Supporting content-based image retrieval and computer-aided diagnosis systems with association rule-based techniques

In this work, we take advantage of association rule mining to support two types of medical systems: the Content-based Image Retrieval (CBIR) systems and the Computer-Aided Diagnosis (CAD) systems. For content-based retrieval, association rules are employed to reduce the dimensionality of the feature vectors that represent the images and to improve the precision of the similarity queries. We refer to the association rule-based method to improve CBIR systems proposed here as Feature selection through Association Rules (FAR). To improve CAD systems, we propose the Image Diagnosis Enhancement through Association rules (IDEA) method. Association rules are employed to suggest a second opinion to the radiologist or a preliminary diagnosis of a new image. A second opinion automatically obtained can either accelerate the process of diagnosing or to strengthen a hypothesis, increasing the probability of a prescribed treatment be successful. Two new algorithms are proposed to support the IDEA method: to pre-process low-level features and to propose a preliminary diagnosis based on association rules. We performed several experiments to validate the proposed methods. The results indicate that association rules can be successfully applied to improve CBIR and CAD systems, empowering the arsenal of techniques to support medical image analysis in medical systems. (C) 2009 Elsevier B.V. All rights reserved.

Mesenchymal stromal cells up-regulate CD39 and increase adenosine production to suppress activated T-lymphocytes

Mesenchymal stromal cells (MSCs) suppress T cell responses through mechanisms not completely understood. Adenosine is a strong immunosuppressant that acts mainly through its receptor A(2a) (ADORA2A). Extracellular adenosine levels are a net result of its production (mediated by CD39 and CD73), and of its conversion into inosine by Adenosine Deaminase (ADA). Here we investigated the involvement of ADO in the immunomodulation promoted by MSCs. Human T lymphocytes were activated and cultured with or without MSCs. Compared to lymphocytes cultured without MSCs, co-cultured lymphocytes were suppressed and expressed higher levels of ADORA2A and lower levels of ADA. In co-cultures, the percentage of MSCs expressing CD39, and of T lymphocytes expressing CD73, increased significantly and adenosine levels were higher. Incubation of MSCs with media conditioned by activated T lymphocytes induced the production of adenosine to levels similar to those observed in co-cultures, indicating that adenosine production was mainly derived from MSCs. Finally, blocking ADORA2A signaling raised lymphocyte proliferation significantly. Our results suggest that some of the immunomodulatory properties of MSCs may, in part, be mediated through the modulation of components related to adenosine signaling. These findings may open new avenues for the development of new treatments for GVHD and other inflammatory diseases. (C) 2011 Elsevier B.V. All rights reserved.

Antioxidant Effect of Thiamine on Acutely Alcoholized Rats and Lack of Efficacy Using Thiamine or Glucose to Reduce Blood Alcohol Content

Although there is no consensus about the use of glucose and thiamine for the treatment of acute ethanol intoxication, this is a routine practice in many countries. Our objective was to determine the efficacy of this treatment and the changes it causes in the antioxidant status of the liver. Male Wistar rats were intoxicated with an ethanol dose of 5 g/kg and divided into three groups: ethanol (EtOH; untreated), EtOH+G (treated with glucose), and EtOH+B1 (treated with thiamine). Blood and urinary ethanol as well as hepatic malondialdehyde, reduced glutathione and vitamin E were determined in all animals. Blood alcohol levels did not differ between groups, although urinary excretion was about four times higher in the group treated with thiamine (EtOH+B1). The malondialdehyde, reduced glutathione and vitamin E values used here as parameters of the antioxidant system of the liver showed improvement for the thiamine-treated group (EtOH+B1). Treatment with glucose or thiamine was ineffective in reducing blood alcohol levels in rats with acute ethanol intoxication. However, the beneficial effect of thiamine as an antioxidant for ethanol metabolism was demonstrated. Further investigations are necessary to clarify the urinary excretion of ethanol reported here for the first time and the possibility of using thiamine as an antioxidant in situations of chronic alcohol use.

