Macrophage monocultures previously incubated in the presence of CTX displayed increased LXA4 secretion (59% at 24 h, Fig. 6B). Differences in the levels of LXA4 were not observed at 12 h (Fig. 6A) or at 48 h (Fig. 6C). In contrast,

CTX enhanced the 15-epi-LXA4 production by macrophage monocultures in all the time periods evaluated (9.3-fold at 12 h, Fig. 6D; 5.5-fold at 24 h, Fig. 6E; 2.7-fold at 48 h, Fig. 6F), compared to control monocultures. The supernatants of co-cultures of macrophages pre-incubated with CTX and LLC-WRC 256 cells produced significantly increased LXA4 levels only at 24 h (25%, Fig. 6B). Differences in the levels of LXA4 in the co-cultures of CTX-treated macrophages and tumour cells were not observed at 12 h (Fig. 6A) or 48 h (Fig. 6C). As shown in Fig. 6D, treatment with CTX did MEK inhibitor not affect the levels of 15-epi-LXA4 secreted by the macrophages in co-cultures with the tumour cells. However, the 15-epi-LXA4 levels were gradually induced over 24 h (2.3-fold,

Fig. 6E) and 48 h (2.1-fold, Fig. 6F), when compared to the controls (co-cultures with macrophages pre-incubated with culture medium and LLC-WRC 256 tumour cells). The level of 15-epi-LXA4 in the LLC-WRC 256 cell monocultures was below the limits of sensitivity of the assay that was used (data not shown). In this study, an experimental model represented by macrophages cultivated together with tumour cells at a 10:1 ratio was used to evaluate the secretory activity of macrophages pre-treated with CTX growing in contact with tumour cells and the influence of Bortezomib concentration this contact on tumour cell proliferation. The data presented here demonstrate that macrophages pre-treated with CTX (0.3 μg/mL) for 2 h increased their release or secretion of effector molecules such as H2O2, NO and cytokines and exhibited a cytotoxic effect on tumour cells. It is important to mention that the proliferation and nitric oxide production assays was determined using macrophages co-cultivated

with three different tumour cell lines, such as, LLC-WRC 256 tumour cells, B16F10 murine melanoma cells and human breast cancer cell line MCF-7. Likewise that observed in the co-cultures GNA12 with LLC-WRC 256 cells, macrophages pre-treated with CTX, inhibited proliferation of B16–F10 and MCF-7 (31% and 38%, respectively, data not shown). Additionally, an increase of production of NO in these co-cultures (26% and 50%, respectively, data not shown) was observed. Therefore, since the same effect observed regardless the tumour cell type, only the LLC WRC 256 lineage was performed in subsequent evaluation. As shown in Fig. 1A, a marked induction of H2O2 liberation by CTX was observed after 24 h in both macrophage monocultures and co-cultures. After this period, liberation of H2O2 occurs in lower levels. Treating the macrophages with CTX resulted in an increased production of NO after 48 h of culture, as shown in Fig. 1B.

This Alpelisib avenue of research is still in its infancy, and research is needed to resolve problems of the current assay, including interferences from other compounds in the complex sample matrix which may induce a non taste-receptor mediated response by the cells [67]. There is currently a dearth of information on the taste attributes of bioactive protein hydrolysates or peptides. Research applying sensomics mapping, instrumental taste sensing

or cell-based systems to the study of bioactive peptides could accelerate the acquisition of important knowledge in this field. Bioactive peptides and protein hydrolysates hold great promise as valuable functional ingredients

in healthy diets to fight the global epidemic of non-communicable Gemcitabine mouse diseases. However, in order to realize this potential, several challenges must be addressed (Table 2). The high cost and multi-step nature of existing processes for bioactive peptide production implores the need to apply a systematic approach for identifying the best conditions to release ‘cryptides’ with target bioactivity from the parent protein source, and for developing innovative production and purification strategies to obtain peptide fractions with high potency and yield. Bioinformatics tools may be useful to guide the empirical approach and may also provide a better understanding at the molecular level of the peptide structure–activity relationship. Standardized methodology for analysis and robust clinical trials to evaluate efficacy and metabolic fate of the established products are of critical importance for quality assurance and justification of health claims. Finally, research must be conducted on the taste and other sensory quality attributes of bioactive peptides to ensure their successful adoption as functional

