The effects of cocoa on the immune system

Cocoa is a food relatively rich in polyphenols, which makes it a potent antioxidant. Due to its activity as an antioxidant, as well as through other mechanisms, cocoa consumption has been reported to be beneficial for cardiovascular health, brain functions, and cancer prevention. Furthermore, cocoa influences the immune system, in particular the inflammatory innate response and the systemic and intestinal adaptive immune response. Preclinical studies have demonstrated that a cocoa-enriched diet modifies T-cell functions that conduce to a modulation of the synthesis of systemic and gut antibodies. In this regard, it seems that a cocoa diet in rats produces changes in the lymphocyte composition of secondary lymphoid tissues and the cytokines secreted by T cells. These results suggest that it is possible that cocoa could inhibit the function of Th2 cells, and in line with this, the preventive effect of cocoa on IgE synthesis in a rat allergy model has been reported, which opens up new perspectives when considering the beneficial effects of cocoa compounds. On the other hand, cocoa intake modifies the functionality of gut-associated lymphoid tissue by means of modulating IgA secretion and intestinal microbiota. The mechanisms involved in these influences are discussed here. Further research may elucidate the cocoa compounds involved in such an effect and also the possible medical approaches to these repercussions

Percepción del dolor en pacientes postoperados de cirugía cardiaca

Pain is defined as an unpleasant sensory or emotional experience, associated with tissue damage, that is a reality linked to the surgical procedure and the postoperative period. Objective: Knowing the degree of pain experienced by patients after cardiac surgery, depending on the type of intervention they underwent, over the post-operative period in an intensive care unit (ICU). Method: Descriptive observational study. Pain was assessed by the visual analog scale (VAS), going from 0 to 10, thereby obtaining the first VAS1 assessment at 2 h post-extubation and every 8 hours thereafter up to 48 hours or until discharge to floor VAS7. It included patients having undergone cardiac surgery [valve surgery, bypass, combined procedure (including valve surgery and bypass) and mediastinitis]. Data were processed using Spss.v 20. Results: 120 patients 70 years old on average (standard deviation (SD): 13.3 years old) were included, out of which 70% were male. 40.8% of them had underwent bypass coronary revascularization. Patients subjected to the bypass technique showed an VAS1 mean value of 4.35 (SD: 2.45), unlike those subjected to valve surgery, who showed a mean value of 2.89 (SD: 2.27), those subjected to the combined procedure, who showed a mean value of 3.87 (SD: 2.90), and those with mediastinitis, who showed a mean value of 3.33 (SD: 3.51); (p < 0.031). 28.5% of patients had underwent revascularization (n = 49 ) by an internal mam mary artery (IMA) graft. These patients showed a mean value for VAS1 of 5.4 (SD: 1.89), unlike those who had underwent a combined procedure [IMA and saphenous vein (SV)], who showed a mean value of 3.9 (SD: 2.6), and those who had underwent a SV procedure , who showed a mean value of 3.5 (SD: 2.1); (p < 0.045). Conclusions: Patients having underwent bypass and IMA procedures perceive more pain than in other cardiac surgery and graft interventions

Amelioration of Duchenne muscular dystrophy in mdx mice by elimination of matrix-associated fibrin-driven inflammation coupled to the αMβ2 leukocyte integrin receptor

In Duchenne muscular dystrophy (DMD), a persistently altered and reorganizing extracellular matrix (ECM) within inflamed muscle promotes damage and dysfunction. However, the molecular determinants of the ECM that mediate inflammatory changes and faulty tissue reorganization remain poorly defined. Here, we show that fibrin deposition is a conspicuous consequence of muscle-vascular damage in dystrophic muscles of DMD patients and mdx mice and that elimination of fibrin(ogen) attenuated dystrophy progression in mdx mice. These benefits appear to be tied to: (i) a decrease in leukocyte integrin α(M)β(2)-mediated proinflammatory programs, thereby attenuating counterproductive inflammation and muscle degeneration; and (ii) a release of satellite cells from persistent inhibitory signals, thereby promoting regeneration. Remarkably, Fib-gamma(390-396A) (Fibγ(390-396A)) mice expressing a mutant form of fibrinogen with normal clotting function, but lacking the α(M)β(2) binding motif, ameliorated dystrophic pathology. Delivery of a fibrinogen/α(M)β(2) blocking peptide was similarly beneficial. Conversely, intramuscular fibrinogen delivery sufficed to induce inflammation and degeneration in fibrinogen-null mice. Thus, local fibrin(ogen) deposition drives dystrophic muscle inflammation and dysfunction, and disruption of fibrin(ogen)-α(M)β(2) interactions may provide a novel strategy for DMD treatment.

Tumor necrosis factor-alpha mediates changes in tissue protein turnover in a rat cancer cachexia model.

Rats bearing the Yoshida AH-130 ascites hepatoma showed enhanced fractional rates of protein degradation in gastrocnemius muscle, heart, and liver, while fractional synthesis rates were similar to those in non-tumor bearing rats. This hypercatabolic pattern was associated with marked perturbations of the hormonal homeostasis and presence of tumor necrosis factor in the circulation. The daily administration of a goat anti-murine TNF IgG to tumor-bearing rats decreased protein degradation rates in skeletal muscle, heart, and liver as compared with tumor-bearing rats receiving a nonimmune goat IgG. The anti-TNF treatment was also effective in attenuating early perturbations in insulin and corticosterone homeostasis. Although these results suggest that tumor necrosis factor plays a significant role in mediating the changes in protein turnover and hormone levels elicited by tumor growth, the inability of such treatment to prevent a reduction in body weight implies that other mediators or tumor-related events were also involved.

Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease

Background and aims: Increased pancreatitis associated protein (PAP) mRNA has been reported in active inflammatory bowel disease (IBD). The aims of the current study were to characterise PAP production in IBD and the effects of PAP on inflammation. Patients and methods: Serum PAP levels were determined in healthy controls (n¿=¿29), inflammatory controls (n¿=¿14), and IBD patients (n¿=¿171). Ex vivo PAP secretion in intestinal tissue was measured in 56 IBD patients and 13 healthy controls. Cellular origin of PAP was determined by immunohistochemistry. The effects of exogenous PAP on nuclear factor ¿B (NF¿B) activation, proinflammatory cytokine production, and endothelial adhesion molecule expression were also analysed ex vivo. Results: Patients with active IBD had increased serum PAP levels compared with controls, and these levels correlated with clinical and endoscopic disease severity. Ex vivo intestinal PAP synthesis was increased in active IBD and correlated with endoscopic and histological severity of inflammatory lesions. PAP localised to colonic Paneth cells. Incubation of mucosa from active Crohn¿s disease with PAP dose dependently reduced proinflammatory cytokines secretion. PAP prevented TNF-¿ induced NF¿B activation in monocytic, epithelial, and endothelial cells and reduced proinflammatory cytokine mRNA levels and adhesion molecule expression. Conclusions: PAP is synthesised by Paneth cells and is overexpressed in colonic tissue of active IBD. PAP inhibits NF¿B activation and downregulates cytokine production and adhesion molecule expression in inflamed tissue. It may represent an anti-inflammatory mechanism and new therapeutic strategy in IBD.

Tumor necrosis factor-alpha mediates changes in tissue protein turnover in a rat cancer cachexia model.

Rats bearing the Yoshida AH-130 ascites hepatoma showed enhanced fractional rates of protein degradation in gastrocnemius muscle, heart, and liver, while fractional synthesis rates were similar to those in non-tumor bearing rats. This hypercatabolic pattern was associated with marked perturbations of the hormonal homeostasis and presence of tumor necrosis factor in the circulation. The daily administration of a goat anti-murine TNF IgG to tumor-bearing rats decreased protein degradation rates in skeletal muscle, heart, and liver as compared with tumor-bearing rats receiving a nonimmune goat IgG. The anti-TNF treatment was also effective in attenuating early perturbations in insulin and corticosterone homeostasis. Although these results suggest that tumor necrosis factor plays a significant role in mediating the changes in protein turnover and hormone levels elicited by tumor growth, the inability of such treatment to prevent a reduction in body weight implies that other mediators or tumor-related events were also involved.

An integrative computational analysis provides evidence for FBN1-associated network deregulation in trisomy 21

Although approximately 50% of Down Syndrome (DS) patients have heart abnormalities, they exhibit an overprotection against cardiac abnormalities related with the connective tissue, for example a lower risk of coronary artery disease. A recent study reported a case of a person affected by DS who carried mutations in FBN1, the gene causative for a connective tissue disorder called Marfan Syndrome (MFS). The fact that the person did not have any cardiac alterations suggested compensation effects due to DS. This observation is supported by a previous DS meta-analysis at the molecular level where we have found an overall upregulation of FBN1 (which is usually downregulated in MFS). Additionally, that result was cross-validated with independent expression data from DS heart tissue. The aim of this work is to elucidate the role of FBN1 in DS and to establish a molecular link to MFS and MFS-related syndromes using a computational approach. To reach that, we conducted different analytical approaches over two DS studies (our previous meta-analysis and independent expression data from DS heart tissue) and revealed expression alterations in the FBN1 interaction network, in FBN1 co-expressed genes and FBN1-related pathways. After merging the significant results from different datasets with a Bayesian approach, we prioritized 85 genes that were able to distinguish control from DS cases. We further found evidence for several of these genes (47%), such as FBN1, DCN, and COL1A2, being dysregulated in MFS and MFS-related diseases. Consequently, we further encourage the scientific community to take into account FBN1 and its related network for the study of DS cardiovascular characteristics.

An integrative computational analysis provides evidence for FBN1-associated network deregulation in trisomy 21

Although approximately 50% of Down Syndrome (DS) patients have heart abnormalities, they exhibit an overprotection against cardiac abnormalities related with the connective tissue, for example a lower risk of coronary artery disease. A recent study reported a case of a person affected by DS who carried mutations in FBN1, the gene causative for a connective tissue disorder called Marfan Syndrome (MFS). The fact that the person did not have any cardiac alterations suggested compensation effects due to DS. This observation is supported by a previous DS meta-analysis at the molecular level where we have found an overall upregulation of FBN1 (which is usually downregulated in MFS). Additionally, that result was cross-validated with independent expression data from DS heart tissue. The aim of this work is to elucidate the role of FBN1 in DS and to establish a molecular link to MFS and MFS-related syndromes using a computational approach. To reach that, we conducted different analytical approaches over two DS studies (our previous meta-analysis and independent expression data from DS heart tissue) and revealed expression alterations in the FBN1 interaction network, in FBN1 co-expressed genes and FBN1-related pathways. After merging the significant results from different datasets with a Bayesian approach, we prioritized 85 genes that were able to distinguish control from DS cases. We further found evidence for several of these genes (47%), such as FBN1, DCN, and COL1A2, being dysregulated in MFS and MFS-related diseases. Consequently, we further encourage the scientific community to take into account FBN1 and its related network for the study of DS cardiovascular characteristics.