Food energy content influences food portion size estimation by nutrition students

Background: Food portion size estimation involves a complex mental process that may influence food consumption evaluation. Knowing the variables that influence this process can improve the accuracy of dietary assessment. The present study aimed to evaluate the ability of nutrition students to estimate food portions in usual meals and relate food energy content with errors in food portion size estimation. Methods: Seventy-eight nutrition students, who had already studied food energy content, participated in this cross-sectional study on the estimation of food portions, organised into four meals. The participants estimated the quantity of each food, in grams or millilitres, with the food in view. Estimation errors were quantified, and their magnitude were evaluated. Estimated quantities (EQ) lower than 90% and higher than 110% of the weighed quantity (WQ) were considered to represent underestimation and overestimation, respectively. Correlation between food energy content and error on estimation was analysed by the Spearman correlation, and comparison between the mean EQ and WQ was accomplished by means of the Wilcoxon signed rank test (P < 0.05). Results: A low percentage of estimates (18.5%) were considered accurate (+/- 10% of the actual weight). The most frequently underestimated food items were cauliflower, lettuce, apple and papaya; the most often overestimated items were milk, margarine and sugar. A significant positive correlation between food energy density and estimation was found (r = 0.8166; P = 0.0002). Conclusions: The results obtained in the present study revealed a low percentage of acceptable estimations of food portion size by nutrition students, with trends toward overestimation of high-energy food items and underestimation of low-energy items.

Regulation of chemokine receptor by Toll-like receptor 2 is critical to neutrophil migration and resistance to polymicrobial sepsis

Patients with sepsis have a marked defect in neutrophil migration. Here we identify a key role of Toll-like receptor 2 (TLR2) in the regulation of neutrophil migration and resistance during polymicrobial sepsis. We found that the expression of the chemokine receptor CXCR2 was dramatically down-regulated in circulating neutrophils from WT mice with severe sepsis, which correlates with reduced chemotaxis to CXCL2 in vitro and impaired migration into an infectious focus in vivo. TLR2 deficiency prevented the down-regulation of CXCR2 and failure of neutrophil migration. Moreover, TLR2(-/-) mice exhibited higher bacterial clearance, lower serum inflammatory cytokines, and improved survival rate during severe sepsis compared with WT mice. In vitro, the TLR2 agonist lipoteichoic acid (LTA) down-regulated CXCR2 expression and markedly inhibited the neutrophil chemotaxis and actin polymerization induced by CXCL2. Moreover, neutrophils activated ex vivo by LTA and adoptively transferred into naive WT recipient mice displayed a significantly reduced competence to migrate toward thioglycolate-induced peritonitis. Finally, LTA enhanced the expression of G protein-coupled receptor kinases 2 (GRK2) in neutrophils; increased expression of GRK2 was seen in blood neutrophils from WT mice, but not TLR2(-/-) mice, with severe sepsis. Our findings identify an unexpected detrimental role of TLR2 in polymicrobial sepsis and suggest that inhibition of TLR2 signaling may improve survival from sepsis.

The peripheral pro-nociceptive state induced by repetitive inflammatory stimuli involves continuous activation of protein kinase A and protein kinase C epsilon and its Na(v)1.8 sodium channel functional regulation in the primary sensory neuron

