The same 100 serum samples were also used to establish the cut point for the IFX-HMSA (data not shown). The calculated cut point for IFX-HMSA was 0.98 μg/mL, yielding a clinical specificity of 95%. Currently one of the clinically validated methods for measuring ATI is by using bridging ELISA methodology (Baert et al., 2003), which over the last decade has been used to measure ATI in serum samples from IBD patients treated with IFX. To evaluate the performance of the HMSA to detect ATI in the presence of IFX compared to that of the bridging ELISA assay, we performed BIBW2992 ATI-HMSA on 100 serum samples obtained from IBD patients that were previously

tested to be positive for ATI by the bridging ELISA method. The proportion of shifted area over the total

area and the interpolated ATI from the standard curve (multiplied by the dilution factor of 50) are shown in Fig. 6C and D, respectively. The mean values of ATI in the patient serum samples were significantly higher than those in the drug-naïve healthy controls (mean ± SD = 9.57 ± 11.43 vs. 0.73 ± 0.29 μg/mL, p < 0.0001) as shown in Fig. 7A. Receiver operating characteristic curve analysis of these samples ( Fig. 7B) showed that the area under the curve was 0.986 ± 0.007 (95% CI: 0.973–0.999, p < 0.0001), the sensitivity Crizotinib chemical structure was 95% (95% CI: 88.72%–98.36%), and the odds ratio was 47.50 when a 1.19 μg/mL cut point was used. Good correlation between the ATI values obtained from the ATI-HMSA and the bridging ELISA was also observed, with p < 0.0001 and a Spearman r-value of 0.39 (95% CI: 0.2–0.55) as shown in Fig. 8. Upon re-testing the three samples from the healthy controls with the ATI concentration above the cut point (1.196, 1.201, and 1.219 μg/mL) using ATI-HMSA, the resulting ATI concentrations were all below the cut point. Thus we defined these results as false-positive.

However, among the 100 ATI-positive IBD patient serum samples previously determined by the bridging ELISA, five of the samples were found to be ATI-negative (i.e., containing ATI concentrations below the cut point of 1.19 μg/mL). Tryptophan synthase Repeatedly re-testing these samples showed no shift on the SE-HPLC chromatogram, thus we defined the five samples as true negative. The increased rate of false-positive ATI measurements with the bridging ELISA method may be attributed to an elevated level of nonspecific binding. Since the initial approval of the antibody drug IFX by the United States Food and Drug Administration for the treatment of Crohn’s disease (CD) in 1998, the broad use of anti-TNF therapy in IBD has dramatically improved therapeutic outcome over the past decade (Targan et al., 1997, Colombel et al., 2010, Present et al., 1999, Rutgeerts et al., 1999 and Hanauer et al., 2002). Nevertheless, there is a significant number of patients that either fail to respond (primary non-responders) or lose response (secondary non-responders) to anti-TNF treatments.

, 2004). However, there is a need for more efficient compounds with broader reactivation activity after exposure to different OPs and that are less toxic to humans. The crystal structure of AChE (Bourne et al., 1995, Ekström et al., 2006, Kryger et al., 1998 and Sussman et al., 1991) allows for detailed structural studies on ligand access to the enzyme’s active center gorge and the steric constraints within the active center gorge that govern selectivity during reactivation (Ashani et al., 1995, Grosfeld et al., 1996, Kovarik et al., 2004 and Wong et al., 2000). The orientation of the

compound within the narrow confines of the gorge when the active serine is phosphorylated is an important determinant of the

