Artigos e Materiais de Revistas Científicas - LIM/06
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A coleção de Artigos e Materiais de Revistas Científicas engloba artigos originais, artigos de revisão, artigos de atualização, artigos técnicos, relatos de experiências, resenhas, ensaios, editoriais, cartas ao editor, debates, notas científicas e técnicas, depoimentos, entrevistas e pontos de vista. Consideram-se como artigos científicos originais os trabalhos redigidos para divulgação de informações e resultados sobre determinada pesquisa científica, publicados em periódico científico após avaliação por outros pesquisadores.
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- Enhancing the antischistosomal activity of carvacryl acetate using nanoemulsion(2023) SOUZA, Rafael L. de; MENGARDA, Ana C.; ROQUINI, Daniel B.; MELO, Camila O.; MORAIS, Mayara C. de; ESPIRITO-SANTO, Maria Cristina; SOUSA, Damiao P. de; MORAES, Josue de; OLIVEIRA, Elquio E.Aim: To formulate a carvacryl acetate nanoemulsion (CANE) and test its antischistosomal activity. Materials & methods: CANE was prepared and tested in vitro on Schistosoma mansoni adult worms and both human and animal cell lines. Next, CANE was administered orally to mice infected with either a prepatent infection or a patent infection of S. mansoni. Results: CANE was stable during 90 days of analysis. CANE showed in vitro anthelmintic activity, and no cytotoxic effects were observed. In vivo, CANE was more effective than the free compounds in reducing worm burden and egg production. Treatment with CANE was more effective for prepatent infections than praziquantel. Conclusion: CANE improves antiparasitic properties and may be a promising delivery system for schistosomiasis treatment.
- COVID-19: detection methods in post-mortem samples(2023) TEDESCO, Ilaria; MARINO, Federica Zito; RONCHI, Andrea; NETO, Amaro Nunes Duarte; DOLHNIKOFF, Marisa; MUNICINO, Maurizio; CAMPOBASSO, Carlo Pietro; PANNONE, Giuseppe; FRANCO, RenatoCOVID-19 identification is routinely performed on fresh samples, such as nasopharyngeal and oropharyngeal swabs, even if, the detection of the virus in formalin-fixed paraffinembedded (FFPE) autopsy tissues could help to underlie mechanisms of the pathogenesis that are not well understood. The gold standard for COVID-19 detection in FFPE samples remains the qRT-PCR as in swab samples, contextually other methods have been developed, including immunohistochemistry (IHC), and in situ hybridization (ISH). In this manuscript, we summarize the main data regarding the methods of COVID-19 detection in pulmonary and extra-pulmonary post-mortem samples, and especially the sensitivity and specificity of these assays will be discussed.
- Monkeypox Virus Immune Evasion and Eye Manifestation: Beyond Eyelid Implications(2023) LUCENA-NETO, Francisco D.; FALCAO, Luiz F. M.; VIEIRA-JUNIOR, Adolfo S.; MORAES, Evelly C. S.; DAVID, Joacy P. F.; SILVA, Camilla C.; SOUSA, Jorge R.; DUARTE, Maria I. S.; VASCONCELOS, Pedro F. C.; QUARESMA, Juarez A. S.Monkeypox virus (MPXV), belonging to the Poxviridae family and Orthopoxvirus genus, is closely related to the smallpox virus. Initial prodromal symptoms typically include headache, fever, and lymphadenopathy. This review aims to detail various ocular manifestations and immune evasion associated with the monkeypox viral infection and its complications, making it appropriate as a narrative review. Common external ocular manifestations of MPXV typically involve a generalized pustular rash, keratitis, discharges, and dried secretions related to conjunctival pustules, photophobia, and lacrimation. Orthopoxviruses can evade host immune responses by secreting proteins that antagonize the functions of host IFN gamma, CC and CXC chemokines, IL-1 beta, and the complement system. One of the most important transcription factors downstream of pattern recognition receptors binding is IRF3, which controls the expression of the crucial antiviral molecules IFN alpha and IFN beta. We strongly recommend that ophthalmologists include MPXV as part of their differential diagnosis when they encounter similar cases presenting with ophthalmic manifestations such as conjunctivitis, blepharitis, or corneal lesions. Furthermore, because non-vaccinated individuals are more likely to exhibit these symptoms, it is recommended that healthcare administrators prioritize smallpox vaccination for at-risk groups, including very young children, pregnant women, older adults, and immunocompromised individuals, especially those in close contact with MPXV cases.
- Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions(2023) QUARESMA, Tatiane Costa; VALENTIM, Livia de Aguiar; SOUSA, Jorge Rodrigues de; AARAO, Tinara Leila de Souza; FUZII, Hellen Thais; DUARTE, Maria Irma Seixas; SOUZA, Juarez de; QUARESMA, Juarez Antonio SimoesMycobacterium leprae is the etiological agent of leprosy. Macrophages (M phi s) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of M phi subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with leprosy. Based on the database of treatment-na & iuml;ve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Par & aacute;, Bel & eacute;m, routine clinical screening samples were identified. The monolabeling protocol was used for M1 macrophages (iNOS, IL-6, TNF-alpha) and M2 macrophages (IL-10, IL-13, CD163, Arginase 1, TGF-beta, FGFb), and the double-labeling protocol was used for M4 macrophages (IL-6, MMP7, MRP8, TNF-alpha e CD68). To confirm the M4 macrophage lineage, double labeling of the monoclonal antibodies CD68 and MRP8 was also performed. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 +/- 1.3, p < 0.0001), Borderline (1.6 +/- 0.4, p < 0.0001), and tuberculoid (TT) (12.5 +/- 1.8, p < 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 +/- 2.3, p < 0.0001), Borderline (1.3 +/- 0.2, p < 0.0001), and TT (3.2 +/- 0.7, p < 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 +/- 1.7, p < 0.0001), Borderline (1.2 +/- 0.2, p < 0.0001), and TT (2.6 +/- 0.7, p < 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2 x TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 M phi s constituted the predominant M phi subpopulation in the TT and Borderline forms of leprosy, whereas the M2 M phi s showed increased immunoexpression and M4 was the predominant M phi phenotype in VV leprosy. These results confirm the relationship of the M phi profile with chronic pathological processes of the inflammatory response in leprosy.
- Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection(2023) RUSSO, Momtchilo; MENDES-CORREA, Maria Cassia; LINS, Bruna B.; KERSTEN, Victor; PERNAMBUCO, Paulo C. A.; MARTINS, Toni Ricardo; TOZETTO-MENDOZA, Tania Regina; BOAS, Lucy Santos Vilas; GOMES, Brisa Moreira; DATI, Livia Mendonca Munhoz; DUARTE-NETO, Amaro Nunes; REIGADO, Gustavo Roncoli; FREDERICO, Ana Beatriz T.; CUNHA, Danielle R. de A.; PAULA, Anderson Vicente de; SILVA, Jose Igor G. da; VASCONCELOS, Carlos F. Moreira; CHAMBERGO, Felipe S.; NUNES, Viviane Abreu; BOM, Ana Paula Dinis Ano; CASTILHO, Leda R.; MARTINS, Rodrigo A. P.; HIRATA, Mario Hiroyuki; MIROTTI, Luciana; TRIPP, Ralph A.Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as an adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight loss and mortality indicators. However, when compared with subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta, and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine, which was more robust than homologous immunity.
- Strongyloides infection screening in transplant candidates: What is the best strategy?(2023) GRYSCHEK, Ronaldo Cesar Borges; CORRAL, Marcelo Andreetta; SITTA, Renata Barnabe; GOTTARDI, Maiara; PIERROTTI, Ligia Camera; COSTA, Silvia Figueiredo; ABDALA, Edson; CHIEFFI, Pedro Paulo; PAULA, Fabiana Martins deBackground: The potential that Strongyloides stercoralis infection has to cause major morbidity and high mortality when the disseminated form occurs in transplant patients is of particular concern.Methods: In this study, the objective was to observe S. stercoralis infection in patients who are candidates for transplantation by using parasitological, serological, and molecular techniques and to propose an algorithm for the detection of that infection in transplant candidates.Results: By parasitological techniques, 10% of fecal samples were positive. Anti-Strongyloides antibodies immunoglobulin G were detected in 19.3% and 20.7% of patients by immunofluorescence assay and enzyme-linked immunosorbent assay, respectively. S. stercoralis DNA was observed in 17.3% of samples by conventional polymerase chain reaction and 32.7% of samples by quantitative polymerase chain reaction (qPCR).Conclusion: The set of results allows us to reinforce that a positive result by parasitological techniques and/or qPCR indicates that the specific treatment should be applied. However, the improvement of diagnostic techniques may suggest changes in the screening for strongyloidiasis in these patients. image
- Transcriptome analysis of six tissues obtained post-mortem from sepsis patients(2023) SILVA, Fabiano Pinheiro da; GONCALVES, Andre Nicolau Aquime; DUARTE-NETO, Amaro Nunes; DIAS, Thomaz Luescher; BARBEIRO, Hermes Vieira; BREDA, Cristiane Naffah Souza; BREDA, Leandro Carvalho Dantas; CAMARA, Niels Olsen Saraiva; NAKAYA, Helder I.Septic shock is a life-threatening clinical condition characterized by a robust immune inflammatory response to disseminated infection. Little is known about its impact on the transcriptome of distinct human tissues. To address this, we performed RNA sequencing of samples from the prefrontal cortex, hippocampus, heart, lung, kidney and colon of seven individuals who succumbed to sepsis and seven uninfected controls. We identified that the lungs and colon were the most affected organs. While gene activation dominated, strong inhibitory signals were also detected, particularly in the lungs. We found that septic shock is an extremely heterogeneous disease, not only when different individuals are investigated, but also when comparing different tissues of the same patient. However, several pathways, such as respiratory electron transport and other metabolic functions, revealed distinctive alterations, providing evidence that tissue specificity is a hallmark of sepsis. Strikingly, we found evident signals of accelerated ageing in our sepsis population.
