Prevalencia y susceptibilidad de Cryptococcus neoformans aislados del suelo y excretas de palomas en la ciudad de Maceió ­ AL, Brasil / Prevalência e suscetibilidade de Cryptococcus neoformans isolados do solo e de excretas de pombos na cidade de Maceió ­ AL, Brasil

Introducción: Cryptococcus neoformans es una levadura encapsulada, que se encuentra en fuentes ambientales, incluyendo excrementos de palomas. Tiene una gran relevancia clínica porque es el agente etiológico de la criptococosis, considerada una causa importante de mortalidad en personas inmunocomprometidas en todo el mundo. Objetivo: determinar la prevalencia y susceptibilidad de C. neoformans aislados del suelo y excremento de palomas en la ciudad de Maceió ­ Alagoas, Brasil. Metodología: Se recolectaron 150 muestras (50 de excretas secas, 50 de excretas frescas y 50 del suelo) y cultivaron en Agar Dextrosa Sabouraud. Las colonias aisladas sugestivas de C. neoformans se sometieron a identificación y caracterización mediante análisis morfológicos, actividad de la enzima fenol-oxidasa, sensibilidad a la cicloheximida, desarrollo a 37°C, hidrólisis de urea, asimilación de carbono y nitrógeno y fenotipificación en medio canavanina-glicina-azul de bromotimol. La prueba de susceptibilidad antifúngica se realizó utilizando la técnica de difusión en agar. Resultados: se obtuvieron 36 (24%) muestras positivas para C. neoformans, de las cuales 33 fueron de excretas secas y 3 del suelo cercano al excremento. El perfil de susceptibilidad fue de 100.0% para anfotericina B y 87.4% para ketoconazol, no obstante, hubo un alto porcentaje de resistencia a fluconazol (91.5%) e itraconazol (80.0%). Conclusión: estos hallazgos confirman que las excretas de palomas secas son reservorios de C. neoformans en el medio ambiente, caracterizando un problema de salud única. Además, la anfotericina B exhibió una alta actividad in vitro, representando buena alternativa en el tratamiento de la criptococosis.

Introdução: Cryptococcus neoformans é um fungo leveduriforme encapsulado, encontrado em fontes ambientais, incluindo excretas de pombos. Apresenta grande relevância clínica por ser agente etiológico da criptococose, considerada importante causa de mortalidade em indivíduos imunocomprometidos em todo o mundo. Objetivo: determinar a prevalência e suscetibilidade de C. neoformans isolados do solo e de excretas de pombos na cidade de Maceió, Alagoas. Metodologia: foram coletadas 150 amostras (50 de excretas secas, 50 de excretas frescas e 50 do solo) e cultivadas em Ágar Sabouraud Dextrose. As colônias isoladas sugestivas de C. neoformans foram submetidas à identificação e caracterização por meio de análises morfológicas, atividade da enzima fenoloxidase, sensibilidade à cicloheximida, termotolerância à 37ºC, hidrólise da ureia, assimilação de carbono e nitrogênio e quimiotipagem em ágar L-canavanina-glicina-azul de bromotimol. O teste de suscetibilidade antifúngica foi realizado por meio da técnica de difusão em ágar. Resultados: foram obtidas 36 (24%) amostras positivas para C. neoformans, das quais 33 (91,6%) foram provenientes de excretas secas e 3 (8,3%) do solo próximo a excrementos. O perfil de suscetibilidade foi de 100,0% para a anfotericina B e 87,4% para o cetoconazol, não obstante, verificou-se alto percentual de resistência ao fluconazol (91,8%) e itraconazol (80%). Conclusão: estes achados confirmam que excretas de pombos secas são reservatórios de C. neoformans no ambiente, caracterizando um problema de saúde única. Além disso, a anfotericina B apresentou elevada atividade, in vitro, representando boa alternativa no tratamento da criptococose.

Ethanolic extract of the aerial parts of Passiflora cincinnata Mast. (Passifloraceae) reduces nociceptive and inflammatory events in mice.

