RESUMO

Mycobacterium leprae is the etiological agent of leprosy. Macrophages (Mφs) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of Mφ subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with leprosy. Based on the database of treatment-naïve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Pará, Belém, routine clinical screening samples were identified. The monolabeling protocol was used for M1 macrophages (iNOS, IL-6, TNF-α) and M2 macrophages (IL-10, IL-13, CD163, Arginase 1, TGF-ß, FGFb), and the double-labeling protocol was used for M4 macrophages (IL-6, MMP7, MRP8, TNF-α 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 × TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 Mφs constituted the predominant Mφ subpopulation in the TT and Borderline forms of leprosy, whereas the M2 Mφs showed increased immunoexpression and M4 was the predominant Mφ phenotype in VV leprosy. These results confirm the relationship of the Mφ profile with chronic pathological processes of the inflammatory response in leprosy.

RESUMO

Arboviruses, such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV), present wide global dissemination and a pathogenic profile developed in infected individuals, from non-specific clinical conditions to severe forms, characterised by the promotion of significant lesions in different organs of the harbourer, culminating in multiple organ dysfunction. An analytical cross-sectional study was carried out via the histopathological analysis of 70 samples of liver patients, collected between 2000 and 2017, with confirmed laboratory diagnoses, who died due to infection and complications due to yellow fever (YF), dengue fever (DF), and chikungunya fever (CF), to characterise, quantify, and compare the patterns of histopathological alterations in the liver between the samples. Of the histopathological findings in the human liver samples, there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analysed. Hepatic involvement in cases of YF showed a greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis, and apoptosis were classified according to the degree of tissue damage from severe to very severe. Pathological abnormalities associated with YFV, DENV, and CHIKV infections showed a predominance of changes in the midzonal area. We also noted that, among the arboviruses studied, liver involvement in cases of YFV infection was more intense.

RESUMO

Leprosy is a chronic granulomatous disease that remains a serious public health problem in developing countries. According to the Madrid classification, leprosy presents in four clinical forms: two immunologically unstable forms (indeterminate and borderline) and two stable polar forms (tuberculoid and lepromatous). In leprosy, the relationship of cell death to clinical disease outcome remains unclear. Therefore, we investigated the extent of autophagy and different cell death mechanisms-such as apoptosis, necroptosis, and pyroptosis-in cutaneous lesions of patients with leprosy, as well as the role of these mechanisms in clinical disease progression. This cross-sectional analytical study included 30 patients with a confirmed diagnosis of leprosy, with 10 patients in each of the following groups: lepromatous (LL), tuberculoid (TT), and indeterminate (II) leprosy groups. For histopathological analysis, skin samples were subjected to haematoxylin-eosin staining and immunostaining for apoptotic and necroptotic markers. The results indicated that FasL expression was much higher in the LL form than in the TT and II forms. Similar results (higher expression in the LL form than in the TT and II forms) were observed for caspase 8, RIP1, and RIP3 expressions. MLKL, BAX, and caspase 3 expression levels were highest in the LL form, especially in globular foamy macrophages. Beclin-1 expression was highest in the TT form but was low in LL and II forms. Caspase 1 expression was highest in the LL form, followed by that in the TT and II forms. In conclusion, our study elucidates the role of different cell death mechanisms in the pathophysiology of various forms of leprosy and suggests measures that may be used to control the host response to infection and disease progression.

Assuntos

Hanseníase Virchowiana , Hanseníase , Apoptose , Estudos Transversais , Progressão da Doença , Humanos , Hanseníase/patologia , Mycobacterium leprae

RESUMO

Previous observational studies have demonstrated the development of pulmonary impairments in human T-lymphotropic virus type 1 (HTLV-1) infected individuals. The main observed lesions due to chronic inflammation of viral infection in situ are bronchiectasis and lung-scarring injuries. This lung inflammation may be the causal agent of restrictive and obstructive lung diseases, primarily in tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP-HAM) patients. We conducted a prospective cohort study to compare spirometry and high-resolution computed tomography (HRCT) findings among 28 HTLV-1-carrier patients over the course of 6 years (2014-2019) (male/female: 7/21; mean age: 54.7 ± 9.5, range: 41-68 years). Chest HRCT exams revealed the development and evolution of lung lesions related to TSP-HAM: including centrilobular nodules, parenchymal bands, lung cysts, bronchiectasis, ground-glass opacity, mosaic attenuation, and pleural thickening. Spirometry exams showed maintenance of respiratory function, with few alterations in parameters suggestive of obstructive and restrictive disorders primarily in individuals with lung lesions and TSP-HAM. The findings of the present study indicate that pulmonary disease related to HTLV-1 is a progressive disease, with development of new lung lesions, mainly in individuals with TSP-HAM. To improve clinical management of these individuals, we recommend that individuals diagnosed with PET-MAH undergo pulmonary evaluation.