food ingredients that can lead to better health. Fossariinae Papers of particular interest, published within the period of review, have been highlighted as: • of special interest Financial support in the form of a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC RGPIN 121822-11) is gratefully acknowledged. “
“Current Opinion in Food Science 2015, 1:xx–yy This review comes from a themed issue on Food chemistry and biochemistry Edited by Delia B. Rodriguez Amaya doi:10.1016/j.cofs.2014.09.003 S2214-7993/© 2014 Elsevier Ltd. All rights reserved. The human sense of smell is triggered by small, non-polar to medium polar molecules which dock onto receptor proteins of the olfactory epithelium. They signal freshness, quality and authenticity of a food, hence guiding our choice of food.

serrulatus, considered a bona fide novel type of K+ channel neurotoxin. The new toxin, named Ts15 and classified as alpha-KTx 21.1, blocked Kv1.2, Kv1.3, Kv1.6 and Shaker IR in a nanomolar range while it does not block the other KV isoforms tested (Kv1.1, Kv1.4, Kv1.5, Kv2.1, Kv3.1, Kv4.2, Kv4.3 and hERG). We are grateful to Prof. O. Pongs for providing cDNAs for rKv1.2, Kvr1.4, Kvr1.5 and Kvr1.6 channels.

The hKv1.3 clone was kindly provided by Prof. M. L. Garcia, Shaker IR by Prof. G. Yellen, and the hERG clone by Prof. M. Keating. The rKv2.1, hKv3.1, rKv4.2 and rKv4.3 clones were kindly provided by Prof. D.J. Snyders.; G. Mandel (Stony Brook University, Stony Brook, USA) for sharing the rNav1.4 clone; R. G. Kallen (University Galunisertib ic50 of Pennsylvania, Philadelphia, USA) for sharing hNav1.5; A.L.Goldin learn more (University of California, Irvine, USA) for sharing mNav1.6; J. N. Wood (University College, London,

UK) for sharing rNav1.8; S. H. Heinemann (Friedrich-Schiller-Universität, Jena, Germany) for sharing rβ1; M. S. Williamson (IACR Rothamsted, Harpenden, UK) for sharing DmNaV1 and tipE. This work was supported by grants G.0330.06 and G.0257.08(F.W.O. Vlaanderen), UA P6/31(Interuniversity Attraction Poles Program, Belgian State, Belgian Science Policy), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). “
“Bothrops snake venoms are a complex mixture of biological active peptides and proteins (Kini and Evans, 1990 and Rosing and Tans, 1992), which can cause local and systemic lesions including Cytidine deaminase pain, edema, hemorrhage, tissue necrosis, and blood coagulation disorders (Barraviera, 1994, Fonseca, 2001, Melo et al., 2005 and Markland, 1998). Snake venom

metalloproteinases (SVMPs) are members of the super family of zinc-dependent proteinases (Jia and Pérez, 2010, Oliveira et al., 2010 and Markland, 1998) and are associated with hemorrhagic and fibrinolytic activities of the venoms (Lou et al., 2005). Based on their cDNA and structural domains SVMPs are classified into four major groups: PI to PIV Bjarnason and Fox (2004). Members of class PI (20–30 kDa) contain only the zinc-dependent proteolytic domain. Class PII members (30–50 kDa) contain both proteolytic and disintegrin domains. The disintegrin domain presents RGD (Arg-Gly-Asp) or KGD (Lys-Gly-Asp) sequences characteristic of disintegrins, responsible for binding with integrins. Free disintegrins can be found in the snake venom as 5–10 kDa hydrolysis products of class PII members. Class PIII members (50–65 kDa) are comprised of three domains, the proteolytic, the disintegrin-like and the cysteine rich domains. In contrast to PII disintegrins, free disintegrin-like domains are not found in the snake venom.