reactivation mechanism (Musilek et al., 2011). learn more There are several in silico studies that illustrate the ability of this structural model to reliably predict molecular interactions. There is considerable interest in thiosemicarbazones due to their wide pharmacological utility (Beraldo and Gambino, 2004) and versatility as ligands. They have recently been investigated as radical scavengers (Wada et al., 1994) and our previous study (Barcelos et al., 2011) revealed that a thiosemicarbazone derivate, isatin-3-N4-benzilthiosemicarbazone Galunisertib cell line (IBTC), is also effective as an antioxidant and antiatherogenic molecule. Although the use of thiosemicarbazone as an antiatherogenic molecule has been suggested previously (Barcelos et al., 2011), in vitro and in vivo toxicological screening is still needed. Therefore, the aim of this study was to test the toxicological effects of IBTC, a thiosemicarbazone derivate, and to identify the effective concentration of IBTC for protecting and reactivating

cholinesterases after exposure to MAP. In addition, any possible inhibitory effects of IBTC on the thiol-containing enzymes from the blood/liver and brain, namely delta-aminolevulinic acid dehydratase (ALA-D) and Na+/K+-ATPase, respectively, were also evaluated. Fossariinae Docking studies were carried out in silico to evaluate the minimal energy IBTC conformations in the active site of human AChE when the active site serine is phosphorylated by MAP. The synthesis of isatin-3-N4-benzilthiosemicarbazone (IBTC) was performed as described previously (Fonseca et al., 2010) and the chemical structure of IBTC is depicted in Fig. 1. The reagents thiobarbituric acid (TBA), dicloroflouresceine diacetate (DCFH-DA), methyltetrazolium (MTT), ethylene glycol tetraacetic acid (EGTA), Ellman’s reagent (5,5′-dithiobis-(2-nitrobenzoic acid) or DTNB), N,N,N′,N′-tetramethylbenzidine and ouabaine were supplied by Sigma–Aldrich Chemical Co. (St. Louis, MO); acetylthiocholine iodide supplied by Merck. The other used reagents were obtained from local suppliers. Human red blood cells (RBC) were separated from heparinized blood that was drawn from a healthy donor.

In the DYNAMIC + STATIC group, a larger (11.5 N) dynamic load was superimposed upon the 2.0-N static “pre-load”.

Except for these differences in the loading regimen, all three groups received the same treatment. This included isoflurane-induced anesthesia for three alternate days a week for 2 weeks (approximately 7 min/day) during which loading took place. Normal cage activity was allowed between the treatments. High doses of calcein Target Selective Inhibitor Library price (50 mg/kg; Sigma Chemical Co., St. Louis, MO) and alizarin (50 mg/kg; Sigma Chemical Co.) were injected intraperitoneally on the first and last days of the treatments (days 1 and 12), respectively. At 21 weeks of age (day 15), the mice were euthanized and their tibiae, fibulae, femora, ulnae and radii were collected for analysis. The apparatus and protocol for dynamically loading the mouse tibia/fibula have been reported previously [12], [13], [27], [29] and [32]. In brief, the flexed knee and ankle joints are positioned in concave cups; the upper cup, into which the knee is positioned, is attached to the actuator arm of

a servo-hydraulic selleck screening library loading machine (Model HC10; Zwick Testing Machines Ltd., Leominster, UK) and the lower cup to a dynamic load cell. The tibia/fibula is held in place by a low level of continuous static “pre-load”, onto which is superimposed higher levels of intermittent “dynamic” load. In the present study, 2.0 N was used as the static “pre-load” which was held for 400 s according to the original protocol [12]. The 11.5 N of “dynamic” load was superimposed onto the 2.0-N static “pre-load” in a series of very 40 trapezoidal-shaped pulses (0.025 s loading, 0.050 s hold at 13.5 N and 0.025 s unloading) with a 10-s rest interval between each pulse. Strain gauges attached to the medial surface of the tibial shaft of similar 19-week-old female C57BL/6 mice showed that at a proximal/middle site (37% of the bone’s length from its proximal end) a peak load of 13.5 N engendered approximately 1400 microstrain [29]. Although a peak load of 12.0 N can

