Factors associated to mortality in children with critical COVID-19 and multisystem inflammatory syndrome in a resource-poor setting.

SARS-CoV-2 infection in children is usually asymptomatic/mild. However, some patients may develop critical forms. We aimed to describe characteristics and evaluate the factors associated to in-hospital mortality of patients with critical COVID-19/MIS-C in the Amazonian region. This multicenter prospective cohort included critically ill children (1 mo-18 years old), with confirmed COVID-19/MIS-C admitted to 3 tertiary Pediatric Intensive Care Units (PICU) in the Brazilian Amazon, between April/2020 and May/2023. The main outcome was in-hospital mortality and were evaluated using a multivariable Cox proportional regression. We adjusted the model for pediatric risk of mortality score version IV (PRISMIV) score and age/comorbidity. 266 patients were assessed with 187 in the severe COVID-19 group, 79 included in the MIS-C group. In the severe COVID-19 group 108 (57.8%) were male, median age was 23 months, 95 (50.8%) were up to 2 years of age. Forty-two (22.5%) patients in this group died during follow-up in a median time of 11 days (IQR, 2-28). In the MIS-C group, 56 (70.9%) were male, median age was 23 months and median follow-up was 162 days (range, 3-202). Death occurred in 17 (21.5%) patients with a median death time of 7 (IQR, 4-13) days. The mortality was associated with higher levels of Vasoactive Inotropic-Score (VIS), presence of acute respiratory distress syndrome (ARDS), higher levels of Erythrocyte Sedimentation Rate, (ESR) and thrombocytopenia. Critically ill patients with severe COVID-19 and MIS-C from the Brazilian Amazon showed a high mortality rate, within 12 days of hospitalization.

Margaritaria nobilis L.f. (Phyllanthaceae) Ethanolic Extract: Low Acute Oral Toxicity and Antinociceptive Activity.

Margaritaria nobilis L.f. (Phyllanthaceae), a native Brazilian tree occurring mainly in the Amazon, is used in folk medicine for the treatment of abscesses (bark) and cancer-like symptoms (leaves). The present study evaluates the safety of its acute oral administration and its effects on nociception and plasma leakage. The chemical constitution of the leaf's ethanolic extract is determined by ultra-performance liquid chromatography-high-resolution mass spectrometry (LC-MS. Its acute oral toxicity is evaluated in female rats at a dose of 2000 mg/kg, evaluating the occurrence of deaths and Hippocratic, behavioral, hematological, biochemical, and histopathological changes, as well as food and water consumption and weight gain. Antinociceptive activity is evaluated in male mice with acetic-acid-induced peritonitis (APT) and formalin (FT) tests. An open field (OF) test is performed to verify possible interferences in the animals' consciousness or locomotion. LC-MS analysis shows the presence of 44 compounds classified as phenolic acid derivatives, flavonoids and O-glycosylated derivatives, and hydrolyzable tannins. No deaths or significant behavioral, histological, or biochemical changes are observed in the toxicity assessment. In nociception tests, M. nobilis extract significantly reduces abdominal contortions in APT, demonstrating selectivity for inflammatory components (FT second phase), not interfering in neuropathic components (FT first phase) or consciousness and locomotion levels in OF. Additionally, M. nobilis extract inhibits plasma acetic-acid-induced leakage. These data demonstrate the low toxicity of M. nobilis ethanolic extract, as well as its effectiveness in modulating inflammatory nociception and plasma leakage, possibly related to the flavonoids and tannins present in its composition.

The Roots of Deguelia nitidula as a Natural Antibacterial Source against Staphylococcus aureus Strains.

