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As vesículas extracelulares (VEs) são nanoparticulas circundadas por uma bicamada lipídica, que transportam lipídios, proteínas, ácidos nucleicos e metabólitos, e podem ser secretadas por diferentes tipos celulares. Os adipócitos são capazes de sintetizar e secretar VEs pequenas, que, uma vez na circulação, podem alcançar diferentes sistemas orgânicos, permitindo a comunicação intercelular. O objetivo deste estudo foi avaliar o diâmetro e a concentração de VEs pequenas no soro de cães com sobrepeso e obesidade, antes e após a perda de peso. Para isso, foram recrutados 19 cães, sendo nove fêmeas e 10 machos castrados, em bom estado geral e com escore de condição corporal (ECC) ≥ 7. A avaliação inicial dos cães incluiu exame físico e testes laboratoriais. Após avaliação inicial, os cães foram alimentados com uma dieta hipocalórica comercial por quatro meses, e, após esse período, os testes laboratoriais foram reavaliados. As VEs pequenas foram isoladas a partir do sangue total, por meio de centrifugações e ultracentrifugações seriadas, e o equipamento NanoSight foi utilizado para a determinação do diâmetro e da concentração das VEs pequenas presentes no soro antes e após a dieta. Houve uma redução de 10% do peso corporal e de 16,5% do ECC dos cães, além da diminuição de 9% do diâmetro e de 31% da concentração das VEs pequenas, após os quatro meses de alimentação com a dieta hipocalórica. Não foram observadas diferenças em relação às análises bioquímicas e entre os resultados de fêmeas e machos, antes e após a perda de peso. Em conclusão, a redução do peso corporal e do acúmulo de gordura foi capaz de modificar as características (diâmetro e concentração) das VEs pequenas, que foram isoladas a partir do soro de cães com sobrepeso e obesidade.

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The aim of this work was to evaluate, in vitro, the dynamics of nuclear and cytoplasmic maturation of bovine oocytes in traditional IVM medium (CT) and supplemented with fullerol (MF50), for 36 hours. The nuclear maturation of CT (n=300) and MF50 (n=270) every 6 hours, stained with Hoechst33342 and cytoplasmic, the mitochondrial distribution of CT (n=197) and MF50 (n=159) at every 12 hours, stained with Mitotracker Orange. At 6 hours, CT oocytes (19%) were in MI (metaphase I), while in MF50 they were in GV (germ vesicle) or GVB (GV breakeage), repeating at 12 hours. At 18 hours, 46.3% were matured in CT, and 20% in MF50. At 24 hours, 43.9% of maturation was observed in the MF50 group, and 63.8% in the CT. At 30 and 36 hours, the maturation pattern was stable, but with the onset of oocyte degeneration. There was a delay in cytoplasmic maturation with 36 hours (P < 0.05) in MF50 (53.9% of mature gametes), compared to CT (69.8%). With immature cytoplasm, they were 10.4% and 31.7% for CT and MF50 (P< 0.05), respectively. It was concluded that fullerol possibly interfered in the expansion of cumulus oophorus cells, as well as delayed the meiotic progression and cytoplasmic maturation.

O objetivo deste estudo foi avaliar, in vitro, a dinâmica da maturação nuclear e citoplasmática de oócitos bovinos em meio MIV tradicional (TC) e suplementado com fulerol (MF50), durante 36 horas. Na maturação nuclear do TC (n=300) e do MF50 (n=270) a cada seis horas, corados com Hoechst 33342, e na citoplasmática, avaliou-se a distribuição mitocondrial do TC (n=197) e do MF50 (n=159) a cada 12 horas, corados com Mitotracker Orange (Life® Technologies). Às seis horas, oócitos do TC (19%) se encontravam em MI (metáfase I), enquanto no MF50 estavam em VG (vesícula germinativa) ou QVG (quebra VG), repetindo com 12 horas. Às 18 horas, 46,3% estavam maturados no TC, e 20% no MF50. Com 24 horas, verificaram-se 43,9% de maturação no grupo MF50, e 63,8% no TC. Às 30 e 36 horas, o padrão de maturação foi estável, mas com início de degeneração oócitária. Houve retardo na maturação citoplasmática com 36 horas (P<0,05) no MF50 (53,9% de gametas maduros), comparado ao TC (69,8%). Com citoplasma imaturo, foram 10,4% e 31,7% para TC e MF50 (P<0,05), respectivamente. Conclui-se que o fulerol possivelmente interferiu na expansão das células do cumulus oophorus, bem como retardou a progressão meiótica e a maturação citoplasmática dos oócitos.

