The role of bromeliad structural complexity on the presence, spatial distribution and predator avoidance in Tityus neglectus (Scorpiones: Buthidae).

The spatial arrangement of organisms is significantly influenced by the structure of vegetation. Bromeliads, characterized by a remarkable architectural design featuring rosette-like leaf arrangements for rainwater storage, act as habitats for various organisms. These organisms use bromeliads for shelter, foraging, reproduction and the supply of nutrients and moisture. This study investigated how specific aspects of bromeliad structure, such as the number, width and length of leaves, impact the behaviour and distribution patterns of the bromelicolous scorpion Tityus neglectus. In the examination of 110 sampled bromeliads, 33 scorpions were recorded, resulting in an occupancy rate of 30%. The likelihood of scorpion occurrence was associated with the plant's structure. The length and coefficient of variation in the width of leaves appeared as the main predictors, positively influencing scorpion presence while the number of leaves exhibited a negative relation with scorpion occurrence. The distribution of scorpions was uniform across the spatial design of bromeliads. Furthermore, T. neglectus demonstrated the ability to utilize water accumulated in the bromeliad to evade potential predators, submerging itself for, on mean, almost 8 min. We concluded that bromeliad structure is essential in shaping the distribution patterns and anti-predatory behaviour of T. neglectus.

A Novel Treatment for Convex Lateral Crura: The Inverted Spanning Suture.

Rhinoplasty is one of the most complex and challenging procedures in plastic surgery, even for experienced surgeons. Among the steps leading to an aesthetic and functional nose, there is the nasal tip improvement. Today's approach to nasal tip is the product of different techniques shifting through time, mainly from a resection tendency, to preservation and suture use to reshape cartilages. Addressing the lateral crura is vital to an aesthetic nasal tip and it is frequently obtained by adequate suture techniques. The alar-spanning suture described by Perkins is one of such. Regardless of its importance, it was not able to improve convex crura in some cases. The inverted alar-spanning suture (ISS) is an adaptation designed to treat those cases with the suture alone. ISS is a novel technique that can lead to better results treating the convex lateral crura by distributing the force vector in a more effective way. New techniques in rhinoplasty have multiplied, bringing this procedure to a new level and keeping up with the updated notion of restoration instead of excision the ISS is a new, precise, approach to an old problem.

Biochemical, urinary, and acid-base profile in cattle treated with maintenance enteral electrolyte solutions containing calcium propionate, propylene glycol or glycerol.

Enteral fluid therapy administered in continuous flow through the naso-ruminal route for long periods with electrolyte solutions is safe and effective in cattle. The aim of this study was to carry out a comparative assessment between maintenance enteral electrolyte solutions containing calcium propionate, propylene glycol or glycerol administered in continuous flow in cattle. Six heifers were used and the study was carried out in a 6 × 3 crossover design, in which each animal received three different treatments: enteral electrolyte solution containing calcium propionate (ESCaP), enteral electrolyte solution containing glycerol (ESGly) and enteral electrolyte solution containing propylene glycol (ESPrG). Solutions were administered at a rate of 15 mL kg-1 h-1 for 12 h. Serum and urinary biochemical assessment; urinary volume, pH, and specific gravity; and blood gas analysis were measured at 0, 3, 6, 9, 12, and 24 h. All three enteral electrolyte solutions expanded blood volume and increased urine volume without causing electrolyte imbalances. ESCaP caused mild reversible metabolic alkalosis while the most significant glycemic potential was observed in electrolyte solutions containing propylene glycol (ESPrG) and calcium propionate (ESCaP).

Effect of Passiflora setacea juice and its phenolic metabolites on insulin resistance markers in overweight individuals and on microglial cell activity.

Passiflora setacea (PS) is a species of wild Brazilian passion fruit, rich in bioactive compounds. Scientific evidence suggests that food rich in polyphenols can modulate inflammation, thereby playing an important role in preventing chronic non-communicable diseases, such as type 2 diabetes (DT2) and cardiovascular diseases (CVD). This study aimed to investigate the effect of PS consumption on metabolic and inflammatory biomarkers in overweight male volunteers and to identify the underlying mechanism of action using an in vitro study using phenolic metabolites isolated from the plasma of volunteers at physiologically relevant concentrations. Volunteers participated in a double-blind, placebo-controlled (PB) study with two phases: phase I (acute study) and phase II (chronic study). In phase I, 15 volunteers ingested a single dose of 50 g, 150 g of PS pulp and PB in three different interventions. In phase II, nine volunteers ingested 50 g of PS or PB for 14 days. Blood samples were collected before (T0 h) and 3 h (T3 h) (phase I) or 15 days after (phase II) ingestion of PS or PB. Blood biochemical markers, HOMA IR, and inflammatory markers were analyzed and data on BMI, waist circumference, and consumption of polyphenol-rich foods were collected. Phenolic metabolites were extracted from plasma by solid-phase separation and were used to treat BV-2 cells stimulated by LPS or anacardic acid to assess p50, p65 and PPAR-γ activation. It was observed that the consumption of a single dose of PS juice significantly reduced basal insulin levels and HOMA IR. After prolonged consumption for two weeks, PS contributed to the reduction of circulating levels of IL-6. BV-2 cells treated with PS phenolic metabolites showed increased PPAR-γ activity, which resulted in an anti-inflammatory and anti-diabetic effect of PS metabolites. In conclusion, PS juice consumption exerts beneficial effects on inflammatory markers in overweight individuals, being a possible and important tool in the prevention of T2D and CVD in risk groups.