- The Existing Drug Nifuroxazide as an Antischistosomal Agent: In Vitro, In Vivo, and In Silico Studies of Macromolecular Targets(2023) ROQUINI, Vinicius; MENGARDA, Ana C. C.; CAJAS, Rayssa A. A.; MARTINS-DA-SILVA, Milene F. F.; GODOY-SILVA, Julia; SANTOS, Gustavo A. A.; ESPIRITO-SANTO, Maria Cristina C.; PAVANI, Thais F. A.; MELO, Vanusa A. A.; SALVADORI, Maria C. C.; TEIXEIRA, Fernanda S. S.; RANDO, Daniela G. G.; MORAES, Josue deSchistosomiasis is a parasitic disease that afflicts approximately 250 million people worldwide. There is an urgent demand for new antiparasitic agents because praziquantel, the only drug available for the treatment of schistosomiasis, is not universally effective and may derail current progress toward the WHO goal of eliminating this disease as a public health problem by 2030. Nifuroxazide (NFZ), an oral nitrofuran antibiotic, has recently been explored to be repurposed for parasitic diseases. Here, in vitro, in vivo, and in silico studies were conducted to evaluate the activity of NFZ on Schistosoma mansoni. The in vitro study showed significant antiparasitic activity, with 50% effective concentration (EC50) and 90% effective concentration (EC90) values of 8.2 to 10.8 and 13.7 to 19.3 mu M, respectively. NFZ also affected worm pairing and egg production and induced severe damage to the tegument of schistosomes. In vivo, a single oral dose of NFZ (400 mg/kg of body weight) to mice harboring either prepatent or patent S. mansoni infection significantly reduced the total worm burden (similar to 40%). In patent infection, NFZ achieved a high reduction in the number of eggs (similar to 80%), but the drug caused a low reduction in the egg burden of animals with prepatent infection. Finally, results from in silico target fishing methods predicted that serine/threonine kinases could be one of the potential targets for NFZ in S. mansoni. Overall, the present study revealed that NFZ possesses antischistosomal properties, mainly in terms of egg burden reduction in animals with patent S. mansoni infection. IMPORTANCE The increasing recognition of the burden imposed by helminthiasis, associated with the limited therapeutic arsenal, has led to initiatives and strategies to research and develop new drugs for the treatment of schistosomiasis. One of these strategies is drug repurposing, which considers low-risk compounds with potentially reduced costs and shorter time for development. In this study, nifuroxazide (NFZ) was evaluated for its anti-Schistosoma mansoni potential through in vitro, in vivo, and in silico studies. In vitro, NFZ affected worm pairing and egg production and induced severe damage to the tegument of schistosomes. In vivo, a single oral dose of NFZ (400 mg/kg) to mice harboring either prepatent or patent S. mansoni infection significantly reduced the total worm burden and egg production. In silico investigations have identified serine/threonine kinases as a molecular target for NFZ. Collectively, these results implied that NFZ might be a potential therapeutic candidate for the treatment of schistosomiasis.
- Understanding yellow fever-associated myocardial injury: an autopsy study(2023) GIUGNI, Fernando Rabioglio; DEMARCHIAIELLO, Vera; FARIA, Caroline Silverio; POUR, Shahab Zaki; CUNHA, Marielton dos Passos; GIUGNI, Melina Valdo; PINESI, Henrique Trombini; LEDESMA, Felipe Lourenco; MORAIS, Carolina Esteves; HO, Yeh-Li; SZTAJNBOK, Jaques; FERNEZLIAN, Sandra de Morais; SILVA, Luiz Fernando Ferraz da; MAUAD, Thais; ALVES, Venancio Avancini Ferreira; SALDIVA, Paulo Hilario do Nascimento; ANTONANGELO, Leila; DOLHNIKOFF, Marisa; DUARTE-NETO, Amaro NunesBackground Yellow fever (YF) is a viral hemorrhagic fever, endemic in parts of South America and Africa. There is scarce evidence about the pathogenesis of the myocardial injury. The objective of this study is to evaluate the cardiac pathology in fatal cases of YF.Methods This retrospective autopsy study included cases from the Sao Paulo (Brazil) epidemic of 2017-2019. We reviewed medical records and performed cardiac tissue histopathological evaluation, electron microscopy, immunohistochemical assays, RT-qPCR for YF virus (YFV)-RNA, and proteomics analysis on inflammatory and endothelial biomarkers.Findings Seventy-three confirmed YF cases with a median age of 48 (34-60) years were included. We observed myocardial fibrosis in 68 (93.2%) patients; cardiomyocyte hypertrophy in 68 (93.2%); endothelial alterations in 67 (91.8%); fiber necrosis in 50 (68.5%); viral myocarditis in 9 (12.3%); and secondary myocarditis in 5 (6.8%). Four out of five patients with 17DD vaccine-associated viscerotropic disease presented with myocarditis. The cardiac conduction system showed edema, hemorrhages and endothelial fibrinoid necrosis. Immunohistochemistry detected CD68-positive inflammatory interstitial cells and YFV antigens in endothelial and inflammatory cells. YFV-RNA was detected positive in 95.7% of the cardiac samples. The proteomics analysis demonstrated that YF patients had higher levels of multiple inflammatory and endothelial biomarkers in comparison to cardiovascular controls, and higher levels of interferon gamma-induced protein 10 (IP-10) in comparison to sepsis (p = 0.01) and cardiovascular controls (p < 0.001) in Dunn test.Interpretation Myocardial injury is frequent in severe YF, due to multifactorial mechanisms, including direct YFV-mediated damage, endothelial cell injury, and inflammatory response, with a possible prominent role for IP-10.