BACKGROUND: Passiflora cincinnata Mast. is described as a native species from the Caatinga biome, and used by traditional medicine for several pharmacological purposes, such as inflammatory disorders. However, studies that prove its biological activities are scarce. HYPOTHESIS/PURPOSE: This paper aims to evaluate the antinociceptive and anti-inflammatory activities of the aerial parts of Passiflora cincinnata (Pc-EtOH) in mice. METHODS: The chemical composition of Pc-EtOH was assessed by high-performance liquid chromatography coupled to diode array detector (HPLC-DAD). The antinociceptive profile of the extract (given orally: 100, 200 and 400 mg/kg) was established using the in vivo chemical models (acetic acid-induced abdominal constriction and formalin-induced paw licking test) and thermal (hot plate test) of nociception. The role of opioid, potassium channels, TRPV-1, muscarinic, serotoninergic (5-HT3) receptors and the participation of the nitric oxide pathway also was determined. The rota-rod test was used to verify the possible interference of the extract treatment in motor performance. Paw edema induced by carrageenan or histamine, and leukocyte migration, determination of total protein and nitric oxide to the peritoneal cavity were used for anti-inflammatory profile. RESULTS: The presence of flavonoids in the extract was confirmed using HPLC-DAD. At all doses tested the Pc-EtOH significantly reduced the number of writhing and decreased the paw licking time in both phases of the formalin test (p < 0.05). In the hot plate test, the extract increased the reaction time, reducing painful behavior. The antinociceptive mechanism probably involves central and peripheral pathways, involving the pathway of opioid and muscarinic receptors with influence of potassium channels and the nitric oxide pathway. However, the motor coordination test indicated that in the time of 120 min the extract decreases the stay time of the animal in the rota-rod. Pc-EtOH inhibited significantly (p < 0.05) the increase of the edema volume after administration of carrageenan and histamine. In the peritonitis test, acute pre-treatment with Pc-EtOH inhibited leukocyte migration, with a reduction in the number of neutrophils and concentration of total proteins and nitric oxide. CONCLUSION: The present study suggests that Pc-EtOH possesses peripheral and central antinociceptive action, and showed potential in inhibition of release of mediators of the inflammatory process.

LASSBio-1586, an N-acylhydrazone derivative, attenuates nociceptive behavior and the inflammatory response in mice.

Pain and inflammation are complex clinical conditions that are present in a wide variety of disorders. Most drugs used to treat pain and inflammation have potential side effects, which makes it necessary to search for new sources of bioactive molecules. In this paper, we describe the ability of LASSBio-1586, an N-acylhydrazone derivative, to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In these experimental models, LASSBio-1586 significantly (p<0.05) reduced nociceptive behavior. Several methods of acute and chronic inflammation induced by different chemical (carrageenan, histamine, croton oil, arachidonic acid) and physical (cotton pellet) agents were used to evaluate the anti-inflammatory effect of LASSBio-1586. LASSBio-1586 exhibited potent anti-inflammatory activity in all tests (p<0.05). Study of the mechanism of action demonstrated the possible involvement of the nitrergic, serotonergic and histamine signaling pathways. In addition, a molecular docking study was performed, indicating that LASSBio-1586 is able to block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. In summary, LASSBio-1586 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.

Neuropharmacological effects of essential oil from the leaves of Croton conduplicatus Kunth and possible mechanisms of action involved.

