Endothelial activation is associated with albuminuria in multibacillary leprosy.

Leprosy may present kidney and endothelial abnormalities, being a risk factor for complications. However, the involvement of renal and vascular endothelia has been poorly investigated. We aimed to investigate if the levels of systemic endothelial biomarkers are associated with kidney abnormalities and the clinical forms of leprosy. This is a cross-sectional study with leprosy patients enrolled in January 2017 to December 2018, before the initiation of the multidrug therapy. Leprosy-associated clinical and epidemiological data were collected. Two groups were investigated: Paucibacillary (PB) and Multibacillary (MB) infections, for the comparisons. Serum and urine samples were obtained for laboratory analysis. In serum samples, were evaluated the endothelial biomarkers VCAM-1 and ICAM-1. In total, 101 leprosy patients were included, the mean age was 48±Ù¡Ù¥ years and 71 (70%) were male. The multibacillary form occurred in 81 cases (80%), among which 22 had the Virchowian form. Serum creatinine was more elevated in the MB group than in PB patients. In addition, VCAM-1 was elevated in the MB group and was correlated with the bacteriological index (rho = 0.372, p <0.01), the duration of disease symptoms (rho = 0.234, p = 0.04), and the number of skin lesions (rho = 0.468, p <0.001). Moreover, in MB patients who presented albuminuria >15 mg/g of creatinine, VCAM-1 showed a significant correlation with increased albuminuria and improved the correlation with the number of skin lesions (rho= 0.563, p=0.010). In conclusion, higher systemic VCAM-1 levels were associated with the multibacillary clinical form of leprosy and with increased albuminuria. Prospective studies are necessary to establish a cause-effect and evaluate the preventive role of these biomarkers to improve the clinical care.

Acute kidney injury due to systemic Loxoscelism: a cross-sectional study in Northeast Brazil.

INTRODUCTION: Loxoscelism is a clinical condition involving spiders of the genus Loxosceles. One of the most severe complications is acute kidney injury (AKI). This study aimed to investigate AKI and other complications associated with loxoscelism. METHODS: We analyzed cases diagnosed with loxoscelism in an area where most accidents were caused by Loxosceles amazonica from January 2010 to December 2015. AKI was defined according to the KDIGO criteria. RESULTS: Forty-five patients were recorded: 95.6% presented characteristic necrotic skin lesions and 13.3% AKI. CONCLUSIONS: Loxoscelism could cause kidney involvement which is uncommon and could lead to the death of these patients.

Acute kidney injury due to systemic Loxoscelism: a cross-sectional study in Northeast Brazil

Abstract INTRODUCTION: Loxoscelism is a clinical condition involving spiders of the genus Loxosceles. One of the most severe complications is acute kidney injury (AKI). This study aimed to investigate AKI and other complications associated with loxoscelism. METHODS: We analyzed cases diagnosed with loxoscelism in an area where most accidents were caused by Loxosceles amazonica from January 2010 to December 2015. AKI was defined according to the KDIGO criteria. RESULTS: Forty-five patients were recorded: 95.6% presented characteristic necrotic skin lesions and 13.3% AKI. CONCLUSIONS: Loxoscelism could cause kidney involvement which is uncommon and could lead to the death of these patients.

Nanoencapsulation of benznidazole in calcium carbonate increases its selectivity to Trypanosoma cruzi.

Chagas disease is a public health problem, affecting about 7 million people worldwide. Benznidazole (BZN) is the main treatment option, but it has limited effectiveness and can cause severe adverse effects. Drug delivery through nanoparticles has attracted the interest of the scientific community aiming to improve therapeutic options. The aim of this study was to evaluate the cytotoxicity of benznidazole-loaded calcium carbonate nanoparticles (BZN@CaCO3) on Trypanosoma cruzi strain Y. It was observed that BZN@CaCO3 was able to reduce the viability of epimastigote, trypomastigote and amastigote forms of T. cruzi with greater potency when compared with BZN. The amount of BZN necessary to obtain the same effect was up to 25 times smaller when loaded with CaCO3 nanoparticles. Also, it was observed that BZN@CaCO3 enhanced the selectivity index. Furthermore, the cell-death mechanism induced by both BZN and BZN@CaCO3 was evaluated, indicating that both substances caused necrosis and changed mitochondrial membrane potential.