- COVID-19 induces more pronounced extracellular matrix deposition than other causes of ARDS(2023) COSTA, Natalia de Souza Xavier; RIBEIRO JUNIOR, Gabriel; NASCIMENTO, Ellen Caroline Toledo do; BRITO, Jose Mara de; ANTONANGELO, Leila; FARIA, Caroline Silverio; MONTEIRO, Jhonatas Sirino; SETUBAL, Joao Carlos; PINHO, Joao Renato Rebello; PEREIRA, Roberta Verciano; SEELAENDER, Marilia; CASTRO, Gabriela Salim de; LIMA, Joanna D. C. C.; MONTEIRO, Renata Aparecida de Almeida; DUARTE-NETO, Amaro Nunes; SALDIVA, Paulo Hilario Nascimento; SILVA, Luiz Fernando Ferraz da; DOLHNIKOFF, Marisa; MAUAD, ThaisBackgroundLung fibrosis is a major concern in severe COVID-19 patients undergoing mechanical ventilation (MV). Lung fibrosis frequency in post-COVID syndrome is highly variable and even if the risk is proportionally small, many patients could be affected. However, there is still no data on lung extracellular matrix (ECM) composition in severe COVID-19 and whether it is different from other aetiologies of ARDS.MethodsWe have quantified different ECM elements and TGF-beta expression in lung tissue of 28 fatal COVID-19 cases and compared to 27 patients that died of other causes of ARDS, divided according to MV duration (up to six days or seven days or more). In COVID-19 cases, ECM elements were correlated with lung transcriptomics and cytokines profile.ResultsWe observed that COVID-19 cases presented significant increased deposition of collagen, fibronectin, versican, and TGF-beta, and decreased decorin density when compared to non-COVID-19 cases of similar MV duration. TGF-beta was precociously increased in COVID-19 patients with MV duration up to six days. Lung collagen was higher in women with COVID-19, with a transition of upregulated genes related to fibrillogenesis to collagen production and ECM disassembly along the MV course.ConclusionsFatal COVID-19 is associated with an early TGF-beta expression lung environment after the MV onset, followed by a disordered ECM assembly. This uncontrolled process resulted in a prominent collagen deposition when compared to other causes of ARDS. Our data provides pathological substrates to better understand the high prevalence of pulmonary abnormalities in patients surviving COVID-19.
- One health approach to toxocariasis in quilombola communities of southern Brazil(2023) SANTAREM, Vamilton Alvares; PANAZZOLO, Giovanni Kalempa; KMETIUK, Louise Bach; DOMINGUES, Orlei Jose; FERREIRA, Isabella Braghin; SOUZA FILHO, Roberto Teixeira de; FARINHAS, Joao Henrique; DOLINE, Fernando Rodrigo; LESCANO, Susana Angelica Zevallos; BIONDO, Leandro Meneguelli; GIUFFRIDA, Rogerio; BIONDO, Alexander Welker; FAVERO, Giovani MarinoBackground Toxocariasis has been listed among the most neglected parasitic diseases worldwide, with approximately one fifth of the global population exposed, particularly those living under poverty. In Brazil, communities of descendants of enslaved blacks (quilombola) have historically had some of the highest rates of vulnerability and poverty, characterized by lack of health assistance, poor quality of life, and nutritional insecurity.Methods A cross-sectional sampling of quilombola individuals living in four communities of southern Brazil, as well as their dogs and the soil, was carried out from December 2021 to March 2022. Sociodemographic and other information such as water source, alimentary habits, and dog and cat ownership were gathered using a semi-structured questionnaire for assessing toxocariasis risk factors. Human serum samples were tested by ELISA for anti-Toxocara spp. IgG antibody detection was carried out on dog feces and hair, and soil samples were surveyed for presence of Toxocara spp. eggs.Results Overall, 172/208 individuals (82.7%, 95% CI = 77.0-87.2) were seropositive, the highest seroprevalence rate to date in Brazil. Male gender (P = 0.029), educational level (P = 0.026), and drinking water source (P = 0.043) were associated with seropositivity by univariate analysis. Final logistic regression revealed increased odds (P = 0.017, OR = 7.6, 95% CI = 1.5-42.7) to have seropositivity in individuals > 50 years old (< 10 years old). As expected, individuals with soil contact were more likely seropositive (P = 0.038, OR = 4.4, 95% CI = 1.1-18.8). Although retrieved in only 5/96 (5.2%) dog feces, Toxocara spp. eggs were found in 18/60 (30.0%) soil samples.Conclusions The high vulnerability and seroprevalence observed in quilombola communities clearly demand a One Health approach for detection, monitoring, and prevention of infection by Toxocara spp. in both human and dog populations.