ETHNOPHARMACOLOGICAL RELEVANCE: Croton conduplicatus Kunth (Euphorbiaceae) is a Brazilian aromatic medicinal plant, widely known as "quebra-faca". In folk medicine, its leaves and stem-barks are used as a natural analgesic for the treatment of headaches. AIM OF THE STUDY: In this study, we describe for the first time the neuropharmacological potential of the essential oil obtained from the leaves of Croton conduplicatus (EO) in experimental models of pain, anxiety and insomnia. The mechanisms of action involved in these activities were also investigated. MATERIAL AND METHODS: Different experimental models were used to evaluate the antinociceptive (acetic acid, formalin-induced nociception and hot plate tests), anxiolytic (elevated plus maze and hole board tests) and sedative (thiopental-induced sleeping time) effects of EO in mice. EO was evaluated in three different doses (25, 50 and 100 mg/kg, i.p.) and compared with positive and negative controls in all experimental protocols. When appropriate, animals were pretreated with pharmacological antagonists (naloxone, atropine and flumazenil) in order to evaluate the mechanisms of action involved. A docking study also was performed to identify possible targets involved. RESULTS: EO (25, 50 and 100 mg/kg, i.p.) demonstrated a significant antinociceptive activity in all experimental models. Pretreatment with naloxone or atropine reversed the antinociceptive response (p < 0.05), suggesting the involvement of opioid and muscarinic receptors, respectively. A docking study was performed with the major components identified in EO (1,8 cineole - 21.42%, spathulenol - 15.47%, p-cymene - 12.41% and caryophyllene oxide - 12.15%), demonstrating favorable interaction profile with different subtypes of muscarinic (M2, M3 and M4) and opioids (delta and mu) receptors. EO also showed anxiolytic (mainly at doses of 25 and 50 mg/kg, i.p.) and sedative (only at the dose of 100 mg/kg, i.p.) effects in mice. These pharmacological responses were reversed by flumazenil (p < 0.05), indicating possible involvement of GABAA receptors. CONCLUSION: Our findings support the traditional use of this plant as a natural analgesic and suggest that EO is a multi-target natural product, presenting not only antinociceptive effect but also anxiolytic and sedative activities depending on the dose used.

Cyclodextrins improving the physicochemical and pharmacological properties of antidepressant drugs: a patent review.

INTRODUCTION: Depression is a serious mood disorder and is one of the most common mental illnesses. Despite the availability of several classes of antidepressants, a substantial percentage of patients are unresponsive to these drugs, which have a slow onset of action in addition to producing undesirable side effects. Some scientific evidence suggests that cyclodextrins (CDs) can improve the physicochemical and pharmacological profile of antidepressant drugs (ADDs). The purpose of this paper is to disclose current data technology prospects involving antidepressant drugs and cyclodextrins. AREAS COVERED: We conducted a patent review to evaluate the antidepressive activity of the compounds complexed in CDs, and we analyzed whether these complexes improved their physicochemical properties and pharmacological action. The present review used 8 specialized patent databases for patent research, using the term 'cyclodextrin' combined with 'antidepressive agents' and its related terms. We found 608 patents. In the end, considering the inclusion criteria, 27 patents reporting the benefits of complexation of ADDs with CDs were included. EXPERT OPINION: The use of CDs can be considered an important tool for the optimization of physicochemical and pharmacological properties of ADDs, such as stability, solubility and bioavailability.

Essential Oils and Their Major Compounds in the Treatment of Chronic Inflammation: A Review of Antioxidant Potential in Preclinical Studies and Molecular Mechanisms.

Inflammatory diseases result from the body's response to tissue damage, and if the resolution is not adequate or the stimulus persists, there will be progression from acute inflammation to chronic inflammation, leading to the development of cancer and neurodegenerative and autoimmune diseases. Due to the complexity of events that occur in inflammation associated with the adverse effects of drugs used in clinical practice, it is necessary to search for new biologically active compounds with anti-inflammatory activity. Among natural products, essential oils (EOs) present promising results in preclinical studies, with action in the main mechanisms involved in the pathology of inflammation. The present systematic review summarizes the pharmacological effects of EOs and their compounds in in vitro and in vivo models for inflammation. The research was conducted in the following databases: PubMed, Scopus, BIREME, Scielo, Open Grey, and Science Direct. Based on the inclusion criteria, 30 articles were selected and discussed in this review. The studies listed revealed a potential activity of EOs and their compounds for the treatment of inflammatory diseases, especially in chronic inflammatory conditions, with the main mechanism involving reduction of reactive oxygen and nitrogen species associated with an elevation of antioxidant enzymes as well as the reduction of the nuclear factor kappa B (NF-κB), reducing the expression of proinflammatory cytokines. Thus, this review suggests that EOs and their major compounds are promising tools for the treatment of chronic inflammation.

Influence of Flavonoids on Mechanism of Modulation of Insulin Secretion.

