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1.
Inflammation ; 47(3): 1041-1052, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38198110

RESUMO

Annexin A1 (AnxA1) is a glucocorticoid-inducible protein and an important endogenous modulator of inflammation. However, its effect in the endometrial microenvironment is poorly explained. This study aimed to evaluate the role of endogenous AnxA1 in an endometritis mouse model induced by lipopolysaccharide (LPS). Female C57BL/6 wild-type (WT) and AnxA1-/- mice were divided into two groups: SHAM and LPS. To induce endometritis, mice received a vaginal infusion of 50 µL of LPS (1 mg/mL) dissolved in phosphate-buffered saline. After 24 h, the mice were euthanized, and blood and uteri samples were collected. The endometrium inflammatory scores were significantly increased in the LPS-treated group. AnxA1-/- mice from the LPS group demonstrated a significant increase in the number of degranulated mast cell levels compared to AnxA1-/- SHAM mice. The Western blotting analysis revealed that a lack of AnxA1 promoted the upregulation of NLRP3 and pro-IL-1ß in the acute endometritis animal model compared to WT LPS animals. LPS-induced endometritis increased the number of blood peripheral leukocytes in both WT and AnxA1-/- mice compared with SHAM group mice (p < 0.001). AnxA1-/- mice also showed increased plasma levels of IL-1ß (p < 0.01), IL-6, IL-10, IL-17, and TNF-α (p < 0.05) following LPS-induced endometritis. In conclusion, a lack of endogenous AnxA1 exacerbated the inflammatory response in an endometritis model via NLRP3 dysregulation, increased uterine mast cell activation, and plasma pro-inflammatory cytokine release.


Assuntos
Anexina A1 , Modelos Animais de Doenças , Endometrite , Inflamação , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Animais , Anexina A1/metabolismo , Anexina A1/genética , Feminino , Endometrite/metabolismo , Endometrite/patologia , Endometrite/induzido quimicamente , Camundongos , Inflamação/metabolismo , Inflamação/induzido quimicamente , Lipopolissacarídeos/toxicidade , Camundongos Knockout , Doença Aguda
2.
Front Med (Lausanne) ; 10: 1064938, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37153108

RESUMO

The cornea is the clear dome that covers the front portion of the globe. The primary functions of the cornea are to promote the refraction of light and to protect the eye from invading pathogens, both of which are essential for the preservation of vision. Homeostasis of each cellular layer of the cornea requires the orchestration of multiple processes, including the ability to respond to stress. One mechanism whereby cells respond to stress is autophagy, or the process of "self-eating." Autophagy functions to clear damaged proteins and organelles. During nutrient deprivation, amino acids released from protein breakdown via autophagy are used as a fuel source. Mitophagy, a selective form of autophagy, functions to clear damaged mitochondria. Thus, autophagy and mitophagy are important intracellular degradative processes that sustain tissue homeostasis. Importantly, the inhibition or excessive activation of these processes result in deleterious effects on the cell. In the eye, impairment or inhibition of these mechanisms have been associated with corneal disease, degenerations, and dystrophies. This review summarizes the current body of knowledge on autophagy and mitophagy at all layers in the cornea in both non-infectious and infectious corneal disease, dystrophies, and degenerations. It further highlights the critical gaps in our understanding of mitochondrial dysfunction, with implications for novel therapeutics in clinical practice.

