Female sex hormones mediate the allergic lung reaction by regulating the release of inflammatory mediators and the expression of lung E-selectin in rats

Background: Fluctuations of estradiol and progesterone levels caused by the menstrual cycle worsen asthma symptoms. Conflicting data are reported in literature regarding pro and anti-inflammatory properties of estradiol and progesterone. Methods: Female Wistar rats were ovalbumin (OVA) sensitized 1 day after resection of the ovaries (OVx). Control group consisted of sensitized-rats with intact ovaries (Sham-OVx). Allergic challenge was performed by aerosol (OVA 1%, 15 min) two weeks later. Twenty four hours after challenge, BAL, bone marrow and total blood cells were counted. Lung tissues were used as explants, for expontaneous cytokine secretion in vitro or for immunostaining of E-selectin. Results: We observed an exacerbated cell recruitment into the lungs of OVx rats, reduced blood leukocytes counting and increased the number of bone marrow cells. Estradiol-treated OVx allergic rats reduced, and those treated with progesterone increased, respectively, the number of cells in the BAL and bone marrow. Lungs of OVx allergic rats significantly increased the E-selectin expression, an effect prevented by estradiol but not by progesterone treatment. Systemically, estradiol treatment increased the number of peripheral blood leukocytes in OVx allergic rats when compared to non treated-OVx allergic rats. Cultured-BAL cells of OVx allergic rats released elevated amounts of LTB(4) and nitrites while bone marrow cells increased the release of TNF-alpha and nitrites. Estradiol treatment of OVx allergic rats was associated with a decreased release of TNF-alpha, IL-10, LTB4 and nitrites by bone marrow cells incubates. In contrast, estradiol caused an increase in IL-10 and NO release by cultured-BAL cells. Progesterone significantly increased TNF-alpha by cultured BAL cells and bone marrow cells. Conclusions: Data presented here suggest that upon hormonal oscillations the immune sensitization might trigger an allergic lung inflammation whose phenotype is under control of estradiol. Our data could contribute to the understanding of the protective role of estradiol in some cases of asthma symptoms in fertile ans post-menopausal women clinically observed.

Administration of Mycobacterium leprae rHsp65 Aggravates Experimental Autoimmune Uveitis in Mice

The 60kDa heat shock protein family, Hsp60, constitutes an abundant and highly conserved class of molecules that are highly expressed in chronic-inflammatory and autoimmune processes. Experimental autoimmune uveitis [EAU] is a T cell mediated intraocular inflammatory disease that resembles human uveitis. Mycobacterial and homologous Hsp60 peptides induces uveitis in rats, however their participation in aggravating the disease is poorly known. We here evaluate the effects of the Mycobacterium leprae Hsp65 in the development/progression of EAU and the autoimmune response against the eye through the induction of the endogenous disequilibrium by enhancing the entropy of the immunobiological system with the addition of homologous Hsp. B10. RIII mice were immunized subcutaneously with interphotoreceptor retinoid-binding protein [IRBP], followed by intraperitoneally inoculation of M. leprae recombinant Hsp65 [rHsp65]. We evaluated the proliferative response, cytokine production and the percentage of CD4(+)IL-17(+), CD4(+)IFN-gamma(+) and CD4(+)Foxp3(+) cells ex vivo, by flow cytometry. Disease severity was determined by eye histological examination and serum levels of anti-IRBP and anti-Hsp60/65 measured by ELISA. EAU scores increased in the Hsp65 group and were associated with an expansion of CD4(+)IFN-gamma(+) and CD4(+)IL-17(+) T cells, corroborating with higher levels of IFN-gamma. Our data indicate that rHsp65 is one of the managers with a significant impact over the immune response during autoimmunity, skewing it to a pathogenic state, promoting both Th1 and Th17 commitment. It seems comprehensible that the specificity and primary function of Hsp60 molecules can be considered as a potential pathogenic factor acting as a whistleblower announcing chronic-inflammatory diseases progression.