BACKGROUND: The development of alternatives for insulin secretion control in vivo or in vitro represents an important aspect to be investigated. In this direction, natural products have been progressively explored with this aim. In particular, flavonoids are potential candidates to act as insulin secretagogue. OBJECTIVE: To study the influence of flavonoid on overall modulation mechanisms of insulin secretion. METHODS: The research was conducted in the following databases and platforms: PubMed, Scopus, ISI Web of Knowledge, SciELO, LILACS, and ScienceDirect, and the MeSH terms used for the search were flavonoids, flavones, islets of Langerhans, and insulin-secreting cells. RESULTS: Twelve articles were included and represent the basis of discussion on mechanisms of insulin secretion of flavonoids. Papers in ISI Web of Knowledge were in number of 1, Scopus 44, PubMed 264, ScienceDirect 511, and no papers from LILACS and SciELO databases. CONCLUSION: According to the literature, the majority of flavonoid subclasses can modulate insulin secretion through several pathways, in an indication that corresponding molecule is a potential candidate for active materials to be applied in the treatment of diabetes. SUMMARY: The action of natural products on insulin secretion represents an important investigation topic due to their importance in the diabetes controlIn addition to their typical antioxidant properties, flavonoids contribute to the insulin secretionThe modulation of insulin secretion is induced by flavonoids according to different mechanisms. Abbreviations used: KATP channels: ATP-sensitive K+ channels, GLUT4: Glucose transporter 4, ERK1/2: Extracellular signal-regulated protein kinases 1 and 2, L-VDCCs: L-type voltage-dependent Ca+2 channels, GLUT1: Glucose transporter 1, AMPK: Adenosine monophosphate-activated protein kinase, PTP1B: Protein tyrosine phosphatase 1B, GLUT2: Glucose transporter 2, cAMP: Cyclic adenosine monophosphate, PKA: Protein kinase A, PTK: Protein tyrosine kinase, CaMK II: Ca2+/calmodulin-dependent protein kinase II, GSIS: Glucose-stimulated insulin secretion, Insig-1: Insulin-induced gene 1, IRS-2: Insulin receptor substrate 2, PDX-1: Pancreatic and duodenal homeobox 1, SREBP-1c: Sterol regulatory element binding protein-1c, DMC: Dihydroxy-6'-methoxy-3',5'-dimethylchalcone, GLP-1: Glucagon-like peptide-1, GLP-1R: Glucagon-like peptide 1 receptor.

Antinociceptive Effect of the Essential Oil from Croton conduplicatus Kunth (Euphorbiaceae).

Medicinal plants have been widely used in the treatment of chronic pain. In this study, we describe the antinociceptive effect of the essential oil from Croton conduplicatus (the EO 25, 50, and 100 mg/kg, i.p.), a medicinal plant native to Brazil. Antinociceptive activity was investigated by measuring the nociception induced by acetic acid, formalin, hot plate and carrageenan. A docking study was performed with the major constituents of the EO (E-caryophyllene, caryophyllene oxide, and camphor). The EO reduced nociceptive behavior at all doses tested in the acetic acid-induced nociception test (p < 0.05). The same was observed in both phases (neurogenic and inflammatory) of the formalin test. When the hot-plate test was conducted, the EO (50 mg/kg) extended the latency time after 60 min of treatment. The EO also reduced leukocyte migration at all doses, suggesting that its antinociceptive effect involves both central and peripheral mechanisms. Pretreatment with glibenclamide and atropine reversed the antinociceptive effect of the EO on the formalin test, suggesting the involvement of KATP channels and muscarinic receptors. The docking study revealed a satisfactory interaction profile between the major components of the EO and the different muscarinic receptor subtypes (M2, M3, and M4). These results corroborate the medicinal use of C. conduplicatus in folk medicine.

The anti-hyperalgesic and anti-inflammatory profiles of p-cymene: Evidence for the involvement of opioid system and cytokines.