Behavioral experiments were conducted in a sound-attenuated and air-regulated room, where the animals were habituated 1 h prior to experiments. All animal experimentation reported in this study was performed under established standards of the Brazilian law No. 11.794/2008 in accordance with the Policies on the Use

of Animals and Humans in Neuroscience Research, revised and approved by the Society for Neuroscience Research. Purification of Tx3-1 from the venom of the spider Phoneutria nigriventer was performed following the method of Cordeiro and coworkers (1993). Aβ25-35, learn more Aβ35-25 and 4-aminopyridine (4-AP), were purchased from Sigma (St. Louis, MO, USA). The Tx3-1 and 4-AP dose were based on electrophysiological experiments that evaluated the effect of both compounds on IA currents ( Kushmerick et al., 1999). Aβ aggregation was performed according to Maurice et al. (1996), wherein Dapagliflozin datasheet 3 mM of either 25-35 or 35-25 (used as control) sequence peptide were incubated at 37 °C for 4 days, stored at −20 °C and freshly diluted to the final dose (3 nmol/site; 1 mM) when used. In all behavioral experiments, Aβ25-35, Aβ35-25, Tx3-1, 4-AP or vehicle, were administered by intracerebroventricular

(i.c.v.) route, according to Laursen and Belknap (1986). Briefly, mice were anesthetized with isofluorane until full anesthesia was achieved. The microinjections were performed using a Hamilton 10 μl syringe connected to a specially made 28-gauge stainless steel needle with 3 mm in length. The needle was inserted directly through the skin and skull into the lateral

ventricle, targeted by visualizing an equilateral triangle between the eyes and center of skull to locate bregma, then inserting the needle 1 mm laterally to this point. This avoids the use of unnecessary force since the needle penetrates at the suture line of the skull plates. Compounds were injected in a volume of 5 μl over a 5 s period, followed by a 10 s delay to allow diffusion and prevent backflow. All injections were performed by an experimenter well trained in this technique. Novel object recognition task Chloroambucil was performed in wooden chamber (30 × 30 × 30 cm) with black side and rear walls, front wall made of transparent acrylic and the floor covered with an ethyl vinyl acetate sheet. A light bulb, hanging 60 cm above the behavioral apparatus, provided constant illumination of about 40 lux, and an air-conditioner provided constant background sound isolation. The objects used were plastic mounting bricks, each of them with different shapes and colors, but same size. Throughout the experiments objects were used in a counterbalanced manner and animals did not previously display preference for any of the objects. Chambers and objects were thoroughly cleaned with 30% ethanol before each experiment. Six days after Aβ injection, novel object recognition task was performed according to Wang and coworkers (Wang et al.

melanosticus, R. schneideri, R. margaritifer, R. hypocondrialis, R. major, R. margaritifera, R. crucifer and R. jimi), bufadienolides extracted from the Chinese traditional drug Ch’an Su and from plants (Urginea maritima, U. aphylla, U. maritima and U. hesperia), displaying activity against tumor lines, such as colon (26-L5, CT26.WT), leukemia (K562, U937, ML1), melanoma (MDA/MB-435, B16/F10, SKMEL-28), breast (MCF-7, MDA/MB-231), prostate (DU-145, PC-3, LNCaP), nervous system (Hs683, U373) and primary liver carcinoma (PLC/PRF/5) ( Zhang et al., 1992, Nogawa et al., 2001, Ogasawara et al., 2001, Kamano et al., 2002, Yeh et al., 2003, Cunha-Filho et al., 2010, Sciani et al., 2012 and Banuls et al.,