Impaired Innate Immunity in Tlr4(-/-) Mice but Preserved CD8(+) T Cell Responses against Trypanosoma cruzi in Tlr4-, Tlr2-, Tlr9- or Myd88-Deficient Mice

The murine model of T. cruzi infection has provided compelling evidence that development of host resistance against intracellular protozoans critically depends on the activation of members of the Toll-like receptor (TLR) family via the MyD88 adaptor molecule. However, the possibility that TLR/MyD88 signaling pathways also control the induction of immunoprotective CD8(+) T cell-mediated effector functions has not been investigated to date. We addressed this question by measuring the frequencies of IFN-gamma secreting CD8(+) T cells specific for H-2K(b)-restricted immunodominant peptides as well as the in vivo Ag-specific cytotoxic response in infected animals that are deficient either in TLR2, TLR4, TLR9 or MyD88 signaling pathways. Strikingly, we found that T. cruzi-infected Tlr2(-/-), Tlr4(-/-), Tlr9(-/-) or Myd88(-/-) mice generated both specific cytotoxic responses and IFN-gamma secreting CD8(+) T cells at levels comparable to WT mice, although the frequency of IFN-gamma(+)CD4(+) cells was diminished in infected Myd88(-/-) mice. We also analyzed the efficiency of TLR4-driven immune responses against T. cruzi using TLR4-deficient mice on the C57BL genetic background (B6 and B10). Our studies demonstrated that TLR4 signaling is required for optimal production of IFN-gamma, TNF-alpha and nitric oxide (NO) in the spleen of infected animals and, as a consequence, Tlr4(-/-) mice display higher parasitemia levels. Collectively, our results indicate that TLR4, as well as previously shown for TLR2, TLR9 and MyD88, contributes to the innate immune response and, consequently, resistance in the acute phase of infection, although each of these pathways is not individually essential for the generation of class I-restricted responses against T. cruzi.

Naturally-acquired humoral immune responses against the N- and C-termini of the Plasmodium vivax MSP1 protein in endemic regions of Brazil and Papua New Guinea using a multiplex assay

Background: Progress towards the development of a malaria vaccine against Plasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic. Methods: Glutathione S-transferase (GST) and GST-fusion proteins representing the N-terminus of the merozoite surface protein 1 of P. vivax, PvMSP1-N, and the C-terminus, PvMSP1-C, were covalently coupled to BioPlex carboxylated beads. Recombinant proteins and coupled beads were used, respectively, in ELISA and Bioplex assays using immune sera of P. vivax patients from Brazil and PNG to determine IgG and subclass responses. Concordances between the two methods in the seropositivity responses were evaluated using the Kappa statistic and the Spearman's rank correlation. Results: The results using this methodology were compared with the classical microtitre enzyme-linked immnosorbent assay ( ELISA), showing that the assay was sensitive, reproducible and had good concordance with ELISA; yet, further research into different statistical analyses seems desirable before claiming conclusive results exclusively based on multiplex assays. As expected, results demonstrated that PvMSP1 was immunogenic in natural infections of patients from different endemic regions of Brazil and Papua New Guinea ( PNG), and that age correlated only with antibodies against the C-terminus part of the molecule. Furthermore, the IgG subclass profiles were different in these endemic regions having IgG3 predominantly recognizing PvMSP1 in Brazil and IgG1 predominantly recognizing PvMSP1 in PNG. Conclusions: This study validates the use of the multiplex assay to measure naturally-acquired IgG antibodies against the merozoite surface protein 1 of P. vivax.

Analgesic and Anti-Inflammatory Activities of Salicylaldehyde 2-Chlorobenzoyl Hydrazone (H(2)LASSBio-466), Salicylaldehyde 4-Chlorobenzoyl Hydrazone (H(2)LASSBio-1064) and Their Zinc(II) Complexes

