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1,2,3-Triazole is one of the most flexible chemical scaffolds broadly used in various fields. Here, we report the antileishmanial activity of 1,2,3-triazole derivatives, the ultrastructural alterations induced by their treatment, and the nitric oxide (NO) modulation effect on their efficacy against Leishmania amazonensis in vitro infection. After the screening of eleven compounds, compound 4 exhibited better results against L. amazonensis promastigotes (IC50 = 15.52 ± 3.782 μM) and intracellular amastigotes (IC50 = 4.10 ± 1.136 μM), 50% cytotoxicity concentration at 84.01 ± 3.064 μM against BALB/c peritoneal macrophages, and 20.49-fold selectivity for the parasite over the cells. Compound 4 induced ultrastructural mitochondrial alterations and lipid inclusions in L. amazonensis promastigotes, upregulated tumor necrosis factor α, interleukin (IL)-1β, IL-6, IL-12, and IL-10 messenger RNA expressions, and enhanced the NO production, verified by nitrite (p = 0.0095) and inducible nitric oxide synthase expression (p = 0.0049) quantification, which played an important role in its activity against intramacrophagic L. amazonensis. In silico prediction in association with antileishmanial activity results showed compound 4 as a hit compound with promising potential for further studies of new leishmaniasis treatment options.

Euterpe oleracea (açaí) fruit has approximately 15% pulp, which is partly edible and commercialized, and 85% seeds. Although açaí seeds are rich in catechins—polyphenolic compounds with antioxidant, anti-inflammatory, and antitumor effects—almost 935,000 tons/year of seeds are discarded as industrial waste. This work evaluated the antitumor properties of E. oleracea in vitro and in vivo in a solid Ehrlich tumor in mice. The seed extract presented 86.26 ± 0.189 mg of catechin/g of extract. The palm and pulp extracts did not exhibit in vitro antitumor activity, while the fruit and seed extracts showed cytotoxic effects on the LNCaP prostate cancer cell line, inducing mitochondrial and nuclear alterations. Oral treatments were performed daily at 100, 200, and 400 mg/kg of E. oleracea seed extract. The tumor development and histology were evaluated, along with immunological and toxicological parameters. Treatment at 400 mg/kg reduced the tumor size, nuclear pleomorphism, and mitosis figures, increasing tumor necrosis. Treated groups showed cellularity of lymphoid organs comparable to the untreated group, suggesting less infiltration in the lymph node and spleen and preservation of the bone marrow. The highest doses reduced IL-6 and induced IFN-γ, suggesting antitumor and immunomodulatory effects. Thus, açaí seeds can be an important source of compounds with antitumor and immunoprotective properties.

The aim of this review was to identify anti-inflammatory and antioxidant therapeutic agents and their effects on patients with chagasic myocarditis. A systematic review of the MEDLINE, EMBASE, WEB OF SCIENCE, SCOPUS, LILACS and CENTRAL databases (Cochrane Library) was carried out without language restrictions. The descriptors used were: ‘Chagas cardiomyopathy’, ‘treatment’, ‘Chagas disease’, ‘anti-inflammatory agents’, ‘Trypanosoma cruzi’ and ‘antioxidants’. A total of 4,138 articles was identified, six of which were selected for data extraction. Of these, four were related to antioxidant therapy with vitamins C and E supplementation, and two using anti-inflammatory therapy. The studies were carried out in Brazil and were published between 2002 and 2017. Antioxidant therapy with vitamin C and E supplementation increases the activity of antioxidant enzymes and reduces the oxidative markers. There is no conclusive data to support the use of vitamin supplementation and anti-inflammatory therapy in the treatment of chagasic cardiomyopathy. However, the studies indicate the possibility of vitamin supplementation as a new approach to the treatment of Chagas disease. Antioxidant therapy was proven to be a viable alternative for attenuating the oxidative damage caused by chronic chagasic cardiopathy, leading to a better prognosis for patients.

A serological, molecular and histopathological study was carried out in order to investigate occurrences of Toxoplasma gondii in pigs slaughtered with and without inspection service. Serum samples were collected from 60 pigs to detect anti-T. gondii antibody by indirect fluorescent antibody (IFAT). Tongue, masseter and diaphragm fragments were also collected for parasite DNA detection by means of the polymerase chain reaction (PCR) and histopathological analysis. The serological results showed that 77% (44/60) of the pigs were positive. Regarding PCR, 66.67% (40/60) were positive for T. gondii. Among the tissues evaluated, the diaphragm was the one with the highest frequency of positivity (40%; 24/60), followed by the masseter (38.33%; 23/60) and tongue (33.3%; 20/60). Histopathological changes were only observed in the diaphragm, which presented inflammatory infiltrates of lymphohistiocytic and neutrophilic types. These results not only show the potential threat of T. gondii to human health, but also demonstrate the dynamic epidemiological situation of toxoplasmosis in pigs in the city of São Luís, providing support for food security regarding pigs and for T. gondii control programs in Brazil. Resumo Realizou-se um estudo sorológico, molecular e histopatológico com o objetivo de verificar a ocorrência de Toxoplasma gondii em suínos abatidos com e sem serviço de inspeção. Foram coletados soros de 60 suínos para a pesquisa de anticorpos anti-T. gondii pela reação de imunofluorescência indireta (RIFI). Também foram coletados fragmentos de língua, masseter e diafragma para a detecção do DNA do parasito por meio da reação em cadeia da polimerase (PCR) e análise histopatológica. A análise sorológica demonstrou que 77% (44/60) dos suínos apresentaram anticorpos anti-T. gondii. Com relação ao PCR, 66,67% (40/60) foram positivos para T. gondii. Dentre os tecidos avaliados, o diafragma foi o que obteve maior frequência de positividade (40%; 24/60), seguidos de masseter (38,33%; 23/60) e língua (33,3%; 20/60). Alterações histopatológicas foram observadas apenas no diafragma, que apresentou infiltrado inflamatório do tipo linfohistiocitário e neutrofílico. Esses resultados não evidenciam apenas a ameaça potencial de T. gondii à saúde humana, mas também demonstram a dinâmica situação epidemiológica da toxoplasmose em suínos na região da cidade de São Luís, fornecendo suporte para a segurança alimentar de suínos e programas de controle de T. gondii no país.