Qualidade do sono e fatores associados em universitários do Centro-Oeste do Brasil / Sleep quality and associated factors in university students in the Midwest of Brazil

INTRODUÇÃO: A qualidade do sono é uma das queixas mais frequentes entre estudantes universitários. OBJETIVOS: Identificar a prevalência de má qualidade do sono e os fatores associados em acadêmicos da área da saúde de uma universidade do Centro-Oeste do Brasil. MÉTODOS: Estudo transversal com uma amostra de 2171 universitários com média de idade de 22,7 (±3,9). O desfecho, sono de má qualidade, foi avaliado por meio da versão brasileira do questionário Pittsburgh Sleep Quality Index (PSQI-BR). As variáveis independentes (demográficas, socioeconômicas e comportamentais) foram avaliadas por meio de um questionário padronizado. As análises multivariadas foram realizadas por meio de Regressão de Poisson, estimando-se as Razões de Prevalências (RP) ajustadas e seus respectivos Intervalos de Confiança de 95% (IC95%). RESULTADOS: A média do escore do PSQI-BR foi 7,0. A prevalência de má qualidade do sono foi de 63,5% (IC95% 61,4-65,5), sendo 60,3% nos homens e 64,8% nas mulheres. Após análise ajustada, auto percepção de saúde razoável/ruim esteve associada com má qualidade do sono em ambos os sexos. Além disso, para os homens, a prevalência de má qualidade do sono foi maior para os estudantes que fumavam; e foi menor para aqueles que consumiam adequadamente frutas, legumes e verduras e eram suficientemente ativos. Já para as mulheres, a prevalência de má qualidade do sono foi maior naquelas com 24 ou mais anos de idade, sem companheiro, que consumiam bebidas alcoólicas e que cursavam medicina. CONCLUSÃO: Verificou-se elevada prevalência do desfecho na amostra. Além disso, a má qualidade do sono ocorre de forma diferente entre homens e mulheres. Ressalva-se a importância do monitoramento da má qualidade do sono em estudantes universitários.

INTRODUCTION: Sleep quality is one of the most frequent complaints among college students. OBJETIVE: To identify the prevalence of poor sleep quality and associated factors in health care academics at a university in the Midwest of Brazil. METHODS: Cross-sectional study with a sample of 2171 university students with a mean age of 22.7 (±3.9). The outcome, poor quality sleep, was assessed using the Brazilian version of the Pittsburgh Sleep Quality Index (PSQI-BR) questionnaire. Independent variables (demographic, socioeconomic and behavioral) were assessed using a standardized questionnaire. Multivariate analyzes were performed using Poisson Regression, estimating the adjusted Prevalence Ratios (PR) and their respective 95% Confidence Intervals (95%CI). RESULTS: The mean score of the PSQI-BR was 7.0. The prevalence of poor sleep quality was 63.5% (95%CI 61.4-65.5), being 60.3% in men and 64.8% in women. After adjusted analysis, reasonable/poor self-rated health was associated with poor sleep quality in both sexes. Furthermore, for men, the prevalence of poor sleep quality was higher for students who smoked; and it was lower for those who adequately consumed fruits and vegetables and were sufficiently active. As for women, the prevalence of poor sleep quality was higher in those aged 24 or over, without a partner, who consumed alcoholic beverages and who were studying medicine. CONCLUSION: There was a high prevalence of the outcome in the sample. Furthermore, poor sleep quality occurs differently between men and women. Thus, we emphasize the importance of monitoring poor sleep quality in college students.

