Association between peripheral perfusion, microcirculation and mortality in sepsis: a systematic review / Associação entre perfusão periférica, microcirculação e mortalidade em sepse: uma revisão sistemática

Abstract Although increasing evidence supports the monitoring of peripheral perfusion in septic patients, no systematic review has been undertaken to explore the strength of association between poor perfusion assessed in microcirculation of peripheral tissues and mortality. A search of the most important databases was carried out to find articles published until February 2018 that met the criteria of this study using different keywords: sepsis, mortality, prognosis, microcirculation and peripheral perfusion. The inclusion criteria were studies that assessed association between peripheral perfusion/microcirculation and mortality in sepsis. The exclusion criteria adopted were: review articles, animal/pre-clinical studies, meta-analyzes, abstracts, annals of congress, editorials, letters, case-reports, duplicate and articles that did not present abstracts and/or had no text. In the 26 articles were chosen in which 2465 patients with sepsis were evaluated using at least one recognized method for monitoring peripheral perfusion. The review demonstrated a heterogeneous critically ill group with a mortality-rate between 3% and 71% (median = 37% [28%-43%]). The most commonly used methods for measurement were Near-Infrared Spectroscopy (NIRS) (7 articles) and Sidestream Dark-Field (SDF) imaging (5 articles). The vascular bed most studied was the sublingual/buccal microcirculation (8 articles), followed by fingertip (4 articles). The majority of the studies (23 articles) demonstrated a clear relationship between poor peripheral perfusion and mortality. In conclusion, the diagnosis of hypoperfusion/microcirculatory abnormalities in peripheral non-vital organs was associated with increased mortality. However, additional studies must be undertaken to verify if this association can be considered a marker of the gravity or a trigger factor for organ failure in sepsis.

Resumo Embora evidências crescentes apoiem a monitoração da perfusão periférica em pacientes sépticos, nenhuma revisão sistemática foi feita para explorar a força da associação entre a má perfusão avaliada na microcirculação dos tecidos periféricos e a mortalidade. Uma busca nas bases de dados mais importantes foi feita para encontrar artigos publicados até fevereiro de 2018 que correspondessem aos critérios deste estudo, com diferentes palavras-chave: sepse, mortalidade, prognóstico, microcirculação e perfusão periférica. Os critérios de inclusão foram estudos que avaliaram a associação entre perfusão/microcirculação periférica e mortalidade em sepse. Os critérios de exclusão adotados foram os seguintes: artigos de revisão, estudos com animais/pré-clínicos, metanálises, resumos, anais de congressos, editoriais, cartas, relatos de casos, artigos duplicados e artigos que não continham resumos e/ou texto. Foram selecionados 26 artigos nos quais 2465 pacientes com sepse foram avaliados com pelo menos um método reconhecido para monitorar a perfusão periférica. A revisão demonstrou um grupo heterogêneo de pacientes gravemente enfermos com uma taxa de mortalidade entre 3% e 71% (mediana = 37% [28%-43%]). Os métodos de avaliação mais comumente usados foram a espectroscopia na região do infravermelho próximo (Near-Infrared Spectroscopy - NIRS) (7 artigos) e a análise de imagens em campo escuro (Sidestream Dark-Field - SDF) (5 artigos). O leito vascular mais avaliado foi a microcirculação sublingual/bucal (8 artigos), seguida pela ponta do dedo (4 artigos). A maioria dos estudos (23 artigos) demonstrou uma clara relação entre má perfusão periférica e mortalidade. Em conclusão, o diagnóstico de hipoperfusão/anormalidades microcirculatórias em órgãos não vitais periféricos foi associado ao aumento da mortalidade. No entanto, estudos adicionais devem ser feitos para verificar se essa associação pode ser considerada um marcador da gravidade ou um fator desencadeante da falência de órgãos na sepse.