1,2,3-Triazole is one of the most flexible chemical scaffolds broadly used in various fields. Here, we report the antileishmanial activity of 1,2,3-triazole derivatives, the ultrastructural alterations induced by their treatment, and the nitric oxide (NO) modulation effect on their efficacy against

Açaí berry is a fruit from the tree commonly known as açaízeiro (Euterpe oleracea Mart.) originated from the Amazonian region and widely consumed in Brazil. There are several reports of the anti-inflammatory activity of its pulp and few data about the seed’s potential in inflammation control. This work aimed to evaluate the effect of catechin-rich açaí extract on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and carrageenan-induced paw edema. The treatment with E. oleracea ethyl acetate extract (EO-ACET) was used in an in vitro model performed with macrophages stimulated by LPS, in which pro-inflammatory markers were evaluated, and in an in vivo model of acute inflammation, in which edema inhibition was evaluated. EO-ACET showed an absence of endotoxins, and did not display cytotoxic effects in RAW 264.7 cells. LPS-stimulated cells treated with EO-ACET displayed low levels of nitrite and interleukins (IL’s), IL-1β, IL-6 and IL-12, when compared to untreated cells. EO-ACET treatment was able to inhibit carrageenan-induced paw edema at 500 and 1000 mg/kg, in which no acute inflammatory reaction or low mast cell counts were observed by histology at the site of inoculation of λ-carrageenan. These findings provide more evidence to support further studies with E. oleracea seeds for the treatment of inflammation.

Syzygium aromaticum has a diversity of biological activities due to the chemical compounds found in its plant products such as total phenolic compounds and flavonoids. The present work describes the chemical analysis and antimicrobial, antioxidant, and antitrypanosomal activity of the essential oil of S. aromaticum. Eugenol (53.23%) as the major compound was verified by gas chromatography-mass spectrometry. S. aromaticum essential oil was more effective against S. aureus (MIC 50 μg/mL) than eugenol (MIC 250 μg/mL). Eugenol presented higher antioxidant activity than S. aromaticum essential oil, with an EC50 of 12.66 and 78.98 µg/mL, respectively. S. aromaticum essential oil and eugenol exhibited Trypanosoma cruzi inhibitory activity, with IC50 of 28.68 ± 1.073 and 31.97 ± 1.061 μg/mL against epimastigotes and IC50 of 64.51 ± 1.658 and 45.73 ± 1.252 μg/mL against intracellular amastigotes, respectively. Both compounds presented low cytotoxicity, with S. aromaticum essential oil displaying 15.5-fold greater selectivity for the parasite than the cells. Nitrite levels in T. cruzi-stimulated cells were reduced by essential oil (47.01%; p = 0.002) and eugenol (48.05%; p = 0.003) treatment. The trypanocidal activity of S. aromaticum essential oil showed that it is reasonable to use it in future research in the search for new therapeutic alternatives for trypanosomiasis.

Aniba rosaeodora is one of the most widely used plants in the perfumery industry, being used as medicinal plant in the Brazilian Amazon. This work aimed to evaluate the chemical composition of A. rosaeodora essential oil and its biological activities. A. rosaeodora essential oil presented linalool (93.60%) as its major compound. The A. rosaeodora essential oil and linalool showed activity against all the bacteria strains tested, standard strains and marine environment bacteria, with the lower minimum inhibitory concentration being observed for S. aureus. An efficient antioxidant activity of A. rosaeodora essential oil and linalool (EC50: 15.46 and 6.78 &micro, g/mL, respectively) was evidenced by the inhibition of the 2,2-azinobis- (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical. The antitrypanosomal activity of A. rosaeodora essential oil and linalool was observed at high concentrations against epimatigote forms (inhibitory concentration for 50% of parasites (IC50): 150.5 &plusmn, 1.08 and 198.6 &plusmn, 1.12 &micro, g/mL, respectively), and even higher against intracellular amastigotes of T. cruzi (IC50: 911.6 &plusmn, 1.15 and 249.6 &plusmn, 1.18 &micro, g/mL, respectively). Both A. rosaeodora essential oil and linalool did not exhibit a cytotoxic effect in BALB/c peritoneal macrophages, and both reduced nitrite levels in unstimulated cells revealing a potential effect in NO production. These data revealed the pharmacological potential of A. rosaeodora essential oil and linalool, encouraging further studies.