Evaluation of the anti-snakebite, antimicrobial and antioxidant potential of Philodendron megalophyllum Schott (Araceae), traditionally used in accidents caused by snakes in the western region of Pará, Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: In the region of Western Pará, Amazonia, Brazil, Philodendron megalophyllum is widely used for the treatment of envenomations caused by bites from venomous snakes. The traditional use of plants is usually done through oral administration of an infusion (decoction) soon after the bite occurs. The efficiency of aqueous extracts of P. megalophyllum was demonstrated for blocking the activity of the venom of Bothrops sp., but only for a pre-incubation protocol (venom:extract), which fails to simulate the real form of use of this species. In this context, the objective of this research was to evaluate the anti-snakebite potential of the aqueous extract of P. megalophyllum to inhibit for the biological activity induced by Bothrops atrox venom (BaV) using traditional treatment methods. MATERIAL AND METHODS: Initially, an aqueous extract using the stem of P. megalophyllum (AEPm) was prepared following the standard procedure used by the residents of the rural area along the Tapajós River (Eixo Forte region) in Santarém, PA, Brazil. The phytochemical profile of AEPm was conducted using thin layer chromatography (TLC) and phenolic compounds were quantified through colorimetric trials. The cytotoxicity of AEPm was evaluated using the MRC-5 human fibroblast line, and the antioxidant potential was measured using DPPH methods and cell culture. AEPm antimicrobial action was evaluated by the 96-well plate microdilution and the minimum inhibitory concentration (MIC) methods using 18 types of microorganisms including bacteria that are present in the oral cavity of snakes. AEPm blocking potential was tested against BaV activity in vitro (fibrinolytic) and in vivo (defibrinating and hemorrhagic). In order to test for an interaction between BaV and AEPm SDS-PAGE electrophoresis was conducted. RESULTS: The presence of coumarins, fatty acids, and hydrolysable tannins were detected in the AEPm. The colorimetric trials showed that AEPm had a high concentration of condensed tannins (20.1 ± 1.2%). The potential of AEPm for blocking of hemorrhagic and fibrinolytic activity of BaV showed a maximum reduction of 86.1% and 96.5%, respectively, for the pre-incubation protocol (1:10, venom:extract). However, when the extract was administered orally there was no significant blocking of these activities. The interaction of BaV and AEPm showed a modification of the profile of proteic bands when compared to the pattern of bands obtained from the BaV alone. The AEPm was not considered toxic, demonstrated antioxidant activity, and was capable of reducing the growth of 10 of the 18 studied microorganisms. CONCLUSION: Although the stem of P. megalophyllum is indicated by traditional medicine techniques as effective against snakebites, the extract, when tested orally was not able to significantly inhibit (p ˃ 0.05) hemorrhage and defibrinating activity induced by the B. atrox venom. On the other hand, the extract yielded a promising result with respect to antioxidant and antimicrobial potential, and after further studies it could be used as a complementary treatment for localized action and secondary infections that frequently occur with snakebites from the genus of Bothrops sp.

Evaluation of the anti-snakebite, antimicrobial and antioxidant potential of Philodendron megalophyllum Schott (Araceae), traditionally used in accidents caused by snakes in the western region of Pará, Brazil

Ethnopharmacological relevance In the region of Western Pará, Amazonia, Brazil, Philodendron megalophyllum is widely used for the treatment of envenomations caused by bites from venomous snakes. The traditional use of plants is usually done through oral administration of an infusion (decoction) soon after the bite occurs. The efficiency of aqueous extracts of P. megalophyllum was demonstrated for blocking the activity of the venom of Bothrops sp., but only for a pre-incubation protocol (venom:extract), which fails to simulate the real form of use of this species. In this context, the objective of this research was to evaluate the anti-snakebite potential of the aqueous extract of P. megalophyllum to inhibit for the biological activity induced by Bothrops atrox venom (BaV) using traditional treatment methods. Material and methods Initially, an aqueous extract using the stem of P. megalophyllum (AEPm) was prepared following the standard procedure used by the residents of the rural area along the Tapajós River (Eixo Forte region) in Santarém, PA, Brazil. The phytochemical profile of AEPm was conducted using thin layer chromatography (TLC) and phenolic compounds were quantified through colorimetric trials. The cytotoxicity of AEPm was evaluated using the MRC-5 human fibroblast line, and the antioxidant potential was measured using DPPH methods and cell culture. AEPm antimicrobial action was evaluated by the 96-well plate microdilution and the minimum inhibitory concentration (MIC) methods using 18 types of microorganisms including bacteria that are present in the oral cavity of snakes. AEPm blocking potential was tested against BaV activity in vitro (fibrinolytic) and in vivo (defibrinating and hemorrhagic). In order to test for an interaction between BaV and AEPm SDS-PAGE electrophoresis was conducted. Results The presence of coumarins, fatty acids, and hydrolysable tannins were detected in the AEPm. The colorimetric trials showed that AEPm had a high concentration of condensed tannins (20.1 ± 1.2%). The potential of AEPm for blocking of hemorrhagic and fibrinolytic activity of BaV showed a maximum reduction of 86.1% and 96.5%, respectively, for the pre-incubation protocol (1:10, venom:extract). However, when the extract was administered orally there was no significant blocking of these activities. The interaction of BaV and AEPm showed a modification of the profile of proteic bands when compared to the pattern of bands obtained from the BaV alone. The AEPm was not considered toxic, demonstrated antioxidant activity, and was capable of reducing the growth of 10 of the 18 studied microorganisms. Conclusion Although the stem of P. megalophyllum is indicated by traditional medicine techniques as effective against snakebites, the extract, when tested orally was not able to significantly inhibit (p > 0.05) hemorrhage and defibrinating activity induced by the B. atrox venom. On the other hand, the extract yielded a promising result with respect to antioxidant and antimicrobial potential, and after further studies it could be used as a complementary treatment for localized action and secondary infections that frequently occur with snakebites from the genus of Bothrops sp

