Juvenia Bezerra Fontenele

Analgesic and anti-inflammatory activities of a fraction rich in oncocalyxone A isolated from Auxemma oncocalyx.

In the present work we studied the antinociceptive and antiedematogenic effects of a quinone fraction (QF) isolated from the heartwood of Auxemma oncocalyx Taub. The major constituent of QF, which represented around 80% of this fraction, was a terpenoid quinone named oncocalyxone A (1). Results show that QF (10 and 30 mg/kg body wt., i.p.) significantly inhibited paw edema induced by carrageenan at the second, third, and fourth hours. The effect was dose-dependent and long lasting, and QF was less effective orally. An antiedematogenic effect was also demonstrated in the dextran-induced paw edema. In this model, however, QF was somewhat less potent. QF (1 and 5 mg/kg body wt., i.p.) inhibited acetic acid-induced abdominal contractions in mice in a dose-dependent manner. In addition, QF (5 and 10 mg/kg body wt., i.p.) inhibited only the second phase (inflammatory) in the formalin test, and showed no effect in the hot-plate test in mice. The antinociceptive activity of QF was predominantly peripheral and independent of the opioid system. The observed effects of QF are, at least in part, probably due to the presence of oncocalyxone A (1).

Antiplatelet effects of piplartine, an alkamide isolated from Piper tuberculatum : possible involvement of cyclooxygenase blockade and antioxidant activity

Objectives Piplartine (piperlongumine; 5,6‐dihydro‐1‐[1‐oxo‐3‐(3,4,5‐trimethoxyphenyl]‐2(1H) pyridinone) is an alkaloid amide isolated from Piper species (Piperaceae). It has been reported to show multiple pharmacological activities in vitro and in vivo.

Potential Role for Valproate in the Treatment of High-Risk Brain Tumors of Childhood—Results from a Retrospective Observational Cohort Study

Although substantial progress has been made in pediatric brain tumor management, patients with brainstem tumors and high-grade gliomas, as well as patients less than 3 years of age with high-risk malignant tumors, have a poorer prognosis. The authors have been treating these patients with radiotherapy and standard carboplatin and vincristine chemotherapy. Since January 2007 the authors have been using valproate as anticonvulsant for prophylaxis. The authors performed a retrospective cohort analysis of pediatric patients with high-risk brain tumors treated with chemotherapy, radiotherapy, and valproate prophylaxis, comparing this group with a historical control. The 2007–2008 group was comprised of 22 patients, 15 with brainstem tumors (7 diffuse intrinsic pontine glioma [DIPG], 3 focal, the remaining infiltrating with a solid portion), 4 with diencephalic tumors (2 thalamic), and 3 with supratentorial high-grade tumors (1 glioblastoma, 1 recurrent grade III ependymoma, 1 with gliomatosis). There were 15 patients alive (68%) after a mean follow-up time of 19 months. Survival function comparison by log rank test was highly significant (P = .004) with a hazard ratio of 0.31 (0.14–0.70). Radiological response showed 3 complete responses (14%), 8 partial responses (36%), 5 stable diseases (23%), and 5 progresssive diseases (23%). The authors hypothesize that valproate may have potentiated the antiangiogenic effect of vincristine, diminished expression of resistance to carboplatin, and sensitized tumor cells to radiotherapy. The authors suggest that clinical trials of carboplatin and vincristine associated with oral continuous low-dose valproate are indicated for pediatric patients with high-risk brain tumor.

Effects of Amburoside A and Isokaempferide, Polyphenols from Amburana cearensis, on Rodent Inflammatory Processes and Myeloperoxidase Activity in Human Neutrophils

The present study evaluated the anti-inflammatory activity of amburoside A (a phenol glucoside) and isokaempferide (a flavonol) isolated from the trunk bark of Amburana cearensis, a medicinal plant used in northeast Brazil for the treatment of asthma. Animals (male Wistar rats or Swiss mice) pre-treated with amburoside A (25 and 50 mg/kg) or isokaempferide (12.5, 25 and 50 mg/kg), orally or intraperitoneally, showed a significant inhibition of the paw oedema induced by carrageenan (1%), prostaglandin E(2) (30 nmol/paw), histamine (200 microg/paw) or serotonin (200 microg/paw). Histological and morphometric evaluations of the rat paw oedema induced by carrageenan showed that amburoside A and isokaempferide also inhibited the accumulation of inflammatory cells. Amburoside A reduced significantly the paw oedema and the increase in vascular permeability induced by dextran, as related to the control group. Similar results were observed with the isokaempferide pre-treatment. Furthermore, amburoside A or isokaempferide inhibited both leucocyte and neutrophil migrations, in mouse peritoneal cavity, after the carrageenan injection. The polyphenols were not cytotoxic and blocked N-formyl-methyl-leucyl-phenylalanine-induced myeloperoxidase release and activity in human neutrophils. In addition, amburoside A and isokaempferide at 50 and 100 microg/ml concentrations reduced significantly the lipopolysaccharide-mediated increase in tumour necrosis factor-alpha (TNF-alpha) levels. These results provide, for the first time, evidence to support the anti-inflammatory activity of amburoside A and isokaempferide that seems to be related to an inhibition of inflammatory mediators, such as TNF-alpha, as well as histamine, serotonin and prostaglandin E(2), besides leucocyte infiltration in a dose- or concentration-dependent manner. These anti-inflammatory effects can be explained, at least in part, by the ability of these compounds to reduce neutrophil degranulation, myeloperoxidase activity, mediators as well as TNF-alpha secretion.

