Quercetin as a shuttle for labile iron

The antioxidant activity of flavonoids may involve their ability to complex body iron in non-redox-active forms. In this study, it was found that the catechol flavonoids rutin and quercetin are able to suppress redox-active labile plasma iron (LPI) in both buffered solution and in iron-overloaded sera. Both flavonoids are effective in loading the metal into the iron-transport protein transferrin. Iron derivatives of quercetin and rutin are able to permeate cell membranes, however, only free quercetin is able to gain access to the cytosol and decrease intracellular labile iron pools. These results suggest that the antioxidant activity of quercetin may be dependent on its ability to shuttle labile iron from cell compartments followed by its transfer to transferrin. (C) 2011 Elsevier Inc. All rights reserved.

Procalcitonin (PCT) and C-reactive Protein (CRP) as severe systemic infection markers in febrile neutropenic adults

Abstract Background Procalcitonin (PCT) is an inflammatory marker that has been used as indicator of severe bacterial infection. We evaluated the concentrations of PCT as a marker for systemic infection compared to C-reactive protein (CRP) in patients neutropenic febrile. Methods 52 adult patients were enrolled in the study. Blood sample was collected in order to determine the serum concentrations of PCT, CRP and other hematological parameters at the onset of fever. The patients were divided into 2 groups, one with severe infection (n = 26) and the other in which the patients did not present such an infection (n = 26). Then PCT and CRP concentrations at the fever onset were compared between groups using non parametric statistical tests, ROC curve, sensitivity, specificity, likelihood ratio, and Spearman's correlation coefficient. Results The mean of PCT was significantly higher in the group with severe infection (6.7 ng/mL versus 0.6 ng/mL – p = 0.0075) comparing with CRP. Serum concentrations of 0.245 ng/mL of PCT displayed 100% de sensitivity and 69.2% specificity. PCT concentrations of 2,145 ng/mL presented a likelihood ratio of 13, which was not observed for any concentration of CRP. Conclusion PCT seems to be an useful marker for the diagnosis of systemic infection in febrile neutropenic patients, probably better than CRP.

Influência da suplementação de creatina sobre a massa óssea de ratos espontaneamente hipertensos

INTRODUÇÃO: Recentes evidências indicam que a suplementação de creatina (Cr) é capaz de aumentar a densidade mineral óssea (DMO) no fêmur de ratos saudáveis em crescimento. Entretanto, há poucos estudos que testam a efetividade da suplementação desse nutriente em condições de perda óssea. OBJETIVO: Investigar o efeito da suplementação de Cr na DMO e no conteúdo mineral ósseo (CMO) de ratos espontaneamente hipertensos (SHR), um modelo experimental de baixa massa óssea. MATERIAIS E MÉTODOS: Dezesseis ratos SHR machos com 8 meses de idade foram randomizados em dois grupos experimentais pareados pelo peso corporal, a saber: 1) Pl: SHR tratados com placebo (água destilada; n = 8); e 2) Cr: SHR tratados com Cr (n = 8). Após nove semanas de suplementação os animais foram eutanasiados e o fêmur e a coluna vertebral (L1-L4) foram analisados por densitometria óssea (Dual Energy X-Ray Absorptiometry). RESULTADOS: Não houve diferença significativa na DMO (Pl = 0,249 ± 0,003 g/cm² vs. Cr = 0,249 ± 0,004 g/cm²; P = 0,95) e no CMO (Pl = 0,509 ± 0,150 g vs. Cr = 0,509 ± 0,017 g; P = 0,99) da coluna vertebral e na DMO (Pl = 0,210 ± 0,004 g/cm² vs. Cr = 0,206 ± 0,004 g/cm2;P = 0,49) e no CMO (Pl = 0,407 ± 0,021 g vs. Cr = 0,385 ± 0,021 g; P = 0,46) do fêmur total entre os grupos experimentais. CONCLUSÃO: Neste estudo, usando um modelo experimental de baixa massa óssea, a suplementação de Cr não afetou a massa óssea.