Evaluation of the anti-snakebite, antimicrobial and antioxidant potential of Philodendron megalophyllum Schott (Araceae), traditionally used in accidents caused by snakes in the western region of Pará, Brazil

Ethnopharmacological relevance In the region of Western Pará, Amazonia, Brazil, Philodendron megalophyllum is widely used for the treatment of envenomations caused by bites from venomous snakes. The traditional use of plants is usually done through oral administration of an infusion (decoction) soon after the bite occurs. The efficiency of aqueous extracts of P. megalophyllum was demonstrated for blocking the activity of the venom of Bothrops sp., but only for a pre-incubation protocol (venom:extract), which fails to simulate the real form of use of this species. In this context, the objective of this research was to evaluate the anti-snakebite potential of the aqueous extract of P. megalophyllum to inhibit for the biological activity induced by Bothrops atrox venom (BaV) using traditional treatment methods. Material and methods Initially, an aqueous extract using the stem of P. megalophyllum (AEPm) was prepared following the standard procedure used by the residents of the rural area along the Tapajós River (Eixo Forte region) in Santarém, PA, Brazil. The phytochemical profile of AEPm was conducted using thin layer chromatography (TLC) and phenolic compounds were quantified through colorimetric trials. The cytotoxicity of AEPm was evaluated using the MRC-5 human fibroblast line, and the antioxidant potential was measured using DPPH methods and cell culture. AEPm antimicrobial action was evaluated by the 96-well plate microdilution and the minimum inhibitory concentration (MIC) methods using 18 types of microorganisms including bacteria that are present in the oral cavity of snakes. AEPm blocking potential was tested against BaV activity in vitro (fibrinolytic) and in vivo (defibrinating and hemorrhagic). In order to test for an interaction between BaV and AEPm SDS-PAGE electrophoresis was conducted. Results The presence of coumarins, fatty acids, and hydrolysable tannins were detected in the AEPm. The colorimetric trials showed that AEPm had a high concentration of condensed tannins (20.1 ± 1.2%). The potential of AEPm for blocking of hemorrhagic and fibrinolytic activity of BaV showed a maximum reduction of 86.1% and 96.5%, respectively, for the pre-incubation protocol (1:10, venom:extract). However, when the extract was administered orally there was no significant blocking of these activities. The interaction of BaV and AEPm showed a modification of the profile of proteic bands when compared to the pattern of bands obtained from the BaV alone. The AEPm was not considered toxic, demonstrated antioxidant activity, and was capable of reducing the growth of 10 of the 18 studied microorganisms. Conclusion Although the stem of P. megalophyllum is indicated by traditional medicine techniques as effective against snakebites, the extract, when tested orally was not able to significantly inhibit (p > 0.05) hemorrhage and defibrinating activity induced by the B. atrox venom. On the other hand, the extract yielded a promising result with respect to antioxidant and antimicrobial potential, and after further studies it could be used as a complementary treatment for localized action and secondary infections that frequently occur with snakebites from the genus of Bothrops sp

Assessment of the anti-snakebite properties of extracts of Aniba fragrans Ducke (Lauraceae) used in folk medicine as complementary treatment in cases of envenomation by Bothrops atrox.

ETHNOPHARMACOLOGICAL RELEVANCE: Extracts of leaves and bark of Aniba fragrans are used as tea (decoction) to treat snakebites in communities in the Brazilian Amazon. The aqueous extract of the leaves of A. fragrans has been proven to be effective against Bothrops venom, but only when pre-incubated with the venom. This study sought to assess the potential of different types of extract of this species to inhibit the biological activities of Bothrops atrox venom (BaV) when used the same way as in folk medicine. The main classes of secondary metabolites and the concentrations of phenolics in the extracts were also determined. MATERIALS AND METHODS: Four types of extract of A. fragrans were prepared: aqueous extract of the leaf (AEL), aqueous extract of the bark (AEB), hydroalcoholic leaf extract (HLE) and extract of the residue from hydrodistillation of the leaf (ERHL). The phytochemical profiles of the aqueous extracts were determined using thin layer chromatography (TLC), and the concentrations of phenolics were measured by colorimetric assays. To investigate the potential of the extracts to inhibit the biological activities of BaV, in vitro tests for antiphospholipase and antifibrinolytic activities were performed. In vivo tests for antihemorrhagic and antidefibrinating activities were also carried out, as well as antimicrobial tests for activity against the main bacteria found in the oral cavity of snakes. Interaction between the extracts and the proteins in BaV was assessed by electrophoresis (SDS-PAGE) and Western blot (WB). The cytotoxicity of the extracts was assessed in a strain of MRC-5 human fibroblasts. RESULTS: Terpenoids, flavonoids and condensed and hydrolysable tannins were detected in all the extracts. Metabolites such as coumarins, fatty acids and alkaloids were present in some extracts but not in others, indicating different phytochemical profiles. Phenolics content varied between extracts, and there were more tannins in AEB and HLE. In the in vitro tests, the extracts inhibited the phospholipase and fibrinolytic activities of BaV in the two ratios of venom to extract used. HLE exhibited effective antimicrobial action as it inhibited growth of 11 of the 15 bacteria investigated, including Morganella morganii, the main bacteria described in the oral cavity of snakes. The extracts failed to inhibit the defibrinating activity of BaV, and only the Bothrops antivenom had a significant effect (96.1%) on this activity. BaV-induced hemorrhage was completely inhibited by AEL and AEB when the pre-incubation (venom:extract) protocol was used. When administered orally, as in folk medicine, both AEB and AEL produced significant inhibition of hemorrhagic activity (maximum inhibition 46.5% and 39.2%, respectively). SDS-PAGE and WB of the extracts pre-incubated with BaV showed that the main proteins in the venom had been precipitated by the extracts. None of the four extracts showed cytotoxic effects in the tests carried out with a human fibroblast cell line. CONCLUSION: In addition to being effective in reducing hemorrhage when administered orally, the extracts displayed a high antimicrobial potential against microorganisms involved in secondary infections at the site of the snakebite. Once the extracts have been tested in accordance with the appropriate regulations, this species could potentially be used to produce a phytomedicine for complementary treatment of the secondary infections due to bacteria that aggravate the local signs and symptoms after snakebite envenomation.