2013). Hellebregenin, for example, is highly cytotoxic to HL-60 cells without causing DNA damage but inducing morphological changes characteristic buy C646 of cell death by apoptosis ( Cunha-Filho et al., 2010). Previous studies have reported the

cytotoxicity of the compounds identified in R. marina (1, 2, 3, and 4) and R. guttatus (2) venoms. Bufalin (3) showed the most potent cytotoxic activity, followed by telocinobufagin (1), resibufogenin (4), and marinobufagin (2) against the following cancer cell lines: leukemia (HL-60), colon (HCT-116), glioblastoma (SF-295), ovarian (OVCAR-8), melanoma (MDA-MB435), human gastric R428 (BGC-823), hepatoma (Bel-7402), cervical carcinoma (HeLa), and primary liver carcinoma (PLC/PRF/5) ( Kamano et al., 1998, Ye et al., 2006 and Cunha-Filho et al., 2010). The higher cytotoxic activity of venom extracts from R. marina in comparison with R. guttatus can be attributed to the presence of three other bufadienolides (1, 3, and 4) as well as marinobufagin (2), a bufadienolide identified only in R. guttatus venom. The above findings suggest synergistic effects due to the presence of different active principles contributing to the same activity ( Wattenberg, 1985). Thus, it is proposed that compounds present in the extracts act together to kill neoplastic cells. Regarding chemotherapeutic

potential, it is important to determine if the antineoplastic substance shows harmful effects on normal cells (Anazetti Loperamide et al., 2003 and Santos et al., 2010). Accordingly, primary cultures of PBMC were prepared to assess this injurious potential of the extracts. Surprisingly, most of them were not cytotoxic to PBMC as seen as with transformed cells, where the extract RMF-1 was up to 80-fold more selective against leukemia cells when compared to dividing leukocytes, a very desired advantage in new anticancer leads to overcome adverse effects due to a narrow therapeutic window, multiple drug resistance and morphological and physiological similarities between transformed and normal cells. Meanwhile, Dox showed a selectivity coefficient of 45 determined by IC50 in PBMC/IC50 in HL-60. R.

Flvcr1afl/fl;alb-cre mice showed the recombinant allele only in the liver ( Supplementary Figure 1B) and a strong reduction of hepatic Flvcr1a expression ( Supplementary Figure 1C and D). As expected, Flvcr1a mRNA could not be detected in primary hepatocytes isolated from Atezolizumab in vivo Flvcr1afl/fl;alb-cre mice ( Supplementary Figure 1E), demonstrating that this mouse is a liver-specific knockout model

for Flvcr1a. Flvcr1afl/fl;alb-cre mice showed no gross liver abnormalities ( Supplementary Figure 1F). Blood analysis did not reveal any difference between Flvcr1afl/fl;alb-cre and Flvcr1afl/fl mice ( Supplementary Table 1). To evaluate if the deletion of Flvcr1a alters hepatic heme homeostasis, we analyzed the livers of 2- and 6-month-old Flvcr1afl/fl;alb-cre compared with those of an Flvcr1afl/fl counterpart. Hepatic heme and iron content were comparable at 2 months of age, but were Inhibitor Library order significantly higher in 6-month-old Flvcr1afl/fl;alb-cre than in Flvcr1afl/fl mice ( Figure 1A and B). Iron accumulation in 6-month-old Flvcr1afl/fl;alb-cre mice was further confirmed by Perl’s staining on liver sections ( Figure 1B). Consistently, Flvcr1afl/fl;alb-cre mice showed an enhanced HO activity as well as an increased bilirubin

excretion in the bile compared with Flvcr1afl/fl mice ( Figure 1C). In addition, Flvcr1afl/fl;alb-cre mice showed increased lipid peroxidation in the liver ( Figure 1D). The analysis of hepatic gene expression revealed that Flvcr1afl/fl;alb-cre mice up-regulated genes that encode for proteins involved in heme metabolism (Ho-1), 18 and 19 iron export (Fpn) 20 and 21 and storage (H- and L-Ferritin), 22 and antioxidant response (Txnrd1, γ-gcs, Sod1), 23 compared