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Nonalcoholic fatty liver disease (NAFLD), characterized by hepatosteatosis and steatohepatitis, is intrinsically related to obesity. Our previous study reported on the anti-obese activity of α,ß-amyrin (AMY), a pentacyclic triterpene isolated from Protium heptaphyllum. This study investigated its ability to prevent fatty liver and the underlying mechanism using the mouse model of NAFLD. NAFLD was induced in male Swiss mice fed a high fat diet (HFD) for 15 weeks. The controls were fed a normal chow diet (ND). The mice were simultaneously treated with AMY at 10 and 20 mg/kg or fenofibrate at 50 mg/kg. Lipid levels along with metabolic and inflammatory parameters were assessed in liver and serum. The liver sections were histologically examined using H&E staining. RT-qPCR and western blotting assays were performed to analyze signaling mechanisms. Mice fed HFD developed severe hepatic steatosis with elevated triglycerides and lipid droplets compared with ND controls. This was associated with a decrease in AMP-activated protein kinase (AMPK) activity, an increase of mechanistic target of rapamycin complex 1 (mTORC1) signaling, and enhanced sterol regulatory element binding protein 1 (SREBP1) expression, which have roles in lipogenesis, inhibition of lipolysis, and inflammatory response. AMY treatment reversed these signaling activities and decreased the severity of hepatic steatosis and inflammatory response, evidenced by serum and liver parameters as well as histological findings. AMY-induced reduction in hepatic steatosis seemed to involve AMPK-mTORC1-SREBP1 signaling pathways, which supported its beneficial role in the prevention and treatment of NAFLD.

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The study evaluated the effect of the supernatant of placental explants from preeclamptic (PE) and normotensive (NT) pregnant women after tissue treatment with or without vitamin D (VD) on oxidative stress and nitric oxide (NO) bioavailability in human umbilical vein endothelial cells (HUVEC). Placental explants were prepared from eight NT and eight PE women, and supernatants were obtained after incubation with or without hydrogen peroxide (H2O2) and/or VD. HUVEC were cultured for 24 h with supernatants, and the following parameters were analyzed in HUVEC cultures: NO, nitrate (NO3-), and nitrite (NO2-) levels, lipid peroxidation, and intracellular reactive oxygen species (ROS). Results showed that the production of NO3-, NO2-, malondialdehyde (MDA), and ROS were significantly higher in HUVEC treated with explant supernatant from PE compared to NT pregnant women, while the supernatant of PE explants treated with VD led to a decrease in these parameters. A significantly high production of NO was detected in HUVEC cultured with control supernatant of NT group, and in cultures treated with supernatant of PE explants treated with VD. Taken together, these results demonstrated that cultures of placental explants from PE women with VD treatment generated a supernatant that decreased oxidative stress and increased the bioavailability of NO in endothelial cells.

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Nonalcoholic fatty liver disease (NAFLD), characterized by hepatosteatosis and steatohepatitis, is intrinsically related to obesity. Our previous study reported on the anti-obese activity of α,β-amyrin (AMY), a pentacyclic triterpene isolated from Protium heptaphyllum. This study investigated its ability to prevent fatty liver and the underlying mechanism using the mouse model of NAFLD. NAFLD was induced in male Swiss mice fed a high fat diet (HFD) for 15 weeks. The controls were fed a normal chow diet (ND). The mice were simultaneously treated with AMY at 10 and 20 mg/kg or fenofibrate at 50 mg/kg. Lipid levels along with metabolic and inflammatory parameters were assessed in liver and serum. The liver sections were histologically examined using H&E staining. RT-qPCR and western blotting assays were performed to analyze signaling mechanisms. Mice fed HFD developed severe hepatic steatosis with elevated triglycerides and lipid droplets compared with ND controls. This was associated with a decrease in AMP-activated protein kinase (AMPK) activity, an increase of mechanistic target of rapamycin complex 1 (mTORC1) signaling, and enhanced sterol regulatory element binding protein 1 (SREBP1) expression, which have roles in lipogenesis, inhibition of lipolysis, and inflammatory response. AMY treatment reversed these signaling activities and decreased the severity of hepatic steatosis and inflammatory response, evidenced by serum and liver parameters as well as histological findings. AMY-induced reduction in hepatic steatosis seemed to involve AMPK-mTORC1-SREBP1 signaling pathways, which supported its beneficial role in the prevention and treatment of NAFLD.