Assessment of the anti-snakebite properties of extracts of Aniba fragrans Ducke (Lauraceae) used in folk medicine as complementary treatment in cases of envenomation by Bothrops atrox

Ethnopharmacological relevance: Extracts of leaves and bark of Aniba fragrans are used as tea (decoction) to treat snakebites in communities in the Brazilian Amazon. The aqueous extract of the leaves of A. fragrans has been proven to be effective against Bothrops venom, but only when pre-incubated with the venom. This study sought to assess the potential of different types of extract of this species to inhibit the biological activities of Bothrops atrox venom (BaV) when used the same way as in folk medicine. The main classes of secondary metabolites and the concentrations of phenolics in the extracts were also determined. Materials and methods: Four types of extract of A. fragrans were prepared: aqueous extract of the leaf (AEL), aqueous extract of the bark (AEB), hydroalcoholic leaf extract (HLE) and extract of the residue from hydro distillation of the leaf (ERHL). The phytochemical profiles of the aqueous extracts were determined using thin layer chromatography (TLC), and the concentrations of phenolics were measured by colorimetric assays. To investigate the potential of the extracts to inhibit the biological activities of BaV, in vitro tests for antiphospholipase and antifibrinolytic activities were performed. In vivo tests for antihemorrhagic and antidefibrinating activities were also carried out, as well as antimicrobial tests for activity against the main bacteria found in the oral cavity of snakes. Interaction between the extracts and the proteins in BaV was assessed by electrophoresis (SDS-PAGE) and Western blot (WB). The cytotoxicity of the extracts was assessed in a strain of MRC-5 human fibroblasts. Results: Terpenoids, flavonoids and condensed and hydrolysable tannins were detected in all the extracts. Metabolites such as coumarins, fatty acids and alkaloids were present in some extracts but not in others, indicating different phytochemical profiles. Phenolics content varied between extracts, and there were more tannins in AEB and HLE. In the in vitro tests, the extracts inhibited the phospholipase and fibrinolytic activities of BaV in the two ratios of venom to extract used. HLE exhibited effective antimicrobial action as it inhibited growth of 11 of the 15 bacteria investigated, including Morganella morganii, the main bacteria described in the oral cavity of snakes. The extracts failed to inhibit the defibrinating activity of BaV, and only the Bothrops antivenom had a significant effect (96.1%) on this activity. Bay-induced hemorrhage was completely inhibited by AEL and AEB when the pre-incubation (venom:extract) protocol was used. When administered orally, as in folk medicine, both AEB and AEL produced significant inhibition of hemorrhagic activity (maximum inhibition 46.5% and 39.2%, respectively). SDS-PAGE and WB of the extracts pre-incubated with BaV showed that the main proteins in the venom had been precipitated by the extracts. None of the four extracts showed cytotoxic effects in the tests carried out with a human fibroblast cell line. Conclusion: In addition to being effective in reducing hemorrhage when administered orally, the extracts displayed a high antimicrobial potential against microorganisms involved in secondary infections at the site of the snakebite. Once the extracts have been tested in accordance with the appropriate regulations, this species could potentially be used to produce a phytomedicine for complementary treatment of the secondary infections due to bacteria that aggravate the local signs and symptoms after snakebite envenomation.