Assuntos

Infecções por HTLV-I/diagnóstico por imagem , Lesão Pulmonar/diagnóstico por imagem , Pneumonia/diagnóstico por imagem , Adulto , Idoso , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos

RESUMO

This was a cross-sectional prospective study. We performed a multivariate statistical analysis of the neurological signs and symptoms of patients infected with human T cell lymphotropic virus type 1 (HTLV-1) in an attempt to separate them into distinct groups and identify clinical-neurological manifestations that could differentiate the various profiles. The study was performed in the city of Belém (state of Pará), located in the Amazon region of Brazil, from 2014 to 2016. We determined muscle strength and tone, reflexes, sensations, sphincter function, gait, and the Expanded Disability Status Scale score among individuals with HTLV-I. We then used exploratory statistical methods in an attempt to find different profiles and establish distinct groups. We analyzed 60 patients with HTLV-1. The filtering of the data, performed with mixed PCA, gave rise to a streamlined database with the most informative data and suggested the formation of three statistically distinct groups: asymptomatic carriers (AC), mono/oligosymptomatic (MOS), and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSPd), AC and MOS (p = 0.002), AC and HAM/TSPd (p < 0.001), and HAM/TSPd and MOS (p = 0.001). The subsequent cluster analysis confirmed the formation of three clusters. The classification and regression tree demonstrated that altered gait was the most important variable for the classification of an individual with HAM/TSPd and that, in the absence of this impairment, hyperreflexia characterized MOS. The present study was able to separate patients infected by HTLV-1 into three clinical groups (AC, HAM/TSPd, and MOS) and identify clinical manifestations that could differentiate the various patient groups.

Assuntos

Vírus Linfotrópico T Tipo 1 Humano/patogenicidade , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/fisiopatologia , Reflexo Anormal , Adulto , Doenças Assintomáticas , Análise por Conglomerados , Estudos Transversais , Avaliação da Deficiência , Feminino , Marcha/fisiologia , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Paraparesia Espástica Tropical/classificação , Paraparesia Espástica Tropical/virologia , Análise de Componente Principal , Estudos Prospectivos , Índice de Gravidade de Doença

RESUMO

BACKGROUND: Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection (STI) in the world. Approximately 80% of infected women are asymptomatic, although this infection can lead to serious complications in the female reproductive tract. Few data on Chlamydia infection are available in rural Amazonian communities. OBJECTIVES: To evaluate the prevalence of sexual C. trachomatis infection in women from Marajó Archipelago communities in the Amazon region of Brazil and to identify associated factors and genotypes. METHODS: We utilized amplification of the ompA gene by nested PCR. Positive samples were genotyped by sequencing. Study participants completed a questionnaire on social, epidemiological, and reproductive health variables. A Poisson regression was used to evaluate the degree of association of these variables with the infection. RESULTS: The sexual infection by C. trachomatis was observed in 4% (16/393) of the subjects, and was more often found in women aged ≤25 (14.3%; 95% CI = 2.83-35.47; p <0.001), and in women with a household income of less than one Brazilian monthly minimum wage (5.2%; 95% CI = 1.33-11.37; p = 0.014). The ompA gene was sequenced in 13 samples, revealing F genotypes (38.4%, n = 5), D (23%, n = 3), E (15.3%, n = 2), Ia (7.6%, N = 1), J (7.6%, n = 1) and B (7.6%, n = 1). CONCLUSIONS: We recorded a high prevalence of sexual infection by C. trachomatis in young and poor women from the interior of the Brazilian Amazon. This high prevalence and the frequencies of the main genotypes were similar to those found in major Brazilian urban centers. Our results reinforce the importance of the screening of this neglected infection, and the prevention of later sequelae in young women from rural and urban areas of Brazil.