3.
FEBS J ; 290(3): 620-648, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-34847289

RESUMO

Diabetes is a complex and multifactorial disease that affects millions of people worldwide, reducing the quality of life significantly, and results in grave consequences for our health care system. In type 2 diabetes (T2D), the lack of ß-cell compensatory mechanisms overcoming peripherally developed insulin resistance is a paramount factor leading to disturbed blood glucose levels and lipid metabolism. Impaired ß-cell functions and insulin resistance have been studied extensively resulting in a good understanding of these pathways but much less is known about interorgan crosstalk, which we define as signaling between tissues by secreted factors. Besides hormones and organokines, dysregulated blood glucose and long-lasting hyperglycemia in T2D is associated with changes in metabolism with metabolites from different tissues contributing to the development of this disease. Recent data suggest that metabolites, such as lipids including free fatty acids and amino acids, play important roles in the interorgan crosstalk during the development of T2D. In general, metabolic remodeling affects physiological homeostasis and impacts the development of T2D. Hence, we highlight the importance of metabolic interorgan crosstalk in this review to gain enhanced knowledge of the pathophysiology of T2D, which may lead to new therapeutic approaches to treat this disease.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Resistência à Insulina/genética , Glicemia/metabolismo , Qualidade de Vida , Aminoácidos/metabolismo
4.
Cells ; 11(16)2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36010643

RESUMO

Mitochondrial dysfunction is a major pathophysiological event leading to the onset of diabetic complications. This study investigated the temporal effects of hyperglycemia on mitochondrial metabolism in corneal epithelial cells. To accomplish this, human telomerase-immortalized corneal epithelial cells were cultured in a defined growth medium containing 6 mM glucose. To simulate hyperglycemia, cells were cultured in a medium containing 25 mM D-glucose, and control cells were cultured in mannitol. Using metabolic flux analysis, there was a hyperosmolar-mediated increase in mitochondrial respiration after 24 h. By day 5, there was a decrease in spare respiratory capacity in cells subject to high glucose that remained suppressed throughout the 14-day period. Although respiration remained high through day 9, glycolysis was decreased. Mitochondrial respiration was decreased by day 14. This was accompanied by the restoration of glycolysis to normoglycemic levels. These changes paralleled a decrease in mitochondrial polarization and cell cycle arrest. Together, these data show that chronic but not acute hyperglycemic stress leads to mitochondrial dysfunction. Moreover, the hyperglycemia-induced loss of spare respiratory capacity reduces the ability of corneal epithelial cells to respond to subsequent stress. Compromised mitochondrial function represents a previously unexplored mechanism that likely contributes to corneal complications in diabetes.


Assuntos
Diabetes Mellitus , Hiperglicemia , Córnea/metabolismo , Diabetes Mellitus/metabolismo , Células Epiteliais/metabolismo , Glucose/metabolismo , Humanos , Hiperglicemia/metabolismo , Mitocôndrias/metabolismo
5.
Toxicol Lett ; 363: 27-35, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35561849

RESUMO

Cisplatin is an antineoplastic agent widely used, and no effective treatments capable of preventing cisplatin-induced ototoxicity and neurotoxicity in humans have yet been identified. This study evaluated the effect of the anti-inflammatory annexin A1 (AnxA1)-derived peptide Ac2-26 in a cisplatin-induced ototoxicity model. Wistar rats received intraperitoneal injections of cisplatin (10 mg/kg/day) for 3 days to induce hearing loss, and Ac2-26 (1 mg/kg) was administered 15 min before cisplatin administration. Control animals received an equal volume of saline. Hearing thresholds were measured by distortion product otoacoustic emissions (DPOAE) before and after treatments. Pharmacological treatment with Ac2-26 protected against cisplatin-induced hearing loss, as evidenced by DPOAE results showing similar signal-noise ratios between the control and Ac2-26-treated groups. These otoprotective effects of Ac2-26 were associated with an increased number of ganglion neurons compared with the untreated cisplatin group. Additionally, Ac2-26 treatment produced reduced immunoreactivity on cleaved caspase 3 and phosphorylated ERK levels in the ganglion neurons, compared to the untreated group, supporting the neuroprotective effects of the Ac2-26. Our results suggest that Ac2-26 has a substantial otoprotective effect in this cisplatin-induced ototoxicity model mediated by neuroprotection and the regulation of the ERK pathway.