induce significant osteogenic responses in both cortical and trabecular bone [27], we selected a higher peak load (13.5 N) which was sufficient to induce woven bone formation in the loaded tibia [29]. Woven bone is generally seen in areas where the strain-related stimulus is high. Sample et al. [30] reported that it was at the “high” level of peak load that dynamic loading of the ulna resulted in (re)modelling responses in other bones that were not loaded. By using a loading regimen that stimulated woven bone formation, we sought to provide a stringent test for the presence of regional or systemic influences on mechanically adaptive (re)modelling in bones other than those being loaded. The tibiae, fibulae, femora, ulnae and radii from both sides in each animal were collected after sacrifice, stored in 70% ethanol and scanned by μCT (SkyScan 1172; SkyScan, Kontich, Belgium) with a pixel size of 5 μm.

Detailed experimental results and results of factorial ANOVAs are shown in Supplementary Fig. 1. Table 2 shows F and p values from ANCOVAs for significant tests taking verbal IQ, non-verbal IQ and processing speed as covariates. There were significant group differences in three measures. First, in the subitizing task counting-range slope was less steep in DD than in controls in the

4–6 number range. This was due to a larger drop in accuracy for number 6 in controls than in DD (see star in Supplementary Fig. 1D). Second, there was a larger congruency effect in DD than in control participants in non-symbolic magnitude comparison (see star in Supplementary Fig. 1F). Third, correct rejection performance was worse in DD than in controls in the

Stop-signal task (see star in Supplementary Fig. 1E). In ANOVAS MK-2206 mouse there was an additional marginal group × congruency interaction in the animal size Stroop task due to a marginally larger congruency effect in DD than in controls ( Supplementary Fig. 1B). The trail-making task was scored on a 0–2 scale. Accuracy was practically the same in both groups in both trail-making A/B: All DD participants and all but one control scored maximum on trail-making A (a NVP-BKM120 single control scored 0). Scores were also matched on trail-making B (number of DD/Control participants with particular scores: Score 2: 8/7; Score 1: 2/2; Score 0: 2/3). Importantly, both permutation testing and confidence interval estimation showed that symbolic and non-symbolic slope was a highly non-discriminative parameter between groups. Fig. 3 shows effect sizes. In detail, in the non-symbolic discrimination task the mean ratio effect was −1.75 ± .5% (mean and SE; accuracy for each ratio: 97.2 ± 1.1, 95.6 ± 1.4 and 93.7 ± 1.6%) in the DD group and −1.70 ± .4% in the control

group (accuracy for each ratio: 97.7 ± .9, 95.2 ± 1.8 and 94.3 ± 1.8%). In the symbolic discrimination task the mean distance effect was −3.26 ± 1.4% Calpain (distance 1 minus distance 4) in the DD group and −5.24 ± 1.4% in the control group (accuracy for each level of distance: DD: 91.5 ± 1.9 and 94.8% ± 1.3; controls: 89.0 ± 2.3 and 94.2 ± 1.6%). Fig. 3B summarizes main findings in RT with permutation testing and t statistics and bootstrapped 95% confidence intervals for effect sizes. Detailed experimental results and results of factorial ANOVAs are shown in Supplementary Fig. 2. Table 3 shows F and p values from ANCOVAs for significant tests taking verbal IQ, non-verbal IQ and processing speed as covariates. There were significant group differences in four measures. First, there was a larger facilitation effect in the numerical Stroop task in DD than in control participants ( Supplementary Fig. 2G). The negative effect means that RT sped up more in the congruent relative to the neutral condition in DD than in control participants.

