Aspectos hormonais e imunológicos associados às formas graves e complicações da hanseníase

Detalhes bibliográficos
Autor(a) principal: Oliveira, Daniela Teles de
Data de Publicação: 2017
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFS
Texto Completo: https://ri.ufs.br/handle/riufs/3637
Resumo: Leprosy is a chronic, infectious-contagious disease caused by the Mycobacterium leprae bacillus. This is transmitted by airway and infects phagocytic cells of the skin and the Schwann cells of the peripheral nerves. Despite clinical treatment, patients may present with inflammatory complications such as leprosy reactions and lesions on peripheral nerves which may progress to physical disability. The disease may present different profiles of immune responses that are related to its clinical manifestations. Although it is known about the immune response in leprosy and the influence of hormones in the evolution of infections, there is still no understanding to generate markers that can define the most serious clinical forms and inflammatory complications of the disease. Therefore, this work aimed to identify immunological and hormonal aspects associated with the clinical presentation and complications of leprosy. The methodology included a cross-sectional study comparing groups based on the collection of clinical data and serum markers (immunological and hormonal) of healthy contact controls and patients with leprosy. In addition, a cohort study was carried out with monthly follow up and up to one year after clinical discharge in order to evaluate the occurrence of reactional episodes and/or physical disability. Serum levels of hormones (adrenocorticotrophic- ACTH, cortisol, Insulin-like growth factor type 1-IGF-1 and testosterone) and cytokines (INF-ɣ, IL-12p70, IL-17A, IL1-β, IL-10 and TNF-ɣ was related to clinical forms (indeterminate-IL, tuberculoid-TT, boderline-BL and lepromatous- LL), operational classification (paucibacillary-PB and multibacillary-MB), presence of reactional episodes and physical disability. There was a higher proportion of MB men (54.3%). MB patients also had a higher frequency of reaction episodes (44.4%) and physical disability (76.5%) when compared to patients with PB. As regards the presence of circulating hormones, high levels of ACTH were found in MB (24.2 ±13.1 ng/ml, p= 0.002) and PB (23.5 ± 14.9 ng/ml, p = 0.007) when compared whit controls (11.9 ± 12.3 ng/ml). High levels of cortisol were also detected in TT patients (12.1 ± 4.7 μg/dl) compared to controls (8.4 ± 2.7 μg/dl, p = 0.003), BL (9.02 ± 4 , 8 μg/dL, p = 0.004) and LL (8.9 ± 2.7 μg/dL, p = 0.03). Patients who had leprosy before treatment had lower levels of ACTH (19.7 ± 10.3 ng/ml) and cortisol (8.5±3.9 ng/ml; p= 0.04) when compared with the patients without reaction. A positive correlation was observed when correlating ACTH and cortisol between the hormones (CI: 0.35-0.65, r= 0.52, p <0.0001). Higher IGF-1 levels were obtained in IL patients (6.5 ± 6.4 ng/ml) than in the other forms (TT 3.03 ± 3.5 ng/ml; BL 3.1 ± 4.5 ng/ml; LL 3.6 ± 2.5 ng/ml). Patients with physical disabilities (grades 1 and 2) have lower levels of IGF-1 (2.8 ± 1.6 ng/ml) compared to those without this limitation (grade 0: 4.5 ± 2,7 ng/ml, p= 0.007). High testosterone levels were found in men over 50 years of age and MB (6.58 ± 3.2 ng/ml) when compared to PB men (4.21 ± 2.3 ng/ml) and controls (4.26 ± 0,8 ng/ml). Regarding the evaluation of immunological markers, all the cytokines evaluated were increased in the patients, in comparison to the controls, highlighting INF-ɣ (79.02 ± 26.9 pg/ml), IL-10 (156.4 ± 53 pg/ml) and TNF-α (463.3±160.6 pg/ml) that were elevated in the LL forms. Regarding IL-17A, patients with TT presented higher levels (49.2±10.5 pg/ml) when compared to patients with LL (40.7 ± 4.6 pg/ml). IL1-β was elevated in IL forms (62.9 ± 16.3 pg/ml) when compared to more severe forms of the disease and controls. Finally, the increase in INF-ɣ (97.1 ± 44.5 pg/ml, p= 0.02) and TNF-α (407.3 ± 82.08 pg/ml, p= 0.04) was related in MB patients to the occurrence of reaction episode. The latter was also higher in patients with physical disability (354.3 ± 92.2 pg/ml, p= 0.04). The hormonal and immunological markers support the hypothesis that the interaction between leprosy and the neuroendocrine and immunological systems play an important role in the natural course of M. leprae infection. Reduced concentrations of cortisol and IGF-1, high testosterone concentrations related to the worst clinical outcome suggest that these hormones are important modulators of the inflammatory episode and supports future therapeutical studies as well as the attempt of prophylactic treatment. In addition, IL-17 and IL-1β cytokines act to control bacillus multiplication. The cytokines IFN-ɣ and TNF-α were associated with the presence of a reaction suggesting a deleterious effect on the lesion.