Assuntos
Anexina A1 , Antineoplásicos , Perda Auditiva , Ototoxicidade , Animais , Anexina A1/farmacologia , Antineoplásicos/toxicidade , Cisplatino/toxicidade , Perda Auditiva/induzido quimicamente , Perda Auditiva/prevenção & controle , Emissões Otoacústicas Espontâneas , Ototoxicidade/prevenção & controle , Peptídeos/farmacologia , Ratos , Ratos Wistar
6.
Rev Bras Ginecol Obstet ; 44(2): 169-177, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35213915

RESUMO

OBJECTIVE: To evaluate genital hygiene among women with and without bacterial vaginosis (BV) and/or vulvovaginal candidiasis (VVC). METHODS: A cross-sectional study of reproductive-aged women who underwent gynecological and laboratory tests and fulfilled a genital hygiene questionnaire. RESULTS: This study evaluated 166 healthy controls and 141 women diagnosed with either BV (n = 72), VVC (n = 61), or both (n = 8). The use of intimate soap and moist wipes after urination was more frequent among healthy women (p = 0.042 and 0.032, respectively). Compared to controls, bactericidal soap was more used by women with BV (p = 0.05). CONCLUSION: Some hygiene habits were associated to BV and/or VVC. Clinical trials should address this important issue in women's health.


OBJETIVO: Avaliar a higiene genital de mulheres com e sem vaginose bacteriana (VB) e/ou candidíase vulvovaginal (CVV). MéTODOS: Estudo transversal com mulheres em idade reprodutiva submetidas a exames ginecológicos e laboratoriais e preenchimento de questionário de higiene genital. RESULTADOS: Este estudo avaliou 166 controles saudáveis e 141 mulheres com diagnóstico de VB (n = 72), VVC (n = 61) ou ambas (n = 8). O uso de sabonete íntimo e lenços umedecidos após a micção foram hábitos mais frequentes entre mulheres saudáveis (p = 0,042 e 0,032, respectivamente). Em comparação com os controles, o sabonete bactericida foi mais usado por mulheres com VB (p = 0,05). CONCLUSãO: Alguns hábitos de higiene foram associados à VB e/ou VVC. Os ensaios clínicos devem abordar esta questão importante na saúde da mulher.


Assuntos
Candidíase Vulvovaginal , Vaginose Bacteriana , Adulto , Candidíase Vulvovaginal/diagnóstico , Estudos Transversais , Feminino , Hábitos , Humanos , Higiene , Comportamento Sexual , Vagina/microbiologia , Vaginose Bacteriana/diagnóstico
7.
Cells ; 11(2)2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-35053343

RESUMO

Formyl peptide receptors (Fprs) are a G-protein-coupled receptor family mainly expressed on leukocytes. The activation of Fpr1 and Fpr2 triggers a cascade of signaling events, leading to leukocyte migration, cytokine release, and increased phagocytosis. In this study, we evaluate the effects of the Fpr1 and Fpr2 agonists Ac9-12 and WKYMV, respectively, in carrageenan-induced acute peritonitis and LPS-stimulated macrophages. Peritonitis was induced in male C57BL/6 mice through the intraperitoneal injection of 1 mL of 3% carrageenan solution or saline (control). Pre-treatments with Ac9-12 and WKYMV reduced leukocyte influx to the peritoneal cavity, particularly neutrophils and monocytes, and the release of IL-1ß. The addition of the Fpr2 antagonist WRW4 reversed only the anti-inflammatory actions of WKYMV. In vitro, the administration of Boc2 and WRW4 reversed the effects of Ac9-12 and WKYMV, respectively, in the production of IL-6 by LPS-stimulated macrophages. These biological effects of peptides were differently regulated by ERK and p38 signaling pathways. Lipidomic analysis evidenced that Ac9-12 and WKYMV altered the intracellular lipid profile of LPS-stimulated macrophages, revealing an increased concentration of several glycerophospholipids, suggesting regulation of inflammatory pathways triggered by LPS. Overall, our data indicate the therapeutic potential of Ac9-12 and WKYMV via Fpr1 or Fpr2-activation in the inflammatory response and macrophage activation.