Under the microscope, only insignificant remnants of white matter can Panobinostat mouse be seen within this zone. The stroke of the occipital lobe therefore caused a degeneration of the entire stratum sagittale externum in the

temporal lobe. A marked contrast is the cingulum in the gyrus hippocampi, which usually joins the stratum sagittale externum and is now stained deep black.Plate 1, Plate 2, Plate 3 and Plate 4 Burdach, 1826, Sachs, 1893, Sachs, 1905, Sachs, 1909. “
“Conceptual knowledge for objects comprises a diverse set of information about their sensory qualities, motor plans and verbal associations. How are these disparate sources of information linked to form a concept? According to one influential view, originally proposed by Wernicke (Wernicke, 1900; as cited in Eggert, 1977), conceptual knowledge for objects arises from the co-activation of their sensory-motor properties within a network of modality-specific

processing regions that are widely distributed throughout the cortex (Barsalou, 2008, Martin, 2007 and Pulvermuller, 2001). This approach makes two key predictions concerning the breakdown of conceptual knowledge under brain damage. First, damage to a single, modality-specific region should give rise to knowledge deficits that disproportionately affect properties in that selleck inhibitor modality and, by extension, categories of objects for which the affected modality is particularly central (Capitani et al., 2003, Mahon and Caramazza, 2009 and Warrington and Shallice, 1984). So, for example, damage to regions of inferior parietal cortex involved in representing skilled actions should impair knowledge of how objects are manipulated and lead to a disproportionate deficit for tools (Buxbaum & Saffran, 2002). The second prediction concerns global, pan-modal conceptual

impairments. According to Wernicke and his modern counterparts, these should only occur as a result of global cortical damage, because only damage to all of the modality-specific regions would be sufficient to produce a global impairment. This prediction is challenged by tuclazepam the neurodegenerative syndrome of semantic dementia (SD). SD patients suffer from a global conceptual knowledge deficit that affects all categories of object and word (Hoffman and Lambon Ralph, 2011 and Lambon Ralph et al., 2007) and all sensory-motor modalities (Bozeat et al., 2000, Bozeat et al., 2002, Luzzi et al., 2007 and Piwnica-Worms et al., 2010), yet the cerebral atrophy and hypometabolism that gives rise to this debilitating impairment is not global: it is focused bilaterally on the anterior ventrolateral and polar portions of the temporal lobes (Galton et al., 2001 and Mion et al., 2010). Evidence from functional neuroimaging (Binney et al., 2010 and Visser and Lambon Ralph, 2011) and transcranial magnetic stimulation (Pobric et al., 2007 and Pobric et al.

The absence of this ciliate in the zebra mussels examined by Raabe (1956) is more difficult to interpret as very little is currently known about its ecology and biology. The levels of infection of D. polymorpha with C. acuminatus and Ophryoglena sp. recorded in our study are comparable to those in other European PFT�� water bodies ( Molloy et al., 1997, Mastitsky, 2004 and Karatayev et al., 2007). The quantitative dominance of C. acuminatus over Ophryoglena sp. observed in our samples is also consistent

with previous studies. Such a dominant position of C. acuminatus is generally explained by its commensal relationship with D. polymorpha, allowing the ciliate to reach high numbers without causing any significant harm to its host ( Molloy et al., 1997 and Karatayev et al., 2007). In contrast, Ophryoglena sp. is a true parasite ( Molloy et al., 1997 and Karatayev et al., 2002), whose levels of infection are likely to be inversely related to the fitness of its host. The numbers of C. acuminatus and Ophryoglena sp. in zebra mussels were significantly positively associated with temperature ( Tables 1, 2). Whereas such a positive relationship has been well documented in previous works for C. acuminatus ( Karatayev et al., 2000a and Karatayev et al., 2003), the existing data for Ophryoglena sp. are controversial. As in our results ( Figure 4), CDK inhibitor the highest levels

of the prevalence and intensity of Ophryoglena sp. infection in D. polymorpha from the Dnieper-Bug Canal, Belarus, were observed in summer months ( Karatayev et al. 2002). However, considerably Tolmetin lower levels of the Ophryoglena sp. infection in zebra mussels were recorded in summer than in winter months in the Drozdy Reservoir, Belarus ( Karatayev et al. 2003) and in the River Meuse, NE France ( Minguez & Giambirini 2012). Additional investigations would help to better understand the seasonal dynamics of this parasitic ciliate in D. polymorpha and the role of temperature and other environmental factors in this process. In his study in the Vistula Lagoon, Raabe (1956) found C. acuminatus to be less tolerant to salinity than its host D. polymorpha, so that the prevalence of infection declined to 0% with increasing

