Molecular characterization of Brazilian FeLV strains in São Luis, Maranhão Brazil.

The feline leukemia virus (FeLV) belongs to the Retroviridae family and Gammaretrovirus genus, and causes a variety of neoplastic and non-neoplastic diseases in domestic cats (Felis catus), such as thymic and multicentric lymphomas, myelodysplastic syndromes, acute myeloid leukemia, aplastic anemia, and immunodeficiency. The aim of the present study was to carry out the molecular characterization of FeLV-positive samples and determine the circulating viral subtype in the city of São Luís, Maranhão, Brazil, as well as identify its phylogenetic relationship and genetic diversity. The FIV Ac/FeLV Ag Test Kit (Alere™) and the commercial immunoenzymatic assay kit (Alere™) were used to detect the positive samples, which were subsequently confirmed by ELISA (ELISA - SNAP® Combo FeLV/FIV). To confirm the presence of proviral DNA, a polymerase chain reaction (PCR) was performed to amplify the target fragments of 450, 235, and 166 bp of the FeLV gag gene. For the detection of FeLV subtypes, nested PCR was performed for FeLV-A, B, and C, with amplification of 2350-, 1072-, 866-, and 1755-bp fragments for the FeLV env gene. The results obtained by nested PCR showed that the four positive samples amplified the A and B subtypes. The C subtype was not amplified. There was an AB combination but no ABC combination. Phylogenetic analysis revealed similarities (78% bootstrap) between the subtype circulating in Brazil and FeLV-AB and with the subtypes of Eastern Asia (Japan) and Southeast Asia (Malaysia), demonstrating that this subtype possesses high genetic variability and a differentiated genotype.

Anti-inflammatory and antioxidant therapies for chagasic myocarditis: a systematic review.

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.

Epidemiological aspects and spatial patterns of human visceral leishmaniasis in Brazil.

Human visceral leishmaniasis (HVL) cases are important public health problems due to their zoonotic aspect, with high rates of morbidity and mortality in Brazil. The aim of this this study was to identify spatial patterns in both rates of HVL cases in Brazilian states during the period from 2006 to 2015. This is an ecological study, using geoprocessing tools to create choropleth maps, based on secondary data from open access platforms, to identify priority areas for control actions of the disease. Data were collected in 2017 and analysed according to the global and local Moran's I, using TerraView 4.2.2 software. Similar clusters were observed in neighbouring municipalities in thematic maps of HVL, suggesting spatial similarity in the distribution of the disease in humans mainly in the North and Northeast Regions, which concentrate the states with the highest rates of HVL. Heterogeneous spatial patterns were observed in the distribution of HVL, which show municipalities that need higher priority in the intensification of disease surveillance and control strategies.

1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Study.

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 ± 4.392 µM against promastigotes, IC50: 17.78 ± 3.257 µM against intracellular amastigotes, CC50: 547.88 ± 3.256 µM 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.

Feline immudeficiency virus subtypes B and A in cats from São Luis, Maranhão, Brazil.

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 São Luís, Maranhão 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 São Luís and the first report of subtype A in Brazil. New variations of the virus are also reported.

Epidemiological, clinical and laboratory aspects of human visceral leishmaniasis (HVL) associated with human immunodeficiency virus (HIV) coinfection: a systematic review.

Coinfection with human visceral leishmaniasis (HVL) and human immunodeficiency virus (HIV) has become an emerging public health problem in several parts of the world, with high morbidity and mortality rates. A systematic review was carried out in the literature available in PubMed, Scielo and Lilacs related to HVL associated with HIV coinfection, seeking to analyze epidemiological, clinical and laboratory aspects. Of the 265 articles found, 15 articles were included in the qualitative analysis, which referred to the results of HVL treatment in patients coinfected with HIV. In the published articles between 2007 and 2015, 1171 cases of HVL/HIV coinfection were identified, 86% males, average age 34 years, liposomal amphotericin B was the most commonly used drug, cure rates 68 and 20% relapses and 19% deaths, five different countries, bone marrow was used in 10/15 manuscripts. HVL/HIV coinfection is a major challenge for public health, mainly due to the difficulty in establishing an accurate diagnosis, low response to treatment with high relapse rates and evolution to death. In addition, these two pathogens act concomitantly for the depletion of the immune system, contributing to worsening the clinical picture of these diseases, which requires effective surveillance and epidemiological control measures.

Spatial distribution and seasonality of Biomphalaria spp. in São Luís (Maranhão, Brazil).