Assuntos
Inflamação/patologia , Oligopeptídeos/farmacologia , Peptídeos/farmacologia , Receptores de Formil Peptídeo/agonistas , Animais , Movimento Celular/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Lipidômica , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peritonite/patologia , Células RAW 264.7 , Receptores de Formil Peptídeo/metabolismo
9.
Braz J Microbiol ; 52(4): 2363-2371, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34628621

RESUMO

INTRODUCTION: The influence of vaccination on composition of the human microbiome at distinct sites has been recognized as an essential component in the development of new vaccine strategies. The HPV vaccine is widely used to prevent cervical cancer; however, the influence of HPV vaccine on the vaginal microbiota has not been previously investigated. In his study, we performed an initial characterization of the microbiome and cytokine composition in the vagina following administration of the bivalent vaccine against HPV 16/18. MATERIAL AND METHODS: In this exploratory study, fifteen women between 18 and 40 years received three doses of the HPV-16/18 AS04-adjuvanted vaccine (Cervarix®). Cervicovaginal samples were collected before the first dose and 30 days after the third dose. HPV genotyping was performed by the XGEN Flow Chip technique. The cytokines IFN-γ, IL-2, IL-12p70, TNF-α, GM-CSF, IL-4, IL-5, IL-10, and IL-13 were quantitated by multiplex immunoassay. The vaginal microbiome was identified by analysis of the V3/V4 region of the bacterial 16S rRNA gene. RESULTS: The most abundant bacterial species in the vaginal microbiome was Lactobacillus crispatus, followed by L. iners. Bacterial diversity and dominant organisms were unchanged following vaccination. Small decreases in levels of pro and anti-inflammatory cytokines were observed following HPV vaccination, but there was no association between vaginal cytokine levels and microbiome composition. CONCLUSION: Vaginal microbiome is not altered following administration of the standard three-dose HPV-16/18 AS04-adjuvanted (Cervarix®) vaccine.


Assuntos
Bactérias , Citocinas , Microbiota , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Vagina , Adulto , Bactérias/efeitos dos fármacos , Bactérias/genética , Citocinas/imunologia , Feminino , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Microbiota/efeitos dos fármacos , Microbiota/genética , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/farmacologia , RNA Ribossômico 16S/genética , Vagina/microbiologia , Adulto Jovem
10.
Cells ; 10(1)2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440601

RESUMO

This study evaluated the role of endogenous and exogenous annexin A1 (AnxA1) in the activation of the NLRP3 inflammasome in isolated peritoneal neutrophils. C57BL/6 wild-type (WT) and AnxA1 knockout mice (AnxA1-/-) received 0.3% carrageenan intraperitoneally and, after 3 h, the peritoneal exudate was collected. WT and AnxA1-/- neutrophils were then stimulated with lipopolysaccharide, followed by the NLRP3 agonists nigericin or ATP. To determine the exogenous effect of AnxA1, the neutrophils were pretreated with the AnxA1-derived peptide Ac2-26 followed by the NLRP3 agonists. Ac2-26 administration reduced NLRP3-derived IL-1ß production by WT neutrophils after nigericin and ATP stimulation. However, IL-1ß release was impaired in AnxA1-/- neutrophils stimulated by both agonists, and there was no further impairment in IL-1ß release with Ac2-26 treatment before stimulation. Despite this, ATP- and nigericin-stimulated AnxA1-/- neutrophils had increased levels of cleaved caspase-1. The lipidomics of supernatants from nigericin-stimulated WT and AnxA1-/- neutrophils showed potential lipid biomarkers of cell stress and activation, including specific sphingolipids and glycerophospholipids. AnxA1 peptidomimetic treatment also increased the concentration of phosphatidylserines and oxidized phosphocholines, which are lipid biomarkers related to the inflammatory resolution pathway. Together, our results indicate that exogenous AnxA1 negatively regulates NLRP3-derived IL-1ß production by neutrophils, while endogenous AnxA1 is required for the activation of the NLRP3 machinery.