with Flvcr1afl/fl mice ( Figure 1E and F; Supplementary Figure 2 for gene expression analysis of 2-month-old mice). On the other hand, expression of the other known heme exporter Abcg2 was not increased ASK1 in the liver of Flvcr1afl/fl;alb-cre mice ( Supplementary Figure 3), indicating that no other heme exporter was able to compensate for the lack of Flvcr1a. The phenotype of liver-specific Flvcr1a knockout mice suggests that FLVCR1a-mediated heme export prevents hepatic heme accumulation. To further address this point, mice were injected with hemin, the substrate of FLVCR1a. One hour after heme injection, heme accumulated in the liver of both Flvcr1afl/fl;alb-cre and Flvcr1afl/fl mice at the same extent, but bilirubin production was significantly higher in Flvcr1afl/fl;alb-cre mice than in Flvcr1afl/fl mice, likely because of the enhanced HO activity ( Figure 2A and B). Consistently, if animals were pretreated with the heme analog Tin-Protoporphyrin IX that inhibits HO, before heme injection, Flvcr1afl/fl;alb-cre mice showed a significantly higher hepatic heme content 1 hour after heme infusion compared with control mice ( Figure 2C).

A value of p < 0.05 was considered as statistically significant. Spectral and size properties of CdTe-QDs that were used in this study have been recently published by us (Nguyen et al., 2013). Cytotoxicity of CdTe-QDs in HepG2 cells was examined for changes in bioreducing activity using the MTT assay to estimate cellular capacity to reduce

MTT to its formazan. Loss in HepG2 bioreduction caused by CdTe-QDs appeared to be time- and dose-dependent (Fig. 1). The earliest changes were observed at 6 h with 1.0 μg/ml, and the lowest observable effects were observed with 0.1 μg/ml at 12 h exposure. At the longest exposure duration (24 h), CdTe-QDs caused a significant drop Trametinib in bioreduction at all doses, with maximal effects being ∼25% relative to control. Examination by microscopy showed that, even at this high

dose and exposure, cells had not detached (data not shown) and most still learn more retained at least some capacity to reduce MTT to formazan, albeit at a much lower level compared to PBS-treated controls. The effect of CdTe-QDs on the production of ROS was examined by observing fluorescence of oxidized DHE in HepG2 by confocal microscopy. CdTe-QD treatment caused increased intensity and area of fluorescence from DHE oxidation compared to PBS-controls, indicating that excess ROS levels were induced by CdTe-QDs (Fig. 2A, B and E). Both CdCl2 and menadione treatments also showed an increase in ROS levels in test cells. CdCl2 treatment, however, caused a lower level of ROS generation than CdTe-QD treatment (p < 0.05) ( Fig. 2A–E). Several oxidative stress markers were selected to measure the effects of CdTe-QDs on the oxidative status of HepG2 cells. Exposures of HepG2 cells to CdTe-QDs caused a significant

depletion of reduced glutathione (GSH) (Fig. 3A). Furthermore, CdTe-QDs caused drops in the GSH/GSSG ratio by 2.4-fold, compared to PBS treated controls (Fig. 3A and B). CdCl2 caused a greater depletion of reduced GSH (p < 0.05), but a lower effect on the GSH/GSSG ratio compared to CdTe-QDs (p < 0.05) ( Fig. 3A and B). SOD activity was measured in both cytosolic and mitochondrial fractions (Fig. 3C). About 30% increase in SOD activity, in both cytosolic and mitochondrial extracts, occurred with CdTe-QD treatment. CdCl2 treatment also resulted in increased cytosolic and mitochondrial SOD activities, but to a lesser extent, Olopatadine compared to CdTe-QD treatment. Nrf2 activation was found to be 2-fold (p < 0.001) greater in CdTe-QD-treated cells, compared with control cells ( Fig. 3D), whereas CdCl2 caused a marginal increase (1.11-fold) in Nrf2 activation ( Fig. 3D). Compared to PBS-treated control cells, CdTe-QDs caused a reduction in GST activity by 1.95-fold (p < 0.001) and CdCl2 also caused a significant decrease in GST activity (1.65-fold, p < 0.001). To determine whether the decrease in GST activity was due to CdTe-QDs reducing GST protein levels directly, quantification of GST-α was performed.