Assuntos

Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis/fisiologia , Ilhas/epidemiologia , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Chlamydia trachomatis/genética , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , Saúde Reprodutiva , Fatores de Risco , Comportamento Sexual , Adulto Jovem

RESUMO

Objective To investigate the relation between oxidative stress markers, human papillomavirus infection and cervical cancer precursor lesions. Methods The study comprised women aged 14 to 60 years living in communities located by Amazon rivers in the state of Pará (Itaituba, Limoeiro do Ajuru and Bragança, 126, 68 and 43 women respectively). Papanicolau smears and polymerase chain reaction tests for human papillomavirus DNA detection were performed. Blood samples were collected to test malondialdehyde, total and oxidized glutathione levels. Results Malondialdehyde, total and oxidized glutathione concentrations did not differ significantly (p>0.05) between women with and without low-grade squamous intraepithelial lesions across communities. Malondialdehyde levels (8.02nmols/mL) were almost five times higher in human papillomavirus-positive compared to human papillomavirus-negative women (1.70nmols/mL) living in Itaituba (statistically significant difference; p<0.05). Malondialdehyde levels did not differ significantly (p>0.05) between human papillomavirus-positive and human papillomavirus-negative women living in remaining communities. Significant (p<0.05) differences in total glutathione levels between human papillomavirus-positive and human papillomavirus-negative women (8.20µg/mL and 1.47µg/mL, respectively) were limited to those living in Bragança. Conclusion Malondialdehyde and total glutathione levels were significantly associated with human papillomavirus infection. However, lack of similar associations with squamous lesions suggest oxidative stress alone does not explain correlations with cervical carcinogenesis. Other factors may therefore be involved.

Assuntos

Dissulfeto de Glutationa/sangue , Glutationa Peroxidase/sangue , Malondialdeído/sangue , Estresse Oxidativo/fisiologia , Infecções por Papillomavirus/sangue , Lesões Intraepiteliais Escamosas Cervicais/sangue , Neoplasias do Colo do Útero/sangue , Adolescente , Adulto , Biomarcadores Tumorais/sangue , Brasil , Estudos Transversais , DNA Viral , Feminino , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Reação em Cadeia da Polimerase , Valores de Referência , Rios , Índice de Gravidade de Doença , Lesões Intraepiteliais Escamosas Cervicais/virologia , Estatísticas não Paramétricas , Neoplasias do Colo do Útero/virologia , Adulto Jovem

RESUMO

Parvovirus B19 (PVB19) is a virus found in the skin that causes asymptomatic infections and can exist in the host for long periods to time. The virus induces a local inflammatory response and is associated with the development of arthritis and other autoimmunes diseases. Parvovirus B19 DNA was investigated by PCR in the skin of 20 patients with psoriasis and 20 patients with eczema. Additionally, immunohistochemistry was used to characterize the expression of cytokines in these lesions. The sociodemographic variables were similar in the two groups studied. Psoriasis vulgaris was the most common clinical type in men (50%) and women (80%) (p = 0.0106). Comorbidities were observed in most patients with psoriasis (75%), with an OR of 14 (p = 0.0068). Another important finding was the high prevalence (50%) of psychiatric disorders in patients with psoriasis (OR = 16, p = 0.0218). Only two patients (10%) with psoriasis were positive for PVB19. Comparison of cytokine expression showed the same cytokine profile in the two groups (p > 0.05). However, expression of TNF-α tended to be higher in psoriasis patients. There was no significant positivity for PVB19 in the two groups studied. Immunohistochemistry showed higher expression of TNF-α in psoriasis lesions compared to the eczema group.

Assuntos

Eczema/imunologia , Infecções por Parvoviridae/imunologia , Parvovirus B19 Humano/patogenicidade , Psoríase/imunologia , Dermatopatias/imunologia , Dermatopatias/virologia , Pele/imunologia , Pele/virologia , Infecções Assintomáticas , Brasil , Citocinas/metabolismo , DNA Viral/análise , Eczema/complicações , Eczema/epidemiologia , Eczema/virologia , Feminino , Humanos , Imuno-Histoquímica , Interferon gama/metabolismo , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Masculino , Pessoa de Meia-Idade , Infecções por Parvoviridae/complicações , Infecções por Parvoviridae/epidemiologia , Infecções por Parvoviridae/virologia , Parvovirus B19 Humano/genética , Parvovirus B19 Humano/imunologia , Parvovirus B19 Humano/isolamento & purificação , Prevalência , Psoríase/complicações , Psoríase/epidemiologia , Psoríase/virologia , Pele/patologia , Dermatopatias/epidemiologia , Dermatopatias/patologia , Fator de Necrose Tumoral alfa/metabolismo