- Risk factors for toxocariasis during incarceration: the One Health intervention approach(2023) SANTAREM, Vamilton Alvares; PINTO, Gabriel Luis Brucinski; SOUZA FILHO, Roberto Teixeira de; FERREIRA, Isabella Braghin; LESCANO, Susana Angelica Zevallos; GONZALES, William Henry Roldan; KOSLOSKI, Jully; RIBEIRO, Juliano; GIUFFRIDA, Rogerio; SANTOS, Andrea Pires dos; KMETIUK, Louise Bach; BIONDO, Alexander WelkerDespite potential exposure to soil-transmitted helminths, especially when stray dogs and cats are present, toxocariasis in inmate populations remains to be established. Accordingly, the present study assessed the seroprevalence and associated risk factors of toxocariasis at the Women's State Penitentiary of Parana, Brazil. A total of 234/370 (63.2%; 95% CI 58.2-68.0) women inmates and 28/87 (32.2%; 95% CI 23.3-42.6) correctional officers were seropositive for anti-Toxocara spp. IgG by ELISA, with inmates 2.62-fold more likely positive (p = 0.00000026). The univariate model has identified that non-white (OR = 1.58, p = 0.047) and older than 39 years (OR = 1.28, p = 0.032) inmates were associated with mild but significant odds for seropositivity. Elementary or higher educational level was considered a protective factor for seropositivity. The presence of Toxocara spp. eggs was observed in 10/15 (66.7%) collected soil samples by centrifuge-flotation in Zinc Sulfate, and molecular analysis by PCR identified only Toxocara cati in these eggs. An intervention program was established with regular trap-neuter-release, with gradual removal for adoption (donation campaigns), treatment, and euthanasia when necessary (particularly due to advanced sporotrichosis). In addition, an educational awareness agenda was proposed, aiming to reduce soil contamination and accidental intake by the incarcerated population. A total of 40 feral cats were trapped, 20 males and 20 females, mostly adults. After trapping, 36 cats were neutered, treated, and microchipped in the Veterinary Teaching Hospital (VTH) at the Federal University of Parana. Five trapped feral cats were euthanized, four diagnosed with advanced sporotrichosis, and one already neutered cat (not herein) with complications due to feline immunodeficiency virus (FIV). Female inmates presented higher seroprevalence for Toxocara spp. antibodies when compared to correctional officers, significantly associated with age, selfdeclared ethnicity (non-white), and lack of formal education. Despite the non-natural scenario of a state penitentiary, the One Health approach of Toxocara spp. has highlighted the interdisciplinary nature of the study and its relevance in understanding the complex interactions between human, animal, and environmental factors, particularly impacting female inmates. Further studies should establish the rate of inmate infection over time while deprived of liberty.