Deguelia nitidula (Benth.) A.M.G.Azevedo & R.A.Camargo (Fabaceae) is an herbaceous plant distributed in the Brazilian Amazon, and it is called "raiz do sol" (sun roots). On Marajó Island, quilombola communities use its prepared roots to treat skin diseases commonly caused by fungi, viruses, and bacteria. Thus, in this study, the extract, and its fractions from D. nitidula roots were used to perform in vitro cytotoxic and antibacterial assays against Staphylococcus aureus strains. Thereafter, liquid chromatography-mass spectrometry (LC-MS) was used for the metabolite annotation process. The ethanolic extract of D. nitidula roots show significant bactericidal activity against S. aureus with IC50 82 µg.mL-1 and a selectivity index (SI) of 21.35. Furthermore, the SREFr2 and SREFr3 fractions show a potent bactericidal activity, i.e., MIC of 46.8 µg.mL-1 for both, and MBC of 375 and 93.7 µg.mL-1, respectively. As showcased, SREFr3 shows safe and effective antibacterial activity mainly in respect to the excellent selectivity index (SI = 82.06). On the other hand, SREFr2 shows low selectivity (SI = 6.8), which characterizes it as not safe for therapeutic use. Otherwise, due to a limited amount of reference MS2 spectra in public libraries, up to now, it was not possible to perform a complete metabolite annotation. Despite that, our antibacterial results for SREFr3 and correlated substructures of amino acid derivatives show that the roots of D. nitidula are a natural source of specialized metabolites, which can be isolated in the future, and then used as a support for further bio-guided research, as well as natural drug development.

Alterations in CD39/CD73 axis of T cells associated with COVID-19 severity.

Purinergic signaling modulates immune function and is involved in the immunopathogenesis of several viral infections. This study aimed to investigate alterations in purinergic pathways in coronavirus disease 2019 (COVID-19) patients. Mild and severe COVID-19 patients had lower extracellular adenosine triphosphate and adenosine levels, and higher cytokines than healthy controls. Mild COVID-19 patients presented lower frequencies of CD4+ CD25+ CD39+ (activated/memory regulatory T cell [mTreg]) and increased frequencies of high-differentiated (CD27- CD28- ) CD8+ T cells compared with healthy controls. Severe COVID-19 patients also showed higher frequencies of CD4+ CD39+ , CD4+ CD25- CD39+ (memory T effector cell), and high-differentiated CD8+ T cells (CD27- CD28- ), and diminished frequencies of CD4+ CD73+ , CD4+ CD25+ CD39+ mTreg cell, CD8+ CD73+ , and low-differentiated CD8+ T cells (CD27+ CD28+ ) in the blood in relation to mild COVID-19 patients and controls. Moreover, severe COVID-19 patients presented higher expression of PD-1 on low-differentiated CD8+ T cells. Both severe and mild COVID-19 patients presented higher frequencies of CD4+ Annexin-V+ and CD8+ Annexin-V+ T cells, indicating increased T-cell apoptosis. Plasma samples collected from severe COVID-19 patients were able to decrease the expression of CD73 on CD4+ and CD8+ T cells of a healthy donor. Interestingly, the in vitro incubation of peripheral blood mononuclear cell from severe COVID-19 patients with adenosine reduced the nuclear factor-κB activation in T cells and monocytes. Together, these data add new knowledge to the COVID-19 immunopathology through purinergic regulation.

ß-Lapachone Increases Survival of Septic Mice by Regulating Inflammatory and Oxidative Response.

Sepsis is characterized by a dysregulated immune response to infection characterized by an early hyperinflammatory and oxidative response followed by a subsequent immunosuppression phase. Although there have been some advances in the treatment of sepsis, mortality rates remain high, urging for the search of new therapies. ß-Lapachone (ß-Lap) is a natural compound obtained from Tabebuia avellanedae Lorentz ex Griseb. with several pharmacological properties including bactericidal, anti-inflammatory, and antioxidant activity. Thus, the aim of this study was to evaluate the effects of ß-Lap in a mouse sepsis model. To this, we tested two therapeutic protocols in mice submitted to cecal ligation and puncture- (CLP-) induced sepsis. First, we found that in pretreated animals, ß-Lap reduced the systemic inflammatory response and improved bacterial clearance and mouse survival. Moreover, ß-Lap also decreased lipid peroxidation and increased the total antioxidant capacity in the serum and peritoneal cavity of septic animals. In the model of severe sepsis, the posttreatment with ß-Lap was able to increase the survival of animals and maintain the antioxidant defense function. In conclusion, the ß-Lap was able to increase the survival of septic animals by a mechanism involving immunomodulatory and antioxidant protective effects.