Assuntos
Anexina A1/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neutrófilos/metabolismo , Animais , Inflamassomos/ultraestrutura , Interleucina-1beta/metabolismo , Lipídeos/química , Masculino , Camundongos Endogâmicos C57BL , Ativação de Neutrófilo , Neutrófilos/ultraestrutura
11.
Microb Pathog ; 150: 104689, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33307121

RESUMO

Annexin A1 (AnxA1) is an anti-inflammatory protein expressed in various cell types, especially macrophages and neutrophils. Because neutrophils play important roles in infections and inflammatory processes and the relationship between AnxA1 and Candida spp. infections is not well-understood, our study examined whether AnxA1 can serve as a target protein for the regulation of the immune response during fungal infections. C57BL/6 wild-type (WT) and AnxA1 knockout (AnxA1-/-) peritoneal neutrophils were coinfected with Candida albicans or Candida auris for 4 h. AnxA1-/- neutrophils exhibited a marked increase in cyclooxygenase 2 (COX-2), phosphorylated extracellular signal-related kinase (ERK), p-38, and c-Jun N-terminal kinase (JNK) levels after coinfection with both Candida spp. A lipidomics approach showed that AnxA1 deficiency produced marked differences in the supernatant lipid profiles of both control neutrophils and neutrophils coinfected with Candida spp. compared with WT cells, especially the levels of glycerophospholipids and glycerolipids. Our results showed that endogenous AnxA1 regulates the neutrophil response under fungal infection conditions, altering lipid membrane organization and metabolism.


Assuntos
Anexina A1 , Candidíase , Animais , Anexina A1/genética , Candida albicans , Candidíase Invasiva , Camundongos , Neutrófilos
12.
Rev Bras Ginecol Obstet ; 42(10): 634-641, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33129219

RESUMO

OBJECTIVE: To identify clinical, microscopic, and biochemical characteristics that differentiate cytolytic vaginosis (CV) from vulvovaginal candidiasis (VVC). METHODS: The present cross-sectional study analyzed the vaginal contents of 24 non-pregnant women aged 18 to 42 years who were attended at the Genital Infections Clinic at Centro de Atenção Integral à Saúde da Mulher da Universidade Estadual de Campinas (CAISM-UNICAMP). They were diagnosed either with (CV = 8, VVC = 8) or without vulvovaginitis or vaginal dysbiosis (controls). The socio-demographic, clinical, and gynecological data were obtained from a detailed patient interview. Samples of the vaginal contents were collected for analysis of vaginal pH, gram stain, and specific fungal culture. The Kruskal-Wallis and Fisher exact tests were used to compare the differences between the groups. Odds ratios were used to compare the categorical variables. The significance level was considered at p < 0.05. RESULTS: Both women with CV and VVC had a lumpy vaginal discharge (p = 0,002) and vaginal hyperemia (p = 0.001), compared with controls. The inflammatory process was more intense in the VVC group (p = 0.001). In the CV group, there was statistical significance for the lactobacillus amount (p = 0.006), vaginal epithelium lysis (p = 0.001), and vaginal pH (p = 0.0002). CONCLUSION: Cytolytic vaginosis and VVC diagnoses rarely differ on clinical characteristics but have different laboratorial findings. The present study highlights the importance of conducting an accurate investigation through laboratory tests rather than clinical criteria to avoid misdiagnosis.