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The study evaluated the effect of the supernatant of placental explants from preeclamptic (PE) and normotensive (NT) pregnant women after tissue treatment with or without vitamin D (VD) on oxidative stress and nitric oxide (NO) bioavailability in human umbilical vein endothelial cells (HUVEC). Placental explants were prepared from eight NT and eight PE women, and supernatants were obtained after incubation with or without hydrogen peroxide (H2O2) and/or VD. HUVEC were cultured for 24 h with supernatants, and the following parameters were analyzed in HUVEC cultures: NO, nitrate (NO3-), and nitrite (NO2-) levels, lipid peroxidation, and intracellular reactive oxygen species (ROS). Results showed that the production of NO3-, NO2-, malondialdehyde (MDA), and ROS were significantly higher in HUVEC treated with explant supernatant from PE compared to NT pregnant women, while the supernatant of PE explants treated with VD led to a decrease in these parameters. A significantly high production of NO was detected in HUVEC cultured with control supernatant of NT group, and in cultures treated with supernatant of PE explants treated with VD. Taken together, these results demonstrated that cultures of placental explants from PE women with VD treatment generated a supernatant that decreased oxidative stress and increased the bioavailability of NO in endothelial cells.

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Raising backyard birds is a common practice in Brazil, mainly in the countryside or suburban areas. However, the level of respiratory pathogens in these animals is unknown. We sampled two hundred chickens from 19 backyard flocks near commercial poultry farms and performed ELISA to Infectious Bronchitis Virus, avian Metapneumovirus, Mycoplasma synoviae and Mycoplasma gallisepticum. We evaluated the association between the predictive ability of ELISA and Hemagglutination-inhibition (HI)by comparing results from eight flocks positive to Mycoplasma gallisepticum on ELISA. Besides, we assessed essential biosecurity measures in the properties (multiple species birds, rodent control, hygienic conditions, and water quality for the bird`s consumption). We could access the vaccination program only on four properties; in three of them, the birds were supposedly vaccinated for IBV. Overall the properties had a poor score for the biosecurity measures, and the seroprevalence in backyard poultry flocks for IBV, a MPV, MS, and MG were respectively 87.5% (14/16), 89.5% (17/19), 100 (19/19) and MG 84.21% (16/19). We found low specificity and predictive value between ELISA and HI in MG analysis and a positive correlation between the presence of clinical symptoms and mean MG titers. Backyard chicken are pathogens reservoirs and pose a risk for the commercial poultry farms in the region, and further efforts of the governmental entities and private sector of poultry production should consider these information to avoid future economic losses.

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Raising backyard birds is a common practice in Brazil, mainly in the countryside or suburban areas. However, the level of respiratory pathogens in these animals is unknown. We sampled two hundred chickens from 19 backyard flocks near commercial poultry farms and performed ELISA to Infectious Bronchitis Virus, avian Metapneumovirus, Mycoplasma synoviae and Mycoplasma gallisepticum. We evaluated the association between the predictive ability of ELISA and Hemagglutination-inhibition (HI)by comparing results from eight flocks positive to Mycoplasma gallisepticum on ELISA. Besides, we assessed essential biosecurity measures in the properties (multiple species birds, rodent control, hygienic conditions, and water quality for the bird`s consumption). We could access the vaccination program only on four properties; in three of them, the birds were supposedly vaccinated for IBV. Overall the properties had a poor score for the biosecurity measures, and the seroprevalence in backyard poultry flocks for IBV, a MPV, MS, and MG were respectively 87.5% (14/16), 89.5% (17/19), 100 (19/19) and MG 84.21% (16/19). We found low specificity and predictive value between ELISA and HI in MG analysis and a positive correlation between the presence of clinical symptoms and mean MG titers. Backyard chicken are pathogens reservoirs and pose a risk for the commercial poultry farms in the region, and further efforts of the governmental entities and private sector of poultry production should consider these information to avoid future economic losses.(AU)