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spelling Oliveira, Daniela Teles deJesus, Amélia Maria Ribeiro dehttp://lattes.cnpq.br/62373518066589382017-09-26T12:07:38Z2017-09-26T12:07:38Z2017-06-09OLIVEIRA, Daniela Teles de. Aspectos hormonais e imunológicos associados às formas graves e complicações da hanseníase. 2017. 116 f. Tese (Pós-Graduação em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2017.https://ri.ufs.br/handle/riufs/3637Leprosy is a chronic, infectious-contagious disease caused by the Mycobacterium leprae bacillus. This is transmitted by airway and infects phagocytic cells of the skin and the Schwann cells of the peripheral nerves. Despite clinical treatment, patients may present with inflammatory complications such as leprosy reactions and lesions on peripheral nerves which may progress to physical disability. The disease may present different profiles of immune responses that are related to its clinical manifestations. Although it is known about the immune response in leprosy and the influence of hormones in the evolution of infections, there is still no understanding to generate markers that can define the most serious clinical forms and inflammatory complications of the disease. Therefore, this work aimed to identify immunological and hormonal aspects associated with the clinical presentation and complications of leprosy. The methodology included a cross-sectional study comparing groups based on the collection of clinical data and serum markers (immunological and hormonal) of healthy contact controls and patients with leprosy. In addition, a cohort study was carried out with monthly follow up and up to one year after clinical discharge in order to evaluate the occurrence of reactional episodes and/or physical disability. Serum levels of hormones (adrenocorticotrophic- ACTH, cortisol, Insulin-like growth factor type 1-IGF-1 and testosterone) and cytokines (INF-ɣ, IL-12p70, IL-17A, IL1-β, IL-10 and TNF-ɣ was related to clinical forms (indeterminate-IL, tuberculoid-TT, boderline-BL and lepromatous- LL), operational classification (paucibacillary-PB and multibacillary-MB), presence of reactional episodes and physical disability. There was a higher proportion of MB men (54.3%). MB patients also had a higher frequency of reaction episodes (44.4%) and physical disability (76.5%) when compared to patients with PB. As regards the presence of circulating hormones, high levels of ACTH were found in MB (24.2 ±13.1 ng/ml, p= 0.002) and PB (23.5 ± 14.9 ng/ml, p = 0.007) when compared whit controls (11.9 ± 12.3 ng/ml). High levels of cortisol were also detected in TT patients (12.1 ± 4.7 μg/dl) compared to controls (8.4 ± 2.7 μg/dl, p = 0.003), BL (9.02 ± 4 , 8 μg/dL, p = 0.004) and LL (8.9 ± 2.7 μg/dL, p = 0.03). Patients who had leprosy before treatment had lower levels of ACTH (19.7 ± 10.3 ng/ml) and cortisol (8.5±3.9 ng/ml; p= 0.04) when compared with the patients without reaction. A positive correlation was observed when correlating ACTH and cortisol between the hormones (CI: 0.35-0.65, r= 0.52, p <0.0001). Higher IGF-1 levels were obtained in IL patients (6.5 ± 6.4 ng/ml) than in the other forms (TT 3.03 ± 3.5 ng/ml; BL 3.1 ± 4.5 ng/ml; LL 3.6 ± 2.5 ng/ml). Patients with physical disabilities (grades 1 and 2) have lower levels of IGF-1 (2.8 ± 1.6 ng/ml) compared to those without this limitation (grade 0: 4.5 ± 2,7 ng/ml, p= 0.007). High testosterone levels were found in men over 50 years of age and MB (6.58 ± 3.2 ng/ml) when compared to PB men (4.21 ± 2.3 ng/ml) and controls (4.26 ± 0,8 ng/ml). Regarding the evaluation of immunological markers, all the cytokines evaluated were increased in the patients, in comparison