Immunological Responses to a Brazilian Jiu-Jitsu High-Intensity Interval Training Session.

The objective of the study was to characterize immunological responses to a Brazilian Jiu-Jitsu high-intensity interval training session. Neuromuscular function, blood, and salivary samples were obtained after a Brazilian Jiu-Jitsu high-intensity interval training session. Saliva and blood samples were collected at Pre- (before the warm-up) and immediately Post-training. Neuromuscular function was evaluated by lower body muscle testing. The horizontal countermovement jump was performed at Pre (after the warm-up) and immediately Post blood and saliva collection, and approximately 5 minutes Post-training. The horizontal countermovement jump performance did not present any significant changes Post-training, while blood leukocytes, urea, IgA and salivary alpha-amylase showed a significant increase. Salivary alpha-amylase activity increased more than six times immediately Post compared to Pre-training. Saliva volume, secretion rate, and uric acid were not significantly different between Pre and Post condition. A Brazilian Jiu-Jitsu high-intensity interval training session elicited an increase in the blood cells responsible for antibody production and muscle damage adaptation after exercise. On the other hand, neuromuscular performance was not significantly affected Post-training, suggesting that immunological and performance responses were not necessarily associated.

Involvement of CC chemokines in gammadelta T lymphocyte trafficking during allergic inflammation: the role of CCL2/CCR2 pathway.

In the present study, we show that the intra-thoracic injection of ovalbumin (OVA, 12.5 microg per cavity) into C57BL/10 mice induced a significant increase in gammadelta T lymphocyte numbers in the pleural cavity, blood and thoracic lymph node of challenged mice. Such increase was significant within 12 h, peaked within 48 h and returned to basal counts within 120 h. Levels of CC chemokine ligand (CCL)-2/monocyte chemotactic protein-1, CCL5/regulated upon activation, normal T cell expressed and secreted, CCL3/macrophage inflammatory protein-1 alpha and CCL25/thymus-expressed chemokine were above control values in pleural washes recovered 24 h after OVA challenge (OPW) and were likely produced by pleural macrophages and mesothelial cells. Antigenic challenge also induced an up-regulation in CC chemokine receptor (CCR)-2, CCR5 and CCR9 on gammadelta T cells from pleural cavities, blood and lymph nodes, suggesting that cells found in mice pleural cavity migrate from secondary lymphoid organs into the inflammatory site via blood stream. The in vitro neutralization of CCL2 (but not of CCL3, CCL5 or CCL25) abrogated OPW-induced gammadelta T lymphocyte transmigration. Confirming such results, the in vivo administration of alpha-CCL2 mAb inhibited gammadelta T lymphocyte accumulation in the pleural cavity of challenged mice, whereas the blockade of CCL3, CCL5 or CCL25 showed no effect on gammadelta T cell mobilization. In addition, OVA challenge failed to induce gammadelta T lymphocyte accumulation in the pleural cavity of C57BL/6 CCR2 knockout mice, which also showed decreased numbers of these cells in blood and lymph nodes when compared with wild-type mice. Overall, such results demonstrate that CCR2/CCL2 pathway is crucial for gammadelta T lymphocyte mobilization during the allergic response.

Antinociceptive and antiedematogenic activities of fenofibrate, an agonist of PPAR alpha, and pioglitazone, an agonist of PPAR gamma.

Peroxisome proliferator activated receptors (PPAR) are ligand-regulated transcription factors that control the expression of many genes. The antiinflammatory activity of fibrates, PPARalpha agonists, and thiazolidinediones, PPARgamma agonists, has been demonstrated in many in vitro and a few in vivo studies. In the present study, we evaluated the effect of acute (100 or 300 mg/kg, p.o.) or prolonged (100 or 300 mg/kg day, 7 days, p.o.) treatment with fenofibrate and acute treatment with pioglitazone (doses ranging from 1 to 50 mg/kg, i.p.), PPARalpha and PPARgamma agonists, respectively, on experimental models of nociception and edema, in order to expand the knowledge of their potential antiinflammatory activities. Fenofibrate and pioglitazone did not inhibit the nociceptive response in the hot-plate model and the first phase of formaldehyde induced nociceptive response in mice. However, treatment with pioglitazone and prolonged treatment with fenofibrate inhibited the second phase of this response. Mechanical allodynia induced by carrageenan in rats was inhibited by prolonged treatment with fenofibrate, but not by acute treatment with pioglitazone or fenofibrate. Both drugs inhibited paw edema induced by carrageenan in rats. Fenofibrate did not inhibit mechanical allodynia or paw edema induced by phorbol-12,13-didecanoate (PDD), a protein kinase C activator, in rats. Pioglitazone inhibited paw edema, but not mechanical allodynia, induced by PDD. The results represent the first demonstration of the antinociceptive and antiedematogenic activities of fenofibrate and pioglitazone and give further support to the potential use of PPAR agonists in the treatment of different inflammatory diseases.