In the present study, the participation of the Na(v)1.8 sodium channel was investigated in the development of the peripheral pro-nociceptive state induced by daily intraplantar injections of PGE(2) in rats and its regulation in vivo by protein kinase A (PKA) and protein kinase C epsilon (PKC epsilon) as well. In the prostaglandin E(2) (PGE(2))-induced persistent hypernociception, the Na(v)1.8 mRNA in the dorsal root ganglia (DRG) was up-regulated. The local treatment with dipyrone abolished this persistent hypernociception but did not alter the Na(v)1.8 mRNA level in the DRG. Daily intrathecal administrations of antisense Na(v)1.8 decreased the Na(v)1.8 mRNA in the DRG and reduced ongoing persistent hypernociception. once the persistent hypernociception had been abolished by dipyrone, but not by Na(v)1.8 antisense treatment, a small dose of PGE(2) restored the hypernociceptive plateau. These data show that, after a period of recurring inflammatory stimuli, an intense and prolonged nociceptive response is elicited by a minimum inflammatory stimulus and that this pro-nociceptive state depends on Na(v)1.8 mRNA up-regulation in the DRG. in addition, during the persistent hypernociceptive state, the PKA and PKC epsilon expression and activity in the DRG are up-regulated and the administration of the PKA and PKC epsilon inhibitors reduce the hypernociception as well as the Na(v)1.8 mRNA level. In the present study, we demonstrated that the functional regulation of the Na(v)1.8 mRNA by PKA and PKC epsilon in the primary sensory neuron is important for the development of the peripheral pro-nociceptive state induced by repetitive inflammatory stimuli and for the maintenance of the behavioral persistent hypernociception. (C) 2008 Elsevier Inc. All rights reserved.

Factors involved in the T helper type 1 and type 2 cell commitment and osteoclast regulation in inflammatory apical diseases

Periapical chronic lesion formation involves activation of the immune response and alveolar bone resorption around the tooth apex. However, the overall roles of T helper type 1 (Th1), Th2, and T-regulatory cell (Treg) responses and osteoclast regulatory factors in periapical cysts and granulomas have not been fully determined. This study aimed to investigate whether different forms of apical periodontitis, namely cysts and granulomas, show different balances of Th1, Th2 regulators, Treg markers, and factors involved in osteoclast chemotaxis and activation. Gene expression of these factors was assessed using quantitative real-time polymerase chain reaction, in samples obtained from healthy gingiva (n = 8), periapical granulomas (n = 20), and cysts (n = 10). Periapical cysts exhibited a greater expression of GATA-3, while a greater expression of T-bet, Foxp3, and interleukin-10 (IL-10) was seen in granulomas. The expression of interferon-gamma, IL-4, and transforming growth factor-beta was similar in both lesions. Regarding osteoclastic factors, while the expression of SDF-1 alpha/CXCL12 and CCR1 was higher in cysts, the expression of RANKL was significantly higher in granulomas. Both lesions exhibited similar expression of CXCR4, CK beta 8/CCL23, and osteoprotegerin, which were significantly higher than in control. Our results showed a predominance of osteoclast activity in granulomas that was correlated with the Th1 response. The concomitant expression of Treg cell markers suggests a possible suppression of the Th1 response in granulomas. On the other hand, in cysts the Th2 activity is augmented. The mechanisms of periradicular lesion development are still not fully understood but the imbalance of immune and osteoclastic cell activity in cysts and granulomas seems to be critically regulated by Treg cells.

Regulation of type 17 helper T-cell function by nitric oxide during inflammation

Type 17 helper T (Th17) cells are implicated in the pathogenesis many of human autoimmune diseases. Development of Th17 can be enhanced by the activation of aryl hydrocarbon receptor (AHR) whose ligands include the environmental pollutant dioxin, potentially linking environmental factors to the increased prevalence of autoimmune disease. We report here that nitric oxide (NO) can suppress the proliferation and function of polarized murine and human Th17 cells. NO also inhibits AHR expression in Th17 cells and the downstream events of AHR activation, including IL-22, IL-23 receptor, and Cyp1a1. Conversely, NO did not affect the polarization of Th17 cells from mice deficient in AHR. Furthermore, mice lacking inducible nitric oxide synthase (Nos2(-/-)) developed more severe experimental autoimmune encephalomyelitis than WT mice, with elevated AHR expression, increased IL-17A, and IL-22 synthesis. NO may therefore represent an important endogenous regulator to prevent overexpansion of Th17 cells and control of autoimmune diseases caused by environmental pollutants.

