91 research outputs found

    Blood-stage antiplasmodial activity and oocyst formation-blockage of metallo copper-cinchonine complex

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    In the fight against malaria, the key is early treatment with antimalarial chemotherapy, such as artemisinin-based combination treatments (ACTs). However, Plasmodium has acquired multidrug resistance, including the emergence of P. falciparum strains with resistance to ACT. The development of novel antimalarial molecules, that are capable of interfering in the asexual and sexual blood stages, is important to slow down the transmission in endemic areas. In this work, we studied the ability of the mettalo copper-cinchonine complex to interfere in the sexual and asexual stages of Plasmodium. The tested compound in the in vitro assay was a cinchonine derivative, named CinCu (Bis[Cinchoninium Tetrachlorocuprate(II)]trihydrate). Its biological functions were assessed by antiplasmodial activity in vitro against chloroquine-resistant P. falciparum W2 strain. The mice model of P. berghei ANKA infection was used to analyze the antimalarial activity of CinCu and chloroquine and their acute toxicity. The oocyst formation-blocking assay was performed by experimental infection of Anopheles aquasalis with P. vivax infected blood, which was treated with different concentrations of CinCu, cinchonine, and primaquine. We found that CinCu was able to suppress as high as 81.58% of parasitemia in vitro, being considered a molecule with high antiplasmodial activity and low toxicity. The in vivo analysis showed that CinCu suppressed parasitemia at 34% up to 87.19%, being a partially active molecule against the blood-stage forms of P. berghei ANKA, without inducing severe clinical signs in the treated groups. The transmission-blocking assay revealed that both cinchonine and primaquine were able to reduce the infection intensity of P. vivax in A. aquasalis, leading to a decrease in the number of oocysts recovered from the mosquitoes’ midgut. Regarding the effect of CinCu, the copper-complex was not able to induce inhibition of P. vivax infection; however, it was able to induce an important reduction in the intensity of oocyst formation by about 2.4 times. It is plausible that the metallo-compound also be able to interfere with the differentiation of parasite stages and/or ookinete-secreted chitinase into the peritrophic matrix of mosquitoes, promoting a reduction in the number of oocysts formed. Taken together, the results suggest that this compound is promising as a prototype for the development of new antimalarial drugs. Furthermore, our study can draw a new pathway for repositioning already-known antimalarial drugs by editing their chemical structure to improve the antimalarial activity against the asexual and sexual stages of the parasite

    Ileal Intussusception Caused by Vanek's Tumor: A Case Report

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    Inflammatory fibroid polyps (Vanek's tumor) are rare benign localized lesions originating in the submucosa of the gastrointestinal tract. Intussusceptions due to inflammatory fibroid polyps are uncommon; moreover, ileo-ileal intussusception with small bowel necrosis and perforation has rarely been reported. We report a 56-year-old woman who was admitted two days after complaints of nausea and vomiting. Abdominal examination revealed distension, signs of gastrointestinal perforation and clanging intestinal sounds. The patient underwent a emergency laparotomy which found a 17-cm invaginated mid-ileal segment with necrosis, perforation and fecal peritonitis. The ileal segment was resected and single-layer end-to-end anastomosis was performed. Histopathological analysis showed an ulcerative lesion with variable cellularity, formed by spindle cells with small number of mitosis and an abundant inflammatory infiltrate comprising mainly eosinophils. Immunohistochemistry confirmed the diagnosis of ileal Vanek's tumor. Although inflammatory fibroid polyps are seen very rarely in adults, they are among the probable diagnoses that should be considered in obstructive tumors of the small bowel causing intussusception with intestinal necrosis and perforation

    Jejunal Diverticular Perforation due to Enterolith

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    Jejunal diverticulosis is a rare entity with variable clinical and anatomical presentations. Although there is no consensus on the management of asymptomatic jejunal diverticular disease, some complications are potentially life-threatening and require early surgical treatment. Small bowel perforation secondary to jejunal diverticulitis by enteroliths is rare. The aim of this study was to report a case of small intestinal perforation caused by a large jejunal enterolith. An 86-year-old woman was admitted with signs of diffuse peritonitis. After initial fluid recovery the patient underwent emergency laparotomy. The surgery showed that she had small bowel diverticular disease, mainly localized in the proximal jejunum. The peritonitis was due to intestinal perforation caused by an enterolith 12 cm in length, localized inside one of these diverticula. The intestinal segment containing the perforated diverticulum with the enterolith was removed and an end-to-end anastomosis was done to reconstruct the intestinal transit. The patient recovered well and was discharged from hospital on the 5th postoperative day. There were no signs of abdominal pain 1 year after the surgical procedure. Although jejunal diverticular disease with its complications, such as formation of enteroliths, is difficult to suspect in patients with peritonitis, it should be considered as a possible source of abdominal infection in the elderly patient when more common diagnoses have been excluded