Salicylaldehyde 2-chlorobenzoyl hydrazone (H(2)LASSBio-466), salicylaldehyde 4-chlorobenzoyl hydrazone (H(2)LASSBio-1064) and their complexes [Zn(LASSBio-466) H(2)O](2) (1) and [Zn(HLASSBio-1064) Cl](2) (2) were evaluated in animal models of peripheral and central nociception, and acute inflammation. All studied compounds significantly inhibited acetic acid-induced writhing response. Upon coordination the anti-nociceptive activity was favored in the complex 1. H(2)LASSBio-466 inhibited only the first phase of the formalin test, while 1 was active in the second phase, like indomethacin, indicating its ability to inhibit nociception associated with the inflammatory response. Hence coordination to zinc(II) altered the pharmacological profile of H(2)LASSBio-466. H(2)LASSBio-1064 inhibited both phases but this effect was not improved by coordination. The studied compounds did not increase the latency of response in the hot plate model, indicating their lack of central anti-nociceptive activity. All compounds showed levels of inhibition of zymosan-induced peritonitis comparable or superior to indomethacin, indicating an expressive anti-inflammatory profile.

Quantification of some nonsteroidal anti-inflammatory drugs as reducing agents of Cu(II)/4,4 '-dicarboxy-2,2 '-biquinoline complexes in cationic micellar medium

A simple method was developed for spectrophotometric determination of some nonsteroidal anti-inflammatory drugs (meloxicam, piroxicam and tenoxicam) based on the reduction of copper(II) in buffered solution (pH 7.0) and micellar medium containing 4,4'-dicarboxy-2,2'-buffered solution (pH 7.0) and micellar medium containing 4,4'-dicarboxy-2,2'-biquinoline acid. The-biquinoline acid. The absorbance values at 558 nm, characteristic of the formed Cu(I)/4,4'-dicarboxy-2,2'-biquinoline complexes, are linear with the concentrations (5.7-40 mmol L(-1), n = 5) of these oxicams (meloxicam r = 0.998; piroxicam and tenoxicam r = 0.999). The limit of detection values, in mmol L(-1), calculated for meloxicam (2.7), piroxicam (1.2) and tenoxicam (1.3) was obtained with 99% confidence level and the relative standard deviations for meloxicam (3.1%), piroxicam (5.1%) and tenoxicam (1.2%) were calculated using a 25 mmol L(-1) solution (n = 7). Mean recovery values for meloxicam, piroxicam and tenoxicam forms were 100 +/- 6.9, 98.6 +/- 3.6 and 99.4 +/- 2.5%, respectively. The conditional potential of Cu(II)/Cu(I) in complex medium of 7.5 mmol L(-1) BCA was determined to be 629 +/- 11 mV vs. NHE.

Kallikrein-Kinin System Mediated Inflammation in Alzheimer`s Disease In Vivo

The Kallikrein-Kinin System (KKS) has been associated to inflammatory and immunogenic responses in the peripheral and central nervous system by the activation of two receptors, namely B1 receptor and B2 receptor. The B1 receptor is absent or under-expressed in physiological conditions, being up-regulated during tissue injury or in the presence of cytokines. The B2 receptor is constitutive and mediates most of the biological effects of kinins. Some authors suggest a link between the KKS and the neuroinflammation in Alzheimer`s disease (AD). We have recently described an increase in bradykinin (BK) in the cerebrospinal fluid and in densities of B1 and B2 receptors in brain areas related to memory, after chronic infusion of amyloid-beta (A beta) peptide in rats, which was accompanied by memory disruption and neuronal loss. Mice lacking B1 or B2 receptors presented reduced cognitive deficits related to the learning process, after acute intracerebroventricular (i.c.v). administration of A. Nevertheless, our group showed an early disruption of cognitive function by i.c.v. chronic infusion of A beta after a learned task, in the knock-out B2 mice. This suggests a neuroprotective role for B2 receptors. In knock-out B1 mice the memory disruption was absent, implying the participation of this receptor in neurodegenerative processes. The acute or chronic infusion of A beta can lead to different responses of the brain tissue. In this way, the proper involvement of KKS on neuroinflammation in AD probably depends on the amount of A beta injected. Though, BK applied to neurons can exert inflammatory effects, whereas in glial cells, BK can have a potential protective role for neurons, by inhibiting proinflammatory cytokines. This review discusses this duality concerning the KKS and neuroinflammation in AD in vivo.