The current standard treatment for leishmaniasis has remained the same for over 100 years, despite inducing several adverse effects and increasing cases of resistance. In this study we evaluated the in vitro antileishmanial activity of 1,4-disubstituted-1,2,3 triazole compounds and carried out in silico predictive study of their pharmacokinetic and toxicity properties. Ten compounds were analyzed, with compound 6 notably presenting IC50: 14.64 &plusmn, 4.392 &micro, M against promastigotes, IC50: 17.78 &plusmn, 3.257 &micro, M against intracellular amastigotes, CC50: 547.88 &plusmn, 3.256 &micro, M against BALB/c peritoneal macrophages, and 30.81-fold selectivity for the parasite over the cells. It also resulted in a remarkable decrease in all the parameters of in vitro infection. Ultrastructural analysis revealed lipid corpuscles, a nucleus with discontinuity of the nuclear membrane, a change in nuclear chromatin, and kinetoplast swelling with breakdown of the mitochondrial cristae and electron-density loss induced by 1,4-disubstituted-1,2,3-triazole treatment. In addition, compound 6 enhanced 2.3-fold the nitrite levels in the Leishmania-stimulated macrophages. In silico pharmacokinetic prediction of compound 6 revealed that it is not recommended for topical formulation cutaneous leishmaniasis treatment, however the other properties exhibited results that were similar or even better than miltefosine, making it a good candidate for further in vivo studies against Leishmania parasites.

Leishmaniasis is a complex of diseases caused by protozoa of the genus Leishmania and affects millions of people around the world. Several species of plants are used by traditional communities for the treatment of this disease, among which is Carapa guianensis Aubl. (Meliaceae), popularly known as andiroba. The objective of the present work was to conduct a chemical study of C. guianensis seed oil and its limonoid-rich fractions, with the aim of identifying its secondary metabolites, particularly the limonoids, in addition to investigating its anti-Leishmania potential. The chemical analyses of the C. guianensis seed oil and fractions were obtained by electrospray ionization mass spectrometry (ESI-MS). The cytotoxic activity was tested against peritoneal macrophages, and antileishmanial activity was evaluated against promastigotes and intracellular amastigotes of Leishmania amazonensis. All the C. guianensis seed oil samples analyzed exhibited the same pattern of fatty acids, while the limonoids 7-deacetoxy-7-hydroxygedunin, deacetyldihydrogedunin, deoxygedunin, andirobin, gedunin, 11β-hydroxygedunin, 17-glycolyldeoxygedunin, 6α-acetoxygedunin, and 6α,11β-diacetoxygedunin were identified in the limonoid-rich fractions of the oil. The C. guianensis seed oil did not exhibit antileishmanial activity, and cytotoxicity was higher than 1000 μg/mL. Three limonoid-rich oil fractions demonstrated activity against promastigotes (IC50 of 10.53±0.050, 25.3±0.057, and 56.9±0.043μg/mL) and intracellular amastigotes (IC50 of 27.31±0.091, 78.42±0.086, and 352.2±0.145 μg/mL) of L. amazonensis, as well as cytotoxicity against peritoneal macrophages (CC50 of 78.55±1.406, 139.0±1.523, and 607.7±1.217 μg/mL). The anti-Leishmania activity of the limonoid-rich fractions of C. guianensis can be attributed to the limonoids 11β-hydroxygedunin and 6α,11β-diacetoxygedunin detected in the chemical analysis.

The complications involved in current leishmaniasis treatment indicate the urgent need for new therapeutic strategies. In research into new compounds from natural products that possess antileishmanial activity, Ocimum canum species from the Brazilian Amazon have been little studied. Therefore, the present study aimed to evaluate the chemical composition and antileishmanial activity of O. canum essential oil and the ultrastructural alterations it induced in Leishmania amazonensis. Preliminary antimicrobial, antitrypanosomal and in vitro cytotoxic activity were also analyzed. Chemical constituents assessed by gas chromatography-mass spectrometry analyzes identified thymol (42.15%), p-cymene (21.17%) and γ-terpinene (19.81%) as major compounds. The O. canum essential oil displayed antimicrobial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Antiprotozoal activity showed IC50 of 17.4 μg/mL and 13.1 μg/mL for L. amazonensis promastigote and intracellular amastigote, respectively, and 60.0 μg/mL for Trypanosoma cruzi. Selectivity index showed selectivity for L. amazonensis pormastigote (18.1) and amastigote intracellular (24.0), but not for T. cruzi (5.2) when compared with cytotoxicity against BALB/c peritoneal macrophages (CC50 315.3 μg/mL). The ultrastructural alterations observed in L. amazonensis treated with O. canum essential oil were autophagosome-like structures, which were multivesicular and had lipid bodies, discontinuity of the nucleus membrane and exocytic activity by the flagellar pocket. The results evidenced the rich chemical composition of O. canum essential oil, as well its antileishmanial activity and high selectivity index for these parasites, although not for cells, revealing its potential for further in vivo studies.