Cloak and dagger: the case for adult onset still disease and hemophagocytic lymphohistiocytosis

Adult onset Still’s disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology. Systemic onset juvenile idiopathic arthritis (SoJIA) is the preferred nomenclature of Still’s disease. Strong association with so-called macrophage activation syndrome (MAS) may provide a clue to the understanding of the distinctive pathogenetic features of SoJIA. MAS is a severe, potentially life-threatening complication characterized by the excessive activation of well-differentiated macrophages. It is more appropriately named autoimmune disease associated reactive hemophagocytic lymphohistiocytosis (ReHLH), a subset of a histiocytic disorder: class II histiocytosis hemophagocytic lymphohistiocytosis (HLH). The relation of SoJIA with HLH is still under debate. We propose that MAS, HLH, SoJIA, and AOSD are indeed the same disease, in different clinical presentations that may be classified based on severity and laboratory findings, but with essentially the same physiopathogenesis. We propose that the case described by Hong & Lee (Rheumatol Int 2008) was actually an AOSD-associated MAS/RHS/ReHLH fulminant disease.

Doxycycline protects against pilocarpine-induced convulsions in rats, through its antioxidant effect and modulation of brain amino acids

This work evaluated doxycycline (2nd generation tetracycline) protection against pilocarpine-induced convulsions in rats. The animals were treated with doxycycline (Dox: 10 to100 mg/kg, i.p., 7days), 30min before the pilocarpine injection (P: 300mg/kg, i.p.) and observed for cholinergic signs, latencies to the first convulsion and death. Amino acid concentrations, lipid peroxidation and nitrite levels in temporal cortices were determined as well as the radical scavenging activity. Doxycycline increased latencies to the first convulsion and death as compared to the untreated P300 group. It also decreased glutamate and aspartate, increased GABA, blocked nitrite formation, reduced TBARS contents and showed a radical scavenging activity. Finally, doxycycline decreased the number of degenerating neurons (evaluated by fluoro-jade staining) and increased the number of viable neurons (assessed by cresyl violet staining) as compared do the P300 group. The antioxidant effect associated with decreased levels of excitatory and increased levels of inhibitory amino acids could explain the neuroprotective effect of doxycycline.

Protective Effects of Amburoside A, a Phenol Glucoside from Amburana cearensis, against CCl4-Induced Hepatotoxicity in Rats

The aim of this study was to investigate the possible beneficial effects of amburoside A, AMB [4-(O-beta- D-glycopyranosyl)benzyl protocatechoate], against carbon tetrachloride (CCl (4)) toxicity in rats. AMB is a phenol glucoside from the Brazilian medicinal plant Amburana cearensis, popularly used for the treatment of respiratory tract affections. Acute AMB (25 and 50 mg/kg, I. P. or P. O.) treatments of CCl (4)-intoxicated rats significantly inhibited the increase in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, as compared to the group treated with CCl (4) only. Histological studies showed less centrolobular necrosis and inflammatory cell infiltrates in the liver of animals treated with AMB plus CCl (4), when compared to the group treated with CCl (4) alone. In hepatic tissues, AMB at both doses inhibited CCl (4)-induced thiobarbituric acid-reactive substances (TBARS) formation, indicating a blockade of CCl (4)-induced lipid peroxidation. AMB also reversed the decrement in glutathione contents of hepatic tissues in CCl (4)-intoxicated rats. Furthermore, it restored catalase activity to normal values, which was significantly increased after CCl (4) treatment. Our results indicate that CCl (4)-induced oxidative damage in hepatic tissues is reversed by AMB treatment. The protective effect of AMB is probably due to the phenolic nature of this glucoside.

Antiplatelet Effect of Lonchocarpin and Derricin Isolated from Lonchocarpus sericeus.