Characterization of the antinociceptive and anti-inflammatory activities of riboflavin in different experimental models.

Riboflavin, similar to other vitamins of the B complex, presents anti-inflammatory activity but its full characterization has not yet been carried out. Therefore, we aimed to investigate the effect of this vitamin in different models of nociception, edema, fever and formation of fibrovascular tissue. Riboflavin (25, 50 or 100 mg/kg, i.p.) did not alter the motor activity of mice in the rota-rod or the open field models. The second phase of the nociceptive response induced by formalin in mice was inhibited by riboflavin (50 or 100 mg/kg). The first phase of this response and the nociceptive behavior in the hot-plate model were inhibited only by the highest dose of this vitamin. Riboflavin (25, 50 or 100 mg/kg, i.p.), administered immediately and 2 h after the injection of carrageenan, induced antiedema and antinociceptive effects. The antinociceptive effect was not inhibited by the pretreatment with cadmium sulfate (1 mg/kg), an inhibitor of flavokinase. Riboflavin (50 or 100 mg/kg, i.p., 0 and 2 h) also inhibited the fever induced by lipopolysaccharide (LPS) in rats. Moreover, the formation of fibrovascular tissue induced by s.c. implant of a cotton pellet was inhibited by riboflavin (50 or 100 mg/kg, i.p., twice a day for one week). Riboflavin (10 or 25 mg/kg, i.p.) also exacerbated the effect of morphine (2, 4 or 8 mg/kg, i.p.) in the mouse formalin test. In conclusion, the study demonstrates the antinociceptive and anti-inflammatory activities of riboflavin in different experimental models. These results, associated with the fact that riboflavin is a safe drug, is approved for clinical use and exacerbates the antinociceptive effect of morphine, may warrant clinical trials to assess its potential in the treatment of different painful or inflammatory conditions.

Antinociceptive, antiedematogenic and antiangiogenic effects of benzaldehyde semicarbazone.

Semicarbazones induce an anticonvulsant effect in different experimental models. As some anticonvulsant drugs also have anti-inflammatory activity, the effects of benzaldehyde semicarbazone (BS) on models of nociception, edema and angiogenesis were investigated. BS (10, 25 or 50 mg/kg, i.p.) markedly inhibited the second phase of nociceptive response induced by formaldehyde (0.34%, 20 microl) in mice, but only the highest dose inhibited the first phase of this response. The thermal hyperalgesia and mechanical allodynia induced by carrageenan (1%, 50 microl, i.pl.) in rats were also inhibited by BS (50 mg/kg, i.p.). However, treatment of mice with BS did not induce an antinociceptive effect in the hot-plate model. The paw edema induced by carrageenan (1%, 50 microl, i.pl.) in rats was inhibited by BS (25 or 50 mg/kg, i.p.). Treatment of mice with BS (0.25, 0.5 or 2.5 mg/kg/day, i.p., 7 days) also inhibited angiogenesis induced by subcutaneous implantation of a sponge disc. It is unlikely that the antinociceptive effect induced by BS results from motor incoordination or a muscle relaxing effect, as the mice treated with this drug displayed no behavioral impairment in the rotarod apparatus. In conclusion, we demonstrated that BS presents antinociceptive, antiedematogenic and antiangiogenic activities. An extensive investigation of the pharmacological actions of BS and its derivatives is justified and may lead to the development of new clinically useful drugs.

Pharmacological investigation of the nociceptive response and edema induced by venom of the scorpion Tityus serrulatus.