Central nervous system and analgesic profiles of Lippia genus

Abstract Many people use medicinal plants to relieve disorders related to the central nervous system, such as depression, epilepsy, anxiety and pain, even though the effectiveness of most of them has not yet been proven through scientific studies. Plants of the Lippia genus, Verbenaceae, are widely used in ethnobotany as a food, for seasoning and in antiseptic remedies. They are also marketed and used for the treatment of different types of pain, including stomach ache, abdominal pain and headache, as well as being used as sedatives, anxiolytics and anticonvulsants. Despite their widespread use, there are no reviews on the central nervous system profile of plants of this genus. Therefore, the databases Medline-PubMed, Embase, Scopus and Web of Science were searched using the terms Lippia and biologic activity. Thirty-five papers were found. Eleven species of Lippia showed central nervous system activity, with leaves and the aerial parts of plants being the most commonly used, especially in aqueous and ethanol extracts or volatile oil. The species are composed mainly of terpenoids and phenylpropanoids, including polyketides, flavonoids and in less quantity some alkaloids. Although several species of Lippia present analgesic activity, most studies have not explored the mechanisms responsible for this effect, however, there is some evidence that volatile oils and constituents of the extracts may be responsible for the relief of some CNS disorders, but the effects on pain modulation seem to be the most exploited so far.

The influence of non-steroidal anti-inflammatory drugs and paracetamol used for pain control of orthodontic tooth movement: a systematic review

ABSTRACT The present study aimed to perform a systematic literature review to determine if there is a non-steroidal anti-inflammatory drug (NSAID) that interferes less within tooth movement. This research was performed according to the PRISMA statement. Articles were searched in eight electronic databases (PubMed, Scopus, Embase, Web of Science, LILACS, SciELO, Google Scholar, and Open Grey). Only experimental studies on male Wistar rats were selected, which included experiments related to the influence of NSAIDs on orthodontic movement. Studies in animals with pathological conditions, literature review articles, letters to the editor and/or editorials, case reports, abstracts, books, and book chapters were excluded. Each of the steps of this systematic literature review was performed by two examiners independently. Results: the total sample consisted of 505 articles, from which 6 studies were eligible after a qualitative analysis. From the drugs assessed, paracetamol was unanimous for not interfering within orthodontic movement when compared to the control group. However, drugs such as aspirin, ibuprofen, sodium diclofenac, and selective cyclooxygenase-2 inhibitors caused a reduction in tooth movement when compared to the control group. Conclusion: paracetamol could be considered the drug of choice for pain relief because it interferes less within tooth movement.

Natural products assessed in animal models for orofacial pain – a systematic review

ABSTRACT Orofacial pain is related to tissues of the head, face, neck and all the intraoral structures; it is rather debilitating to the patient and also difficult to treat. There are relatively few studies dedicated to the use of natural products to alleviate orofacial pain in preclinical experiment models (performed in experimental animals which provide support for clinical trials). Main objectives of the present systematic review summarize the studies on natural products assessed in animal models for orofacial pain seeking to give evidence to future development of new pharmaceutical products to manage the orofacial pain. Our review includes a thorough search of literature using the terms of orofacial pain, facial pain, medicinal plants and natural products. This search was performed using to retrieve English language articles in Medline-PubMed, Scopus and Web of Science. A total of eighteen studies were included in our survey for the inclusion criteria. Firstly, this review identified 210 citations from electronic search, after removal of duplicates and screening for relevant titles and abstracts, a total of eighteen articles were selected to the inclusion criteria established. Our findings suggest that natural products can be a promising or a trump tool for the development of new drugs to treat orofacial pain conditions, but the researchers that deal with experimental preclinical trials of new drugs (including natural products or synthetic drugs) for orofacial pain conditions urgently need to show translational evidence (with clinical approach) of these compounds.