    Aspectos Gerais Do Lúpus Eritematoso Sistêmico

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    O lúpus eritematoso sistêmico (LES) é uma doença inflamatória crônica, rara e de natureza autoimune, que oferece diversos riscos e limitações para os seus portadores. Uma das representações da doença é afetar múltiplas células sendo as principais as da pele, das juntas, do sangue e dos rins, podendo apresentar diversas complicações no decorrer da vida. Além disso, alguns estudos apontam que o LES pode afetar o sistema nervoso central (SNC), porém estas alterações não tiveram comprovações o suficiente para afirmação deste conteúdo. Os episódios de LES acometem principalmente pacientes do sexo feminino e a associação de fatores ambientais, hormonais e genéticos é indicada por sua etiologia. Objetivo: consiste em uma revisão de informações relativas aos aspectos clínicos do lúpus eritematoso sistêmico. Método: Busca de informações em bases científicas online, incluído apenas estudos realizados nos últimos 30 anos Conclusão: LES é uma doença de natureza autoimune, crônica e sua etiologia está ligada a uma herança genética e a fatores exógenos e suas manifestações clínicas variam. Os anticorpos mais analisados no lúpus são, geralmente, IgM ou IgG. Na suspeita da doença são utilizados critérios mundialmente estabelecidos pela American College of Rheumatology (ACR). Os pacientes com LES possuem uma considerável gama de tratamentos

    Antifungal activity of amphotericin B conjugated to nanosized magnetite in the treatment of paracoccidioidomycosis

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    This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid) magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications

    Worldwide COVID-19 spreading explained: traveling numbers as a primary driver for the pandemic.

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    The spread of SARS-CoV-2 and the distribution of cases worldwide followed no clear biogeographic, climatic, or cultural trend. Conversely, the internationally busiest cities in all countries tended to be the hardest hit, suggesting a basic, mathematically neutral pattern of the new coronavirus early dissemination. We tested whether the number of flight passengers per time and the number of international frontiers could explain the number of cases of COVID-19 worldwide by a stepwise regression. Analysis were taken by 22 May 2020, a period when one would claim that early patterns of the pandemic establishment were still detectable, despite of community transmission in various places. The number of passengers arriving in a country and the number of international borders explained significantly 49% of the variance in the distribution of the number of cases of COVID-19, and number of passengers explained significantly 14.2% of data variance for cases per million inhabitants. Ecological neutral theory may explain a considerable part of the early distribution of SARS-CoV-2 and should be taken into consideration to define preventive international actions before a next pandemic

    Identification of metabolic pathways influenced by the G-protein coupled receptors GprB and GprD in Aspergillus nidulans

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    Heterotrimeric G-protein-mediated signaling pathways play a pivotal role in transmembrane signaling in eukaryotes. Our main aim was to identify signaling pathways regulated by A. nidulans GprB and GprD G-protein coupled receptors (GPCRs). When these two null mutant strains were compared to the wild-type strain, the DeltagprB mutant showed an increased protein kinase A (PKA) activity while growing in glucose 1% and during starvation. In contrast, the DeltagprD has a much lower PKA activity upon starvation. Transcriptomics and (1)H NMR-based metabolomics were performed on two single null mutants grown on glucose. We noted modulation in the expression of 11 secondary metabolism gene clusters when the DeltagprB and DeltagprD mutant strains were grown in 1% glucose. Several members of the sterigmatocystin-aflatoxin gene cluster presented down-regulation in both mutant strains. The genes of the NR-PKS monodictyphenone biosynthesis cluster had overall increased mRNA accumulation in DeltagprB, while in the DeltagprD mutant strain the genes had decreased mRNA accumulation. Principal component analysis of the metabolomic data demonstrated that there was a significant metabolite shift in the DeltagprD strain. The (1)H NMR analysis revealed significant expression of essential amino acids with elevated levels in the DeltagprD strain, compared to the wild-type and DeltagprB strains. With the results, we demonstrated the differential expression of a variety of genes related mainly to secondary metabolism, sexual development, stress signaling, and amino acid metabolism. We propose that the absence of GPCRs triggered stress responses at the genetic level. The data suggested an intimate relationship among different G-protein coupled receptors, fine-tune regulation of secondary and amino acid metabolisms, and fungal development
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