Assessment of the anti-snakebite properties of extracts of Aniba fragrans Ducke (Lauraceae) used in folk medicine as complementary treatment in cases of envenomation by Bothrops atrox

Ethnopharmacological relevance: Extracts of leaves and bark of Aniba fragrans are used as tea (decoction) to treat snakebites in communities in the Brazilian Amazon. The aqueous extract of the leaves of A. fragrans has been proven to be effective against Bothrops venom, but only when pre-incubated with the venom. This study sought to assess the potential of different types of extract of this species to inhibit the biological activities of Bothrops atrox venom (BaV) when used the same way as in folk medicine. The main classes of secondary metabolites and the concentrations of phenolics in the extracts were also determined. Materials and methods: Four types of extract of A. fragrans were prepared: aqueous extract of the leaf (AEL), aqueous extract of the bark (AEB), hydroalcoholic leaf extract (HLE) and extract of the residue from hydro distillation of the leaf (ERHL). The phytochemical profiles of the aqueous extracts were determined using thin layer chromatography (TLC), and the concentrations of phenolics were measured by colorimetric assays. To investigate the potential of the extracts to inhibit the biological activities of BaV, in vitro tests for antiphospholipase and antifibrinolytic activities were performed. In vivo tests for antihemorrhagic and antidefibrinating activities were also carried out, as well as antimicrobial tests for activity against the main bacteria found in the oral cavity of snakes. Interaction between the extracts and the proteins in BaV was assessed by electrophoresis (SDS-PAGE) and Western blot (WB). The cytotoxicity of the extracts was assessed in a strain of MRC-5 human fibroblasts. Results: Terpenoids, flavonoids and condensed and hydrolysable tannins were detected in all the extracts. Metabolites such as coumarins, fatty acids and alkaloids were present in some extracts but not in others, indicating different phytochemical profiles. Phenolics content varied between extracts, and there were more tannins in AEB and HLE. In the in vitro tests, the extracts inhibited the phospholipase and fibrinolytic activities of BaV in the two ratios of venom to extract used. HLE exhibited effective antimicrobial action as it inhibited growth of 11 of the 15 bacteria investigated, including Morganella morganii, the main bacteria described in the oral cavity of snakes. The extracts failed to inhibit the defibrinating activity of BaV, and only the Bothrops antivenom had a significant effect (96.1%) on this activity. Bay-induced hemorrhage was completely inhibited by AEL and AEB when the pre-incubation (venom:extract) protocol was used. When administered orally, as in folk medicine, both AEB and AEL produced significant inhibition of hemorrhagic activity (maximum inhibition 46.5% and 39.2%, respectively). SDS-PAGE and WB of the extracts pre-incubated with BaV showed that the main proteins in the venom had been precipitated by the extracts. None of the four extracts showed cytotoxic effects in the tests carried out with a human fibroblast cell line. Conclusion: In addition to being effective in reducing hemorrhage when administered orally, the extracts displayed a high antimicrobial potential against microorganisms involved in secondary infections at the site of the snakebite. Once the extracts have been tested in accordance with the appropriate regulations, this species could potentially be used to produce a phytomedicine for complementary treatment of the secondary infections due to bacteria that aggravate the local signs and symptoms after snakebite envenomation.

Tuberculose (TB) miliar após o uso de adalimumabe na doença de Crohn (DC): um relato de caso / Miliar tuberculosis after the use of adalimumab in the Crohn's disease: a case report

O adalimumabe é uma imunoglobulina monoclonal humana que bloqueia os efeitos do TNF alfa, mostrando-se efetivo nas doenças inflamatórias intestinais. É relatado um caso de tuberculose (TB) miliar secundária ao uso de adalimumabe. Paciente feminina, 39 anos, com diagnóstico de Doença de Crohn (DC), prova tuberculínica (PPD) prévio não reator e radiografia de tórax prévia sem particularidades estava em uso contínuo de mesalazina, azatioprina e adalimumabe quando apresentou quadro de febre diária e noturna por 15 dias, associada à sudorese e anorexia. Foi internada para investigação, onde se observou nos exames laboratoriais PCR > 90 e VHS de 60mm. Na tomografia computadorizada (TC) de tórax identificou-se pneumopatia bilateral com aspecto de distribuição miliar e linfonodomegalia mediastinal sugerindo processo infeccioso por TB. A pesquisa de BAAR no escarro (três amostras) foi negativa. O diagnóstico final foi de TB miliar. O tratamento instituído foi com rifampicina, isoniazida, pirazinamida e etambutol. A paciente apresentou boa evolução, recebendo alta hospitalar após sete dias de internação. Necessitou de pausa temporária do uso da azatioprina e do adalimumabe, permanecendo apenas com mesalazina para o tratamento de manutenção da DC e retomou a aplicação de adalimumabe dois meses após o início do tratamento. A exclusão da TB pulmonar latente é obrigatória antes do uso de bloqueadores do TNF-α. No presente relato, a paciente apresentava PPD não reator e uma radiografia de tórax prévia sem particularidades, no entanto apresentou a complicação pulmonar oportunista.