Evaluation of the orofacial antinociceptive profile of the ethyl acetate fraction and its major constituent, rosmarinic acid, from the leaves of Hyptis pectinata on rodents

ABSTRACT Hyptis pectinata (L.) Poit., Lamiaceae, popularly known as "sambacaitá," is an aromatic shrub largely grown in the Brazilian northeastern. We investigated the antinociceptive effects of the ethyl acetate fraction obtained from the leaves of H. pectinata and of its main constituent rosmarinic acid, on formalin (2%)-, glutamate (25 µM)- and capsaicin (2.5 µg)-induced orofacial nociception in rodents. Male mice were pretreated with ethyl acetate fraction (100, 200 or 400 mg/kg, p.o.), rosmarinic acid (10 or 20 mg/kg, p.o.), morphine (5 mg/kg, i.p.), or vehicle (distilled water + 0.2% Tween 80). Ethyl acetate fraction reduced the nociceptive face-rubbing behavior during the two phase of the formalin test, whereas pretreatment with rosmarinic acid decreased the pain behavior in the second phase. Ethyl acetate fraction produced significant antinociceptive effects in the capsaicin and glutamate tests. This study showed that oral administration of ethyl acetate fraction produced potent antinociceptive effects compared to treatment with rosmarinic acid.

Development of standardized extractive solution from Lippia sidoides by factorial design and their redox active profile

AbstractThe aim of this study was to evaluate the influences of variables of preparation on total flavonoids content from extractive solution of Lippia sidoides Cham., Verbenaceae. Thus a 23 factorial design was used to study the importance of plant proportion, the extraction method and solvent on the extraction of flavonoid. The methodology of determination of chemicals in factorial design was validated according to the parameters required by Brazilian Health Agency. The extraction solution was selected through a full factorial design where the best conditions to achieve the highest content of flavonoids were: 7.5% (w/v) of plant with ethanol 50% (v/v) as solvent. The polyphenols content was determined by LC method and its relationship with the antioxidant and free radical scavenging activities was evaluated. The free radical scavenging activities and antioxidant potentials were determined for different concentrations using various in vitro models. Our results indicate that extracts exhibited a significant dose-dependent antioxidant effect as evaluated by TRAP/TAR assays. Besides, we observed an antioxidant activity against hydroxyl radicals and nitric oxide, and protection against lipid peroxidation in vitro. Our results suggest that the extract presents significant in vitro antioxidant potential indicating promising perspectives for its use as pharmaceutical/or food additive.

Hyptis pectinata gel prevents alveolar bone resorption in experimental periodontitis in rats

Hyptis pectinata (L.) Poit., Lamiaceae, is an aromatic, abundant and broadly used plant species in Sergipe to treat oral and gastrointestinal pain and inflammation. The aim of the present study was to analyze the relation between periodontitis and changes in the corporal mass and alveolar bone structure after induction of experimental periodontal disease in rat treated or not treated with H. pectinata gel at 5% (GS5%) and 10% (GS10%), comparing their effects with doxycycline gel at 10% (D10%, positive control), vehicle gel (negative control) and a group with experimental periodontal disease, but non-treated. The gels were locally applied in the gingival region immediately after the experimental periodontal disease induction by ligature (3×/day, 11 days). Bone destruction was determined through clinical exam, histopathological analysis and cone beam computed tomography of the experimental animals (n = 36). After 11 days of periodontitis induction, all groups that received ligature presented a decrease in the corporal mass, except to the naïve group (without experimental periodontal disease) (p < 0.05). Computed tomography results have shown healthy bone structure in the group I and bone resorption for the test groups. Histopathological analysis confirmed the healthy bone structure for naïve group animals, while the test groups exhibited bone loss in several degrees. In particular, the non-treated group animals had an intense inflammatory process. When the periodontium of the animals treated with GS10% was histopathologically analyzed, insertion periodontium was preserved. The results for these groups were significantly different of the vehicle group (p < 0.05). According to the results, the gel based in the aqueous extract of H. pectinata at 10% can prevent bone loss in experimental periodontal disease similarly to doxycycline 10%.

Evaluation of the adherence by patients treated in a psychosocial ambulatory care setting in northeastern Brazil.