Involvement of median raphe nucleus 5-HT1A receptors in the regulation of generalized anxiety-related defensive behaviours in rats

Changes in 5-HT1A receptor-mediated neurotransmission at the level of the median raphe nucleus (MRN) are reported to affect the expression of defensive responses that are associated with generalized anxiety disorder (e.g. inhibitory avoidance) but not with panic (e.g. escape). The objective of this study was to further explore the involvement of MRN 5-HT1A receptors in the regulation of generalized anxiety-related behaviours. Results of experiment 1 showed that intra-MRN injection of the 5-HT1A/7 receptor agonist 8-OH-DPAT (0.6 nmol) in male Wistar rats impaired the acquisition of inhibitory avoidance, without interfering with the performance of escape in the elevated T-maze test of anxiety. Pre-treatment with the 5-HT1A receptor antagonist WAY-100635 (0.18 nmol) fully blocked this anxiolytic-like effect. As revealed by experiment 2, intra-MRN injection of 8-OH-DPAT (0.6, 3 or 15 nmol) also caused anxiolytic effect in rats submitted to the light-dark transition test, another animal model that has been associated with generalized anxiety. In the same test, intra-MRN injection of WAY-100635 (0.18, 0.37 or 0.74 nmol) caused the opposite effect. Overall, the current findings support the view that MRN 5-HT neurons, through the regulation of 5-HT1A somatodendritic autoreceptors, are implicated in the regulation of generalized anxiety-associated behaviours. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Involvement of the lateral habenula in the regulation of generalized anxiety- and panic-related defensive responses in rats

Recently obtained evidence points to the involvement of the lateral habenular nuclei (LHb) in the mediation of coping defensive responses to threatening/stressful stimuli. Nevertheless, the role of this brain area in the regulation of defensive responses that have been associated with specific subtypes of anxiety disorders recognized in clinical settings is presently unknown. To address this question, we investigated the effects of either electrolytic lesions or chemical stimulation of the LHb on the defensive behaviors generated in rats by the elevated T-maze. This experimental model allows the measurement, in a same rat, of two defensive behaviors, inhibitory avoidance and escape, that have been related in terms of psychopathology to generalized anxiety and panic disorders, respectively. Bilateral electrolytic lesions of the LHb (1 mA, 10 s) impaired inhibitory avoidance acquisition and facilitated escape performance. On the other hand, chemical stimulation of the LHb by bilateral microinjection of kainic acid (30-60 pmol/0.2 mu L) had the opposite effect, i.e., facilitated inhibitory avoidance and impaired escape. The present results indicate that the LHb exerts an opposed regulatory control on generalized anxiety- and panic-related defensive responses in rats. (c) 2008 Elsevier Inc. All rights reserved.

Dorsal raphe nucleus regulation of a panic-like defensive behavior evoked by chemical stimulation of the rat dorsal periaqueductal gray matter

Electrical or chemical stimulation of the dorsal periaqueductal gray matter (DPAG) evokes escape, a defensive behavior that has been related to panic attacks. Injection of 5-HT(1A) or 5-HT(2A) receptor agonists into this midbrain area inhibits this response. It has been proposed that the impairment of 5-HT mechanisms controlling escape at the level of the DPAG may underlie the susceptibility to panic attacks that characterizes the panic disorder. In this study we evaluated the effects of the pharmacological manipulation of the dorsal raphe nucleus (DRN), which are the main source of 5-HT input to the DPAG, on the escape response evoked in rats by the intra-DPAG injection of the nitric oxide donor SIN-1. The results showed that DRN administration of the 5-HT(1A) receptor agonist 8-OH-DPAT which inhibits the activity of 5-HT neurons favored the expression of escape induced by SIN-1. Intra-DRN injection of the excitatory amino acid kainic acid or the 5-HT(1A) receptor antagonist WAY-100635 did not change escape expression. However, both compounds fully blocked the escape reaction generated by intra-DPAG injection of the excitatory amino acid D,L-homocysteic acid (DLH). Overall, the results indicate that 5-HT neurons in the DRN exert a bidirectional control upon escape behavior generated by the DPAG. Taking into account the effect of WAY-100635 on DLH-induced escape, they also strengthen the view that DRN 5-HT(1A) autoreceptors are under tonic inhibitory influence by 5-HT. (C) 2010 Elsevier B.V. All rights reserved.