Intervention to reduce C-reactive protein determination requests for acute infections at an emergency department

Introduction C-reactive protein (CRP) levels rise during inflammatory processes and have been ordered for rheumatic disease follow-up since the 1950s. The number of tests ordered in the emergency setting has increased, but without evident improvement in medical care quality. Objective To determine the pattern of CRP determinations in the emergency department (ED) of a university hospital in Sao Paulo, Brazil, and to evaluate the effect of an intervention with staff and students about the best use of the test in the ED. Methods Data regarding CRP testing requests, related diagnoses and the number of monthly consultations in the hospital ED were analysed before and after the intervention. Because of an increase in CRP measurement requests from 2007 to 2009, the author started discussing the role of CRP determinations in the medical decision-making process in early 2010. Staff and faculty members openly discussed the pattern of requests in the hospital and related current medical literature. During 2010, the medical staff worked as multipliers to change the behaviour of new students and residents. The results of the first 4 months after the intervention were presented at another general meeting in July 2010. Results From 2007 to 2009, there were 11 786 CRP measurement requests with a clear exponential trend. After the intervention, during the calendar year 2010, there was a 48% reduction in adjusted annual CRP requests. Pneumonia, fever and urinary tract infections were the most common reasons for CRP requests. Discussion Inexpensive, well-directed, interactive educational interventions may affect professional behaviour and curb rates of laboratory tests.

GLUT4 content decreases along with insulin resistance and high levels of inflammatory markers in rats with metabolic syndrome

Background: Metabolic syndrome is characterized by insulin resistance, which is closely related to GLUT4 content in insulin-sensitive tissues. Thus, we evaluated the GLUT4 expression, insulin resistance and inflammation, characteristics of the metabolic syndrome, in an experimental model. Methods: Spontaneously hypertensive neonate rats (18/group) were treated with monosodium glutamate (MetS) during 9 days, and compared with Wistar-Kyoto (C) and saline-treated SHR (H). Blood pressure (BP) and lipid levels, C-reactive protein (CRP), interleukin 6 (IL-6), TNF-alpha and adiponectin were evaluated. GLUT4 protein was analysed in the heart, white adipose tissue and gastrocnemius. Studies were performed at 3 (3-mo), 6 (6-mo) and 9 (9-mo) months of age. Results: MetS rats were more insulin resistant (p<0.001, all ages) and had higher BP (3-mo: p<0.001, 6-mo: p = 0.001, 9-mo: p = 0.015) as compared to C. At 6 months, CRP, IL-6 and TNF-alpha were higher (p<0.001, all comparisons) in MetS rats vs H, but adiponectin was lower in MetS at 9 months (MetS: 32 +/- 2, H: 42 +/- 2, C: 45 +/- 2 pg/mL; p<0.001). GLUT4 protein was reduced in MetS as compared to C rats at 3, 6 and 9-mo, respectively (Heart: 54%, 50% and 57%; Gastrocnemius: 37%, 56% and 50%; Adipose tissue: 69%, 61% and 69%). Conclusions: MSG-treated SHR presented all metabolic syndrome characteristics, as well as reduced GLUT4 content, which must play a key role in the impaired glycemic homeostasis of the metabolic syndrome.

Persistence of Inflammatory Response to Intense Exercise in Diabetic Rats

In this study we evaluated the onset and resolution of inflammation in control and streptozotocin-induced diabetic rats subjected to a single session of intense exercise. The following measurements were carried out prior to, immediately after, and 2 and 24 hours after exercise: plasma levels of proinflammatory cytokines (TNF-alpha, IL-1 beta, IL-6, CINC-2 alpha/beta, MIP-3 alpha, and IL-6), immunoglobulins (IgA and IgM), acute phase proteins (CRP and C3), and creatine kinase (CK) activity. We also examined the occurrence of macrophage death by measurements of macrophages necrosis (loss of membrane integrity) and DNA fragmentation. An increase was observed in the concentration of IL-1 beta (3.3-fold) and TNF-alpha (2.0-fold) and in the proportion of necrotic macrophages (4.5-fold) in diabetic rats 24 hours after exercise, while the control group showed basal measurements. Twenty-four hours after the exercise, serum CK activity was elevated in diabetic rats but not in control animals. We concluded that lesion and inflammations resulting from intense exercise were greater and lasted longer in diabetic animals than in nondiabetic control rats.