to the controls, highlighting INF-ɣ (79.02 ± 26.9 pg/ml), IL-10 (156.4 ± 53 pg/ml) and TNF-α (463.3±160.6 pg/ml) that were elevated in the LL forms. Regarding IL-17A, patients with TT presented higher levels (49.2±10.5 pg/ml) when compared to patients with LL (40.7 ± 4.6 pg/ml). IL1-β was elevated in IL forms (62.9 ± 16.3 pg/ml) when compared to more severe forms of the disease and controls. Finally, the increase in INF-ɣ (97.1 ± 44.5 pg/ml, p= 0.02) and TNF-α (407.3 ± 82.08 pg/ml, p= 0.04) was related in MB patients to the occurrence of reaction episode. The latter was also higher in patients with physical disability (354.3 ± 92.2 pg/ml, p= 0.04). The hormonal and immunological markers support the hypothesis that the interaction between leprosy and the neuroendocrine and immunological systems play an important role in the natural course of M. leprae infection. Reduced concentrations of cortisol and IGF-1, high testosterone concentrations related to the worst clinical outcome suggest that these hormones are important modulators of the inflammatory episode and supports future therapeutical studies as well as the attempt of prophylactic treatment. In addition, IL-17 and IL-1β cytokines act to control bacillus multiplication. The cytokines IFN-ɣ and TNF-α were associated with the presence of a reaction suggesting a deleterious effect on the lesion.A Hanseníase é uma doença crônica, infecto-contagiosa, causada pelo bacilo Mycobacterium leprae. Este é transmitido por via aérea superior e infecta células fagocíticas da pele e as células de Schwann dos nervos periféricos. Apesar do tratamento clínico, os pacientes podem apresentar complicações inflamatórias como as reações hansênicas e lesões em nervos periféricos o que pode evoluir para incapacidade física. A doença pode apresentar diferentes perfis de respostas imunológicas que estão relacionadas com as suas manifestações clínicas. Embora se conheça sobre a resposta imune na hanseníase e da influencia hormônal na evolução de infecções, ainda não há entendimento para gerar marcadores que possam definir as formas clínicas mais graves e complicações inflamatórias da doença. Diante disso, esse trabalho objetivou identificar aspectos imunológicos e hormonais associados à apresentação clínica e complicações da hanseníase. A metodologia incluiu um estudo transversal de comparação de grupos baseado na coleta de dados clínicos e marcadores séricos (imunológicos e hormonais) de controles contactantes sadios e pacientes com hanseníase. Além disso foi realizado um estudo de coorte com acompanhamento mensal e até um ano após a alta clínica a fim de avaliar o surgimento de episódios reacionais e/ou incapacidade física. Foram realizadas dosagem séricas de hormônios (adenocorticotrófico-ACTH, cortisol, fator de crescimento semelhante à insulina tipo 1- IGF-1 e testosterona) e de citocinas (INF-ɣ, IL-12p70, IL-17A, IL1-β, IL-10 e TNF-α) e, em seguida, relacionados às formas clínicas (Indeterminada- HI, Tuberculóide- HT, Dimorfa- HD e Virchowiana- HV), classificação operacional (Paucibacilar-PB e Multibacilar-MB), presença de episódios reacionais e incapacidade física. Os resultados encontraram maior proporção de homens MB (54,3%). Os pacientes MB também apresentaram maior frequência de episódios reacional (44,4%) e incapacidade física (76,5%) em comparação aos pacientes PB. Quanto à presença de hormônios circulantes foi encontrado níveis elevados de ACTH em MB (24,2±13,1 ng/ml; p= 0,002) e PB (23,5±14,9 ng/ml; p= 0,007) quando comparados aos controles (11,9±12,3 ng/ml). Concentrações elevadas de cortisol também foram detectados nos pacientes HT (12,1±4,7 μg/dl) em relação aos controles (8,4±2,7 μg/dl, p= 0,003), HD (9,02±4,8 μg/dl; p= 0,004) e os HV (8,9±2,7 μg/dl; p= 0,03). Os pacientes que apresentaram reação hansênica antes do tratamento tiveram níveis mais baixos de ACTH (19,7±10,3 ng/ml) e cortisol (8,5±3,9 ng/ml; p= 0,04) quando comparados com os pacientes sem reação. Também foi observado correlação positiva entre ACTH e cortisol (IC: 0,35-0,65; r=0,52; p<0,0001). Foram obtidos níveis mais altos de IGF-1 nos pacientes HI (6,5±6,4 ng/ml) que nas demais formas (HT 3,03±3,5 ng/ml; HD 3,1±4,5 ng/ml; HV 3,6±2,5 ng/ml). Os pacientes com incapacidades físicas (graus 1 e 2) apresentam concentrações mais baixas de IGF-1 (2,8±1,6 ng/ml) quando comparados aos que não apresentam essa limitação (grau 0: 4,5±2,7 ng/ml; p= 0,007). Níveis elevados de testosterona foram encontrados em homens acima de 50 anos e MB (6,58± 3,2 ng/ml) quando comparado aos homens PB (4,21± 2,3 ng/ml) e com os controles (4,26± 0,8 ng/ml). Em relação à avaliação de marcadores imunológicos todas as citocinas avaliadas estiveram aumentadas nos pacientes, em relação aos controles, destacando INF-ɣ (79,02 ± 26,9 pg/ml), IL-10 (156,4 ± 53 pg/ml) e TNF-α (463,3 ± 160,6 pg/ml) que estavam elevadas nas HV. Em relação à IL-17A, os pacientes com HT apresentaram níveis mais elevados (49,2 ± 10,5 pg/ml) quando comparados aos valores de pacientes com HV (40,7 ± 4,6 pg/ml). Já a IL1-β esteve elevada formas HI (62,9 ± 16,3 pg/ml) quando comparada às formas mais graves da doença e aos controles. Por fim o aumento em INF-ɣ (97,1 ± 44,5 pg/ml, p= 0,02) e TNF-α (407,3 ± 82,08 pg/ml, p= 0,04) esteve relacionado, nos pacientes MB, à ocorrência de episódio reacional. E esta última, também, mais elevada nos pacientes com incapacidade física (354,3 ± 92,2 pg/ml, p= 0,04). Os marcadores hormonais e imunológicos acima descritos suportam a hipótese de que a interação entre a hanseníase e os sistemas neuroendócrinos e imunológicos desempenham um papel importante no curso natural da infecção pelo M. Leprae. Concentrações reduzidas de cortisol e IGF-1, altas concentrações de testosterona relacionadas ao pior desfecho clínico sugerem esses hormônios sejam importantes moduladores do episódio inflamatório e dá suporte estudos terapeuticos futuros bem como a tentativa de tratamento profilático. Além disso, as citocinas IL-17 e IL-1β atuam no controle da multiplicação do bacilo. Já as citocinas IFN- ɣ e TNF-α foram associadas a presença de reação sugerindo um efeito deletério na lesão.application/pdfporUniversidade Federal de SergipePós-Graduação em Ciências da SaúdeUFSBrasilHanseníaseHanseníase (complicações)HormôniosImunologiaReação hansênicaIncapacidade físicaLeprosyHormonesImmunologyLeprosy reactionPhysical disabilityCIENCIAS DA SAUDEAspectos hormonais e imunológicos associados às formas graves e complicações da hanseníaseHormonal and immunological aspects associated with severe forms and complications of leprosyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSTEXTDANIELA_TELES_OLIVEIRA.pdf.txtDANIELA_TELES_OLIVEIRA.pdf.txtExtracted texttext/plain218487https://ri.ufs.br/jspui/bitstream/riufs/3637/2/DANIELA_TELES_OLIVEIRA.pdf.txt95e7085dbbb3098f44391966e2dac0f1MD52THUMBNAILDANIELA_TELES_OLIVEIRA.pdf.jpgDANIELA_TELES_OLIVEIRA.pdf.jpgGenerated Thumbnailimage/jpeg1256https://ri.ufs.br/jspui/bitstream/riufs/3637/3/DANIELA_TELES_OLIVEIRA.pdf.jpg60e0874e6b3a8610378612cc56d37f56MD53ORIGINALDANIELA_TELES_OLIVEIRA.pdfapplication/pdf2069946https://ri.ufs.br/jspui/bitstream/riufs/3637/1/DANIELA_TELES_OLIVEIRA.pdf722a40f58d9e15f8df32b0995093a669MD51riufs/36372017-11-28 16:06:47.309oai:ufs.br:riufs/3637Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2017-11-28T19:06:47Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false