Two of the three vector species of Schistosoma mansoni Sambon, 1907 in Brazil occur in the state of Maranhão: Biomphalaria glabrata (Say, 1818) and Biomphalaria straminea (Dunker, 1848). For the implementation of effective measures to combat schistosomiasis, it is necessary to identify the spatial and seasonal dynamics of these snails. Therefore, this work brought together information from malacological survey carried out in São Luís (Maranhão, Brazil) to identify the spatial and seasonal distribution patterns of Biomphalaria spp. snails. We used data from malacological surveys of the Municipal Health Secretary of São Luís, conducted between 2006 and 2013 in 23 neighborhoods. We also used data from the mollusk surveys that we conducted for 2 years (2012-2014) in four of these neighborhoods. During the 8-year period (2006-2013), 15,990 specimens of Biomphalaria spp. were collected. There was a positive association between precipitation and the abundance of mollusks of the genus Biomphalaria. During 2012-2014, a total of 2487 snail specimens were obtained (B. glabrata: 1046 specimens; B. straminea: 1426 specimens). There was a positive correlation between precipitation and B. straminea abundance. High density of human occupation and high precipitation are two factors that affect the distribution and density of Biomphalaria spp.

Sulforaphane Modulates Joint Inflammation in a Murine Model of Complete Freund's Adjuvant-Induced Mono-Arthritis.

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.

Main lesions in the central nervous system of dogs due to Leishmania infantum infection.

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.

N-acetyl-cysteine inhibits liver oxidative stress markers in BALB/c mice infected with Leishmania amazonensis.

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-1ß, 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.

One Plant, Many Uses: A Review of the Pharmacological Applications of Morinda citrifolia.

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.

Morinda citrifolia Linn. fruit (Noni) juice induces an increase in NO production and death of Leishmania amazonensis amastigotes in peritoneal macrophages from BALB/c.

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.

Leishmanicidal, cytotoxicity and wound healing potential of Arrabidaea chica Verlot.

BACKGROUND: Leishmaniasis includes a wide complex of diseases that affect humans and other mammals, and can range from a mild cutaneous form to a severe visceral type. The safety of the standard treatment using pentavalent antimony is a concern due to its toxic effects. The search for alternative, effective and less toxic treatments has led to the testing of natural products. The present study aimed to evaluate the cytotoxic, leishmanicidal and healing potential of Arrabidaea chica. METHODS: The crude ethanolic extract, as well as the chloroform, methanol and ethyl acetate fractions of A. chica were prepared and phytochemical analysis was performed. Cytotoxic evaluation was carried out through MTT colorimetric assay, and the 50% cellular cytotoxicity was determined. After that, the effect of the extract and fractions against Leishmania amazonensis promastigotes, at intervals of 24, 48 and 72 h, was analyzed, and 50% inhibitory concentration was determined. The healing effect of the plant was also tested in surgical lesions in Swiss mice skin. RESULTS: Phytochemical screening showed that the crude extracts contained flavonoids, tannins, anthocyanidins and chalcones. The leishmanicidal potential of A. chica produced satisfactory results in concentrations of between 60 and 155.9 µg/mL. Cytotoxic assay revealed a 50% reduction in viable cells at a concentration of 189.9 µg/mL. The healing results indicated that the treated group exhibited more pronounced signs of lesion resolution in the early period, but this pattern did not persist throughout the treatment. CONCLUSIONS: The results of the present study demonstrate that A. chica has cytotoxic and leishmanicidal potential but its healing effect must be better studied.

Leishmanicidal and immunomodulatory activity of Terminalia catappa in Leishmania amazonensisin vitro infection.

Leishmaniases are infectious-parasitic diseases that impact public health around the world. Antileishmanial drugs presented toxicity and increase in parasitic resistance. Studies with natural products show an alternative to this effect, and several metabolites have demonstrated potential in the treatment of various diseases. Terminalia catappa is a plant species with promising pharmaceutical properties. The objective of this work was to evaluate the therapeutic potential of extracts and fractions of T. catappa on Leishmania amazonensis and investigate the immunomodulatory mechanisms associated with its action. In anti-Leishmania assays, the ethyl acetate fraction exhibited activity against promastigotes (IC50 86.07 ± 1.09 µg/mL) and low cytotoxicity (CC50 517.70 ± 1.68 µg/mL). The ethyl acetate fraction also inhibited the intracellular parasite (IC50 25.74 ± 1.08 µg/mL) with a selectivity index of 20.11. Treatment with T. catappa ethyl acetate fraction did not alter nitrite production by peritoneal macrophages stimulated with L. amazonensis, although there was a decrease in unstimulated macrophages treated at 50 µg/mL (p = 0.0048). The T. catappa ethyl acetate fraction at 100 µg/mL increased TNF-α levels (p = 0.0238) and downregulated HO-1 (p = 0.0030) and ferritin (p = 0.0002) gene expression in L. amazonensis-stimulated macrophages. Additionally, the total flavonoid and ellagic acid content for ethyl acetate fraction was 13.41 ± 1.86 mg QE/g and 79.25 mg/g, respectively. In conclusion, the T. catappa ethyl acetate fraction showed leishmanicidal activity against different forms of L. amazonensis and displayed immunomodulatory mechanisms, including TNF-α production and expression of pro and antioxidant genes.