RESUMO

ABSTRACT Objective To investigate the relation between oxidative stress markers, human papillomavirus infection and cervical cancer precursor lesions. Methods The study comprised women aged 14 to 60 years living in communities located by Amazon rivers in the state of Pará (Itaituba, Limoeiro do Ajuru and Bragança, 126, 68 and 43 women respectively). Papanicolau smears and polymerase chain reaction tests for human papillomavirus DNA detection were performed. Blood samples were collected to test malondialdehyde, total and oxidized glutathione levels. Results Malondialdehyde, total and oxidized glutathione concentrations did not differ significantly (p>0.05) between women with and without low-grade squamous intraepithelial lesions across communities. Malondialdehyde levels (8.02nmols/mL) were almost five times higher in human papillomavirus-positive compared to human papillomavirus-negative women (1.70nmols/mL) living in Itaituba (statistically significant difference; p<0.05). Malondialdehyde levels did not differ significantly (p>0.05) between human papillomavirus-positive and human papillomavirus-negative women living in remaining communities. Significant (p<0.05) differences in total glutathione levels between human papillomavirus-positive and human papillomavirus-negative women (8.20μg/mL and 1.47μg/mL, respectively) were limited to those living in Bragança. Conclusion Malondialdehyde and total glutathione levels were significantly associated with human papillomavirus infection. However, lack of similar associations with squamous lesions suggest oxidative stress alone does not explain correlations with cervical carcinogenesis. Other factors may therefore be involved.

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RESUMO Objetivo Avaliar a relação de marcadores de estresse oxidativo com a infecção pelo papilomavírus humano e as lesões precursoras do câncer cervical. Métodos Foram incluídas mulheres ribeirinhas da Amazônia (a saber: 126 do município de Itaituba, 68 de Limoeiro do Ajuru e 43 de Bragança), todas do Estado do Pará, de 14 a 60 anos. Foram realizados testes Papanicolau e de reação em cadeia de polimerase para a detecção de DNA do papilomavírus humano. Coleta de amostras de sangue foi realizada para a avaliação do malondialdeído e a determinação da glutationa total e oxidada. Resultados As concentrações oxidativas do malondialdeído e os teores de glutationa total e oxidada não apresentaram diferença significativa (p>0,05) nas mulheres com e sem lesão intraepitelial escamosa de baixo grau, em todas as comunidades pesquisadas. Mulheres com papilomavírus humano em Itaituba apresentaram níveis de malondialdeído (8,02nmols/mL) quase cinco vezes maior quando relacionadas àquelas sem o HPV (1,70nmols/mL), com diferença estatística significativa (p<0,05). As outras comunidades não mostraram diferença estatística significativa entre as concentrações de malondialdeído nas mulheres com e sem papilomavírus humano (p>0,05). Os teores de glutationa total mostraram diferença significativa (p<0,05) somente em Bragança naquelas com (8,20µg/mL) e sem a infecção pelo papilomavírus humano (1,47µg/mL). Conclusão Houve associação significativa da resposta oxidativa do malondialdeído e da glutationa total com a infecção pelo papilomavírus humano, porém não houve diferença quando associada à lesão escamosa, sugerindo que o estresse oxidativo isoladamente não explica a relação com a carcinogênese do colo uterino, que deve ser influenciada ainda por outros fatores.

Assuntos

Humanos , Feminino , Adolescente , Adulto , Adulto Jovem , Neoplasias do Colo do Útero/sangue , Estresse Oxidativo/fisiologia , Dissulfeto de Glutationa/sangue , Infecções por Papillomavirus/sangue , Lesões Intraepiteliais Escamosas Cervicais/sangue , Glutationa Peroxidase/sangue , Malondialdeído/sangue , Papillomaviridae/isolamento & purificação , Valores de Referência , Índice de Gravidade de Doença , Brasil , DNA Viral , Biomarcadores Tumorais/sangue , Neoplasias do Colo do Útero/virologia , Reação em Cadeia da Polimerase , Estudos Transversais , Estatísticas não Paramétricas , Infecções por Papillomavirus/complicações , Rios , Teste de Papanicolaou , Lesões Intraepiteliais Escamosas Cervicais/virologia , Pessoa de Meia-Idade

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0186055.].