- One health approach to toxocariasis in Brazilian indigenous populations, their dogs, and soil contamination(2023) SANTAREM, Vamilton Alvares; DOLINE, Fernando Rodrigo; FERREIRA, Isabella Braghin; FARINHAS, Joao Henrique; BIONDO, Leandro Meneguelli; SOUZA FILHO, Roberto Teixeira de; PETTAN-BREWER, Christina; GIUFFRIDA, Rogerio; LESCANO, Susana Angelica Zevallos; SANTOS, Andrea Pires dos; KMETIUK, Louise Bach; BIONDO, Alexander WelkerIntroduction: Although socioeconomic vulnerability and lifestyle factors may contribute to the transmission of Toxocara spp., no study has investigated indigenous populations in Brazil using the One Health approach. Methods: Accordingly, this study assessed anti-Toxocara spp. antibodies in Brazilian indigenous people and healthcare professionals by enzyme-linked immunosorbent assay. Presence of Toxocara spp. eggs (feces and hair) in dogs as definitive hosts and in soil samples of the indigenous communities were also recovered and molecularly investigated. Results: Overall, 342/463 (73.9%) indigenous individuals and 46/147 (31.3%) non-indigenous healthcare professionals were seropositive for Toxocara spp. In addition, T. canis eggs were retrieved from 9/194 (4.6%) dog fecal samples and 4/204 (2.0%) dog hair samples, mainly from the Parana State communities (3/42; 7.1%). Soil contamination was observed only in the Parana State communities (36/90; 40.0%), with the molecular detection of T. canis. River water consumption was also associated with indigenous seropositivity (Odds ratio, 11.4). Discussion: Indigenous individuals in Parana State communities were 2.72-fold more likely to be seropositive than those in Sao Paulo State, likely due to a lack of sanitary infrastructure. In this scenario, a primarily soil-transmitted disease may also have become waterborne, with embryonated eggs probably spread to water supplies by rain. Full-time healthcare professionals in daily contact with indigenous communities were 9.2-fold more likely to be seropositive than professionals who visited sporadically, suggesting exposure to Toxocara spp. during their work and raising health concerns. In addition, the findings herein showed a significantly higher seroprevalence in indigenous people than in healthcare workers (.2 = 85.5; p < 0.0001), likely due to overtime exposure to Toxocara spp. In conclusion, Brazilian indigenous communities are highly exposed to toxocariasis, with poor infrastructure and contact with contaminated river water as associated risk factors and a higher risk of infection in healthcare professionals working full-time in these communities.
- TREATMENT WITH HUMAN UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS IN A PIG MODEL OF SEPSIS-INDUCED ACUTE KIDNEY INJURY: EFFECTS ON MICROVASCULAR ENDOTHELIAL CELLS AND TUBULAR CELLS IN THE KIDNEY(2023) MAIA, Debora Rothstein Ramos; OTSUKI, Denise Aya; RODRIGUES, Camila Eleuterio; ZBORIL, Sabrina; SANCHES, Talita Rojas; NETO, Amaro Nunes Duarte; ANDRADE, Lucia; AULER, Jose Otavio CostaBackground: Approximately 50% of patients with sepsis develop acute kidney injury (AKI), which is predictive of poor outcomes, with mortality rates of up to 70%. The endothelium is a major target for treatments aimed at preventing the complications of sepsis. We hypothesized that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could attenuate tubular and endothelial injury in a porcine model of sepsis-induced AKI. Methods: Anesthetized pigs were induced to fecal peritonitis, resulting in septic shock, and were randomized to treatment with fluids, vasopressors, and antibiotics (sepsis group; n = 11) or to that same treatment plus infusion of 1 x 106 cells/kg of hUC-MSCs (sepsis+MSC group; n = 11). Results: At 24 h after sepsis induction, changes in serum creatinine and mean arterial pressure were comparable between the two groups, as was mortality. However, the sepsis+MSC group showed some significant differences in comparison with the sepsis group: lower fractional excretions of sodium and potassium; greater epithelial sodium channel protein expression; and lower protein expression of the Na-K-2Cl cotransporter and aquaporin 2 in the renal medulla. Expression of P-selectin, thrombomodulin, and vascular endothelial growth factor was significantly lower in the sepsis+MSC group than in the sepsis group, whereas that of Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-kappa B) was lower in the former. Conclusion: Treatment with hUC-MSCs seems to protect endothelial and tubular cells in sepsis-induced AKI, possibly via the TLR4/NF-kappa B signaling pathway. Therefore, it might be an effective treatment for sepsis-induced AKI.