Species of the Vernonia genius are widely distributed across the world. In traditional communities, they are commonly used in popular medicine for the treatment of inflammatory diseases. The objective of the present study was to evaluate the anti-inflammatory activity of Vernonia polysphaera Baker hydroalcoholic extract. A λ-carrageenan-induced paw edema and peritonitis model was established in BALB/c mice. The in vitro activity of the extract was measured on LPS-stimulated RAW 264.7 cells. There was no toxic effect on mice or on the cells treated with the extract. Animals treated with V. polysphaera extract demonstrated inhibition of paw edema in comparison with the untreated animals at all the analyzed doses. In peritonitis, treatment with the extract at a dose of 500 mg/kg resulted in a lower total leukocyte count in the peritoneal fluid and blood and lower levels of IL-1β, IL-6, TNF-α and PGE-2 than the control group. Cells treated with 50 and 100 μg/mL of the extract exhibited lower levels of nitrite and pro-inflammatory cytokine production and lower COX-2, NF-κB expression. The V. polysphaera extract demonstrated an anti-inflammatory effect, interfering with cell migration, reducing pro-inflammatory cytokine levels and COX-2 expression and consequent interference with PGE-2, as well as inhibiting NF-κB transcription.

Objective The current treatment of leishmaniasis induces strong side effects and increasing numbers of cases of resistance to reference drugs have been reported. The discovery of the therapeutic properties of active substances in plant extracts represents an interesting field of research into a more efficient treatment against leishmaniasis. Morinda citrifolia, commonly known as noni, has demonstrated promising results as antileishmanial and immunomodulator. Thus, the aim of this work was to evaluate activity against axenic amastigote and hydrogen peroxide induction capacity by M. citrifolia fruit juice. Results Phytochemical screening identified anthraquinones, flavonoids, alkaloids, terpenoids, steroids, saponins, coumarins, phenolic compounds, tannins, anthocyanidins and chalcones. Noni juice exhibited dose-dependent activity and an IC50 of 240.1 µg/mL for axenic amastigotes. An absence of endotoxins was observed at the concentrations analyzed, while no cytotoxic effects were identified. Noni juice induced hydrogen peroxide production in BALB/c peritoneal macrophages but not in macrophages infected with Leishmania amazonensis. M. citrifolia fruit juice exhibited antileishmanial activity against L. amazonensis axenic amastigotes and activated macrophages by hydrogen peroxide induction, asserting its potential for further research into new forms of leishmaniasis treatment.

Feline immunodeficiency virus (FIV) is a retrovirus of the genus Lentivirus that is distributed worldwide, with prevalence rates varying between 2.5% and 44%. FIV causes immunosuppression, with depletion of TCD4+ lymphocytes, with the majority of clinical signs caused by secondary and opportunistic infections. Blood samples were collected from nine domestic cats (Felis catus domesticus) from the city of Sao Luis, Maranhao State, Brazil. All samples were positive in a rapid immunochromatographic test (SNAP® Combo FeLV Ag/FIV Antibody Test) and in a polymerase chain reaction (PCR) assay. Phylogenetic analysis showed that six samples clustered within subtype B, one within subtype A, and two did not cluster with any known subtype. Five unique haplotypes (Hap-1, Hap-2, Hap-3, Hap-5 and Hap-6) and a shared haplotype (Hap-4) were found, this last one being the most frequent. This is the first report on the genetic diversity of FIV in the city of Sao Luis and the first report of subtype A in Brazil. New variations of the virus are also reported.

Morinda citrifolia, also known as noni, is commonly used in popular medicine in Brazil. Many parts of the noni tree are utilized in such practices, including the roots, leaves and seeds. Through a search of online databases, the present article reviews 92 research studies on the biological actions of M. citrifolia. The paper will discuss the therapeutic effects of noni and its compounds in a variety of forms of presentation, focusing on studies that support its traditional use. A large and diverse number of properties were identified, which were divided into immunostimulatory, antitumor, antidiabetic, anti-obesity, antibacterial and anti-septic, antifungal, antiviral, leishmanicidal, antiinflammatory, antinociceptive and analgesic, antioxidant, neuroprotective, wound healing, antiallergic, antiangiogenic, antiemetic and anti-nausea, anti-gastric ulcer and oesophagitis, anthelmintic, antimutagenic, antipsychotic, anxiolytic, photoprotective, anti-wrinkle and periodontal tissue regeneration activities. While it was concluded that although M. citrifolia is widely and successfully used for the treatment or prevention of various diseases, it should be consumed carefully, and only after exhaustive studies into its chemical constituents and mechanisms of action, both in in vitro and in vivo models, as well as clinical trials. Copyright © 2017 John Wiley & Sons, Ltd.

Schistosomiasis is a neglected disease that affects millions of people around the world, being common in the state of Maranhão. A total of 225 rodents of the Holochilus sciureus species from the Western Lowland Maranhão were studied, of which 144 animals (64%) exhibited Schistosoma eggs in their feces samples. Macroscopic lesions characterized as well-defined whitish areas on the liver and spleen surfaces were observed. Histopathological examination revealed multifocal granulomas in the esophagus, liver, spleen, pancreas and duodenum, with structures compatible with Schistosoma mansoni eggs, as well as severe hepatic micro-vacuolar degeneration, multifocal and coalescent, with proliferation of random bile ducts and associated epithelial hyperplasia to areas of fibrosis. Adult forms of the parasite were observed in the blood vessels of the portal space. The lungs exhibited moderate and diffuse interstitial pneumonia with intralesional S. mansoni eggs. In the kidneys, hyaline cylinders were observed in the pelvis and diffuse hemorrhage. In conclusion, H. sciureus displays a pathological picture similar to human being. This rodent plays a role as sentinel in Baixada Maranhense.