In the treatment of the mental disorders, the lack of adherenceto the pharmacotherapy is observed in about 50% of people and is responsible lot more morbidity, besides being the main cause of psychiatric morbidity and rehospitalization. This work sought to evaluate the adherenceto the medical treatment frompatients attended in a Primary Health Care Center in the municipal district of Aracaju – Sergipe. For that, an exploratory, descriptive and observational studywas accomplished, with transversal design, in the period from August 2011 to November 2011, carried outthrough interview applications. This research finds that more than 55% of the sample hadlow education; 41.4% were single and 42.8% presented other health problems, besides the mental disorder. Regarding to the knowledge level on the used medications, this variable presented good results, since 60% of the patients were classified in the category “know well”. Likewise, the results revealed that 49.3% of the investigated patients did not adhere to treatment, having as main causes of non-adherence the forgetfulness (53%), the lack of the medication in the health units (47%) or the lack of financial resources for the purchase of the medication (45%) – all these were considered as unintentional causes of non-adherence. Anyway it is an unpublished study in the outpatient attention context in Mental Health in the State, the results are expected to contribute for the evaluation and planning actions in the specialized component of the Pharmaceutical Assistance and in the precepts invigoration perspective of the psychiatric reform, focusing on the full approach of the attention towards the mental health and the rational use of psychotropic medicines.

Phytochemical study and antinociceptive effect of the hexanic extract of leaves from Combretum duarteanum and friedelin, a triterpene isolated from the hexanic extract, in orofacial nociceptive protocols

Combretum duarteanum Cambess, Combretaceae, is a plant widely distributed in Northeastern Brazil and, in folk medicine, stems and leaves are used for pain treatment. We investigated the antinociceptive effects of the hexanic extract of leaves from C. duarteanum and of friedelin, its main compound, in formalin-, glutamate- and capsaicin- induced orofacial nociception models. In order to isolate friedelin from the hexanic extract, flash chromatography technique was used. Male mice (n = 8/group) were pretreated with hexanic extract, friedelin, morphine or vehicle, before the injection of algogen agents into the right upper lip (perinasal area). The test of formalin-induced orofacial nociception showed that hexanic extract and friedelin significantly reduced nociception (p < 0.001) in both phases of testing. In the glutamate and capsaicin-induced orofacial nociception tests, pre-treatment with hexanic extract produced a significant reduction of orofacial nociception (p < 0.001) at all doses tested.The results suggest the hexanic extract and friedelin possess antinociceptive effects in models of orofacial nociception in rodents.

Evaluation of wound healing activity of atranorin, a lichen secondary metabolite, on rodents

The aim of this study was to investigate the wound healing activity of atranorin cream (Patent requested) on excision wounds. Seventy-two male rats were anesthetized and an excisional wound was performed. Then the rats were randomly assigned into three groups: untreated control group; atranorin 1 (group treated with 1% AT ointment); and atranorin 5 (group treated with 5% AT ointment). Six animals of each group were euthanized 3, 7, 14 or 21 days after surgical procedures and the wounded areas were analyzed and removed. Serial histological sections were obtained and stained by histochemical techniques (Hematoxilin-Eosin-HEand Sirius red) and immunohistochemical techniques. Topical application of atranorin reduced wound areas, induced earlier granulation tissue formation, increased cell proliferation, improved collagenization and modulated the myofibroblasts differentiation when compared to control animals. It is suggested that atranorin modulates the wound healing process. These data suggest that this formulation based on atranorin extracted from Cladina kalbii AHTI may be a new biotechnological product for wound healing clinical applications.