HORMONAL RESPONSES TO DIFFERENT RESISTANCE EXERCISE SCHEMES OF SIMILAR TOTAL VOLUME

Uchida, MC, Crewther, BT, Ugrinowitsch, C, Bacurau, RFP, Moriscot, AS, and Aoki, MS. J Strength Cond Res 23(7): 2003-2008, 2009-This study assessed the effect of different resistance exercise scheme (RES) designs of similar total of load lifted on the responses of testosterone, cortisol, and creatine kinase (CK). Twenty-seven healthy males performed 1 of 4 bench press workouts described by the 1 repetition maximum (1RM) load: 4 sets of maximum repetitions at 50%-1RM (50%-1RM RES), 5 sets of maximum repetitions at 75%-1RM (75%-1RM RES), 10 sets of maximum repetitions at 90%-1RM (90%1RM RES), or 8 sets of maximum repetitions at 110%-1RM (110%-1RM RES). Each RES was equated by the total volume of load lifted (repetitions x sets x load). Blood samples, collected pre-exercise (Pre) and post-exercise (Post) at 1 and 24 hours (24 h), were analyzed for total and free testosterone, total cortisol, and CK. In general, testosterone and cortisol showed little change within or between the different RES (p > 0.05), possibly because of the relatively low volume lifted and/ or the small muscle mass activated by the bench press exercise. Cortisol was elevated after the 75%-1RM RES at the Post sample, with this response also exceeding the other RES (p < 0.05). The 24 h CK response was also elevated after the 75%-1RM RES (p < 0.05), thereby suggesting greater training strain for the same volume of load. These results confirm previous recommendations regarding the prescription of resistance exercise and the importance of total volume as a stimulus for activating the endocrine system and achieving long-term adaptation.

SALIVARY HORMONE AND IMMUNE RESPONSES TO THREE RESISTANCE EXERCISE SCHEMES IN ELITE FEMALE ATHLETES

Nunes, JA, Crewther, BT, Ugrinowitsch, C, Tricoli, V, Viveiros, L, de Rose Jr, D, and Aoki, MS. Salivary hormone and immune responses to three resistance exercise schemes in elite female athletes J Strength Cond Res 25(8): 2322-2327, 2011-This study examined the salivary hormone and immune responses of elite female athletes to 3 different resistance exercise schemes. Fourteen female basketball players each performed an endurance scheme (ES-4 sets of 12 reps, 60% of 1 repetition maximum (1RM) load, 1-minute rest periods), a strength-hypertrophy scheme (SHS-1 set of 5RM, 1 set of 4RM, 1 set of 3RM, 1 set of 2RM, and 1set of 1RM with 3-minute rest periods, followed by 3 sets of 10RM with 2-minute rest periods) and a power scheme (PS-3 sets of 10 reps, 50% 1RM load, 3-minute rest periods) using the same exercises (bench press, squat, and biceps curl). Saliva samples were collected at 07:30 hours, pre-exercise (Pre) at 09:30 hours, postexercise (Post), and at 17:30 hours. Matching samples were also taken on a nonexercising control day. The samples were analyzed for testosterone, cortisol (C), and immunoglobulin A concentrations. The total volume of load lifted differed among the 3 schemes (SHS > ES > PS, p < 0.05). Postexercise C concentrations increased after all schemes, compared to control values (p < 0.05). In the SHS, the postexercise C response was also greater than pre-exercise data (p < 0.05). The current findings confirm that high-volume resistance exercise schemes can stimulate greater C secretion because of higher metabolic demand. In terms of practical applications, acute changes in C may be used to evaluate the metabolic demands of different resistance exercise schemes, or as a tool for monitoring training strain.

Effect of bench press exercise intensity on muscle soreness and inflammatory mediators