CONTEXT: Pain corresponds to the most frequent reason for visits to physicians, and its control by conventional drugs is accompanied by several side effects, making treatment difficult. For this reason, new chemical entities derived from natural products still hold great promise for the future of drug discovery to pain treatment. OBJECTIVE: The objective of this study was to evaluate the antinociceptive and anti-inflammatory profiles of p-cymene (PC), a monocyclic monoterpene, and its possible mechanisms of action. MATERIALS AND METHODS: Mice treated acutely with PC (25, 50, or 100 mg/kg, i.p.) were screened for carrageenan-induced hyperalgesia and the inflammatory components of its cascade (30-180 min), carrageenan-induced pleurisy (4 h), and tail-flick test (1-8 h). Also, we observed the PC effect on the generation of nitric oxide by macrophages and the activation of neurons in the periaqueductal gray (PAG) by immunofluorescence. RESULTS: PC reduced (p < 0.001) the hyperalgesia induced by carrageenan, TNF-α, dopamine, and PGE2. PC decrease total leukocyte migration (100 mg/kg: p < 0.01), neutrophils (50 and 100 mg/kg: p < 0.05 and 0.001), and TNF-α (25, 50, and 100 mg/kg: p < 0.01, 0.05, and 0.001, respectively), besides reducing NO production (p < 0.05) in vitro. PC produced antinociceptive effect in tail-flick test (p < 0.05), which was antagonized by naloxone, naltrindole, nor-BNI, and CTOP, and increased (p < 0.001) the number of c-Fos-immunoreactive neurons in PAG. DISCUSSION AND CONCLUSION: These results provide information about the anti-hyperalgesic and anti-inflammatory properties of PC suggesting a possible involvement of the opioid system and modulating some pro-inflammatory cytokines.

The role of flavonoids on oxidative stress in epilepsy.

BACKGROUNDS: Oxidative stress can result from excessive free-radical production and it is likely implicated as a possible mechanism involved in the initiation and progression of epileptogenesis. Flavonoids can protect the brain from oxidative stress. In the central nervous system (CNS) several flavonoids bind to the benzodiazepine site on the GABAA-receptor resulting in anticonvulsive effects. OBJECTIVE: This review provides an overview about the role of flavonoids in oxidative stress in epilepsy. The mechanism of action of flavonoids and its relation to the chemical structure is also discussed. RESULTS/CONCLUSIONS: There is evidence that suggests that flavonoids have potential for neuroprotection in epilepsy.

Antinociceptive effect of Encholirium spectabile: A Bromeliaceae from the Brazilian caatinga biome.

BACKGROUND: Encholirium spectabile is a species found in outcrops rocky throughout the Brazilian Caatinga. OBJECTIVE: This study was carried out to evaluate the antinociceptive effects of ethanolic extract of the leaves from E. spectabile (Es-EtOH) in mice using chemical and thermal models of nociception. MATERIAL AND METHODS: HPLC was used to determine the fingerprint chromatogram. The Es-EtOH was examined for its antinociceptive activity at the doses of 100, 200 and 400 mg/kg intraperitoneal (i.p.). The evaluation of antinociceptive activity was carried out by the acetic acid-induced writhing, formalin and hot plate tests in mice. Rota-rod test was used for the evaluation of motor coordination. RESULTS: In the acetic acid-induced writhing test, the Es-EtOH (100, 200 and 400 mg/kg, i.p.) reduced the number of writhings by 68.59, 79.33 and 65.28%, respectively. Additionally, Es-EtOH (100, 200 and 400 mg/kg, i.p.) decreased by 34.14, 52.61 and 60.97% the paw licking time in the first phase, as well as 89.56, 79.90 and 96.71% in the second phase of the formalin test, respectively. Es-EtOH also showed effect in the hot plate test, since increased the latency time at dose of 100 mg/kg after 60 minutes. In addition, Es-EtOH did not impair motor coordination. The presence of phenolic compounds in the extract was confirmed using HPLC. These results indicate that Es-EtOH has antinociceptive activity, probably of peripheral origin. The mechanism involved is not completely understood but, at least in part there is the participation of opioid receptors.

Phytochemical screening and anti-inflammatory activity of Cnidoscolus quercifolius (Euphorbiaceae) in mice.