- N-(4-Methoxyphenyl)Pentanamide, a Simplified Derivative of Albendazole, Displays Anthelmintic Properties against the Nematode Toxocara canis(2022) SILVA, Tais C.; MENGARDA, Ana C.; LEMES, Bruna L.; LESCANO, Susana A. Z.; SOUZA, Dalete Christine S.; LAGO, Joao Henrique G.; MORAESA, Josue deInfections caused by parasitic helminths have enormous health, social, and economic impacts worldwide. The treatment and control of these diseases have been dependent on a limited set of drugs, many of which have become less effective, necessitating the search for novel anthelmintic agents. In this study, a simplified compound, N-(4-methoxyphenyl)pentanamide (N4MP), based on the structure of the most widely used anthelmintic (albendazole), was chemically prepared using 4-anisidine and pentanoic acid. N-(4-Methoxyphenyl)pentanamide was evaluated in vitro against the nematode Toxocara canis, an ascarid roundworm of animals that can infect humans. Similar to albendazole, bioassays showed that N-(4-methoxyphenyl)pentanamide affected the viability of parasites in a time- and concentration-dependent manner. Interestingly, N-(4-methoxyphenyl)pentanamide showed a profile of lower cytotoxicity to human and animal cell lines than albendazole. Pharmacokinetic, drug-likeness, and medicinal chemistry friendliness studies demonstrated an excellent drug-likeness profile for N-(4-methoxyphenyl)pentanamide as well as an adherence to major pharmaceutical companies' filters. Collectively, the results of this study demonstrate that the molecular simplification of albendazole to give N-(4-methoxyphenyl)pentanamide may be an important pipeline in the discovery of novel anthelmintic agents. IMPORTANCE Infections caused by parasitic helminths have enormous health, social, and economic impacts worldwide. The treatment and control of these diseases have been dependent on a limited set of drugs, many of which have become less effective, necessitating the search for novel anthelmintic agents. Considering this scenario, the present study reports the preparation of N-(4-methoxyphenyl)pentanamide (N4MP), a simplified molecule based on the structure of the most widely used anthelmintic (albendazole). N4MP was evaluated in vitro against the nematode Toxocara canis, a common ascarid roundworm of domestic animals that can infect humans. Similar to albendazole, bioassays showed that N4MP affected the viability of parasites in a time- and concentration-dependent manner but displayed a profile of lower cytotoxicity to human and animal cell lines than albendazole. Therefore, this study demonstrates that the molecular simplification of albendazole to give N4MP may be an important pipeline in the discovery of novel anthelmintic agents.
- Risk factors for cancer in patients with primary biliary cholangitis and autoimmune hepatitis and primary biliary cholangitis overlap syndrome(2023) BRAGA, Michelle Harriz; CANCADO, Guilherme Grossi Lopes; BITTENCOURT, Paulo Lisboa; COUTO, Claudia Alves; GUEDES, Laura Vilar; LIMA, Andre Mourao Costa; FERRAZ, Maria Lucia Gomes; VILLELA-NOGUEIRA, Cristiane Alves; NARDELLI, Mateus Jorge; FARIA, Luciana Costa; GOMES, Nathalia Mota de Faria; OLIVEIRA, Elze Maria Gomes; ROTMAN, Vivian; OLIVEIRA, Maria Beatriz; CUNHA, Simone Muniz Carvalho Fernandes da; CUNHA-SILVA, Marlone; MENDES, Liliana Sampaio Costa; IVANTES, Claudia Alexandra Pontes; CODES, Liana; BORGES, Valeria Ferreira de Almeida e; PACE, Fabio Heleno de Lima; PESSOA, Mario Guimaraes; SIGNORELLI, Izabelle Venturini; CORAL, Gabriela Perdomo; GALIZZI FILHO, Joao; CHAGAS, Aline Lopes; TERRABUIO, Debora Raquel Benedita; CANCADO, Eduardo Luiz RachidIntroduction and objectives: Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) and PBC over-lap syndrome (AIH/PBC) have been associated with a higher risk of hepatocellular carcinoma (HCC) and extra-hepatic malignancy (EHM). This study aims to assess potential risk factors associated with cancer development in PBC and AIH/PBC. Materials and methods: The Brazilian Cholestasis Study Group database was reviewed to compare clinical and laboratory features of PBC patients with HCC and EHM with those without cancer. Results: Among the 752 PBC patients enrolled, 64 of them with AIH/PBC, 87 cancers were identified in 72 patients, including 20 cases of HCC and 67 of EHM. Patients with HCC had a higher prevalence of cirrhosis
- Oral lichen planus: case series and experience in a tertiary dermatology service in Brazil(2023) ERTHAL, Aline; LOURENCO, Silvia Vanessa; NICO, Marcello Menta SimonsenBackground: Lichen planus is an inflammatory disease that can affect both the skin and mucous membranes, including the oral mucosa. There is very little original Brazilian dermatology literature about oral lichen planus. Objective: To describe the clinical, pathological, and treatment data of 201 patients diagnosed with oral lichen planus followed at the Stomatology Outpatient Clinic of Hospital das Clinicas, Universidade de Sao Paulo, from 2003 to 2021. Method: The patients demographic profile, the morpho-topographic features of the lesions, the treatment employed, and the possible presence of squamous cell carcinoma were analyzed. Results: The disease was more common in women over 50 years of age, tending to be chronic, with a large number of cases showing cicatricial sequelae in the mucosa. Topical treatment with potent corticosteroids was shown to be effective in the vast majority of cases. Squamous cell carcinoma in oral lichen planus cicatricial sequelae was observed in eight cases. Study limitations: Retrospective study of medical records, with gaps regarding the filling out of data; unequal observation time among the studied cases. Conclusions: This is the largest Brazilian dermatology series on oral lichen planus. The response to topical corticoid therapy was excellent in the vast majority of cases. The high prevalence of atrophic lesions, demonstrating the chronicity and tissue destruction potential of this disease, may explain the large number of cases of squamous cell carcinoma. (c) 2023 Sociedade Brasileira de Dermatologia.