In this study we characterized the nociceptive response and edema induced by the venom of the scorpion Tityus serrulatus in rats and mice and carried out a preliminary pharmacological investigation of the mechanisms involved in these responses. Intraplantar injection of the venom (1 or 10mug) induced edema and a marked ipsilateral nociceptive response, characterized by thermal and mechanical allodynia and paw licking behaviour. The nociceptive response was inhibited by previous intraperitoneal administration of indomethacin (4mg/kg), dipyrone (200mg/kg), cyproheptadine (10mg/kg) or morphine (5 or 10mg/kg), but not by dexamethasone (1 or 4mg/kg) or promethazine (1 or 5mg/kg). The edema was inhibited by previous treatment with promethazine (5 or 10mg/kg) or cyproheptadine (5 or 10mg/kg), but not by indomethacin (2 or 4mg/kg), dexamethasone (1 or 4mg/kg) or cromolyn (40 or 80mg/kg). Some bioactive amines, including histamine and 5-hydroxytryptamine, were found in the venom in low concentrations. In conclusion, the nociceptive response and edema induced by the venom of T. serrulatus may result from the action of multiple mediators including eicosanoids, histamine and 5-hydroxytryptamine. These results may lead to a better understanding of the host response to potent animal toxins and also give insights into a more rational pharmacological approach to alleviate the intense pain associated with the scorpion envenomation.

Leishmania (Viannia) braziliensis metacyclic promastigotes purified using Bauhinia purpurea lectin are complement resistant and highly infective for macrophages in vitro and hamsters in vivo.

In this study we characterised metacyclogenesis in axenic culture of Leishmania (Viannia) braziliensis, the causative agent of mucocutaneous leishmaniasis in the New World. Metacyclogenesis of other species of Leishmania has been shown by morphological changes as well as molecular modifications in the lipophosphoglycan, the major cell surface glycoconjugate of the promastigotes. In order to obtain metacyclic forms of L. braziliensis we tested a panel of different lectins. Our results showed that Bauhinia purpurea lectin facilitated the purification of metacyclic promastigotes from stationary-phase culture by negative selection. The B. purpurea non-agglutinated promastigotes had a slender short cell body and long flagella, typical of metacyclic morphology. The ultrastructural analysis showed that B. purpurea non-agglutinated promastigotes have a dense and thicker glycocalyx. They are resistant to complement lysis, and highly infective for macrophage in vitro and hamsters in vivo. Contrary to procyclic promastigotes, B. purpurea non-agglutinated forms were poorly recognised by sand fly gut epithelial cells. These results suggest that the B. purpurea non-agglutinated promastigotes are the metacyclic forms of L. braziliensis.

In vivo evidence for a role of protein kinase C in peripheral nociceptive processing.

1. The present study was designed to characterize the nociceptive response induced by protein kinase C (PKC) peripheral activation and to investigate if this biochemical event is important for the nociceptive response induced by formaldehyde, and bradykinin (BK). 2. Intraplantar injection of phorbol-12,13-didecanoate (PDD; 0.01, 0.1 or 1 microg), a PKC activator, but not of 4 alpha-PDD (inactive analogue), dose-dependently induced thermal hyperalgesia in rats. This response was not observed at the contralateral hindpaw. Intraplantar injection of PDD (0.01, 0.1 or 1 microg) also induced mechanical allodynia. In mice, injection of PDD (0.1 or 1 microg) into the dorsum of the hindpaw induced a spontaneous licking behaviour. 3. Intraplantar co-injection of chelerythrine (10 or 50 microg), a PKC inhibitor, attenuated the thermal hyperalgesia induced by PDD (0.1 microg) in rats. 4. The second phase of the nociceptive response induced by the injection of formaldehyde (0.92%, 20 microl) into the dorsum of mice hindpaws was inhibited by ipsi-, but not contralateral, pre-treatment with chelerythrine (1 microg). 5. Intraplantar injection of BK (10 microg) induced mechanical allodynia in rats. Ipsi- but not contralateral injection of bisindolylmaleimide I (10 microg), a PKC inhibitor, inhibited BK-induced mechanical allodynia. 6. In conclusion, this study demonstrates that PKC activation at peripheral tissues leads to the development of spontaneous nociceptive response, thermal hyperalgesia and mechanical allodynia. Most importantly, it also gives in vivo evidence that peripheral PKC activation is essential for the full establishment of the nociceptive response induced by two different inflammatory stimuli.