salinity. Neither C. acuminatus nor Ophryoglena sp. demonstrated such a pattern in the Curonian Lagoon. This, however, could be explained by the relatively low average monthly salinities we observed (≤ 4.5 PSU most of the time), preventing confident statistical inference. In addition to the ciliates, we found D. polymorpha to be infected with unidentified nematodes. Several studies conducted in freshwater lakes in Europe ( Karatayev et al., 2003, Mastitsky and Gagarin, 2004 and Mastitsky et al., 2008) suggest that these worms were probably free-living species typically inhabiting periphyton. The most common species of nematodes documented thus far in zebra mussels are oxyphilic representatives of the family Chromadoridae ( Mastitsky and Gagarin, 2004 and Mastitsky et al., 2008).

We have tested for the first time if DEXA had any protective effect against the myotoxic effect of the B. jararacussu venom in vitro and these data indicate that DEXA has no interaction with the venom components, nor with the muscle tissue, and it does not interfere with the anticytotoxic effect of EP extract constituents

which was active in this condition. Our results suggest that the in vivo effect may be due to the DEXA anti-inflammatory properties. The inflammatory parameters investigated in vivo showed that both B. jararaca and B. jararacussu venoms induce local edema at the inoculation site confirming previous works ( Milani Jr et al., 1997; Olivo et al., 2007). In our observations B. jararacussu Ipilimumab venom increased the leukocytes counts in mice blood and EDL muscles 24 h after the perimuscular injection. These results are similar to the report of Carneiro et al. (2008) who described that B. jararaca venom increased the blood leukocyte count before the local cell increasing. Both DEXA and EP extract alone reduced the edema generated by the venoms injections, and we observed an increase in this anti-edematogenic effect

in the group receiving both treatments. Interestingly, mice that received the treatment with DEXA showed a higher blood leukocyte count, while those who received EP extract maintained the same range of the animals receiving only venom injection. When we performed the EDL muscle leukocytes count 24 h after the B. jararacussu venom injection we observed an ATM inhibitor increase in their number. The local presence of leukocytes after Bothrops venoms injections has been Cell Penetrating Peptide investigated under different experimental conditions with various snake species, such as: Bothrops asper, Bothrops lanceolatus, and B. jararaca in different inoculation sites like peritoneum, skin and skeletal muscles ( Gutierrez et al., 1986; Farsky et al., 1997; Costa et al., 2002; Zamuner et al., 2001).

However, the exact mechanism of cell migration to the inoculation site is yet to be elucidated. It has been demonstrated in vitro that peptides toxins purified from B. jararacussu venom can activate neutrophil migration ( Elifio-Esposito et al., 2011). Nevertheless, according to Farsky et al. (1997) the local leukocyte increase induced by injection of B. jararaca venom is dependent on activation or secretion of endogenous compounds such as cytokines. The treatment with DEXA showed muscle tissue leukocyte count reduction in mouse EDL muscle. Similar DEXA effect has been reported with B. jararacussu inoculated in the peritoneum ( Pereira et al., 2009), which also showed an antiedema effect against this venom. Perretti and Flower (1993), although not using venoms in their investigations, described an antimigratory effect of DEXA on mouse leukocytes and correlated this effect with annexin 1 production. Mancuso et al.