Chemical Composition, Toxicity, Antinociceptive, and Anti-Inflammatory Activity of Dry Aqueous Extract of Varronia multispicata (Cham.) Borhidi (Cordiaceae) Leaves.

Varronia multispicata (Cham.) Borhidi (Cordiaceae), an herbaceous plant distributed in tropical and subtropical regions is native of Brazil and widely used in folk medicine to treat respiratory and digestive diseases, inflammation, and some types of infections. Thus, this study aimed to investigate acute oral toxicity, antinociceptive, and anti-inflammatory activities of dry aqueous extract of V. multispicata (AEVm) and to identify its compounds. Extract was obtained by lyophilized leaf infusion and its composition was analyzed by ultra-performance liquid chromatography-high resolution mass spectrometry (LC-MS). Acute oral toxicity was evaluated in female rats treated with AEVm (2,000 mg/kg) in a single oral dose. Mortality, body weight changes, feed and water intake, organ weights, histological and biochemical parameters were screened for 14 days. Antinociceptive activity was evaluated by writhing (WT), formalin (FT), and hot plate (HP) tests in male mice while anti-inflammatory activity was performed by carrageenan (CPE) and dextran (DPE)-induced paw edema tests and carrageenan-induced peritonitis (CP) test in male rats. Additionally, spontaneous open-field (OF) locomotion was evaluated. LC-MS analysis revealed the presence of flavonoids with biological activity. In toxicity evaluation, extract did not cause deaths in dose of 2,000 mg/kg, and there were no significant behavioral or biochemical alterations. Additionally, evidence of hepatoprotective and antioxidant activity was observed. In pharmacological evaluation AEVm showed dose-dependent antinociceptive activity in WT, with a median effective dose of 146.89 mg/kg, which showed selectivity by inflammatory base processes (FT first phase; p < 0.001), showing no activity in neuropathic nociception components (FT second phase and HP) or about consciousness and locomotion in OF. AEVm also showed significant anti-inflammatory activity, inhibiting CPE (p < 0.001) and cell migration (p < 0.05) and nitric oxide (NO) production (p < 0,01) in CP test. These data demonstrate that AEVm has low oral toxicity-with evidence of hepatoprotective and antioxidant properties-antinociceptive and anti-inflammatory activity, supporting V. multispicata traditional use, possibly related to flavonoids present in its constitution.

Aerobic Physical Exercise as a Neuroprotector Strategy for Ethanol Binge-Drinking Effects in the Hippocampus and Systemic Redox Status in Rats.

The heavy and episodic EtOH drinking pattern, equivalent to weekend consumption, characterizes the binge-drinking pattern and promotes a misbalance of encephalic metabolic functions, concurring to neurodegeneration and cerebral dysfunction. And for being a legal drug, it has global public health and social relevance. In this way, we aimed to investigate the effects of physical training, in a treadmill, on the deleterious effects of EtOH on hippocampal functions, related to memory and learning. For this, we used 40 Wistar rats, divided into four groups: Control group, Trained group (trained animals with doses of distilled water), EtOH group (nontrained animals with doses of 3 g/kg/day of EtOH, 20% w/v), and Trained+EtOH group (trained animals exposed to EtOH). The physical exercise was performed by running on a treadmill for 5 days a week for 4 weeks, and all doses of EtOH were administered through intragastric gavage in four repeated cycles of EtOH in binge. After the experimental period, the animals were submitted to the object recognition task and Morris water maze test, and after being euthanized, the blood and hippocampus were collected for Trolox Equivalent Antioxidant Capacity (TEAC), Reduced Glutathione Content (GSH), and Nitrite and Lipid Peroxidation (LPO) level measurements. Our results showed that EtOH caused marked oxidative stress and mnemonic damage, and the physical exercise promoted neuroprotective effects, among them, the modulation of oxidative biochemistry in plasma (by restoring GSH levels) and in the hippocampus (by reducing LPO levels and increasing antioxidant parameters) and cognitive function improvement. Therefore, physical exercise can be an important prophylactic and therapeutic tool in order to ameliorate and even prevent the deleterious effects of EtOH on cognitive functions.