The resistance mechanisms of bacteria and protozoans have evidenced the need of discover new compounds with potential pharmaceutical activity against pathogenic microorganisms. Medicinal plants have been for centuries a promising alternative as sources of new drugs. The objective of this work was to evaluate the chemical composition, antimicrobial and antileishmanial activities of Cinnamomum zeylanicum, Origanum vulgare, and Curcuma longa essential oils. Chemical analysis was performed by gas chromatography-mass spectrometry. Antimicrobial activity was performed by disk diffusion and minimum inhibitory concentration (MIC) test. Antileishmanial activity was performed against antipromastigote and intracellular amastigote of Leishmania amazonensis. Cytotoxic and nitrite production were realized in BALB/c peritoneal macrophages. The major compounds of the essential oils were cinnamic aldehyde (46.30%) in C. zeylanicum, cis-p-menth-2-en-1-ol (33.88%) and linalyl acetate (13.90%) in O. vulgare, and turmerone (55.43%) in C. longa. The MIC showed significant antimicrobial activity of C. longa essential oil against S. aureus (83.3 ± 14.43 µg/mL). Antipromastigote activity showed IC50 values >500 µg/mL to C. zeylanicum, 308.4 ± 1.402 µg/mL to O. vulgare, and 405.5 ± 1.119 µg/mL to C. longa essential oil. Activity against intracellular amastigote of L. amazonensis showed IC50 of 63.3 ± 1.369 µg/mL and cytotoxic was not observed, resulting in selectivity index higher than 15.79 to parasite. C. longa essential oil decreased nitrite production in peritoneal macrophages, but not in Leishmania-infected cells. The chemical composition of the three essential oils is directly associated to its potential biological action, as the antimicrobial activity. C. longa presented a potent antileishmanial activity against promastigote and intracellular amastigote of L. amazonensis, although this activity is not linked to nitric oxide, since C. longa essential oil inhibits its production.

The objective of this prospection was to study the use of molecular markers in turtles. For this, information was obtained on scientific articles in Science Direct, Web of Science and SCOPUS databases as well as on patent documents in INPI, WIPO and EPO databases. Thus, a large number of published studies involving molecular markers were found, although this number is lower when associated with use in turtles. Regarding patents, only one was filed (in 2011), indicating research opportunities in this area.

Several axonal growth inhibitors have already been identified following spinal cord injury, the most known being myelin-derived proteins, such as Nogo-A. The present study aimed to correlate the formation of glial scar with the beginning of growth inhibitor, Nogo-A, release in rats previously submitted to compressive spinal cord injury. For this, 12 male and female Wistar rats (250 ± 50g) were divided into 3 groups of 4 animals each, according to the animals' euthanasia time after spinal cord injury (G3 - three days; G5 - five days; G7 - seven days). Spinal cord injuries were induced by means of dorsal laminectomy of the T10 vertebra and epidural compression. Histopathological evaluation and immunoreactivity of the Nogo-A axonal growth inhibitor were performed. It was observed that there was the release of the axonal inhibitor Nogo-A after 24h after the occurrence of spinal cord injury, and that the glial scar must be maintained, in this time interval, in order to guarantee the rebalancing of the post-trauma environment. Thus, it is suggested that the glial scar should be maintained in the acute phase of the lesion, guaranteeing its numerous benefits for the rebalancing of the post-injured environment and, after 24 hours, when the release of the studied axonal growth inhibitor begins, it should be removed. Ya se han identificado varios inhibidores del crecimiento axonal después de una lesión de la médula espinal, siendo los más conocidos proteínas derivadas de la mielina, como Nogo-A. El presente estudio tuvo como objetivo correlacionar la formación de cicatrices gliales con el comienzo de la liberación del inhibidor del crecimiento. Axonal Nogo-A en ratas previamente sometidas a lesión medular por compresión. Para ello, se dividieron 12 ratas Wistar macho y hembra (250 ± 50g) en 3 grupos de 4 animales cada uno, según el tiempo de eutanasia de los animales tras la lesión medular (G3 - tres días; G5 - cinco días; G7 - siete días). Las lesiones medulares se indujeron mediante laminectomía dorsal de la vértebra T10 y compresión epidural. Se realizó la evaluación histopatológica y la inmunorreactividad del inhibidor del crecimiento axonal Nogo-A. Se observó que hubo liberación del inhibidor axonal Nogo-A a las 24 h de ocurrida la lesión medular, y que la cicatriz glial debe mantenerse, en este intervalo de tiempo, para garantizar el reequilibrio del postraumatismo. ambiente. Así, se sugiere que la cicatriz glial se mantenga en la fase aguda de la lesión, garantizando sus numerosos beneficios para el reequilibrio del ambiente post-lesionado y, a las 24 horas, cuando comience la liberación del inhibidor del crecimiento axonal estudiado, debería ser eliminado. Diversos inibidores de crescimento axonal já foram identificados acompanhando a lesão medular, sendo as mais conhecidas as proteínas derivadas de mielina, como o Nogo-A. O presente trabalho teve como objetivo correlacionar a formação da cicatriz glial com o início da liberação do inibidor de crescimento axonal Nogo-A em ratos previamente submetidos à lesão medular compressiva. Para isso, 12 ratos Wistar, machos e fêmeas (250 ± 50g), foram divididos em 3 grupos de 4 animais cada, de acordo com o tempo de eutanásia dos animais após a lesão medular (G3 - três dias; G5 - cinco dias; G7 - sete dias). Foi realizada a indução das lesões medulares por meio de laminectomia dorsal da vértebra T10 e compressão epidural. A avaliação histopatológica e da imunorreatividade do inibidor de crescimento axonal Nogo-A foram realizadas. Foi observado que houve a liberação do inibidor axonal Nogo-A a partir de 24h após a ocorrência de lesão medular, e que cicatriz da glia deve ser mantida, nesse intervalo de tempo, para que garanta o reequilíbrio do meio pós-trauma. Dessa forma, sugere-se que a cicatriz glial deve ser mantida na fase aguda da lesão, garantindo seus inúmeros benefícios ao reequilíbrio do ambiente pós-lesionado e, após 24h, quando se inicia a liberação do inibidor de crescimento axonal estudado, esta deve ser removida.