dc.title.por.fl_str_mv Aspectos hormonais e imunológicos associados às formas graves e complicações da hanseníase
dc.title.alternative.eng.fl_str_mv Hormonal and immunological aspects associated with severe forms and complications of leprosy
title Aspectos hormonais e imunológicos associados às formas graves e complicações da hanseníase
spellingShingle Aspectos hormonais e imunológicos associados às formas graves e complicações da hanseníase
Oliveira, Daniela Teles de
Hanseníase
Hanseníase (complicações)
Hormônios
Imunologia
Reação hansênica
Incapacidade física
Leprosy
Hormones
Immunology
Leprosy reaction
Physical disability
CIENCIAS DA SAUDE
title_short Aspectos hormonais e imunológicos associados às formas graves e complicações da hanseníase
title_full Aspectos hormonais e imunológicos associados às formas graves e complicações da hanseníase
title_fullStr Aspectos hormonais e imunológicos associados às formas graves e complicações da hanseníase
title_full_unstemmed Aspectos hormonais e imunológicos associados às formas graves e complicações da hanseníase
title_sort Aspectos hormonais e imunológicos associados às formas graves e complicações da hanseníase
author Oliveira, Daniela Teles de
author_facet Oliveira, Daniela Teles de
author_role author
dc.contributor.author.fl_str_mv Oliveira, Daniela Teles de
dc.contributor.advisor1.fl_str_mv Jesus, Amélia Maria Ribeiro de
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/6237351806658938
contributor_str_mv Jesus, Amélia Maria Ribeiro de
dc.subject.por.fl_str_mv Hanseníase
Hanseníase (complicações)
Hormônios
Imunologia
Reação hansênica
Incapacidade física
topic Hanseníase
Hanseníase (complicações)
Hormônios
Imunologia
Reação hansênica
Incapacidade física
Leprosy
Hormones
Immunology
Leprosy reaction
Physical disability
CIENCIAS DA SAUDE
dc.subject.eng.fl_str_mv Leprosy
Hormones
Immunology
Leprosy reaction
Physical disability
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE
description Leprosy is a chronic, infectious-contagious disease caused by the Mycobacterium leprae bacillus. This is transmitted by airway and infects phagocytic cells of the skin and the Schwann cells of the peripheral nerves. Despite clinical treatment, patients may present with inflammatory complications such as leprosy reactions and lesions on peripheral nerves which may progress to physical disability. The disease may present different profiles of immune responses that are related to its clinical manifestations. Although it is known about the immune response in leprosy and the influence of hormones in the evolution of infections, there is still no understanding to generate markers that can define the most serious clinical forms and inflammatory complications of the disease. Therefore, this work aimed to identify immunological and hormonal aspects associated with the clinical presentation and complications of leprosy. The methodology included a cross-sectional study comparing groups based on the collection of clinical data and serum markers (immunological and hormonal) of healthy contact controls and patients with leprosy. In addition, a cohort study was carried out with monthly follow up and up to one year after clinical discharge in order to evaluate the occurrence of reactional episodes and/or physical disability. Serum levels of hormones (adrenocorticotrophic- ACTH, cortisol, Insulin-like growth factor type 1-IGF-1 and testosterone) and cytokines (INF-ɣ, IL-12p70, IL-17A, IL1-β, IL-10 and TNF-ɣ was related to clinical forms (indeterminate-IL, tuberculoid-TT, boderline-BL and lepromatous- LL), operational classification (paucibacillary-PB and multibacillary-MB), presence of reactional episodes and physical