Antinociceptive effects of an extract, fraction and an isolated compound of the stem bark of Maytenus rigida

The antinociceptive activity of the Maytenus rigida Mart. (Celastraceae) ethanol extract and its ethyl acetate fraction as well as of (-)-4'-methylepigallocatechin (1), a previously isolated compound, was demonstrated in vivo. ED50 for 1 in the writhing test was 14.14 mg/kg. The acetic acid-induced writhing was inhibited by 98.4, 84.4, and 58.3%, respectively, when mice were treated with the ethanol extract, ethyl acetate fraction, and 1. In the hot plate test, mice pretreated with 1 showed significantly increased reaction times (60-89%). Oral administration of 1 significantly inhibited first and second phases of the formalin-induced pain (50 and 26.5%, respectively), whereas indomethacin inhibited only the second phase of the test (41.2%). Ethanol extract and its fraction showed effects on inflammatory pain, while neurogenic and inflammatory pain suppression by 1 is a strong indication of the presence of both central and peripheral effects and suggests its analgesic and anti-inflammatory potential.

Phytochemical screening, antinociceptive and anti-inflammatory activities of Chrysopogon zizanioides essential oil

Chrysopogon zizanioides (L.) Roberty, Poaceae, is a plant widely used in northeast Brazil in folk medicine for the treatment of various pathological conditions, including inflammatory pain. The present study evaluated the antinociceptive and anti-inflammatory effects of C. zizanioides essential oil (EO) in rodents. EO was further characterized by GC/MS. The major components of EO were identified as khusimol (19.57%), E-isovalencenol (13.24%), α-vetivone (5.25%), β-vetivone (4.87%) and hydroxy-valencene (4.64%). Following intraperitoneal injection (i.p.), EO at 50 and 100 mg/kg significantly reduced the number of writhes (51.9 and 64.9%, respectively) and the number of paw licks during phase 2 (56.7 and 86.2%, respectively) of a formalin model when compared to control group animals. However, EO-treated mice were ineffective at all doses in hot-plate and rota-rod tests. The EO inhibited the carrageenan-induced leukocyte migration to the peritoneal cavity in a dose-dependent manner (34.7, 35.4, and 62.5% at doses of 25, 50 and 100 mg/kg, respectively). In the paw edema test, the EO (100 mg/kg) inhibited all three phases of the edema equally well, suggesting that the EO has a non-selective inhibitory effect on the release or actions of these mediators. Our results suggest possible antinociceptive and anti-inflammatory effects of the EO.

Phythochemical screening and antimicrobial activity phythochemical of essential oil from Lippia gracillis

The chemical composition of the essential oil obtained from the fresh and dried leaves of Lippia gracillis Schauer, Verbenaceae, was analyzed by gas chromatography and gas chromatography/mass spectrometry (GC⁄MS). The yield of essential oil extracted from the dried leaves was significantly higher (p<0.05) when compared to the fresh leaves. Seventeen components were identified. The monoterpenes and sesquiterpene hydrocarbons with 96.26 percent (w/w) of the total oil obtained of fresh leaves and 86.99 percent (w/w) of the total oil obtained of dried leaves were the principal compound groups. Thymol was observed dominant (44.42 percent; 21.3 percent), followed by carvacrol (22.21 percent; 21.30 percent), p-cymene (6.23 percent; 8.58 percent), α-pinene (5.65 percent; 19.42 percent), β-caryophyllene (5.61 percent; 3.57 percent) and other minor constitutes, respectively. Microbiological results obtained by agar diffusion method, micro dilution method and minimum inhibitory concentration (MIC) showed that the essential oil has a relevant antimicrobial activity against E. coli (ATCC 10536), E. coli (Ec 27), Pseudomonas aeruginosa (ATCC 15442), S. aureus (ATCC 12692) and S. aureus (Sa 358), with their inhibition zones ranging from 9 to 13 mm and the MIC ranging from 64 to 512 μg/mL.