- Pernio during the COVID-19 pandemic and review of inflammation patterns and mechanisms of hypercoagulability(2020) CAVANAGH, G.; CRIADO, P. R.; PAGLIARI, C.; CARNEIRO, F. R. Oliveira; QUARESMA, J. A. Simões; CAPPEL, M. A.; WAMBIER, C.
- Chronic exposure to cigarette smoke transiently worsens the disease course in a mouse model of pulmonary paracoccidioidomycosis(2022) BUCCHERI, Renata; DUARTE-NETO, Amaro Nunes; SILVA, Flaviano Luiz Batista; HADDAD, Gabrielle Carvalho; SILVA, Leandro Buffoni Roque da; AZEVEDO NETTO, Raymundo; LEDESMA, Felipe Lourenço; TABORDA, Carlos Pelleschi; BENARD, GilABSTRACT Paracoccidioidomycosis (PCM) may present as an acute/subacute clinical form, characterized by a progressive disease arising from the airborne initial infection, or, most often, as an asymptomatic or subclinical infection that may manifest later during an individual’s life, the chronic form. Epidemiological studies show the existence of a strong association between smoking and the development of the chronic form. Current evidence demonstrates that cigarette smoke (CS) has immunosuppressive properties that could be implicated in the increasing susceptibility to the chronic form of PCM. To address this issue, we developed a murine model of a non-progressive pulmonary form of PCM that was exposed to CS at a magnitude that mimicked a moderate smoker. The chronic CS exposure started after 2 weeks and lasted up until 20 weeks post-infection, with the aim of mimicking human natural history, since it is estimated that individuals from endemic areas are infected early in life. The control group consisted of infected but not CS-exposed mice. We assessed the lung fungal burden (colony forming units [CFU]) and the area affected by the granulomatous inflammatory response, fungal dissemination to spleen and liver, and, by immunohistochemistry, the presence of CD4 and CD8 lymphocytes, CD68 and MAC-2 macrophages, and IFN-γ, IL-10 and TNF expressing cells within the granulomatous response. We detected a CS effect as early as 2 weeks after exposure (four weeks post-infection) when the lung CFU of exposed animals was significantly higher than in their non-exposed counterparts. At 12 weeks, the CS-exposed animals presented a more severe disease, as witnessed by the persistent higher lung fungal load (although it did not reach statistical significance [ p = 0.054]), greater dissemination to other organs, greater affected area of the lung, decreased IFN-γ/IL-10 ratio, and higher TNF expression within the granulomas, compared with CS-non-exposed mice. The number of CD4 and CD8 lymphocytes infiltrating the granulomas was similar between both mice groups, but there was a decrease in the number of MAC-2+ macrophages. No difference was noted in the CD68+ macrophage number. However, the follow-up in week 20 showed that the immunological effects of exposure to CS ceased, with both CS and NCS mice showing the same infectious features, i.e., a trend for resolution of the infection. In conclusion, we show that chronic CS-exposure alters the course of the disease in an experimental model of subclinical pulmonary PCM, confirming the epidemiological link between CS-exposure and the chronic form of PCM. However, we also show that this effect is transitory, being detected between 4- and 12-weeks post-infection but not thereafter. The possible immune mechanisms that mediate this effect and the reasons for its transitory effect are discussed.
- What else in times of COVID-19? The role of minimally invasive autopsy for the differential diagnosis of acute respiratory failure in a case of kala-azar(2023) GEBER-JUNIOR, Joao Carlos; MONTEIRO, Renata Aparecida de Almeida; ROCHA, Joao Wilson Pedro da; DUARTE, Edson Luiz Tarsia; NICODEMO, Elizabete; MUNHOZ, Olavo; PAIVA, Edison Ferreira de; MAUAD, Thais; SILVA, Luiz Fernando Ferraz da; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOFF, Marisa; DUARTE-NETO, Amaro NunesVisceral leishmaniasis (VL) is a chronic vector-borne zoonotic disease caused by trypanosomatids, considered endemic in 98 countries, mainly associated with poverty. About 50,000-90,000 cases of VL occur annually worldwide, and Brazil has the second largest number of cases in the world. The clinical picture of VL is fever, hepatosplenomegaly, and pancytopenia, progressing to death in 90% of cases due to secondary infections and multi-organ failure, if left untreated. We describe the case of a 25-year-old female who lived in the metropolitan area of Sao Paulo, who had recently taken touristic trips to several rural areas in Southeastern Brazil and was diagnosed post-mortem. During the hospitalization in a hospital reference for the treatment of COVID-19, the patient developed acute respiratory failure, with chest radiographic changes, and died due to refractory shock. The ultrasound-guided minimally invasive autopsy diagnosed VL (macrophages containing amastigote forms of Leishmania in the spleen, liver and bone marrow), as well as pneumonia and bloodstream infection by gram-negative bacilli.