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Motor neuron disease (MND) represents a wide and heterogeneous expanding group of disorders involving the upper or lower motor neurons, mainly represented by amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy. Primary motor neuronopathies are characterized by progressive degenerative loss of anterior horn cell motoneurons (lower motor neurons) or loss of giant pyramidal Betz cells (upper motor neurons). Despite its well-known natural history, pathophysiological and clinical characteristics for the most common MND, atypical clinical presentation and neurodegenerative mechanisms are commonly observed in rare clinical entities, so-called atypical variants of MND-ALS, including flail-leg syndrome, flail-arm syndrome, facial-onset sensory and motor neuronopathy (FOSMN), finger extension weakness and downbeat nystagmus (FEWDON-MND) and long-lasting and juvenile MND-ALS. Herein, we provide a review article presenting clinical, genetic, pathophysiological and neuroimaging findings of atypical variants of MND-ALS in clinical practice.

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Atypical motor neuron disease represents a rare heterogeneous group of neurodegenerative disorders with clinical, genetic and neuroimaging features distinct from those of the classic spinal or bulbar-onset amyotrophic lateral sclerosis (ALS). O'Sullivan-McLeod syndrome represents an extremely rare lower motor neuronopathy with early adult-onset distal amyotrophy and weakness in the upper limbs with asymmetrical involvement. To add to the few case series and epidemiological and genetic studies describing this variant syndrome, our team here presents a series of seven unrelated Brazilian patients with O'Sullivan-McLeod syndrome in a detailed review of their clinical, neuroimaging, laboratory and neurophysiological findings. A male-to-female ratio of 2.5 to 1 and a mean age at onset of 34.3years was observed, with a mean time delay of 6.6years between symptom-onset and a definitive diagnosis. A positive family history was observed in one case, yet whole-exome sequencing results were negative. Neuroimaging studies were unremarkable. All cases presented with chronic denervation restricted to cervical myotomes and normal sensory nerve conduction studies. This case series, one of the largest groups of patients with O'Sullivan-McLeod syndrome reported in the literature, confirms the sporadic nature of the condition and the difficulties faced in arriving at a definite diagnosis, and also expands the age limit in late adult-onset cases.

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PURPOSE: While falls are common in older people, causing significant mortality and morbidity, this phenomenon has not been extensively studied in the Caribbean. This study aimed to compare falls in older and younger people in this setting. METHODS: We conducted a prospective observational study of older trauma patients in Trinidad, comparing older and younger patients sustaining falls. RESULTS: 1432 adult trauma patients were included (1141 aged 18-64 years and 291 aged 65 years and older). Older fallers were more likely to be female (66.7 vs 47.2%; p < 0.001), suffer from multiple pre-existing diseases (24.7 vs 2.4%; p < 0.001) and take multiple medications (16.1 vs 0.8%; p < 0.001). They also sustained more severe injuries and presented with higher acuity than younger fallers. Admission rates were higher among older fallers (29.9 vs 13.1%; p < 0.001). CONCLUSIONS: In our study, older patients who fell were a distinct group from younger falls victims, with unique demographic, clinical and injury related characteristics. Their increased risk of injury within the home, coupled with their propensity for more severe injuries made them a high risk patient group. More research is needed to better understand this patient group and plan specific preventive interventions.