Phytochemical screening, antinociceptive and anti-inflammatory effects of the essential oil of Myrcia pubiflora in mice

This report aimed to investigate the chemical composition and possible antinociceptive and anti-inflammatory effects of the essential oil from fresh leaves of Myrcia pubiflora DC., Myrtaceae (EOMP), through different experimental tests. The essential oil of M. pubiflora (EOMP) was obtained by hydrodistillation, analyzed by GC-MS, and tested at doses of 25, 50, and 100 mg/kg (i.p.) in three different tests of nociception (acetic acid-induced writhing test, formalin test, and hot plate test) and one test of inflammation (leukocyte migration to the peritoneal cavity) in order to evaluate the motor activity in mice treated with EOMP. The major component of EOMP was caryophyllene oxide (22.16 percent). This oil significantly reduced the number of writhes in an acetic acid test and the time spent licking the paw at the second phase of the formalin test. Furthermore, EOMP inhibited the carrageenan-induced leukocyte migration to the peritoneal cavity. However, administration of EOMP did not alter reaction time in the hot plate test, and did not affect the motor coordination test. These results indicate antinociceptive and anti-inflammatory properties of EOMP probably mediated via inhibition of inflammatory mediator synthesis or other peripheral pathway.

Ocimum basilicum leaf essential oil and (-)-linalool reduce orofacial nociception in rodents: a behavioral and electrophysiological approach

The present study investigated the antinociceptive effects of Ocimum basilicum L. (Lamiaceae) leaf essential oil (LEO) and (-)-linalool (LIN) in formalin (2 percent)-, glutamate (25 µM)- and capsaicin (2.5 µg)- induced orofacial nociception models in mice. The involvement of these substances was further evaluated on the neuronal excitability of the hippocampal dentate gyrus. Male mice (n=8/group) were pretreated separately with LEO and by LIN (50, 100, and 200 mg/kg, i.p.), morphine (5 mg/kg, i.p.) and vehicle (saline + Tween 80 0.2 percent), before injection of nociceptive agent into the right upper lip (perinasal area). The LEO and LIN reduced the nociceptive face-rubbing behaviour in both phases on formalin test. LEO and LIN, at high doses, produced significantly antinociceptive effect in the capsaicin and glutamate tests. In hippocampal slices, LEO inhibited the population spike generated by stimulation of the hylus (antidromic stimulation), with an IC50 of 0.1±0.05 mg/mL. This response was reversibly blocked by lidocaine (0.5 mg/mL), a known voltage-dependent sodium channel antagonist and by LIN (0.5 mg/mL). Our results suggest that LEO and LIN modulate neurogenic and inflammatory pain in the tests of orofacial nociception induced by formalin, capsaicin and glutamate. Part of these effects may be associated with decreased peripheral and central neuronal excitability.

p-Cymene reduces orofacial nociceptive response in mice

This study investigated the possible antinociceptive effect of p-cymene in different tests of orofacial nociception. The animals (mice) were pretreated (i.p.) with p-cymene (25, 50, 100 mg/kg), morphine (5 mg/kg), or vehicle (0.2 percent Tween 80+saline), and were then subsequently administered, subcutaneously into their upper lip: formalin, capsaicin, and glutamate. The nociceptive behavior response was characterized by the time in s that the mice remained rubbing the orofacial region, for a period of 40 min in the formalin test (first phase, 0-6 min; and second phase, 21-40 min), and for 42 and 15 min in the capsaicin and glutamate tests, respectively. To verify the possible opioid involvement in the antinociceptive effects, naloxone (i.p.) was administered into the mice 15 min prior to the pretreatment with p-cymene (100 mg/kg). Finally, whether or not the p-cymene evoked any change in motor performance in the Rota-rod test was evaluated. The results showed that the treatment with p-cymene, at all doses, reduced (p<0.001) the nociceptive behavior in all nociception tests. The antinociceptive effect of p-cymene was antagonized by naloxone (1.5 mg/kg). Additionally, mice treated with p-cymene did not show any change in motor performance. In conclusion, p-cymene attenuated orofacial nociception, suggesting an involvement of the opioid system in this effect. Thus, p-cymene might represent an important biomolecule for management and/or treatment of orofacial pain.