Furthermore, we found that BEAS-2B cells cultured in a medium containing serum show biological responses that are very similar to those of normal human bronchial epithelial cells, as determined by comparison with HBEpCs. These results reveal the importance of appropriate usage of cell lines and culture conditions when performing

safety assessment of nanomaterials for humans in vitro. It is necessary to determine not only the pharmacokinetics of the nanomaterial but also the mechanism of its cellular internalization. The authors declare that they have no competing financial or non-financial interests. We thank the staff of IWR-1 the Division of Instrumental Analysis in the Research Center for Human and Environmental Sciences of Shinshu University for their help. This research was supported by the Regional Innovation Cluster Program (the second stage) of the Ministry of Education, Culture, Sports, Science and Technology, Japan; by JSPS KAKENHI Grant Numbers 19002007 and 24241045, Japan; by the Research and Development of Nanodevices for Practical Utilization of

Nanotechnology of the New Energy and Industrial Technology Development Organization, Japan; and by Japan Regional Innovation Strategy program by the Excellence of the Japan Science and Technology Agency, Adaptable and Seamless Technology Transfer Program through Target-driven R&D, Japan Science and Technology Agency, and Hospital-company collaboration support project for developing/improving problem-solving-type medical equipment by Ministry of Economy, Trade and Industry, Japan. “
“The need for in vitro cell systems as alternatives to animal models for toxicological Selleckchem GSI-IX testing is increasing in response to new

regulations, such as the EU 7th Amendment Directive ( European Commission, 2003), and to ethical considerations like the 3Rs principle ( Schechtman, 2002). Due to their relative homogeneity and ability to be maintained in culture indefinitely, established cell lines have been one of the preferred cell systems employed in the development and validation of in vitro toxicology assays. Most continuous cell lines, however, have been derived from malignant or transformed tissue and fail to replicate the physiology and morphology of normal cells. Historically, hepatic cell lines have been thoroughly Glutathione peroxidase characterized, as they are the prime systems used for drug metabolism and toxicity testing in pre-clinical development ( Guguen-Guillouzo and Guillouzo, 2010 and Brandon et al., 2003). For instance, the hepatoma cell line HepG2 lacks normal metabolic activity and has been engineered to express hepatic cytochrome P450 (CYP) enzymes (CYP3A4, CYP2E1) to study in vitro drug hepatotoxicity caused by compounds such as paracetamol ( Yoshitomi et al., 2001). CYP3A4 and CYP2E1 catalyze the transformation of paracetamol into a highly reactive metabolite responsible for the tissue specific toxicity of the drug.

Additional in vitro experiments were performed

to determine the antioxidant activity of different concentrations of green dwarf banana flour (1-100 μg/mL). The antioxidant activity was evaluated using an assay of lipid peroxidation in rat brain membranes [24] modified from the original protocol described by Gálvez find more et al [25]. The flavonoid quercetin was used as a reference and tested in the same assay system. Luminal content samples were weighed, homogenized, and serially diluted in sterile 0.85% saline. Serial 10-fold dilutions of the homogenates were plated on Man, Rogosa, and Sharpeagar, a specific media for lactic acid bacteria, and were incubated under microaerobic conditions (5% CO2) at 35°C for 120 hours. After incubation, the final colony count was reported as log10 colony-forming units per gram of fecal material. The results are expressed as means ± SEM values, and differences between the means were tested for statistical significance using a 1-way analysis of variance (ANOVA) and post hoc least significance tests. Nonparametric data (scores) are expressed as the median (range) and were analyzed with the Kruskal-Wallis test. Differences between proportions were analyzed with the χ2 test. Statistical