Hydrodissection to create conjunctival flaps in dogs with corneal ulcers.

Background and Aim: Hydrodissection is a liquid injection technique that is rarely used in animal ophthalmic procedures. The use of this technique in the creation of conjunctival flaps for the treatment of corneal ulcers in dogs can improve the outcome, task, and comfort for patients. This study aimed to evaluate the use of hydrodissection in the creation of conjunctival flaps in dogs with corneal ulcers. Materials and Methods: This study focused on a surgical procedure for creating conjunctival flaps in the eyes of 17 dogs with deep corneal ulcers. We divided the patients into two groups: Hydrodissection was performed in the first group (G1) and conventional divulsion without hydrodissection in the second group (G2). In G1, the conjunctival flap was created by subconjunctival injection of 1 mL of 0.9% sodium chloride, followed by flap construction. The flap was constructed through conventional divulsion using iris scissors in the G2. The operative time, degree of bleeding, and ease of conjunctival divulsion were evaluated during the procedure. Blepharospasm, hyperemia, edema, and scarring of the conjunctiva were evaluated during the post-operative period. Post-operative complications, notably suture dehiscence, were recorded in each group. Results: Hydrodissection is an easy-to-perform maneuver that optimizes the construction of conjunctival flaps. There were no statistical differences in the parameters used to evaluate the trans- and post-operative period between the groups. The volume of sodium chloride administered in the conjunctiva ranged from 0.5 mL to 1 mL in G1. Dehiscence of the flap sutures was observed in four patients (two in G1 and two in G2), with no significant difference between the groups. Conclusion: Hydrodissection facilitates the construction of conjunctival flaps in dogs with corneal ulcers, affording greater comfort to patients and proving to be an excellent option for ophthalmologists.

In Vitro Antioxidant and Antitrypanosomal Activities of Extract and Fractions of Terminalia catappa.

Chagas disease is a severe infectious and parasitic disease caused by the protozoan Trypanosoma cruzi and considered a public health problem. Chemotherapeutics are still the main means of control and treatment of the disease, however with some limitations. As an alternative treatment, plants have been pointed out due to their proven pharmacological properties. Many studies carried out with Terminalia catappa have shown several biological activities, but its effect against T. cruzi is still unknown. The objective of this work is to evaluate the therapeutic potential of extracts and fractions obtained from T. catappa on the parasite T. cruzi, in addition to analyzing its antioxidant activity. T. catappa ethyl acetate fraction were produced and submitted the chemical characterization by Liquid Chromatography Coupled to Mass Spectrometry (LC-MS). From all T. catappa extracts and fractions evaluated, the ethyl acetate and the aqueous fraction displayed the best antioxidant activity by the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging method (IC50 of 7.77 ± 1.61 and 5.26 ± 1.26 µg/mL respectively), and by ferric ion reducing (FRAP) method (687.61 ± 0.26 and 1009.32 ± 0.13 µM of Trolox equivalent/mg extract, respectively). The ethyl acetate fraction showed remarkable T. cruzi inhibitory activity with IC50 of 8.86 ± 1.13, 24.91 ± 1.15 and 85.01 ± 1.21 µg/mL against epimastigotes, trypomastigotes and intracellular amastigotes, respectively, and showed no cytotoxicity for Vero cells (CC50 > 1000 µg/mL). The treatment of epimastigotes with the ethyl acetate fraction led to drastic ultrastructural changes such as the loss of cytoplasm organelles, cell disorganization, nucleus damage and the loss of integrity of the parasite. This effect could be due to secondary compounds present in this extract, such as luteolin, kaempferol, quercetin, ellagic acid and derivatives. The ethyl acetate fraction obtained from T. catappa leaves can be an effective alternative in the treatment and control of Chagas disease, and material for further investigations.

Calotropis procera (Aiton) Dryand (Apocynaceae): State of the art of its uses and Applications.