Adalimumab, a human monoclonal immunoglobulin that blocks the effects of tumor necrosis factor alpha (TNF-α), is commonly used for treatment of inflammatory bowel diseases. Here, we report a case of miliary tuberculosis (TB), secondary to the use of adalimumab. A 39 year-old female, undergoing treatment for Crohn's disease (CD) with a drug cocktail comprising mesalazine, azathioprine and adalimumab, exhibited fever for 15 consecutive days accompanied by excessive sweating and anorexia. Prior to initiating treatment for CD, the patient's tuberculin skin test (PPD) was negative and chest x-rays were normal. Upon admission to the hospital for febrile symptoms, blood tests showed C-reactive protein levels >90 and erythrocyte sedimentation rate of 60mm. A CT scan revealed bilateral pneumopathy with miliary dissemination and mediastinal lymphadenopathy, all suggestive of active TB infection. The patient was treated with an antibiotic cocktail consisting of rifampicin, isoniazid, pyrazinamide and ethambutol. During treatment with anitbiotics, mesalazine only was prescribed for managing CD symptoms. The TB infection responded well to the antibiotic cocktail and the patient was discharged after seven days of hospitalization. Adalimumab therapy was re-instated two months after initiation of antibiotic treatment. Although latent TB had been excluded before beginning treatment with TNF-α blockers, this case illustrates that physicians should consider the possibility of opportunistic TB infection when administering immunosuppressive drugs.

Connarus favosus Planch.: An inhibitor of the hemorrhagic activity of Bothrops atrox venom and a potential antioxidant and antibacterial agent.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant species Connarus favosus is used in folk medicine in the west of Pará state, Brazil, to treat snakebites. AIM OF THE STUDY: To investigate the potential of the aqueous extract of Connarus favosus (AECf) to inhibit hemorrhagic and phospholipase A2 activities induced by Bothrops atrox venom (BaV) and to determine the antioxidant and antimicrobial potentials of the extract. MATERIALS AND METHODS: AECf was analyzed phytochemically for phenolics (condensed tannins and hydrolyzable tannins) by colorimetry. Antioxidant activity was evaluated by quantitative assays using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Fe(3+)/phenanthroline. Antimicrobial activity was evaluated by the minimal inhibitory concentration test, and cytotoxicity was evaluated using human fibroblast cells (MRC-5). Inhibition of BaV-induced hemorrhagic activity was assessed after oral administration of the extract using pre-treatment, post-treatment and combined (BA plus AECf) treatment protocols. Inhibition of indirect hemolysis caused by phospholipase A2 (PLA2) was investigated in vitro. Interaction between AECf and BaV was investigated by SDS-PAGE electrophoresis, Western blot (Wb) and zymography. RESULTS: The phytochemical profile of AECf revealed ten secondary metabolite classes, and colorimetry showed high total phenolic and total (condensed and hydrolyzable) tannin content. AECf exhibited high antioxidant and antimicrobial potentials. The IC50 for the cytotoxic effect was 51.91 (46.86-57.50)µg/mL. Inhibition of BaV-induced hemorrhagic activity was significant in all the protocols, and inhibition of PLA2 activity was significant with the two highest concentrations. The BaV/AECf mixture produced the same bands as BaV by itself in SDS-PAGE and Wb although the bands were much fainter. Zymography confirmed the proteolytic activity of BaV, but when the venom was pre-incubated with AECf this activity was blocked. CONCLUSION: AECf was effective in reducing BaV-induced hemorrhagic activity when administered by the same route as that used in folk medicine and exhibited antioxidant and antimicrobial potentials.

Complexo de Carney esporádico com tumor testicular e mixoma atrial: relato de caso / Sporadic Carney complex with testicular tumor and atrial myxoma: case report

O complexo de Carney é uma rara forma de neoplasia endócrina múltipla familial autossômica dominante. Está associado à alteração de pigmentação cutânea e mucosa, doença nodular adrenal pigmentosa primária, mixomas cardíacos e cutâneos, adenomas hipofisários funcionantes, neoplasia testicular, adenoma ou carcinoma de tireoide, além de cistos ovarianos. Aproximadamente 70% dos indivíduos diagnosticados com complexo de Carney têm pais afetados, e 30% apresentam forma esporádica. O objetivo deste estudo foi relatar um caso de complexo de Carney esporádico por mixoma cardíaco e tumor testicular. Ressalta-se a importância do caso por sua raridade e sua forma curiosa de apresentação. Homem, 33 anos, manifestou dois quadros de acidentes vasculares cerebrais em 4 meses. Na investigação apresentou pressão arterial elevada com sopro sistólico discreto e fraqueza muscular (força grau 4 em membro superior direito e grau 3 em membro inferior direito). História mórbida de tumor testicular de células de Sertoli há 7 anos com orquiectomia bilateral. História familiar sem particularidades. Na investigação, evidenciaram-se sobrecarga atrial esquerda ao eletrocardiograma e massa tumoral pedunculada compatível com mixoma atrial esquerdo ao ecocardiograma transesofágico. Foi configurada síndrome de Carney pela presença de dois critérios maiores, e o paciente foi submetido à atriotomia esquerda, com ressecção da massa tumoral e confirmação anatomopatológica. A curiosa apresentação do caso recorda que, diante de um caso de acidente vascular cerebral em paciente jovem, a suspeita clínica seja direcionada a causas mais raras. O complexo de Carney esporádico é raro, dificultando ainda mais a elucidação.