The biomarker signature of 200 genes with the most discriminatory power to separate between skin sensitisers and non-sensitisers was obtained by employing an algorithm for backward elimination (Johansson et al., 2011). To test a substance, cells are treated for 24 h with a maximum concentration of 500 μM for highly soluble Cabozantinib chemical structure non-toxic substances or a concentration yielding 90% viability for toxic substances as measured with PI. Following cell stimulation, the transcriptional levels of the 200 genes, collectively termed the predictive biomarker signature, is evaluated using a whole genome array (Johansson et al., 2013). Classifications of unknown compounds as sensitisers or non-sensitisers are performed GSK-3 phosphorylation with

a support vector machine (SVM) model, trained on the 38 reference chemicals used for GARD development, and the output is a decision value as compared to the classification threshold. Key event 3 is covered with this test method. SensiDerm™ aims to discriminate sensitisers and non-sensitisers based

on pathway-specific biomarker proteins induced in the MUTZ-3 cell line. The biomarker panel comprises the following ten proteins which have been shown to be differentially expressed in MUTZ-3 cells in response to sensitisers compared to non-sensitisers during the assay development: glucose-6-phosphate-1-dehydrogenase, 6-phosphoglucote dehydrogenase, heat shock protein A8, myeloperoxidase (light/heavy chain), S100A4 protein,

S100A8 protein, S100A9 protein, 4F2 cell surface antigen heavy chain, superoxide dismutase, thymosin beta-4-like protein. MUTZ-3 cells are exposed to non-toxic concentrations (>80% viability) of the test substance for 24 h with a maximum concentration of 100 μg/mL. The cellular proteins are then extracted and analysed by mass spectrometry procedure based on selective reaction monitoring. The results of ID-8 the tests are provided as a ratio of protein expression between the exposed cells and cells grown in a control medium, which is then subjected to a polynomial model that provides a score with a threshold to discriminate sensitisers from non-sensitisers (Thierse et al., 2011). This method addresses key event 3 in the skin sensitisation AOP. In order to obtain a common data set for all test methods, ten substances were selected (see Table 2 for identities). The chemicals were purchased from Sigma–Aldrich with at least 95% purity, with the exception of Lactic acid (approx. 90%), then coded and distributed to the test method developers by Cosmetics Europe. They comprised three non-sensitisers including SLS, which is positive in the LLNA, and seven sensitisers covering all sensitiser potency classes as defined by the LLNA (1 weak, 3 moderate, 2 strong, 1 extreme) including the poorly water-soluble lauryl gallate as a specifically challenging substance. Test methods developed by member companies of Cosmetics Europe (i.e.

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il a tissé des liens étroits d’amitié et de partage. La rencontre Ion Channel Ligand Library avec Pierre Lequien ne laissait jamais indifférent. Son enthousiasme, son humour, sa voix, son immense culture, la facilité qu’il avait à trouver le mot juste, parfois provocateur, captait son auditoire. L’empathie naturelle qu’il avait pour les familles et pour ses collaborateurs, nous a tous frappés. Petits détails du quotidien : il envoyait un bouquet de fleurs à chaque collaboratrice qui venait d’accoucher ; il ne manquait jamais de rendre visite à ceux d’entre nous qui étions hospitalisés. Nous sommes nombreux à avoir eu la chance d’avoir été l’élève du professeur Lequien. Je profite de cet hommage pour exprimer toute notre profonde gratitude. L’objet de notre reconnaissance ne se résume pas à ce qu’il a fait. Si je disais qu’il était simple de travailler avec lui, je crois que je ferais sourire ceux qui l’ont côtoyé de près. En réalité, notre gratitude porte bien plus sur ce qu’il nous a

légué. Monsieur Lequien nous a transmis le sens de l’accueil : l’accueil des familles, des internes, des nouvelles puéricultrices, des médecins en formation ou de passage. Je me souviens d’une multitude de détails qui m’ont marqué, comme ce 1er geste à la première heure de notre arrivée lors de l’ouverture de l’hôpital Jeanne-de-Flandre : il a en tout premier serré la main de l’agent administratif avec qui il a fait connaissance. Geste particulièrement symbolique ! Un autre exemple marquant : lors de la première rencontre Ku-0059436 concentration avec les nouveaux internes du service, les 2 premiers messages qu’il leur délivrait était : « Écoutez les parents, ils ont tout à vous apprendre ! » ; « Respectez tous les collaborateurs du service, qu’ils soient soignants ou non soignants ». tetracosactide Grâce à ce sens de l’autre, et à son sens de l’accueil, il a su construire un formidable réseau d’amitié et d’entraide. Tous ces liens tissés au fils des années, que ce soit à l’hôpital ou à l’extérieur de l’hôpital, sont un patrimoine inestimable. Il nous a transmis sa vision de la médecine du nouveau-né : elle consiste