This study compared four different intensities of a bench press exercise for muscle soreness, creatine kinase activity, interleukin (IL)-1, IL-6, tumor necrosis factor- (TNF-), and prostaglandin E2 (PGE2) concentrations in the blood. Thirty-five male Brazilian Army soldiers were randomly assigned to one of five groups: 50% one-repetition maximum (1-RM), 75% 1-RM, 90% 1-RM, 110% 1-RM, and a control group that did not perform the exercise. The total volume (setsrepetitionsload) of the exercise was matched among the exercise groups. Muscle soreness and plasma creatine kinase activity increased markedly (P0.05) after exercise, with no significant differences among the groups. Serum PGE2 concentration also increased markedly (P0.05) after exercise, with a significantly (P0.05) greater increase in the 110% 1-RM group compared with the other groups. A weak but significant (P0.05) correlation was found between peak muscle soreness and peak PGE2 concentration, but no significant correlation was evident between peak muscle soreness and peak creatine kinase activity, or peak creatine kinase activity and peak PGE2 concentration. All groups showed no changes in IL-1, IL-6 or TNF-. Our results suggest that the intensity of bench press exercise does not affect the magnitude of muscle soreness and blood markers of muscle damage and inflammation.

Acute physiological responses to different circuit training protocols

Aim. The purpose of present study was to compare the acute physiological responses to a circuit weight training with the responses to a combined circuit training (weight training and treadmill run). Methods. The sample consisted of 25 individuals at an average state of training, 10 men and 15 female, between 18 and 35 year old. There were selected 60 second sets of resistance exercises to the circuit weight training (CWT). Whereas in the combined circuit training (CCT), the subjects spent 30 seconds on the same resistance exercises and 30 seconds running on the treadmill. The rest intervals between the sets lasted 15 seconds. The analysis of variance (ANOVA) with 5% significance level was utilized to the statistical analysis of the results. Results. Comparing circuit training protocols, it was noted that CCT elicits a higher relative and absolute <(V)over dot>O(2) and energy expenditure values than CWT for both genders (P<0.05). Regarding inter-gender comparison, males showed higher absolute and relative <(V)over dot>O(2) and absolute energy expenditure values for both CWT and CCT than females (P<0.05). Females showed a significant greater % <(V)over dot>O(2max) value for both CWT and CCT. Due to the experimental conditions used to state both circuit training bouts (CWT and CCT), the <(V)over dot>O(2) rate found was higher than the values reported by previous studies which used heavier weight lift. Conclusion. CCT seems adequate to produce cardiovascular improvements and greater energy expenditure for both men and women, while CWT group classes are sufficient only for unfit women.

Contuse lesion of the rat spinal cord of moderate intensity leads to a higher time-dependent secondary neurodegeneration than severe one - An open-window for experimental neuroprotective interventions

Secondary neurodegeneration takes place in the surrounding tissue of spinal cord trauma and modifies substantially the prognosis, considering the small diameter of its transversal axis. We analyzed neuronal and glial responses in rat spinal cord after different degree of contusion promoted by the NYU Impactor. Rats were submitted to vertebrae laminectomy and received moderate or severe contusions. Control animals were sham operated. After 7 and 30 days post surgery, stereological analysis of Nissl staining cellular profiles showed a time progression of the lesion volume after moderate injury, but not after severe injury. The number of neurons was not altered cranial to injury. However, same degree of diminution was seen in the caudal cord 30 days after both severe and moderate injuries. Microdensitometric image analysis demonstrated a microglial reaction in the white matter 30 days after a moderate contusion and showed a widespread astroglial reaction in the white and gray matters 7 days after both severities. Astroglial activation lasted close to lesion and in areas related to Wallerian degeneration. Data showed a more protracted secondary degeneration in rat spinal cord after mild contusion, which offered an opportunity for neuroprotective approaches. Temporal and regional glial responses corroborated to diverse glial cell function in lesioned spinal cord. (C) 2007 Elsevier Ltd. All rights reserved.

Hormonal, metabolic and perceptual responses to different resistance training systems

Aim. The purpose of the present study was to compare the effect of different resistance training systems (Multiple-set [MS] and Pyramid [P]) on hormonal, metabolic and perceptual markers of internal load. Methods. Ten healthy men performed two resistance training sessions (MS and P) which consisted of three exercises (bench press, peck deck and decline bench press) with the same total volume of load lifted. The training sessions were performed 14 days apart and allocated in a counter-balanced order. Hormonal (plasma insulin, growth hormone [GH], testosterone and cortisol) and metabolic (blood glucose and lactate) responses were assessed before and after each exercise bout. Session rating of perceived exertion (session RPE) was taken 30-min following each bout. Results. No difference was observed for session-RPE between P and MS bouts (P>0.05). Plasma GH, cortisol and lactate increased significantly after exercise both bouts (P<0.01), but there were no significant changes between MS and P (P>0.05). Conclusion. It is concluded that the acute bout of resistance exercise following MS and P systems provide similar training strain when the total volume of load lifted is matched.