significance was set at P < .05. Trinitrobenzenesulfonic acid administration resulted in colonic inflammation, which was demonstrated after 7 days by severe necrosis of the mucosa, typically extending 2.8 to 4.9 cm along the colon, bowel wall thickening, and hyperemia (Table 2). This inflammatory process LEE011 was associated with an increase in the colonic weight/length

ratio, incidence of the adherence of the colon to adjacent organs (Table 2), and signs of diarrhea MycoClean Mycoplasma Removal Kit in 100% of the colitic. A histologic assessment of colonic samples from the TNBS control group revealed severe transmural disruption of the normal architecture of the colon, extensive ulceration, and inflammation involving all the intestinal layers of the colon, giving a score value of 14.0 (Table 2). Biochemically, the colonic damage was characterized by a reduction in colonic GSH levels and an increase in MPO and AP (Table 3) activities when compared with noncolitic animals. The treatment of noncolitic animals (healthy rats) with the diet enriched with 10% and 20% dwarf banana flour for 21 days showed no effects on the clinical, macroscopic, and microscopic parameters analyzed. The measurements taken from these animals were similar to those taken from the noncolitic group that received only vehicle (Table 2). No statistical differences were observed in food consumption or weight gain between the experimental groups that received the enriched diet and those that received the normal diet.

A hiperglicemia parece também afetar a perceção das sensações provenientes do tubo AZD6244 research buy digestivo9. Os níveis de glicemia podem assim servir de modulador fisiológico das funções motora e sensorial gastrointestinais9 and 10. O fraco controlo da glicemia por si só tem sido descrito como responsável major dos sintomas GI nos diabéticos10 and 11. Outros fatores que poderão estar implicados são a duração da diabetes e a coexistência de

patologia psiquiátrica embora falte evidência científica que o confirme12. Neste número do Jornal Português de Gastrenterologia é publicado um artigo intitulado «Características manométricas do corpo esofágico em doentes diabéticos tipo 2 de acordo com a glicemia basal matinal» de Jorge JX et al. 13. que pretende averiguar, num grupo de doentes diabéticos, a associação das alterações manométricas esofágicas com os diferentes buy Sunitinib níveis de glicemia Os autores deste trabalho apresentam um estudo realizado em 25 doentes com diabetes mellitus tipo ii, que dividem em 2 grupos de acordo com os níveis de glicemia em jejum: um com níveis inferiores ou iguais a 7 mmol/L, outro com níveis superiores a 7 mmol/L, submetidos a manometria

esofágica estacionária de perfusão. Os resultados encontrados na avaliação da motilidade do corpo esofágico revelaram uma percentagem maior de ondas não-transmitidas no grupo de doentes com glicemias mais elevadas, sendo esta a única diferença estatisticamente significativa demonstrada entre os 2 grupos. Tal como reconhecido

por Jorge JX et al. 13 este trabalho inclui um número muito pequeno de doentes diabéticos o que limita as suas conclusões. Outros aspetos que tornam este estudo pouco robusto são: (1) a ausência de um grupo controlo não-diabético; (2) a inexistência de referência aos sintomas dos doentes, não só a nível gastrointestinal mas também a nível de complicações da própria diabetes (retinopatia, neuropatia periférica, nefropatia). Outra crítica passível de ser colocada a este trabalho diz respeito à técnica de manometria utilizada. Em pleno século xxi, seria recomendado proceder a estudos de investigação da motilidade esofágica com a técnica combinada de manometria com impedância e, de preferência, utilizando a manometria de alta Ribonucleotide reductase resolução. A importância clínica das alterações manométricas encontradas no esófago continua incerta uma vez que a maioria dos doentes se encontra assintomática, apresenta uma dismotilidade silenciosa. No entanto, este estudo de Jorge JX et al.13 deixa em aberto uma questão interessante que consiste na hipótese de averiguar prospetivamente se um controlo mais eficaz dos níveis de glicemia induzirá uma reversibilidade nas alterações manométricas encontradas. “
“As doenças imunomediadas têm tido um rápido incremento de prevalência e início mais precoce.