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BACKGROUND: To determine the patterns of alcohol use among households in Trinidad and Tobago (T&T) and to estimate the association between alcohol use and negative psychological, social, or physical events experienced by the household. METHODS: A convenience sample of 1837 households across T&T. We identified bivariate correlates of alcohol use, and heavy episodic drinking using chi-square and t-test analyses and used multivariable logistic regression to estimate adjusted associations between household alcohol use and experiences within the past 12 months adjusted for sociodemographic covariates. RESULTS: One thousand five hundred two households had complete data for all variables (82% response rate). Nearly two thirds (64%) of households included alcohol users; 57% of household that consumed alcohol also reported heavy episodic drinking. Households that reported alcohol consumption were significantly more likely to report illnesses within the households, relationship problems, and behavioral and antisocial problems with children. Among households where a member was employed, those who consumed alcohol were nearly twice as likely (OR = 1.98; 95% confidence interval (CI) 1.03, 3.82) to have a household member call in sick to work and 2.9 times as likely (OR = 2.9; CI 1.19, 7.04) to have a household member suffer work related problems compared with households who reported not consuming alcohol. CONCLUSIONS: Approximately two thirds of households in T&T reported using alcohol. These households were more likely to report psychological, physical, and social problems. These findings would support efforts to enforce current policies, laws, and regulations as well as new strategies to reduce the impact of harmful alcohol consumption on households in T&T.

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Neem (Azadirachta indica) has attracted the attention of researchers worldwide due to its repellent properties and recognized effects on the morphology and physiology of arthropods, including ticks. Therefore, this study aimed to demonstrate the effects of neem seed oil enriched with azadirachtin on salivary glands of Rhipicephalus sanguineus ticks, targets of great veterinary interest because of their ability to transmit pathogens to dogs. For this, R. sanguineus semi-engorged females were subjected to treatment with neem seed oil, with known azadirachtin concentrations (200, 400 and 600ppm). After dissection, salivary glands were collected and evaluated through morphological techniques in light microscopy, confocal scanning laser microscopy and transmission electron microscopy, so that the possible relation between neem action and further impairment in these ectoparasites feed performance could be established. Neem oil demonstrated a clear dose-dependent effect in the analyzed samples. The agranular (type I) and granular acini (types II and III) showed, particularly in individuals treated with the highest concentrations of the product, cells with irregular shape, intense cytoplasmic disorganization and vacuolation, dilation of rough endoplasmic reticulum lumen, besides alterations in mitochondrial intermembrane space. These morphological damages may indicate modifications in salivary glands physiology, demonstrating the harmful effects of compounds present in neem oil on ticks. These results reinforce the potential of neem as an alternative method for controlling R. sanguineus ticks, instead of synthetic acaricides.

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Since its first isolation in 1844, usnic acid [2,6-diacetyl-7,9-dihydroxy-8,9b-dimethyl-1,3(2H,9bH)-dibenzo-furandione] has become the most extensively studied lichen metabolite and one of the few that are commercially available. Lichens belonging to usnic acid-containing genera have been used as crude drugs throughout the world. There are indications of usnic acid being a potentially interesting candidate for such activities as anti-inflammatory, analgesic, healing, antioxidant, antimicrobial, antiprotozoal, antiviral, larvicidal and UV protection. However, some studies reported the liver toxicity and contact allergy. Thus, further studies are needed to establish the efficacy and safety of usnic acid.

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The concern about the harmful effects caused by synthetic pesticides has led to the search for safe and ecological alternatives for pest control. In this context, the neem tree (Azadirachta indica) stands out due to its repellent properties and effects on various arthropods, including ticks. For this reason, this study aimed to demonstrate the potential of neem as a control method for Rhipicephalus sanguineus ticks, important vectors of diseases in the veterinary point of view. For this, R. sanguineus semi-engorged females were subjected to treatment with neem seed oil enriched with azadirachtin, its main compound, and ovaries were assessed by means of morphological techniques in conventional light microscopy, confocal laser scanning microscopy, and transmission electron microscopy. Neem demonstrated a clear dose-dependent effect in the analyzed samples. The observed oocytes presented, especially in the groups treated with higher concentrations of neem oil, obvious signs of cytoplasmic disorganization, cellular vacuolization, nuclear and nucleolar irregularity, dilation in mitochondrial cristae, alterations in mitochondrial matrix, and swelling of rough endoplasmic reticulum. Intracellular microorganisms were observed in all analyzed groups, reinforcing the importance of ticks in the transmission of pathogens. A greater quantity of microorganisms was noted as the concentration of neem increased, indicating that the damaged oocytes may be more susceptible for their development. Such morphological alterations may promote future damages in reproductive performance of these animals and demonstrate the potential of neem seed oil for the control of R. sanguineus ticks, paving the way for new, cheaper, and safer methods of control.