Abstract In this work, we studied the effects of lonchocarpin (LCC) and derricin (DRC), two chalcones isolated from the hexane fraction of roots from Lonchocarpus sericeus. (Poir.) Kunth (Fabaceae), on human platelet aggregation induced by a variety of agonists. LCC and DRC (200 and 400 µg/ml) significantly inhibited in a dose-dependent manner adenosine 5′-diphosphate (ADP)-, arachidonic acid (AA)-, thrombin (THR)-, collagen (COL)-, and adrenalin (ADR)-induced aggregation. Neither LCC nor DRC had their effects potentiated after association with L-arginine (L-ARG), a NO donor, when the inducer was ADP. In contrast, the addition of LCC or DRC to pentoxifylline (PTX), a known phosphodiesterase inhibitor, caused a significant potentiation of platelet inhibition (41.1% and 47.4%) when compared with LCC (20.3%) or DRC (17.9%) alone. The addition of aspirin or yohimbine (YOH) to LCC or DRC did not change their effects on platelet aggregation induced by AA or ADR, respectively. These results suggest that the antiplatelet effect of LCC and DRC may be mediated mainly by phosphodiesterase activity inhibition or elevation of adenosine 3′:5′-cyclic monophosphate (cAMP) and guanosine 3′:5′-cyclic monophosphate (cGMP) intracellular levels or even by inhibition of thromboxane (TX) formation, as these two substances inhibited the aggregation induced by AA, COL, and THR.

The Operculina macrocarpa (l.) urb. (jalapa) tincture modulates human blood platelet aggregation

ETHNOPHARMACOLOGICAL RELEVANCE Operculina macrocarpa is an ornamental climbing plant of the Northeastern Brazil extensively used in traditional medicine as depurative of the blood and for the treatment of thrombosis. To investigate the antiplatelet and anticoagulant potential of Operculina macrocarpa and to determine the possible mechanisms of action. MATERIAL AND METHODS The Operculina macrocarpa tincture (OMT) was characterized by the polyphenol content and chromatographic profile established by HPLC with detection and quantification of three phenol acids (caffeic, clorogenic and gallic acids). The human platelet aggregation was induced in vitro by the agonists ADP, collagen, thrombin, epinephrine or arachidonic acid, and the antiplatelet effect of OMT was evaluated in the presence or absence of aspirin (a nonselective inhibitor of cyclooxygenase), pentoxifylline (a phosphodiesterase inhibitor), ticlopidine (a P2Y12 purinoceptor antagonist) or ODQ (a selective inhibitor of guanilate cyclase). The effect of OMT on the partial thromboplastin time, prothrombin time and bleeding time were investigated on human or rat plasma. RESULTS The strongest antiplatelet effect of OMT (50-400 µg/mL) was observed on the ADP- induced aggregation with inhibitions up to 55%, while among others agonists (epinephrine, collagen, thrombin and arachidonic acid) maximal inhibitions reached by OMT (200 µg/mL) were on platelet aggregation induced by collagen (18%) or epinephrine (20%). The antiplatelet effect of OMT (400 µg/mL) was comparable to aspirin, a nonspecific inhibitor of cyclooxygenase. The ticlopidine and pentoxifylline increased 5.1 and 3.8 fold the inhibitory effect of OMT on ADP-induced platelet aggregation, respectively. On the other hand, l-arginine, ODQ and aspirin showed a slightly or no effect on antiplatelet effect of OMT. The bleeding time in rats was significantly increased by OMT, but the tincture did not interfere on the activated partial thromboplastin or prothrombin time in human plasma. CONCLUSIONS This study showed that the tincture of Operculina macrocarpa has antiplatelet effect that cannot be attributed to a single biochemical mechanism and at least part of it cannot be related to the OMT inhibition of P2Y12 purinergic receptors.

Analysis of survival and prognostic factors of pediatric patients with brain tumor

OBJECTIVES To estimate survival and evaluate prognostic factors of pediatric patients with central nervous system (CNS) tumors treated in a single center. METHODS Retrospective analysis of survival of 103 children with primary brain tumors diagnosed consecutively from January 2000 to December 2006. Cox regression was used for multivariate analysis of factors that affect overall survival to define possible prognostic factors. RESULTS Median and mean ages were 7.2 and 7.6 years. There was a male predominance (1.22:1). Most patients had medulloblastomas or primitive neuroectodermal tumors (PNET, 38%), or low-grade astrocytomas (18%). The anatomic site of most tumors was the cerebellum (49%) and the brain stem (21%). Five-year survival after diagnosis was 84% for low-grade astrocytomas and 51% for medulloblastomas and PNET. Prognostic factors for overall survival were histopathological type (high-grade astrocytomas and ependymomas; hazard ratio = 3.7 to 3.9), surgery (hazard ratio of 0.5 for completely resected tumors) and radiotherapy (hazard ratio of 0.5 for patients who underwent radiotherapy). CONCLUSIONS Overall survival of pediatric patients with brain tumors in this study was similar to that found in populations of the United States and Europe. The prognostic factors defined for overall survival are also similar to those published in previous studies.