Trypanocidal activity of polysaccharide extract from Genipa americana leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: The parts of the Genipa americana (Rubiaceae) tree, also known as "jenipapo" or "jenipapeiro", has been used in traditional Medicine in parasitic and bacterial infections. Thus, the experimental evolution of the antiparasitic activity of polysaccharide extracts from Genipa americana leaves, and correlation with antiparasitic and popular use is important. AIM OF THE STUDY: To evaluate the effect of polysaccharide extract obtained from Genipa americana leaves on all Trypanosoma cruzi (Y strain: benznidazole-resistant) developmental forms, a protozoan that causes Chagas' disease. MATERIALS AND METHODS: An extract rich in polysaccharides was obtained from the leaves of Genipa americana (GaEPL) by associating depigmentation in methanol followed by extraction of polysaccharides in NaOH and precipitation with ethanol. Cytotoxicity to mammalian cells (LLC-MK2) was determined using an MTT assay. Antiparasitic activity was evaluated against epimastigote, trypomastigote and amastigote forms of T. cruzi. Cell-death mechanism was determined in epimastigote forms by flow cytometry analysis after FITC-annexin V (Ax), 7-AAD, and H2DCFDA staining. Striking morphological changes were observed by scanning electron microscope. RESULTS: GaEPL (6.5% yield; 54.6% total carbohydrate; 21.1% uronic acid and 12% protein), inhibited all T. cruzi developmental forms, epimastigotes after periods of 24h (IC50 = 740 ± 0.075µg/mL), 48h (IC50 = 710 ± 0.053µg/mL) and 72h (IC50 = 870 ± 0.052µg/mL) of incubation; trypomastigotes (IC50 = 470 ± 0.082µg/mL) after periods of 24h and intracellular amastigotes (IC50/2 = 235 or IC50 = 470µg/mL) after periods of 24 and 48h of incubation, with no toxicity on LLC-MK2 cells at the used concentrations. Analysis of the possible action mechanism in the parasites suggested cell death by necrosis with the involvement of reactive oxygen species (ROS). The scanning electron microscopy (SEM) confirmed T. cruzi death by necrosis. CONCLUSIONS: GaEPL showed significant activity against the epimastigote, trypomastigote and amastigote forms of T. cruzi, strain Y, suggesting cell death by necrosis with involvement of reactive oxygen species.

Betulinic acid induces cell death by necrosis in Trypanosoma cruzi.

Chagas' disease is a neglected disease caused by the protozoan parasite Trypanosoma cruzi and constitutes a serious health problem worldwide. The treatment is limited, with variable efficacy of benznidazole and nifurtimox. Betulinic Acid (BA), a triterpene, can be found in medicinal herbs and has a wide variety of biological and pharmacological activities. The objective was to evaluate betulinic acid effects on the cell death mechanism in Trypanosoma cruzi strain Y. BA inhibited the growth of epimastigotes in periods of 24h (IC50=73.43µM), 48h (IC50=119.8µM) and 72h (IC50=212.2µM) of incubation; of trypomastigotes (IC50=51.88µM) in periods of 24h and intracellular amastigotes (IC50=25.94µM) in periods of 24 and 48h of incubation, no toxicity on LLC-MK2 cells at the concentrations used. Analysis of the possible mechanism of parasite cell death showed alterations in mitochondrial membrane potential, alterations in cell membrane integrity, an increase in the formation of reactive oxygen species and increase swelling of the reservosomes. In conclusion, betulinic acid was be able to inhibition all developmental forms of Trypanosoma cruzi Y strain with necrotic mechanism and involvement of mitochondrial membrane potential alteration and increase in reactive oxygen species.

Evaluation of the antichagasic activity of batroxicidin, a cathelicidin-related antimicrobial peptide found in Bothrops atrox venom gland.