disability. There was a higher proportion of MB men (54.3%). MB patients also had a higher frequency of reaction episodes (44.4%) and physical disability (76.5%) when compared to patients with PB. As regards the presence of circulating hormones, high levels of ACTH were found in MB (24.2 ±13.1 ng/ml, p= 0.002) and PB (23.5 ± 14.9 ng/ml, p = 0.007) when compared whit controls (11.9 ± 12.3 ng/ml). High levels of cortisol were also detected in TT patients (12.1 ± 4.7 μg/dl) compared to controls (8.4 ± 2.7 μg/dl, p = 0.003), BL (9.02 ± 4 , 8 μg/dL, p = 0.004) and LL (8.9 ± 2.7 μg/dL, p = 0.03). Patients who had leprosy before treatment had lower levels of ACTH (19.7 ± 10.3 ng/ml) and cortisol (8.5±3.9 ng/ml; p= 0.04) when compared with the patients without reaction. A positive correlation was observed when correlating ACTH and cortisol between the hormones (CI: 0.35-0.65, r= 0.52, p <0.0001). Higher IGF-1 levels were obtained in IL patients (6.5 ± 6.4 ng/ml) than in the other forms (TT 3.03 ± 3.5 ng/ml; BL 3.1 ± 4.5 ng/ml; LL 3.6 ± 2.5 ng/ml). Patients with physical disabilities (grades 1 and 2) have lower levels of IGF-1 (2.8 ± 1.6 ng/ml) compared to those without this limitation (grade 0: 4.5 ± 2,7 ng/ml, p= 0.007). High testosterone levels were found in men over 50 years of age and MB (6.58 ± 3.2 ng/ml) when compared to PB men (4.21 ± 2.3 ng/ml) and controls (4.26 ± 0,8 ng/ml). Regarding the evaluation of immunological markers, all the cytokines evaluated were increased in the patients, in comparison to the controls, highlighting INF-ɣ (79.02 ± 26.9 pg/ml), IL-10 (156.4 ± 53 pg/ml) and TNF-α (463.3±160.6 pg/ml) that were elevated in the LL forms. Regarding IL-17A, patients with TT presented higher levels (49.2±10.5 pg/ml) when compared to patients with LL (40.7 ± 4.6 pg/ml). IL1-β was elevated in IL forms (62.9 ± 16.3 pg/ml) when compared to more severe forms of the disease and controls. Finally, the increase in INF-ɣ (97.1 ± 44.5 pg/ml, p= 0.02) and TNF-α (407.3 ± 82.08 pg/ml, p= 0.04) was related in MB patients to the occurrence of reaction episode. The latter was also higher in patients with physical disability (354.3 ± 92.2 pg/ml, p= 0.04). The hormonal and immunological markers support the hypothesis that the interaction between leprosy and the neuroendocrine and immunological systems play an important role in the natural course of M. leprae infection. Reduced concentrations of cortisol and IGF-1, high testosterone concentrations related to the worst clinical outcome suggest that these hormones are important modulators of the inflammatory episode and supports future therapeutical studies as well as the attempt of prophylactic treatment. In addition, IL-17 and IL-1β cytokines act to control bacillus multiplication. The cytokines IFN-ɣ and TNF-α were associated with the presence of a reaction suggesting a deleterious effect on the lesion.
publishDate 2017
dc.date.accessioned.fl_str_mv 2017-09-26T12:07:38Z
dc.date.available.fl_str_mv 2017-09-26T12:07:38Z
dc.date.issued.fl_str_mv 2017-06-09
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dc.identifier.citation.fl_str_mv OLIVEIRA, Daniela Teles de. Aspectos hormonais e imunológicos associados às formas graves e complicações da hanseníase. 2017. 116 f. Tese (Pós-Graduação em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2017.
dc.identifier.uri.fl_str_mv https://ri.ufs.br/handle/riufs/3637
identifier_str_mv OLIVEIRA, Daniela Teles de. Aspectos hormonais e imunológicos associados às formas graves e complicações da hanseníase. 2017. 116 f. Tese (Pós-Graduação em Ciências da Saúde) - Universidade Federal de Sergipe, Aracaju, 2017.
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