Physical Exercise Attenuates Oxidative Stress and Morphofunctional Cerebellar Damages Induced by the Ethanol Binge Drinking Paradigm from Adolescence to Adulthood in Rats.

Ethanol (EtOH) binge drinking is characterized by high EtOH intake during few hours followed by withdrawal. Protection strategies against the damages generated by this binge are poorly explored. Thus, this study is aimed at investigating the protective role of treadmill physical exercise (PE) on the damage caused after repeated cycles of binge-like EtOH exposure in the oxidative biochemistry, morphology, and cerebellar function of rats from adolescence to adulthood. For this, animals were divided into four groups: control group (sedentary animals with doses of distilled water), exercised group (exercised animals with doses of distilled water), EtOH group (sedentary animals with doses of 3 g/kg/day of EtOH, 20% w/v), and exercised+EtOH group (exercised animals with previous mentioned doses of EtOH). The PE occurred on a running treadmill for 5 days a week for 4 weeks, and all doses of EtOH were administered through intragastric gavage in four repeated cycles of EtOH in a binge-like manner. After the EtOH protocol and PE, animals were submitted to open field and beam walking tests. In sequence, the cerebellums were collected for the biochemical and morphological analyses. Biochemical changes were analyzed by measurement of Trolox equivalent antioxidant capacity (TEAC), reduced glutathione content measurements (GSH), and measurement of nitrite and lipid peroxidation (LPO). In morphological analyses, Purkinje cell density evaluation and immunohistochemistry evaluation were measured by antimyelin basic protein (MBP) and antisynaptophysin (SYP). The present findings demonstrate that the binge drinking protocol induced oxidative biochemistry misbalance, from the decrease of TEAC levels and higher LPO related to tissue damage and motor impairment. In addition, we have shown for the first time that treadmill physical exercise reduced tissue and functional alterations displayed by EtOH exposure.

Protective Mechanisms of Butyrate on Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a multifactorial chronic disease, commonly associated with alteration in the composition and function of gut microbiota. This process can lead to a decreased production of short chain fatty acids (SCFAs) by the gut microbiota, mainly butyrate, which is an important immunomodulatory molecule in the intestine. Butyrogenic bacteria normally produces butyrate through carbohydrate fermentation or amino acids degradation pathways. This molecule plays an important protective role in intestinal homeostasis acting in both adaptive immunity and innate immunity. This review summarizes the current knowledge about the role of butyrate on the development of IBD and the protective mechanisms of this metabolite on the intestinal mucosa and the whole body, as reported by in vitro and in vivo studies. Thus, butyrate can regulate the activation of regulatory T cells, increasing the acetylation of histones and decreasing the activation of NF-κB. In addition, it can also stimulate the mucus production from epithelial cells and the rearrangement of tight junction proteins.

Repeated cycles of binge-like ethanol exposure induce immediate and delayed neurobehavioral changes and hippocampal dysfunction in adolescent female rats.