OBJETIVO: Identificar características clínicas, microscópicas e bioquímicas que diferenciam a vaginose citolítica (VC) da candidíase vulvovaginal (CVV). MéTODOS: O presente estudo de corte transversal analisou o conteúdo vaginal de 24 mulheres não grávidas, com idades entre 18 e 42 anos, atendidas no ambulatório de Infecções Genitais do Centro de Atenção Integral à Saúde da Mulher da Universidade Estadual de Campinas (CAISM-UNICAMP). Elas foram diagnosticadas com (CV = 8, CVV = 8) ou sem vulvovaginite ou disbiose vaginal (controles = 8). Os dados sociodemográficos, clínicos e ginecológicos foram obtidos em uma entrevista detalhada do paciente. Amostras do conteúdo vaginal foram coletadas para análise do pH vaginal, coloração de Gram e cultura específica de fungos. Os testes exatos de Kruskal-Wallis e Fisher foram utilizados para comparar as diferenças entre os grupos. A razão de chances foi utilizada para comparar as variáveis categóricas. O nível de significância considerado foi de p < 0,05. RESULTADOS: As mulheres com VC e CVV apresentaram corrimento vaginal irregular (p = 0,002) e hiperemia vaginal (p = 0,001), em comparação aos controles. O processo inflamatório foi mais intenso no grupo CVV (p = 0,001). No grupo VC, houve significância estatística para a quantidade de lactobacilos (p = 0,006), lise do epitélio vaginal (p = 0,001) e pH vaginal (p = 0,0002). CONCLUSãO: Os diagnósticos de VC e CVV raramente diferem nas características clínicas, mas apresentam achados laboratoriais diferentes. O presente estudo destaca a importância de conduzir uma investigação precisa por meio de testes laboratoriais, em vez de critérios apenas clínicos, a fim de evitar erros de diagnóstico.


Assuntos
Candidíase Vulvovaginal/diagnóstico , Vaginose Bacteriana/diagnóstico , Adolescente , Adulto , Carga Bacteriana , Candidíase Vulvovaginal/patologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Vaginose Bacteriana/patologia , Adulto Jovem
13.
Rev. bras. ginecol. obstet ; 42(10): 634-641, Oct. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1144164

RESUMO

Abstract Objective To identify clinical, microscopic, and biochemical characteristics that differentiate cytolytic vaginosis (CV) from vulvovaginal candidiasis (VVC). Methods The present cross-sectional study analyzed the vaginal contents of 24 non-pregnant women aged 18 to 42 years who were attended at the Genital Infections Clinic at Centro de Atenção Integral à Saúde da Mulher da Universidade Estadual de Campinas (CAISM-UNICAMP). They were diagnosed either with (CV = 8, VVC = 8) or without vulvovaginitis or vaginal dysbiosis (controls). The socio-demographic, clinical, and gynecological data were obtained from a detailed patient interview. Samples of the vaginal contents were collected for analysis of vaginal pH, gram stain, and specific fungal culture. The Kruskal-Wallis and Fisher exact tests were used to compare the differences between the groups. Odds ratios were used to compare the categorical variables. The significance level was considered at p < 0.05. Results Both women with CV and VVC had a lumpy vaginal discharge (p = 0,002) and vaginal hyperemia (p = 0.001), compared with controls. The inflammatory process was more intense in the VVC group (p = 0.001). In the CV group, there was statistical significance for the lactobacillus amount (p = 0.006), vaginal epithelium lysis (p = 0.001), and vaginal pH (p = 0.0002). Conclusion Cytolytic vaginosis and VVC diagnoses rarely differ on clinical characteristics but have different laboratorial findings. The present study highlights the importance of conducting an accurate investigation through laboratory tests rather than clinical criteria to avoid misdiagnosis.