BACKGROUND: Cnidoscolus quercifolius is a species popularly known as favela and faveleira, and belonging to the Caatinga biome (semi-arid vegetation, Brazil), where is used in folk medicine as an anti-inflammatory. OBJECTIVE: The aim was to evaluate the anti-inflammatory effect of the ethanolic extract from barks (Cqb-EtOH) and leaves (Cql-EtOH) of C. quercifolius in mice using experimental models of inflammation. MATERIALS AND METHODS: The preliminary phytochemical analysis of the ethanolic extract was performed. The activity was evaluated by paw edema induced by carrageenan and leukocytes migration to the peritoneal cavity induced by carrageenan methods. RESULTS: A preliminary analysis of Cqb-EtOH revealed that it contained coumarins, flavonoids, monoterpenes/diterpenes and naphthoquinones, while the Cql-EtOH showed positive reaction to coumarins, anthracene derivatives, flavonoids, lignans and triterpenes/steroids. Cqb-EtOH and Cql-EtOH (100, 200 and 400 mg/kg) inhibited significantly (P < 0.01) the increase in the edema volume after administration of carrageenan. In the peritonitis test, acute pretreatment with Cqb-EtOH and Cql-EtOH (100, 200 and 400 mg/kg) inhibited the leukocyte migration. CONCLUSIONS: It can be concluded that extracts from the barks and leaves of C. quercifolius have anti-inflammatory activity, which supports the popular use of this plant to treat inflammation. Thus, extracts has significant anti-inflammatory properties, which are related probably to inhibition of release of mediators of the inflammatory process.

Borneol, a bicyclic monoterpene alcohol, reduces nociceptive behavior and inflammatory response in mice.

Borneol, a bicyclic monoterpene, has been evaluated for antinociceptive and anti-inflammatory activities. Antinociceptive and anti-inflammatory activities were studied by measuring nociception by acetic acid, formalin, hot plate, and grip strength tests, while inflammation was prompted by carrageenan-induced peritonitis. The rotarod test was used to evaluate motor coordination. Borneol produced a significant (P < 0.01) reduction of the nociceptive behavior at the early and late phases of paw licking and reduced the writhing reflex in mice (formalin and writhing tests, resp.). When the hot plate test was conducted, borneol (in higher dose) produced an inhibition (P < 0.05) of the nociceptive behavior. Such results were unlikely to be provoked by motor abnormality. Additionally, borneol-treated mice reduced the carrageenan-induced leukocytes migration to the peritoneal cavity. Together, our results suggest that borneol possess significant central and peripheral antinociceptive activity; it has also anti-inflammatory activity. In addition, borneol did not impair motor coordination.

Avaliação da técnica de drenagem linfática manual no tratamento do fibro edema geloide em mulheres / Evaluation of manual lymphatic drainage technique in the treatment of Cellulite in women

Introdução: A drenagem linfática manual (DLM) é uma terapia utilizada no tratamento do fibro edema geloide (FEG). Objetivo: Analisar o efeito da DLM no tratamento do FEG. Métodos: Realizou-se uma avaliação no início e no fim do tratamento em 10 voluntárias com FEG, de grau I ao III, que constava de anamnese, inspeção, palpação, perimetria e testes específicos. Foram feitos registros fotográficos dos glúteos e das coxas superiores. A terapia constou de 10 sessões de DLM com duração de 60 minutos. Na análise de dados, utilizaram-se os testes t pareado, exato de Fisher e Wilcoxon, com nível de significância de p<0.05. Resultados: Houve diferença estatística no grau de satisfação das pacientes com o FEG. Não houve diferença significante no grau do FEG, porém constatou-se melhora clínica no aspecto da pele. Todas as pacientes relataram estar satisfeitas com o tratamento. Não houve diferença estatística na perimetria. Conclusão: A DLM demonstrou ser uma terapêutica coadjuvante no tratamento do FEG, com melhora da autoestima e da satisfação das pacientes.

Introduction: Manual lymphatic drainage (MLD) is a therapy used to treat cellulite. Objective: To analyze the effect of MDL in the treatment of cellulite. Methods: We conducted an evaluation at the beginning and end of treatment in 10 women with cellulite grade I to III, which consisted of anamnesis, inspection, palpation, perimetry and specific tests. Photographic records were made of the buttocks and upper thighs. The therapy consisted of 10 sessions of MLD lasting 60 minutes. In the data analysis used the tests paired t, Fisher exact and Wilcoxon with the significance level of p<0.05. Results: There were statistical differences in the degree of satisfaction of patients with cellulite. There was no significant difference in the degree of cellulite, but was found clinical improvement in skin appearance. All patients reported being satisfied with treatment. There was no statistical difference in perimetry. Conclusion: MLD proved to be an adjuvant therapy in the cellulite treatment, with improved self-esteem and satisfaction of patients.