INFLAMMATORY RESPONSE AND NEUTROPHIL FUNCTIONS IN PLAYERS AFTER A FUTSAL MATCH

de Moura, NR, Cury-Boaventura, MF, Santos, VC, Levada-Pires, AC, Bortolon, JR, Fiamoncini, J, Pithon-Curi, TC, Curi, R, and Hatanaka, E. Inflammatory response and neutrophil functions in players after a futsal match. J Strength Cond Res 26(9): 2507-2514, 2012-Futsal players suffer injuries resulting from muscle fatigue and contact or collision among players. Muscle lesions can be detected by measuring muscle lesion markers such as creatine kinase (CK) and lactate dehydrogenase (LDH) in plasma. After an initial lesion, there is an increase in the plasma levels of C-reactive protein (CRP) and proinflammatory cytokines. These mediators may activate neutrophils and contribute to tissue damage and increase susceptibility to invasive microorganisms. In this study, we investigated the effect of a futsal match on muscle lesion markers, cytokines, and CRP in elite players. The basal and stimulated neutrophil responsiveness after a match was also evaluated based on measurements of neutrophil necrosis, apoptosis, phagocytic capacity, reactive oxygen species (ROS) production, and cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-8, IL-1 beta, IL-10, and IL-1ra) production. Blood samples were taken from 16 players (26.4 +/- 3.2 years, 70.2 +/- 6.9 kg, 59.7 +/- 5.1 ml.kg(-1).min(-1), sports experience of 4.4 +/- 0.9 years) before and immediately after a match. Exercise increased the serum activities of CK (2.5-fold) and LDH (1.3-fold). Playing futsal also increased the serum concentrations of IL-6 (1.6-fold) and CRP (1.6-fold). The TNF-alpha, IL-1 beta, IL-8, IL-1ra, and IL-10 serum levels were not modified in the conditions studied. The futsal match induced neutrophil apoptosis, as indicated by phosphatidylserine externalization (6.0-fold). The exercise induced priming of neutrophils by increasing ROS (1.3-fold), TNF-alpha (5.8-fold), and IL-1 beta (4.8-fold) released in nonstimulated cells. However, in the stimulated condition, the exercise decreased neutrophil function, diminishing the release of ROS by phorbol myristate acetate-stimulated neutrophils (1.5-fold), and the phagocytic capacity (1.6-fold). We concluded that playing futsal induces inflammation, primes and activates neutrophils, and reduces the efficiency of neutrophil phagocytosis immediately after a match.

Plasma levels of complement proteins from the alternative pathway in patients with age-related macular degeneration are independent of Complement Factor H Tyr(402)His polymorphism

Purpose: To investigate the influence of the Factor H (CFH) Tyr(402)His polymorphism on the plasma levels of the alternative pathway proteins CFH, C3, Factor B (FB), Factor D (FD), and Factor I (FI) and the inflammatory marker C-reactive protein (CRP) in 119 patients with age-related macular degeneration (AMD) and 152 unrelated control individuals. Methods: Patients with AMD and the control group were separated according to CFH polymorphism, age, and gender. Plasma complement proteins and CRP concentrations were determined with enzyme-linked immunosorbent assay, immunodiffusion, or nephelometry. Results: Significant differences in the concentrations of FD and FI were observed between the patients with AMD and the control individuals. We observed significantly reduced FD plasma levels in patients with AMD. We also identified a significant decrease in CFH plasma levels in female patients with AMD in relation to female controls. Plasma FI levels were significantly increased in patients with AMD compared to the control group. Regarding gender, a significant increase in FI plasma levels was observed in male patients. Finally, we found no significant correlation between the CFH Tyr(402)His polymorphism and the CFH, C3, FB, FD, FI, and CRP plasma levels. Conclusions: Patients with AMD present altered levels of FD and FI in a manner independent of this CFH polymorphism, and gender apparently contributes to the plasma levels of these two proteins in patients with AMD and control individuals.