Acute and chronic effects of exercise on inflammatory markers and B-type natriuretic peptide in patients with coronary artery disease

Few studies have prospectively addressed the effects of exercise in the inflammatory activity of patients with coronary artery disease (CAD). We sought to evaluate the consequences of an acute bout of exercise on inflammatory markers and BNP in untrained CAD patients before and after randomization to a training program. 34 CAD patients underwent a 50-min acute exercise session on a cycle-ergometer at 65% peak oxygen uptake before and after blood sampling. They were then randomized to a 4-month chronic exercise program (15 patients) or general lifestyle recommendations (19 patients), undergoing a new acute session of exercise after that. In the overall population, acute exercise caused a significant increase in C-reactive protein [CRP; 1.79 (4.49) vs. 1.94 (4.89) mg/L, P < 0.001], monokine induced by interferon-gamma [Mig; 351 (324) vs. 373 (330) pg/mL, P = 0.027] and vascular adhesion molecule-1 [VCAM-1; 226 (82) vs. 252 (110) pg/mL, P = 0.02]. After 4-months, in exercise-trained patients, there was a significant decrease in the inflammatory response provoked by the acute exercise compared to patients in the control group reflected by a significant decrease in the differences between rest and post-exercise levels of CRP [-0.29 (0.84) mg/L vs. -0.11 (0.21) mg/L, P = 0.05]. Resting BNP was also significantly lower in exercise-trained patients when compared to untrained controls [15.6 (16.2) vs. 9.7 (11.4) pg/mL, P = 0.04 and 19.2 (27.8) vs. 23.2 (27.5) pg/mL, P = 0.76; respectively]. Chronic exercise training might partially reverse the inflammatory response caused by acute exercise in CAD patients. These results suggest that regular exercise is an important nonpharmacological strategy to the improvement in inflammation in CAD patients.

Clinic and ambulatory blood pressure responses after resistance exercise

Queiroz, ACC, Gagliardi, JFL, Forjaz, CLM, and Rezk, CC. Clinic and ambulatory blood pressure responses after resistance exercise. J Strength Cond Res 23(2): 571-578, 2009-This study investigated clinic and ambulatory blood pressure (BP) responses after a single bout of low-intensity resistance exercise in normotensive subjects. Fifteen healthy subjects underwent 2 experimental sessions: control-40 minutes of seated rest, and exercise-6 resistance exercises, with 3 sets of as many repetitions as possible until moderate fatigue, with an intensity of 50% of 1-repetition maximum (1RM). Before and for 60 minutes after interventions, clinic BP was measured by auscultatory and oscillometric methods. Postintervention ambulatory BP levels were also measured for 24 hours. In comparison with preintervention values, clinic systolic BP, as measured by the auscultatory method, did not change in the control group, but it decreased after exercise (-3.7 +/- 1.6 mm Hg, p < 0.05). Diastolic and mean BP levels increased after intervention in the control group (+3.4 +/- 1.0 and +3.0 +/- 0.8 mm Hg, respectively, p, 0.05) and decreased in the exercise group (-3.6 +/- 1.7 and -3.4 +/- 1.4 mm Hg, respectively, p < 0.05). Systolic and mean oscillometric BP levels did not change after interventions either in the control or exercise sessions, whereas diastolic BP increased after intervention in the control group (+5.0 +/- 1.7 mm Hg, p < 0.05) but not change after exercise. Ambulatory BP behaviors after interventions were similar in the control and exercise sessions. Significant and positive correlations were observed between preexercise values and postexercise clinic and ambulatory BP decreases. In conclusion, in the whole sample, a single bout of low-intensity resistance exercise decreased postexercise BP under clinic, but not ambulatory, conditions. However, considering individual responses, postexercise clinic and ambulatory hypotensive effects were greater in subjects with higher preexercise BP levels.