Binge-like ethanol intake (BEI) is a socioeconomical problem among adolescents and increasingly affects women. BEI can leave a long-term imprint in the brain, but it is unknown if its effect on cognition and anxiety is cumulative on repeated binge-ethanol episodes. We now submitted female Wistar rats to repeated cycles of binge-like ethanol treatment by intragastrically administering ethanol (3.0 g/kg/day, 20% w/v ethanol; 3 days on/4 days off) starting at postnatal day 35 (PND35). To investigate the short-term effects of BEI during adolescence, rats underwent 1 or 4 cycles of BEI, being evaluated at PND37 and PND58, respectively: both groups displayed anxiety-like behavior in the open field and elevated plus-maze tests, as well as short-term memory deficits in the object recognition task; this was associated with transient decreases of BDNF levels and increases of GFAP levels in the hippocampus. To evaluate the short- and long-lasting effects of BEI in adulthood, rats were subjected to 8 cycles of BEI and evaluated after 7.5 h (PND86) or after 14 days of ethanol withdrawal (PND100). This caused a persistent anxiogenic profile whereas recognition memory was impaired on the short-term, but not 14 days post-administration. The reduced BDNF level observed shortly after BEI recovered upon withdrawal, whereas increased GFAP immunoreactivity was persistent up to 14 days post-administration in adulthood. These findings show that repeated binge-like ethanol episodes from adolescence to adulthood in female rats cause consistent and long-term alterations of anxiety and hippocampal astrogliosis, whereas they trigger a recognition memory deficit paralleled by lower hippocampal BDNF levels, both recovering upon ethanol withdrawal.

Biochemical characterization of a phospholipase A2 homologue from the venom of the social wasp Polybia occidentalis.

BACKGROUND: Wasp venoms constitute a molecular reservoir of new pharmacological substances such as peptides and proteins, biological property holders, many of which are yet to be identified. Exploring these sources may lead to the discovery of molecules hitherto unknown. This study describes, for the first time in hymenopteran venoms, the identification of an enzymatically inactive phospholipase A2 (PLA2) from the venom of the social wasp Polybia occidentalis. METHODS: P. occidentalis venom was fractioned by molecular exclusion and reverse phase chromatography. For the biochemical characterization of the protein, 1D and 2D SDS-PAGE were performed, along with phospholipase activity assays on synthetic substrates, MALDI-TOF mass spectrometry and sequencing by Edman degradation. RESULTS: The protein, called PocTX, was isolated using two chromatographic steps. Based on the phospholipase activity assay, electrophoresis and mass spectrometry, the protein presented a high degree of purity, with a mass of 13,896.47 Da and a basic pI. After sequencing by the Edman degradation method, it was found that the protein showed a high identity with snake venom PLA2 homologues. CONCLUSION: This is the first report of an enzymatically inactive PLA2 isolated from wasp venom, similar to snake PLA2 homologues.

Biochemical characterization of a phospholipase A2 homologue from the venom of the social wasp Polybia occidentalis

Background: Wasp venoms constitute a molecular reservoir of new pharmacological substances such as peptides and proteins, biological property holders, many of which are yet to be identified. Exploring these sources may lead to the discovery of molecules hitherto unknown. This study describes, for the first time in hymenopteran venoms, the identification of an enzymatically inactive phospholipase A2 (PLA2) from the venom of the social wasp Polybia occidentalis. Methods: P. occidentalis venom was fractioned by molecular exclusion and reverse phase chromatography. For the biochemical characterization of the protein, 1D and 2D SDS-PAGE were performed, along with phospholipase activity assays on synthetic substrates, MALDI-TOF mass spectrometry and sequencing by Edman degradation. Results: The protein, called PocTX, was isolated using two chromatographic steps. Based on the phospholipase activity assay, electrophoresis and mass spectrometry, the protein presented a high degree of purity, with a mass of 13,896. 47 Da and a basic pI. After sequencing by the Edman degradation method, it was found that the protein showed a high identity with snake venom PLA2 homologues. Conclusion: This is the first report of an enzymatically inactive PLA2 isolated from wasp venom, similar to snake PLA2 homologues.