Effectiveness, against tuberculosis, of pseudo-ternary complexes: Peptide-DNA-cationic liposome

We report the effects of a synthetic peptide designed to act as a nuclear localization signal on the treatment of tuberculosis. The peptide contains 21 amino acid residues with the following specific domains: nuclear localization signal from SV 40T, cationic shuttle sequence, and cysteamide group at the C-terminus. The peptide was complexed with the plasmid DNAhsp65 and incorporated into cationic liposomes, forming a pseudo-ternary complex. The same cationic liposomes, composed of egg chicken L-alpha-phosphatidylcholine, 1,2-dioleoyl-3-trimethylammonium-propane, and 1,2-dioleoyl-3-trimethylammonium-propane (2:1:1 M), were previously evaluated as a gene carrier for tuberculosis immunization protocols with DNAhsp65. The pseudo-ternary complex presented a controlled size (250 nm), spherical-like shape, and various lamellae in liposomes as evaluated by transmission electron microscopy. An assay of fluorescence probe accessibility confirmed insertion of the peptide/DNA into the liposome structure. Peptide addition conferred no cytotoxicity in vitro, and similar therapeutic effects against tuberculosis were seen with four times less DNA compared with naked DNA treatment. Taken together, the results indicate that the pseudo-ternary complex is a promising gene vaccine for tuberculosis treatment. This work contributes to the development of multifunctional nanostructures in the search for strategies for in vivo DNA delivery. (C) 2011 Elsevier Inc. All rights reserved.

High levels of C-reactive protein are associated with reduced vagal modulation and low physical activity in young adults

The purpose of this study was to examine the relationship between cardiac autonomic control derived from heart rate variability (HRV), high-sensitivity C-reactive protein (hs-CRP) and physical activity (PA) levels measured using accelerometers. A total of 80 healthy university students volunteered to participate in this study (20.56 +/- 0.82 years, 1.36 +/- 1.5 mg/L of hs-CRP). The participants were divided into groups based on tertiles of hs-CRP. Analysis of covariance adjusted to PA was used to assess group differences in HRV. Associations between hs-CRP, HRV indices and PA were analyzed using Pearson's correlation. The participants at the highest tertile of hs-CRP (tertile 3) had lower cardiac vagal modulation (SDNN, tertile 1=78.05 +/- 5.9,tertile 2=82.43 +/- 5.9,tertile 3=56.03 +/- 6.1; SD1, tertile 1=61.27 +/- 5.3, tertile 2=62.93 +/- 5.4, tertile 3=40.03 +/- 5.5). In addition, vagal indices were inversely correlated with hs-CRP but positively correlated with PA (SDNN r=-0.320, SD1 r=-0.377; SDNN r=0.304, SD1 r=0.299; P<0.05). Furthermore, the most physically active subjects had lower levels of hs-CRP and the highest levels of vagal modulation.

Relation of Uric Acid to Serum Levels of High-Sensitivity C-Reactive Protein, Triglycerides, and High-Density Lipoprotein Cholesterol and to Hepatic Steatosis

Increased uric acid (UA) is strongly linked to cardiovascular disease. However, the independent role of UA is still debated because it is associated with several cardiovascular risk factors including obesity and metabolic syndrome. This study assessed the association of UA with increased high-sensitivity C-reactive protein (hs-CRP), increased ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL), sonographically detected hepatic steatosis, and their clustering in the presence and absence of obesity and metabolic syndrome. We evaluated 3,518 employed subjects without clinical cardiovascular disease from November 2008 through July 2010. Prevalence of tis-CRP >= 3 mg/L was 19%, that of TG/HDL >= 3 was 44%, and that of hepatic steatosis was 43%. In multivariable logistic regression after adjusting for traditional cardiovascular risk factors and confounders, highest versus lowest UA quartile was associated with hs-CRP >= 3 mg/L (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.01 to 2.28, p = 0.04), TG/HDL >= 3 (OR 3.29, 95% CI 2.36 to 4.60, p <0.001), and hepatic steatosis (OR 3.10, 95% CI 2.22 to 4.32, p <0.001) independently of obesity and metabolic syndrome. Association of UA with hs-CRP >= 3 mg/L became nonsignificant in analyses stratified by obesity. Ascending UA quartiles compared to the lowest UA quartile demonstrated a graded increase in the odds of having 2 or 3 of these risk conditions and a successive decrease in the odds of having none. In conclusion, high UA levels were associated with increased TG/HDL and hepatic steatosis independently of metabolic syndrome and obesity and with increased hs-CRP independently of metabolic syndrome. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:1787-1792)