Antimicrobial peptides (AMPs) are potential alternatives to conventional antibiotics, as they have a fast mode of action, a low likelihood of resistance development and can act in conjunction with existing drug regimens. We report in this study the effects of batroxicidin (BatxC), a cathelicidin-related AMP from Bothrops atrox venom gland, over Trypanosoma cruzi, a protozoan that causes Chagas' disease. BatxC inhibited all T. cruzi (Y strain: benznidazole-resistant) developmental forms, with selectivity index of 315. Later, separate flow cytometry assays showed T. cruzi cell labeling by 7-aminoactinomycin D, the increase in reactive oxygen species and the loss of mitochondrial membrane potential when the parasite was treated with BatxC, which are indication of necrosis. T. cruzi cell death pathway by a necrotic mechanism was finally confirmed by scanning electron microscopy which observed loss of cell membrane integrity. In conclusion, BatxC was able to inhibit T. cruzi, with high selectivity index, by inducing necrosis.

Antiparasitic effect of Dinoponera quadriceps giant ant venom.

Neglected tropical diseases (NTD) are treated with toxic therapy of limited efficacy. Previously, we studied the antimicrobial effect of Dinoponera quadriceps venom (DqV) against bacteria. To continue the study, we report in this short communication the antimicrobial effect of DqV against Leishmania amazonensis and Trypanosoma cruzi. DqV inhibits the promastigote forms of L. amazonensis and all T. cruzi developmental forms, with low toxicity in host cells. DqV causes cell death in T. cruzi through necrotic and apoptotic mechanisms observed by staining the cells with annexin V-FITC (AX) and propidium iodide (PI), loss of mitochondrial membrane potential by flow cytometry analyses and confocal microscopy and morphological alterations, such as loss of membrane integrity and cell shrinkage by scanning electron microscopy (SEM). In conclusion, we suggest there is an antimicrobial effect also on parasites.

Estudo in vitro da atividade tripanocida de nanopartículas de benzonidazol em carbonato decálcio sobre cepa Y de trypanosoma cruzi cruzi

A doença de Chagas é um problema de saúde pública, afeta cerca de 6 milhões de pessoas emtodo o mundo e causa altos índices de morbidade e mortalidade nas populações afetadas. Obenzonidazol (BZ), fármaco utilizado no tratamento apresenta eficácia limitada e provoca sériosefeitos adversos. O transporte de fármacos por meio de nanopartículas tem demonstradoeficiência quanto à liberação controlada e direcionada de moléculas farmacológicas, além deapresentar propriedades desejáveis, como boa biocompatibilidade e biodegradabilidade. Oobjetivo do presente trabalho foi avaliar a citoxicidade de nanopartículas de benzonidazol emcarbonato de cálcio (BZ@CaCO3) sobre células de hospedeiras LLC-MK2; determinar o efeitotripanocida sobre as formas epimastigotas, tripomastigotas e amastigotas da cepa Y de T. cruzie comparar ao efeito do BZ, bem como, sugerir o mecanismo de morte. Os testes decitotoxicidade utilizando o método do MTT realizados com células LLC-MK2 cultivadas commeio DMEM a 10% de SBF demonstraram CI50 de 55 µg/mL para BZ@CaCO3 e 160 µg/mLpara BZ...

Chagas disease is a public health concern, affects about 6 million people worldwide and causeshigh morbidity and mortality in affected populations. One of the few drugs available fortreatment of this disease is Benznidazole (BZ) was developed over forty years ago, has limitedeffectiveness and cause severe adverse effects. The transport of drugs by nanoparticles hasattracted the interest of the scientific community as it demonstrates efficiency and the controlledand targeted release of pharmacological molecules, in addition to its desirable properties suchas good biocompatibility and biodegradability. The aim of this study was to evaluate thecytotoxicity of benznidazole nanoparticles (BZ@CaCO3) produced with calcium carbonate onLLC-MK2 host cells; to define the trypanocidal effect on epimastigotes, trypomastigote andamastigotes of Trypanosoma cruzi Y strain and compare the effect of BZ, as well as characterizethe nanoparticle-induced death mechanism. The cytotoxicity tests using the MTT methodperformed with LLC-MK2 cells grown in DMEM with 10% FBS showed IC50 of 55 µg/mL forBZ@CaCO3 and 160 µg/mL for BZ...