Calotropis procera (Aiton) Dryand (Apocynaceae), popularly known as milkweed, has been traditionally used to treat diseases particularly associated with gastric disorders, skin disease and inflammatory processes. The present study aimed to review the current scientific evidence regarding the pharmacological effects of C. procera extracted phytochemicals and possible research opportunities as complementary and alternative medicine. Scientific publications were searched in various electronic databases (PubMed, Scopus, Web of Science, Google Scholar, Springer, Wiley, and Mendeley) using the following search terms: Calotropis procera, medicinal plants, toxicity, phytochemical characterization, and biological effects. Collected data showed that cardenolides, steroid glycoside and flavonoids are the main classes of phytochemicals identified in C. procera latex and leaves. In addition, lignans, terpenes, coumarins, and phenolic acids have been reported. These metabolites have been correlated with their biological activities, including mainly antioxidant, anti-inflammatory, antitumoral, hypoglycemic, gastric protective, anti-microbial, insecticide, anti-fungal, anti-parasitic, among others. However, some of the studies were carried out with only a single dose or with a high dose not achievable under physiological conditions. Therefore, the validity of C. procera biological activity may be questionable. Not less important to highlight are the risks associated with its use and the possibility of accumulation of heavy metals that can be toxic. Furthermore, there are no clinical trials with C. procera to date. In conclusion, the need of bioassayguided isolation of bioactive compounds, bioavailability and efficacy, as well as pharmacological and toxicity studies, are needed using in vivo models and clinical trials in order to support the traditionally claimed health benefits.

Effects of Passovia ovata Mistletoe on Pro-Inflammatory Markers In Vitro and In Vivo.

New agents that can suppress inflammatory responses are being sought, since chronic inflammation is associated with several pathologies. This work aims to elucidate phytochemicals from the hydroethanolic extract of mistletoe Passovia ovata (POH) and its anti-inflammatory potential. POH is submitted to HPLC-UV, qualitative analysis of chemical constituents, and flavonoid quantification. Cytotoxicity is evaluated in RAW 264.7 macrophages by MTT. LPS-stimulated RAW 264.7 cells are treated with POH and, after 48 h, the nitrite and cytokine levels are quantified. BALB/c mice are treated by gavage with POH and stimulated with λ-carrageenan to induce paw oedema or peritonitis. POH yield is 25% with anthraquinones, tannins, anthocyanins, anthocyanidins, flavonols, catechins and flavanones present and flavonoid content of 4.44 ± 0.157 mg QE/g dry weight. POH exhibits low cytotoxicity and significantly reduced (p < 0.01) nitrite, IL-1ß, IL-6, and TNF-α quantification at 500 µg/mL. POH at 500 mg/kg prevents paw edema increase and also reduces inflammatory infiltrate and mast cells in the footpad. In the peritonitis model, POH does not influence cytokines levels or cell counts. Overall, POH demonstrates a high concentration of flavonoids and prominent effects in the reduction in pro-inflammatory markers in vitro and in the inhibition of paw oedema.

Visceral leishmaniasis and HIV coinfection in Brazil: epidemiological profile and spatial patterns.

BACKGROUND: Geographical overlap of human visceral leishmaniasis (HVL) and HIV infection favors occurrences of HVL/HIV coinfection. The increasing numbers of cases of HVL/HIV coinfection are a worldwide concern and knowledge of the factors involved can help in developing preventive measures. METHODS: We aimed to identify spatial patterns and describe the epidemiological profile of HVL/HIV coinfection in Brazil from 2007 to 2015. This was an ecological study, in which thematic maps were created through geoprocessing tools, based on secondary data obtained from open-access platforms, to identify priority areas for interventions for controlling HLV/HIV coinfection, using the TerraView 4.2.2 software. RESULTS: We found spatial autocorrelations between the HVL/HIV rates of neighboring municipalities according to the global Moran index (0.10; p<0.01). The highest HVL/HIV rate was in the central-western region. Among the epidemiological characteristics according to the regions, an increasing trend in the annual variation rate was observed, with positive values over the years and statistical significance (p<0.05) in the North with 1.62 (95% CI 0.57 to 2.69; p=0.02) and Northeast with 6.41 (95% CI 2.60 to 10.37; p=0.006). Similarly, increasing trends were observed in the states of Maranhão with 21.34 (95% CI 13.99 to 9.16; p<0.001) and Sergipe with 5.44 (95% CI 0.61 to 10.50; p=0.04). CONCLUSIONS: Our results showed spatial overlap between occurrences of HVL and HIV with spatial patterns of HVL/HIV coinfection, thus revealing that the numbers of cases reported are increasing. Identifying areas with higher coinfection indices contributes to applying interventions and control measures among targeted populations, to prevent new cases.