The diversity of neoplasms observed in dogs can vary geographically depending on individual susceptibility, the habitat of the animals, and environmental characteristics. The aim of this study was to evaluate the epidemiological aspects of neoplasms in dogs treated at the Veterinary Hospital of the State University of Maranhão from 2008 to 2015. We studied the medical records of 1089 dogs affected by neoplasms and treated at a hospital during the period of study, relating to the casuistry with their breed, age, sex and origin. The present study included 764 cases that were confirmed through cytopathology. The most prevalent tumors were transmissible venereal tumors (TVT) (20.17%), adenocarcinoma of the mammary gland (19.53%), mixed malignant tumor of the mammary gland (18.63%), mast cell tumor (11.31%), and mammary carcinoma (6.42%). Females with a mean age of 9.2 years were the most affected, as were SRDs, Poodles, American Pitbulls, and Dobermann Pinschers. According to the cytomorphogenetic classification, the round cell tumors were the most prevalent, with values close to those of epithelial, followed by mixed and mesenchymal cells. La diversidad de neoplasias observadas en perros puede variar geográficamente según la susceptibilidade individual, hábitos de los animales y a los factores ambientales. El objetivo fue evaluar los aspectos epidemiológicos de las neoplasias en perros atendidos en el Hospital Veterinário de UEMA, de 2008 a 2015. En total, se analizaron1089 historias clínicas de perros afectados por neoplasias, atendidos en el Hospital Veterinário durante ese período, relacionando la muestra con la raza, edad, sexo y origen. Entre las historias clínicas analizadas, se observó que 764 casos fueron confirmados mediante aspiración con aguja fina. Las neoplasias más prevalentes fueron TVT (20,17%), adenocarcinoma de mama (19,53%), tumor maligno mixto de mama (18,63%), mastocitoma (11,31%) y carcinoma de mama (6,42%). Las hembras con una edad promedio de 9.2 años fueron los animales más afectados y entre los patrones raciales más frecuentes se destacaron SRD, Poodle, American Pitbull y Dobermann Pinscher, respectivamente. Con respecto a lá classificación citomorfogenética, los tumores de células redondas fueron los más prevalentes, con valores cercanos a los de origen epitelial, seguidos de los mixtos y mesenquimales. A diversidade de neoplasias observadas em cães pode variar geograficamente em função da susceptibilidade individual, hábitos dos animais e aos fatores ambientais. Objetivou-se avaliar os aspectos epidemiológicos das neoplasias em cães atendidos no Hospital Veterinário da UEMA, no período de 2008 a 2015. Foram analisados ao todo, 1089 prontuários de cães acometidos de neoplasias, atendidos no Hospital Veterinário nesse período, relacionando a casuística com a raça, idade, sexo e origem. Dentre os prontuários analisados, foi observado que 764 casos foram confirmados por meio de punção aspirativa com agulha fina. As neoplasias mais prevalentes foram TVT (20,17%), adenocarcinoma mamário (19,53%), tumor misto maligno mamário (18,63%), mastocitoma (11,31%) e carcinoma mamário (6,42%). Fêmeas com média de idade de 9,2 anos foram os animais mais acometidos e dentre os padrões raciais mais frequentes destacaram-se SRD, Poodle, American Pitbull e Dobermann Pinscher, respectivamente. Quanto à classificação citomorfogenética, os tumores de células redondas foram os mais prevalentes, com valores próximos aos de origem epitelial, seguidos pelos mistos e mesenquimais.