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OBJECTIVE: To determine the distribution of alcohol use among households (HHs) in Trinidad and Tobago (T&T) and, whether the HHs where alcohol was used were more likely to suffer negative psychological, social or physical events. DESIGN AND METHODS: A cross-sectional convenience sample of HHs was surveyed from a random sample of enumeration districts (ED). The interviewer-applied, field pre-tested de novo questionnaire had 5 domains and was developed over 1 1/2 years after literature review and consultation. RESULTS: 1695 HHs (from 53 EDs) responded with a response rate (RR) of 92%. Sixty-two (62%) percent of HHs consumed alcohol, distributed with 1-2 users (46%), 3-4+ users (16%). Viewpoints and experiences about alcohol included: 'alcohol consumption at family gatherings is a normal occurrence' (70%). 29% of HHs consumed alcohol in the presence of children. HHs that consumed alcohol were significantly more likely to report in the last 12 months HHs members falling sick, experiencing lifestyle related illnesses, having relationship problems between partners, having strained relationships within the HH, HH members calling in sick to work, behavioural problems of children at home, anti-social problems of children at home/school and violent behaviour by a member of the HH (p

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OBJECTIVE: This study set out to determine what proportion of Trinidad and Tobago (T&T) households (HHs) were willing to support changes in specific policies, laws and regulations in a national alcohol campaign. DESIGN AND METHODS: A cross-sectional convenience sample of HHs were surveyed from a random sample of enumeration districts (ED) in T&T. The interviewer-applied, field pre-tested de novo questionnaire had 5 domains and was developed over 1 1/2 years after extensive literature review and consultation. Many of the WHO 'best buys' were included. RESULTS: 1695 HHs (from 53 ED) responded from a total of 1837 HHs approached, a response rate (RR) of 92%. In a national campaign the following proportions of HHs would support: setting the legal age for drinking at 21 years (82.4%); restricting (73.1%), banning (54.4%) alcohol advertising on TV and other media; banning all alcohol advertising at sports and cultural events (64.8%); banning radio stations playing songs with reference to alcohol use (71.3%); holding sellers of alcohol responsible for the amount of alcohol sold (79.5%); advocating that proof of age to be shown by persons buying alcohol (87.4%); placing more prominent warning labels on products displaying alcohol content (87.2%); placing more prominent warning labels on products showing harmful effects (88.5% ); increasing taxes on alcohol sales (87.7% ). CONCLUSIONS: HHs in T&T were willing to support changes in policies around alcohol, including many of the policies shown by the WHO to be effective in reducing the harmful consumption of alcohol.

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Currently, the necessity of controlling infestation by ticks, especially by Rhipicephalus sanguineus, has led researchers and public health managers around the world to search for new and more efficient control methods. This way, we can highlight neem (Azadirachta indica A. Juss) leaf, bark, and seed extracts, which have been very effective on tick control, and moreover causing less damage to the environment and to the host. This study showed the potential of neem as a control method for R. sanguineus through morphological and morphometric evaluation of the integument and synganglion of females, in semiengorged stage. To attain this, routine techniques of optical microscopy, scanning electron microscopy and morphometry of the cuticle and subcuticle of the integument were applied. Expressive morphological alterations were observed in both organs, presenting a dose-dependent effect. Integument epithelial cells and nerve cells of the synganglion showed signs of cell vacuolation, dilated intercellular boundaries, and cellular disorganization, alterations not previously reported in studies with neem. In addition, variations in subcuticle thickness were also observed. In general, the effects of neem are multiple, and affect the morphology and physiology of target animals in various ways. The results presented in this work are the first evidence of its effects in the coating and nervous system of ticks, thus allowing an indication of neem aqueous extracts as a potential control method of the brown dog tick and opening new perspectives on acaricide use.