Cardiovascular effects of monoterpenes: a review

The monoterpenes are secondary metabolites of plants. They have various pharmacological properties including antifungal, antibacterial, antioxidant, anticancer, anti-spasmodic, hypotensive, and vasorelaxant. The purpose of this research was to review the cardiovascular effects of monoterpenes. The data in this resarch were collected using the Internet portals Pubmed, Scopus, and ISI Web of Knowledge between the years 1987 and 2010. In the study 33 monoterpenes were included, which were related to each of the thirteen individual words: artery, cardiovascular, heart, myocyte, vasorelaxant, vessel, hypotension, hypotensive, cardiomyocyte, ventricular, vasodilatory, aorta, and aortic. The research utilized 22 articles published mainly in the journals Phytomedicine, Fundamental Clinical Pharmacology, Planta Medica, Life Science, European Journal of Pharmacology, and Brazilian Journal of Medical and Biological Research. Of the 33 monoterpenes studied surveyed, sixteen of them had already been studied for their effects on the cardiovascular system: carvacrol, citronellol, p-cymene, eucalyptol (1,8-cineole), linalool, menthol, myrtenal, myrtenol, α-pinene, rotundifolone (piperitenone oxide), sobrerol, thymol, α-limonene, α-terpinen-4-ol, α-terpineol, and perillyl alcohol. The main effects observed were vasorelaxation, decreased heart rate and blood pressure. This review showed that the monoterpenes may be considered promising agents for prevention or treatment of diseases of the cardiovascular system.

Bioassay-guided evaluation of central nervous system effects of citronellal in rodents

The central nervous system (CNS) depressant and anticonvulsant activities of citronellal (CT) were investigated in animal models. The CT in doses of 100, 200 and 400 mg/kg injected by i.p. route in mice caused a significant decrease in the motor activity of animals when compared with the control group. The highest dose of CT significantly reduced the remaining time of the animals on the Rota-rod apparatus up to 2 h. Additionally, CT at doses 100, 200 and 400 mg/ kg (i.p.) was also capable to promote an increase of latency for development of convulsions induced by pentylenetetrazole (PTZ). It was efficient in prevents the tonic convulsions induced by maximal electroshock (MES) in doses of 200 and 400 mg/kg, resulting in 30 and 40 percent of protection, respectively. This compound was also capable to promote an increase of latency for development of convulsions induced by picrotoxin (PIC) at 400 mg/kg. In the same way, the anticonvulsant effect of CT was affected by pretreatment with flumazenil, a selective antagonist of benzodiazepine site of GABA A receptor. These results suggest a possible CNS depressant and anticonvulsant activities.

Assessment of antinociceptive and anti-inflammatory activities of Porophyllum ruderale (Jacq.) Cass., Asteraceae, aqueous extract

The present work investigated the antinociceptive and antiinflammatory activities of the Porophyllum ruderale (Jacq.) Cass., Asteraceae, aqueous extract (PRAE). For this purpose, acetic acid writhing, paw licking induced by formalin, hot-plate and pleurisy tests were performed. The doses of 100, 200 and 400 mg/kg (p.o.) significantly inhibited the writhing 63.4, 89.6 and 94.8 percent, respectively, in comparison with control group. The lick of the paw 1st phase was reduced at the dose of 400 mg/ kg (24.9 percent), while the 2nd phase had reduction at doses 200 and 400 mg/ kg (23.1 and 34.4 percent), respectively. The PRAE inhibited the carrageenaninduced neutrophil migration to the peritoneal cavity in a higher dose (p<0.05). Taken together, our results suggest that the PRAE can constitute target potential for use in therapies of the pain and inflammation.

Citral reduces nociceptive and inflammatory response in rodents

Citral (CIT), which contains the chiral enantiomers, neral (cis) and geranial (trans), is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and anti-inflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001) against acetic acid (0.8 percent) induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05) only at higher dose (200 mg/kg) of CIT in the first phase of the test. CIT significantly reduce (p<0.001) nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg) significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg) significantly reduced (p<0.001) the leukocyte migration in the carrageenan-induced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.