Leishmaniasis is a complex disease that is considered a serious public health problem. Due to the absence of an effective vaccine and debilitating chemotherapy better therapies are urgently needed. This situation has stimulated the search for alternative treatments such as the use of herbal medicines. Several studies conducted with Morinda citrifolia Linn. have shown various biological activities such as antitumor, immunomodulation and antileishmanial activity, however its mechanisms of action are still unknown. This study aimed to analyze the activity of M. citrifolia fruit juice against Leishmania amazonensis and its action on peritoneal macrophages from BALB/c infected with L. amazonensis. Activity against the promastigote forms showed IC50 at 275.3 μg/mL. Transmission electron microscopy was used to evaluate the ultrastructural alterations in the promastigotes treated with the juice and the results showed cytoplasmic vacuolization, lipid inclusion and increased activity of exocytosis. The juice treatment presented an IC50 at 208.4 μg/mL against intracellular amastigotes and led to an increased nitrite production in infected and non-infected macrophages. When macrophages were pre-treated with iNOS inhibitors, aminoguanidine or 1400W, the intracellular amastigotes increased, demonstrating the important role of NO production in M. citrifolia fruit activity. In conclusion, our results reveal that treatment with M. citrifolia fruit juice can increase NO production in peritoneal macrophages and this ability has an important role in the killing of L. amazonensis intracellular amastigotes.

Rheumatoid arthritis (RA) is characterized by inflammation of one or more joints, and affects ~1% of the adult population worldwide. Sulforaphane (SFN) is a natural compound that has been suggested as an antioxidant. Here, SFN’s effects were evaluated in a murine mono-arthritis model. Mono-arthritis was induced in mice by a single intra-articular injection of Complete Freund’s Adjuvant (CFA-10 µg/joint, in 10 µL) into the ipsilateral joint. The contralateral joint received an equal volume of PBS. On the 4th day post-joint inflammation induction, animals received either SFN (10 mg/kg) or vehicle (3% DMSO in saline), intraperitoneally (i.p.), twice a day for 3 days. Joint swelling and secondary mechanical allodynia and hyperalgesia were evaluated over 7 days post-CFA. After this period, animals were culled and their blood and synovial fluid samples were collected for analysis of cell populations, cytokine release and thioredoxin reductase (TrxR) activity. Knee joint samples were also collected for histology. SFN reduced joint swelling and damage whilst increasing the recruitment of Ly6C+ and Ly6G+ cells to CFA-injected joints. SFN-treated animals presented down-regulation of CD11b and CD62L on synovial fluid Ly6G+ cells. Synovial fluid samples obtained from CFA-injected joints and plasma samples of SFN-treated mice presented higher levels of IL-6 and increased activity of TrxR, in comparison with controls. These results indicate that SFN reduces knee joint damage by modulating cell activation/migration to the joints, cytokine production and increasing the activity of TrxR, and therefore, may represent an alternative treatment to joint inflammation.

Background Canine visceral leishmaniasis (CVL) is endemic in São Luís Maranhão/Brazil and it leads a varied clinical picture, including neurological signs. Results Histopathological evaluation showed that 14 dogs exhibited pathological alterations in at least one of the analyzed areas. Of these, mononuclear inflammatory reaction was the most frequent, although other lesions, such as hemorrhage, chromatolysis and gliosis were also observed. The presence of L. infantum amastigotes was confirmed in eight dogs, identified in four regions: telencephalon, hippocampus, thalamus and caudal colliculus, but only one presented neurological signs. Polymerase chain reaction results detected the DNA of the parasite in 11 samples from seven dogs. The positive areas were the telencephalon, thalamus, hippocampus, cerebellum, caudal and rostral colliculus. Conclusion These results reveal that during canine visceral leishmaniasis, the central nervous system may display some alterations, without necessarily exhibiting clinical neurological manifestations. In addition, the L. infantum parasite has the ability to cross the blood brain barrier and penetrate the central nervous system.

Background Bone defects caused by trauma, infection or tumor resection are common in orthopedic clinic and depending on the extent of the fracture; the vast majority require treatment with bone substitutes. Among the bone grafts employees, the autograft is defined as the gold standard, but with some limitations, principally related to morbidity at the site of its removal, with the need to search for other biomaterials as adjuvant in bone regeneration. Therefore, the objective of the present study was to evaluate the use of Chenopodium ambrosioides as a bone graft substitute for the osseointegration of fractures in rabbits, compared to other bone grafts already employed in the surgical routine as Ricinus communis (castor oil) polyurethane and autogenous bone marrow. Methods Forty-eight rabbits were divided into four groups. After anesthesia, a radius fracture was created and the animals were treated with the following grafts: C. ambrosioides graft, autogenous bone marrow, castor oil and saline (control). After 30, 60 and 90 days, the animals were submitted to radiographical and histological analyses and bone alkaline phosphatase, osteocalcin, biomechanical tension, and collagen were measured. We also realized a phytochemical screening and in vitro antioxidant activity including 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical. Results The data showed that the growth of the bone callus was more expressive and biomechanical assessment showed better tensile strength in C. ambrosioides graft. The experimental results also revealed that there was significantly greater activity of the bone alkaline phosphatase and osteocalcin during early fracture healing, similarly to the group receiving autogenous bone marrow. Histologically, immature bone was observed in C. ambrosioides graft at 30 days, whereas the formation of cartilaginous tissue predominated in the other groups. A higher amount of type I collagen was observed in C. ambrosioides graft throughout treatment. It was detected strong presence of flavonoids and appreciable antioxidant activity. Conclusions The results indicate that C. ambrosioides graft and autogenous bone marrow have similar ability to enhance bone regeneration, higher than the castor oil graft, suggesting that the medicinal plant can provide therapeutic benefits for bone tissue.

