments in GH secretion by increasing the GH sensitivity of GH target tissues [13]. It is unknown whether GH sensitivity in relatively GH-deficient patients is increased, and whether those patients could possibly benefit even more from rhGH treatment. The complex dynamics in the GH/IGF-I axis of HIV-infected patients impedes comparison with data from the present study. However, it is possible that we underestimated the effect of rhGH in patients with HALS and relative GH deficiency. There are several limitations to the present study.

For the patient data, with administered contrast agent, the mean

For the patient data, with administered contrast agent, the mean post-contrast signal enhancement is equivalent to about 4 signal units in gray matter,

1 in white matter, 3 in CSF and 64 in blood, with changes over the imaging period following the first post-contrast time point being around −1.3 in gray matter, −0.5 in white matter, 2.2 in CSF and −15 in blood. These small signal differences will be influenced by discretization errors, as the signal is sampled as integer values. However, as the contrast this website agent uptake curves are obtained by averaging data from many voxels, these effects are expected to largely cancel out. Simulations performed based on the data obtained in this study indicate that the discretization error for white matter would be less than 0.01% for data averaged from 1000 voxels, far fewer than that used to generate the curves in Fig. 1. Nevertheless, if the APO866 cost ultimate aim is to compare data on a voxel-by-voxel basis, then discretization errors need to be reduced, possibly by improving scanner electronics

or the procedure used for setting the receiver gain. The theoretical analysis demonstrated that to cause a greater signal enhancement for a given contrast agent concentration, either T10 or r1 must be increased. The 9.15% increase observed in deep gray matter Etave between high- and low Fazekas-rated patients would require the baseline T10 to be increased by 86 ms in the high Fazekas-rated

group compared to the low Fazekas-rated group. While this is greater than the 35-ms increase observed, it is within experimental error. Similarly, the observed differences between high- and low Fazekas-rated groups in cortical gray matter, white matter, CSF and blood Etave of 4.29%, 15.02%, −23.68% and 12.81% would require T10 to differ by 43, 81, −1092 and 180 ms, respectively. The observed mean T10 differences in each of these tissues are 7, 62, −37 and −140 ms, which, while being consistently lower in magnitude than that required to cause the observed enhancement differences, are generally within experimental error of the simulated values due to the large error associated with these measurements. Similarly, if a difference in r1 between high- and low Fazekas-rated patients were to be responsible for the Loperamide differences in Etave, then r1 would need to be altered from its assumed value of 4.3 s−1 mM−1 by 0.43, 0.20, 0.94, −0.93 and 1.04 s−1 mM−1 in each of deep gray matter, cortical gray matter, white matter, CSF and blood, respectively. These changes are equivalent to 9.6%, 4.4%, 20.9%, −20.7% and 23.1% deviations from the assumed r1 in each of the respective tissues. These simulated data suggest that the signal enhancement differences seen in this study of 0.003 in cortical gray and white matter, 0.006 in deep gray matter and 0.

Parasite resistance was also observed in assays performed with LA

Parasite resistance was also observed in assays performed with LAAO from B. atrox, since BMS-734016 a dose of 32 μmol/L was necessary to kill 41.7 ± 2.4% of trypomastigotes ( Alves Paiva et al., 2011). In conclusion, LmLAAO shows a low toxicity in vivo when compared with other enzymes or toxins from snake venoms, but it might be used as cytotoxic tool toward pathogens or cancer cells, as verified by in vitro toxicity experiments. Additionally this study showed, for the first time, the cytotoxic effects of LAAO on AGS cell line (gastric adenocarcinoma) and MCF-7 cell line (breast adenocarcinoma). Furthermore, our analyses show evolutionary sequence and structural

conservation of LAAOs across snake

species, suggesting the existence of selective pressures in the evolution of this enzyme. Therefore, the biochemical, structural and functional characterizations of LmLAAO, demonstrates that it is a novel LAAO molecule with several important biological functions. The work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, under Gramts No 479873/2009-7 and No São Paulo (FAPESP), Brazil, under Grant No 2005/54855-0 check details and Instituto Nacional de Ciência e Tecnologia de Toxinas (INCTTox, Fapesp/CNPq). Model data are available in the PMDB (Protein Model Data Base) under accession number PM0077706 (http://mi.caspur.it/PMDB/user/search.php). The amino acid sequence data are available in the DDBJ/EMBL/GenBank database under the accession number JX171244

(http://www.ebi.ac.uk/ena/data/view/JX171244) and Nucleotide sequence data are available in Ribonuclease T1 the DDBJ/EMBL/GenBank databases under the accession number LMUT0069C (http://www.ebi.ac.uk/ena/data/view/JX171244). We are grateful to Dra Elizabeth Abrahams, Departamento de Parasitología, Facultad de Microbiología, Universidad de Costa Rica, for her contribution with some of Trypanosoma strains tested in cytotoxicity experiments. Thanks are also due to Karla de Castro Figueredo Bordon and Aarón Gómez Argüello for technical assistance. The work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, under Grants No479873/2009-7 and No142711/2007-1 (Ph.D. scholarship), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil, under Grant No2005/54855-0 and Instituto Nacional de Ciência e Tecnologia de Toxinas (INCTTox, Fapesp/CNPq). “
“Physiological pain serves as a warning mechanism that indicates imminent tissue damage. Chronic pain lacks such protective function, since it persists for years without reflecting the severity of a lesion or disease, nor does chronic pain necessarily respond to treatment of the underlying disease cause (McGreevy et al., 2011).