Biochemical characterization of a phospholipase A2 homologue from the venom of the social wasp Polybia occidentalis

Wasp venoms constitute a molecular reservoir of new pharmacological substances such as peptides and proteins, biological property holders, many of which are yet to be identified. Exploring these sources may lead to the discovery of molecules hitherto unknown. This study describes, for the first time in hymenopteran venoms, the identification of an enzymatically inactive phospholipase A2 (PLA2) from the venom of the social wasp Polybia occidentalis. Methods: P. occidentalis venom was fractioned by molecular exclusion and reverse phase chromatography. For the biochemical characterization of the protein, 1D and 2D SDS-PAGE were performed, along with phospholipase activity assays on synthetic substrates, MALDI-TOF mass spectrometry and sequencing by Edman degradation. Results: The protein, called PocTX, was isolated using two chromatographic steps. Based on the phospholipase activity assay, electrophoresis and mass spectrometry, the protein presented a high degree of purity, with a mass of 13,896. 47 Da and a basic pI. After sequencing by the Edman degradation method, it was found that the protein showed a high identity with snake venom PLA2 homologues. Conclusion: This is the first report of an enzymatically inactive PLA2 isolated from wasp venom, similar to snake PLA2 homologues.(AU)

Involvement of electron and hydrogen transfers through redox metabolism on activity and toxicity of the nimesulide.

An electronic study of nimesulide was performed by using density functional theory calculations. The activities of the six different derivatives were related with electron donating or accepting capacities. All compounds which had nitro moiety had low electron donating and high electron accepting capacities. However, the reduced derivative of nimesulide have more electron donating capacity than other compounds. The highest spin density contribution in nitro and lowest spin density contribution on phenoxyl moieties can be related with preferential metabolism by reduction when compared with the oxidation. The redox behavior between nitro and amino groups can be related with anti-inflammatory mechanism of nimesulide. These results explain the redox influence of nitro moiety on biological metabolism and mechanism of nimesulide.

Nociceptin/orphanin FQ-NOP receptor system in inflammatory and immune-mediated diseases.

The neuropeptide nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand of the G-protein-coupled receptor NOP. Cells from the immune system express the precursor preproN/OFQ and the NOP receptor, as well as secrete N/OFQ. The activation of the N/OFQ-NOP pathway can regulate inflammatory and immune responses. Several immune activities, including leukocyte migration, cytokine and chemokine production, and lymphocytes proliferation are influenced by NOP activation. It was demonstrated that cytokines and other stimuli such as Toll-like receptor agonist (e.g., lipopolysaccharide) induce N/OFQ production by cells from innate and adaptive immune response. In this context, N/OFQ could modulate the outcome of inflammatory diseases, such as sepsis and immune-mediated pathologies by mechanisms not clearly elucidated. In fact, clinical studies revealed increased levels of N/OFQ under sepsis, arthritis, and Parkinson's disease. Preclinical and clinical studies pointed to the blockade of NOP receptor signaling as successful strategy for the treatment of inflammatory diseases. This review is focused on experimental and clinical data that suggest the participation of N/OFQ-NOP receptor activation in the modulation of the immune response, highlighting the immunomodulatory potential of NOP antagonists in the inflammatory and immunological disturbances.

Antibacterial activity of the Piper aduncum oil and dillapiole, its main constituent, against multidrug-resistant strains / Actividad antibacteriana del aceite de Piper aduncum y dillapiole, su componente principal, frente a cepas resistentes a múltiples fármacos

The study aimed to evaluate the bactericidal activity of oil essential and dillapiole from P. aduncum against standard and multidrug-resistant strains of Staphylococcus spp. The oil showed antimicrobial action against these strains, but better results were obtained for the standards strains of S. epidermidis and S. aureus, with MIC of 250 and 500 ug/mL, respectively. Dillapiolle was less effective than the oil against the same standard and multi-drug resistant strains (MIC =1000 ug/mL). However, when dillapiolle was tested in combination with myristicin, another component of the oil, it increased its bactericidal activity and showed a synergistic action...