Morinda citrifolia, also known as noni, is commonly used in popular medicine in Brazil. Many parts of the noni tree are utilized in such practices, including the roots, leaves and seeds. Through a search of online databases, the present article reviews 92 research studies on the biological actions of M. citrifolia. The paper will discuss the therapeutic effects of noni and its compounds in a variety of forms of presentation, focusing on studies that support its traditional use. A large and diverse number of properties were identified, which were divided into immunostimulatory, antitumor, antidiabetic, anti-obesity, antibacterial and anti-septic, antifungal, antiviral, leishmanicidal, antiinflammatory, antinociceptive and analgesic, antioxidant, neuroprotective, wound healing, antiallergic, antiangiogenic, antiemetic and anti-nausea, anti-gastric ulcer and oesophagitis, anthelmintic, antimutagenic, antipsychotic, anxiolytic, photoprotective, anti-wrinkle and periodontal tissue regeneration activities. While it was concluded that although M. citrifolia is widely and successfully used for the treatment or prevention of various diseases, it should be consumed carefully, and only after exhaustive studies into its chemical constituents and mechanisms of action, both in in vitro and in vivo models, as well as clinical trials. Copyright © 2017 John WileySons, Ltd.

BACKGROUND Leishmaniasis is a parasitosis caused by several species of the genus Leishmania. These parasites present high resistance against oxidative stress generated by inflammatory cells. OBJECTIVES To investigate oxidative stress and molecular inflammatory markers in BALB/c mice infected with L. amazonensis and the effect of antioxidant treatment on these parameters. METHODS Four months after infection, oxidative and inflammatory parameters of liver, kidneys, spleen, heart and lungs from BALB/c mice were assessed. FINDINGS In liver, L. amazonensis caused thiol oxidation and nitrotyrosine formation; SOD activity and SOD2 protein content were increased while SOD1 protein content decreased. The content of the cytokines IL-1β, IL-6, TNF-α, and the receptor of advanced glycation endproducts (RAGE) increased in liver. Treatment with the antioxidant N-acetyl-cysteine (20 mg/kg b.w) for five days inhibited oxidative stress parameters. MAIN CONCLUSIONS L. amazonensis induces significant alterations in the redox status of liver but not in other organs. Acute antioxidant treatment alleviates oxidative stress in liver, but it had no effect on pro-inflammatory markers. These results indicate that the pathobiology of leishmaniasis is not restricted to the cutaneous manifestations and open perspectives for the development of new therapeutic approaches to the disease, especially for liver function.

Trypanosoma vivax significantly impacts the livestock systems, since it affects animals of economic importance, such as ruminants. It causes disease not only in cattle but also in buffaloes, and it is able to infect a large number of both domestic and wild species. Based on the way the parasite is transmitted to the host, the genus Trypanosoma is classified into two groups: Salivaria and Stercoraria. T. vivax is mainly transmitted in a cyclic manner by the tsetse fly bite in areas where this vector is present. In the American continent, due to the absence of the vector, the parasite has adapted to the mechanical transmission, via bloodsucking insects such as Stomoxys calcitrans and tabanids. In cattle, the incubation period ranges from 9 to 14 days, for virulent isolates, and 9–59 days for the less pathogenic isolates. The main clinical signs of the infection are fever, anemia, miscarriage, appetite loss, lethargy, progressive weight loss, and dysentery. The disease can be controlled by chemical treatment, particularly during early periods of acute disease. However, in cattle with neurological symptoms, the treatment is not efficient because there is recurrence of the disease and death of the animals. Clinical and parasitological relapses observed after the treatment of animals with nervous signs have been associated with the presence of the parasite in the nervous tissue, cerebrospinal fluid, and aqueous humor, where trypanosomes are protected against trypanocidal drugs. The growing incidence of resistance to drugs has complicated the treatment and control of trypanosomiasis in recent times.

There are few studies on human ocular leishmaniasis found in the literature. The purpose of this study was to describe experimental ocular leishmaniasis, caused by Leishmania amazonensis evaluating two different infection routes: intravitreal and instillation in C57BL/10 and BALB/c mice. In this work all animals presented low anti-Leishmania IgM and IgG titers regardless of the infection route or mouse strain. The histopathological eye analysis showed that the mice inoculated by the intravitreal route developed more severe lesions, presenting parasites in the anterior region of the eye 60days after infection. The C57BL/10 mice presented cells containing parasitophorous vacuoles associated with pigmented cells and inflammatory infiltrate, which included mast cells. Ninety days after infection no parasites could be found in either mouse strain, which led us to hypothesize that parasites had been eliminated. In this context, we show that both intravitreal and instillation routes were effective in promoting ocular leishmaniasis infections in C57BL/10 and BALB/c mice. There were no differences in the parasite infection between the two mouse models and it mimicked the ocular lesions described in symptomatic dogs in endemic areas of visceral leishmaniasis.