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Pentavalent antimonials are the first choice for the treatment of human leishmaniasis. However in rural areas the traditional plants may be preferred for the treatment of lesions. In recent years a number of papers are published related to the natural products especially plant derivative with infectious diseases. The present work was undertaken to evaluate the antileishmanial activity of Pterodon pubescens which is a native tree widely distributed over the central region of Brazil and used in folk medicine as wine infusions to treat inflammatory disease. The phytochemical screening and the biological essay of ethanolic extract of Pterodon pudescens (PPE) leaves at the concentrations of 150, 300, 450, 600 µg/ml were tested in vitro in Leishmania amazonensis-infected macrophages to support its traditional medicinal use as a leishmaniasis remedy. Phytochemical screening of PPE has shown the presence of catechemical tannins, steroids, triterpenoids and flavonoids. The biological test suggests that PPE were found to control parasite burden of cell cultures in dose-dependent manner. These findings highlight the fact that the apparent potency of Pterodon pudescens compounds, together with their widely distribution over Latin America and Brazil, may represent a promising antileishmanial agent.

Antimoniais pentavalentes são a primeira escolha para o tratamento das leishmanioses humanas. No entanto, no interior brasileiro plantas tradicionais são usadas para o tratamento dessas lesões. De fato, recentes trabalhos tem relatado o potencial terapêutico de produtos naturais, especialmente derivados de plantas. Neste estudo avaliamos a atividade leishmanicida de Pterodon pubescens, uma árvore nativa, distribuída pela região central brasileira e usada em infusões para tratamento de inflamações. Foi realizada a análise fitoquímica e o ensaio in vitro em macrófagos infectados com Leishmania amazonensis em concentrações de 150, 300, 450, 600 µg/ml do extrato etanólico de folhas de Pterodon pudescens (PPE) para comprovar o uso tradicional desta planta como terapia para as leishmanioses. Os testes fitoquímicos indicaram a presença de taninos catequímicos, flavonas, esteroides, triterpenoides, flavonoides e xantonas. Os ensaios biológicos revelaram que o PPE foi capaz de controlar a carga parasitária em macrófagos de maneira dose dependente. Estes resultados corroboram com o potencial terapêutico de compostos de Pterodon pudescens e, junto com sua ampla distribuição no Brasil, podem representar promissor agente leishmanicida.

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BACKGROUND: Worldwide, dengue is the most prevalent human arbovirus disease. Dengue infection may cause a range of clinical manifestations from self-limiting febrile illness through to a life-threatening syndrome accompanied by both bleeding and shock. Thrombocytopenia is frequently observed in mild and severe disease; however, the mechanisms involved in DENV-induced platelet activation and thrombocytopenia are incompletely understood. PATIENTS AND METHODS: Freshly isolated platelets from patients with dengue were evaluated for markers of activation, mitochondrial alteration and activation of cell death pathways. In parallel, we examined direct DENV-induced activation and apoptosis of platelets obtained from healthy subjects. RESULTS: We found that platelets from DENV-infected patients exhibited increased activation by comparison to control subjects. Moreover, platelets from DENV-infected patients exhibited classic signs of the intrinsic pathway of apoptosis that include increased surface phosphatidylserine exposure, mitochondrial depolarization and activation of caspase-9 and -3. Indeed, thrombocytopenia was shown to strongly associate with enhanced platelet activation and cell death in DENV-infected patients. Platelet activation, mitochondrial dysfunction and caspase-dependent phosphatidylserine exposure on platelets were also observed when platelets from healthy subjects were directly exposed to DENV in vitro. DENV-induced platelet activation was shown to occur through mechanisms largely dependent on DC-SIGN. CONCLUSIONS: Together our results demonstrate that platelets from patients with dengue present signs of activation, mitochondrial dysfunction and activation of the apoptosis caspase cascade, which may contribute to the development of thrombocytopenia in patients with dengue. Our results also suggest the involvement of DC-SIGN as a critical receptor in DENV-dependent platelet activation.

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