Carney complex is a rare form of autosomal dominant multiple endocrine neoplasia familial. Changing skin pigmentation and mucos, primary pigmented nodular adrenal disease, cardiac and cutaneous myxomas, functioning pituitary adenomas, testicular cancer, thyroid adenoma or carcinoma is associated, and ovarian cysts. Approximately 70% of individuals diagnosed with Carney complex have affected parents and 30% have sporadically. The aim of this study was to report a case of sporadic Carney complex due to cardiac myxoma and testicular tumor. We emphasized the importance of the case for its rarity and curious form of presentation. Man, 33, showed two episodes of strokes in 4 months. In research presented high blood pressure with mild systolic murmur and muscle weakness (grade 4 strengthin the right arm and grade 3 in the right lower limb). Morbid history of testicular Sertoli cell tumor 7 years ago with bilateral orchiectomy. No special family history. On investigation, left atrial enlargement and was evident on the electrocardiogram, and transesophageal echocardiogram revealed the presence of pedunculated tumor mass setting a left atrial myxoma. Carney's syndrome was characterized by the existence of two major criteria and patient underwent left atriotomy with resection of the tumor mass and anatomic-pathologic confirmation. The curious case presentation reminded us that before a case of stroke in a young patient should direct the clinical suspicion for rarer causes. The Carney complex sporadic is rare, yet difficult to elucidate.

Virulence factors associated with pediatric shigellosis in Brazilian Amazon.

Shigellosis is a global human health problem and the incidence is highest among children. In the present work, main Shigella virulence genes was examined by PCR and compared to symptoms of pediatric shigellosis. Thirty Shigella isolates were identified from an etiologic study at which 1,339 children ranging 0-10 years old were enrolled. S. flexneri was the most frequent species reaching 60.0% of isolates, 22.2% were S. sonnei, and 6.6% were both S. dysenteriae and S. boydii. All Shigella infected children had diarrhea, but not all were accompanied by others symptoms of bacillary dysentery. Among major virulence genes, the PCR typing revealed ipaBCD was present in all isolates, followed by IpaH7.8, set-1A, set-1B, sen/ospD3, virF, and invE. The pathogenic potential of the ShET-1B subunit was observed in relation to dehydration (P < 0.001) and ShET-2 related to the intestinal injury (P = 0.033) evidenced by the presence of bloody diarrhea. Our results show associations among symptoms of shigellosis and virulence genes of clinical isolates of Shigella spp.

Neutrophils activate macrophages for intracellular killing of Leishmania major through recruitment of TLR4 by neutrophil elastase.

We investigated the role of neutrophil elastase (NE) in interactions between murine inflammatory neutrophils and macrophages infected with the parasite Leishmania major. A blocker peptide specific for NE prevented the neutrophils from inducing microbicidal activity in macrophages. Inflammatory neutrophils from mutant pallid mice were defective in the spontaneous release of NE, failed to induce microbicidal activity in wild-type macrophages, and failed to reduce parasite loads upon transfer in vivo. Conversely, purified NE activated macrophages and induced microbicidal activity dependent on secretion of TNF-alpha. Induction of macrophage microbicidal activity by either neutrophils or purified NE required TLR4 expression by macrophages. Injection of purified NE shortly after infection in vivo reduced the burden of L. major in draining lymph nodes of TLR4-sufficient, but not TLR4-deficient mice. These results indicate that NE plays a previously unrecognized protective role in host responses to L. major infection.

Turnover of neutrophils mediated by Fas ligand drives Leishmania major infection.

Apoptosis mediated by Fas ligand (FasL) initiates inflammation characterized by neutrophilic infiltration. Neutrophils undergo apoptosis and are ingested by macrophages. Clearance of dead neutrophils leads to prostaglandin- and transforming growth factor-beta-dependent replication of Leishmania major in macrophages from susceptible mice. How L. major induces neutrophil turnover in a physiological setting is unknown. We show that BALB/c FasL-sufficient mice are more susceptible to L. major infection than are FasL-deficient mice. FasL promotes the apoptosis of infected resident macrophages and attracts neutrophils. Furthermore, FasL-sufficient neutrophils exacerbate L. major replication in macrophages, whereas FasL-deficient neutrophils induce parasite killing. These contrasting effects are due to delaying apoptosis and the clearance of FasL-deficient neutrophils. The transfer of neutrophils exacerbates infection in FasL-sufficient mice but reduces infection in FasL-deficient mice. Depletion of neutrophils abolishes the susceptibility of FasL-sufficient mice. These data illustrate a deleterious role of the FasL-mediated turnover of neutrophils on L. major infection.