El objetivo del estudio fue evaluar la actividad bactericida de los aceites esenciales y dillapiole de P. aduncum contra cepas estándar y multirresistentes de Staphylococcus spp. El aceite mostró acción antimicrobiana frente a estas cepas, pero se obtuvo mejores resultados para las cepas de S. epidermidis y S. aureus, con MIC de 250 y 500 ug/ml, respectivamente. Dillapiolle fue menos eficaz que el aceite contra cepas estándar y multirresistentes (MIC = 1000 ug/ml). Sin embargo, cuando dillapiolle fue probado en combinación con la miristicina, otro componente del aceite, que aumentó su actividad bactericida y mostró una acción sinérgica...

Antidepressant- and anxiolytic-like activities of an oil extract of propolis in rats.

PURPOSE: Propolis biological effects are mainly attributed to its polyphenolic constituents such as flavonoids and phenolic acids that were recently described in the chemical composition of an extract of propolis obtained with edible vegetal oil (OEP) by our group. The aim of this study was to evaluate the effect of OEP on the behavior of rats. MATERIALS AND METHODS: An in vivo open field (OF), elevated Plus-maze (EPM), and forced swimming (FS) tests were performed to evaluate locomotor activity, anxiolytic- and antidepressant effects of the extract. Besides, oxidative stress levels were measured in rat blood samples after the behavioral assays by evaluation of the Trolox equivalent antioxidant capacity (TEAC) and nitric oxide levels. RESULTS: OEP increased locomotion in the OF test (50mg/kg) and central locomotion and open arm entries in the OF and EPM tests (10-50mg/kg) and decreased the immobility time in the FS test (10-50mg/kg). Moreover, OEP reduced nitric oxide levels in response to swim stress induced in rats. CONCLUSION: OEP exerted stimulant, anxiolytic and antidepressant effects on the Central Nervous System and antioxidant activity in rats, highlighting propolis as a potential therapeutic compound for behavior impairment of anxiety and depression.

Design and evaluation of 4-aminophenol and salicylate derivatives as free-radical scavenger.

This theoretical and experimental study describes the design and evaluation of the free-radical scavenging effect for the molecular association of 4-aminophenol and salicylate derivatives. For this purpose, we employed theoretical methods for the selection of antioxidant drugs and the rapid methods of evaluation: the 1,1-diphenyl-2-picrylhydrazyl radical and the thiobarbituric acid reactive substances in the lipid peroxidation initiated by Fe(2+) and ascorbic acid in human erythrocytes. The associate derivatives exhibited a more potent inhibition than the salicylic acid, while the benzoyl compound exhibited a more potent inhibition than paracetamol. The molecular parameters related to the electron distribution and structure (ionization potential and energy of the highest occupied molecular orbital) correlated very well with the antioxidant action of the compounds studied here in different tests.

Anticoagulant and fibrinogenolytic properties of the venom of Polybia occidentalis social wasp.

Previous studies have shown that venoms of social wasps and bees exhibit strong anticoagulant activity. The present study describes the anticoagulant and fibrinogen-degrading pharmacological properties of the venom of Polybia occidentalis social wasp. The results demonstrated that this venom presented anticoagulant effect, inhibiting the coagulation at different steps of the clotting pathway (intrinsic, extrinsic and common pathway). The venom inhibited platelet aggregation and degraded plasma fibrinogen, possibly containing metal-dependent metalloproteases that specifically cleave the Bß-chain of fibrinogen. In conclusion, fibrinogenolytic and anticoagulant properties of this wasp venom find a potential application in drug development for the treatment of thrombotic disorders. For that, further studies should be carried out in order to identify and isolate the active compounds responsible for these effects.