Comparison between multiple sets and half-pyramid resistance exercise bouts for muscle damage profile

The present study compared the changes in markers of muscle damage after bouts of resistance exercise employing the Multiple-sets (MS) and Half-pyramid (HP) training systems. Ten healthy men (26.1 +/- 6.3 years), who had been involved in regular resistance training, performed MS and HP bouts, 14 days apart, in a randomised, counter-balanced manner. For the MS bout, participants performed three sets of maximum repetitions at 75%-1RM (i.e. 75% of a One Repetition Maximum) for the three exercises, starting with the bench press, followed by pec deck and decline bench press. For the HP bout, the participants performed three sets of maximum repetitions with 67%-1RM, 74%-1RM and 80%-1RM for the first, second and third sets, respectively, for the same three exercise sequences as the MS bout. The total volume of load lifted was equated between both bouts. Muscle soreness, plasma creatine kinase (CK) activity, myoglobin (Mb) and C-reactive protein (CRP) concentrations were assessed before and for three days after each exercise bout, and the changes over time were compared between MS and HP using two-way repeated measures ANOVA. Muscle soreness developed significantly (P<0.01) after both bouts, but no significant difference was observed between MS and HP. Plasma CK activity and Mb concentration increased significantly (P<0.01) without significant differences between bouts, and CRP concentration did not change significantly after either bout. These results suggest that the muscle damage profile is similar for MS and HP, probably due to the similar total volume of load lifted.

Trans fatty acid intake is associated with insulin sensitivity but independently of inflammation

High saturated and trans fatty acid intake, the typical dietary pattern of Western populations, favors a proinflammatory status that contributes to generating insulin resistance (IR). We examined whether the consumption of these fatty acids was associated with IR and inflammatory markers. In this cross-sectional study, 127 non-diabetic individuals were allocated to a group without IR and 56 to another with IR, defined as homeostasis model assessment-IR (HOMA-IR) >2.71. Diet was assessed using 24-h food recalls. Multiple linear regression was employed to test independent associations with HOMA-IR. The IR group presented worse anthropometric, biochemical and inflammatory profiles. Energy intake was correlated with abdominal circumference and inversely with adiponectin concentrations (r = -0.227, P = 0.002), while saturated fat intake correlated with inflammatory markers and trans fat with HOMA-IR (r = 0.160, P = 0.030). Abdominal circumference was associated with HOMA-IR (r = 0.430, P < 0.001). In multiple analysis, HOMA-IR remained associated with trans fat intake (beta = 1.416, P = 0.039) and body mass index (beta = 0.390, P < 0.001), and was also inversely associated with adiponectin (beta = -1.637, P = 0.004). Inclusion of other nutrients (saturated fat and added sugar) or other inflammatory markers (IL-6 and CRP) into the models did not modify these associations. Our study supports that trans fat intake impairs insulin sensitivity. The hypothesis that its effect could depend on transcription factors, resulting in expression of proinflammatory genes, was not corroborated. We speculate that trans fat interferes predominantly with insulin signaling via intracellular kinases, which alter insulin receptor substrates.

Serum C-reactive protein levels predict neurological outcome after aneurysmal subarachnoid hemorrhage

Objectives: Our aim was to evaluate the relationship between serum C-reactive protein (CRP) levels and the neurological prognosis and development of vasospasm in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods: Eighty-two adult patients with aSAH diagnoses were prospectively evaluated. Glasgow Coma Scale (GCS) score, Hunt and Hess grade, Fisher grade, cranial CT scans, digital subtraction angiography studies and daily neurological examinations were recorded. Serial serum CRP measurements were obtained daily between admission and the tenth day. Glasgow Outcome Scale (GOS) and the modified Rankin Scale (mRS) were used to assess the prognosis. Results: Serum CRP levels were related to severity of aSAH. Patients with lower GCS scores and higher Hunt and Hess and Fisher grades presented statistically significant higher serum CRP levels. Patients with higher serum CRP levels had a less favorable prognosis. Conclusions: Increased serum CRP levels were strongly associated with worse clinical prognosis in this study.