en une prise en charge globale et indissociable de l’enfant et de sa famille. Il a formé ses collaborateurs à tous les aspects de la médecine néonatale, que ce soit aux soins les plus techniques de réanimation jusqu’à tous les aspects de la pédiatrie sociale et de la santé publique. Il nous a appris comment maîtriser ou comment faire face aux situations les plus inextricables. Je l’entends dire : « Il n’y a pas de problème, il n’y a que des solutions ». Et si vraiment, il n’y avait pas de solutions, souvenez-vous : « Quand les choses nous échappent, feignons de les avoir voulues ! ». Nous lui sommes reconnaissants pour son dynamisme qui a mobilisé tous ceux qui ont eu la chance de le côtoyer. Il a porté un nombre considérable de projets, dont beaucoup étaient d’avant-gardes.

In conclusion, osteopontin, a chemotactic protein with cytokine-like properties was found to be up-regulated in muscle injury caused by B. lanceolatus (fer-de-lance) snake. The upregulation of OPN occurred during the acute stage of inflammation and during myogenic cell proliferation and differentiation. The expression of OPN by cells

of a myogenic lineage, macrophages and fibroblasts agrees with its role as an adhesive chemotactic matricellular protein with cytokine-like properties that can modulate the expression of myogenic transcriptional factors and, hence, muscle regeneration. In our experimental model, three weeks after envenoming, the regenerating fibers were small, indicating delayed regeneration. Since OPN has been also described as pro-fibrotic protein in adverse conditions, its possible mediation learn more in collagen deposition in the region of myoblast proliferation Ipilimumab order needs to be investigated. As far as we know, this is the only report to associate OPN expression in a rat model of muscle regeneration after the intramuscular injection of Bothrops snake venom. The authors have no conflict of interest related to this work. The authors thank Marta B. Leonardo, MSc, and Glauce Aparecida Pinto, PhD, for excellent technical assistance and Dr. Stephen Hyslop for criticism and revising the language. This work was supported by a grant from Fundação de Amparo à Pesquisa do Estado de São Paulo

(FAPESP, grant no. 2005/60929-7). V.B.S. was supported by an MSc studentship from Coordenação de Florfenicol Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil. S.P.I. was a post-doctoral researcher in the Venom and Toxin Laboratory of M.A.C.H. M.A.C.H. is supported by a research fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil. “
“Microcystins (MCs) are a group of natural toxins produced by cyanobacteria which can be found in lakes, ponds and rivers. These cyanotoxins are hepatotoxic, causing serious human health problems by inhibition of some phosphatase proteins (Terao et al., 1994). MCs cause morphologic damage in the liver, starting with cytoskeletal disruption and loss of sinusoidal

structure. Liver weight is increased due to intrahepatic hemorrhage followed by hemodynamic shock, heart failure and death by hemorrhagic shock (Eriksson et al., 1990 and Chorus and Bartram, 1999). Zhang et al. (2008), demonstrated the role of reactive oxygen species induced by MC-RR on apoptosis sensitivity of Carassius auratus lymphocytes. In Brazil, tilapia species such as Tilapia rendalli and Oreochromis niloticus have been introduced for socioeconomic purposes since 1956 ( Gurgel and Fernando, 1994). Bioaccumulations in fish were observed in salmon that ate crab larvae containing MC ( Williams et al., 1997). Accumulation in liver and muscle of T. rendalli was demonstrated by Soares et al. (2004). This latter study showed that toxins could still be found in fish muscle several days after contamination.