Resumo Objetivo Identificar características clínicas, microscópicas e bioquímicas que diferenciam a vaginose citolítica (VC) da candidíase vulvovaginal (CVV). Métodos O presente estudo de corte transversal analisou o conteúdo vaginal de 24 mulheres não grávidas, com idades entre 18 e 42 anos, atendidas no ambulatório de Infecções Genitais do Centro de Atenção Integral à Saúde da Mulher da Universidade Estadual de Campinas (CAISM-UNICAMP). Elas foram diagnosticadas com (CV = 8, CVV = 8) ou sem vulvovaginite ou disbiose vaginal (controles = 8). Os dados sociodemográficos, clínicos e ginecológicos foram obtidos em uma entrevista detalhada do paciente. Amostras do conteúdo vaginal foram coletadas para análise do pH vaginal, coloração de Gram e cultura específica de fungos. Os testes exatos de Kruskal-Wallis e Fisher foram utilizados para comparar as diferenças entre os grupos. A razão de chances foi utilizada para comparar as variáveis categóricas. O nível de significância considerado foi de p < 0,05. Resultados As mulheres com VC e CVV apresentaram corrimento vaginal irregular (p = 0,002) e hiperemia vaginal (p = 0,001), em comparação aos controles. O processo inflamatório foi mais intenso no grupo CVV (p = 0,001). No grupo VC, houve significância estatística para a quantidade de lactobacilos (p = 0,006), lise do epitélio vaginal (p = 0,001) e pH vaginal (p = 0,0002). Conclusão Os diagnósticos de VC e CVV raramente diferem nas características clínicas, mas apresentam achados laboratoriais diferentes. O presente estudo destaca a importância de conduzir uma investigação precisa por meio de testes laboratoriais, em vez de critérios apenas clínicos, a fim de evitar erros de diagnóstico.


Assuntos
Humanos , Feminino , Adolescente , Adulto , Adulto Jovem , Candidíase Vulvovaginal/diagnóstico , Vaginose Bacteriana/diagnóstico , Candidíase Vulvovaginal/patologia , Projetos Piloto , Estudos Transversais , Valor Preditivo dos Testes , Vaginose Bacteriana/patologia , Carga Bacteriana , Pessoa de Meia-Idade
14.
Cells ; 9(4)2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32283822

RESUMO

Annexin A1 (AnxA1) is a potent anti-inflammatory protein that downregulates proinflammatory cytokine release. This study evaluated the role of AnxA1 in the regulation of NLRP3 inflammasome activation and lipid release by starch-elicited murine peritoneal macrophages. C57bl/6 wild-type (WT) and AnxA1-null (AnxA1-/-) mice received an intraperitoneal injection of 1.5% starch solution for macrophage recruitment. NLRP3 was activated by priming cells with lipopolysaccharide for 3 h, followed by nigericin (1 h) or ATP (30 min) incubation. As expected, nigericin and ATP administration decreased elicited peritoneal macrophage viability and induced IL-1ß release, more pronounced in the AnxA1-/- cells than in the control peritoneal macrophages. In addition, nigericin-activated AnxA1-/- macrophages showed increased levels of NLRP3, while points of co-localization of the AnxA1 protein and NLRP3 inflammasome were detected in WT cells, as demonstrated by ultrastructural analysis. The lipidomic analysis showed a pronounced release of prostaglandins in nigericin-stimulated WT peritoneal macrophages, while ceramides were detected in AnxA1-/- cell supernatants. Different eicosanoid profiles were detected for both genotypes, and our results suggest that endogenous AnxA1 regulates the NLRP3-derived IL-1ß and lipid mediator release in macrophages.


Assuntos
Anexina A1/metabolismo , Inflamassomos/metabolismo , Macrófagos Peritoneais/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Anexina A1/imunologia , Inflamassomos/imunologia , Metabolismo dos Lipídeos , Macrófagos Peritoneais/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
15.
Rev Assoc Med Bras (1992) ; 65(6): 857-863, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31340317

RESUMO

OBJECTIVE: To evaluate endocervical and vaginal environment changes in women using a levonorgestrel-releasing intrauterine system (LNG-IUS). METHODS: A quasi-experimental study included sixty women who had an LNG-IUS inserted in the Family Planning Clinic of UNICAMP between April and November of 2016. Women in reproductive age, non-pregnant, without the use of antibiotics and contraceptives seeking for LNG-IUS insertion were selected for this study. All women were evaluated with regard to vaginal and endocervical pH, vaginal and endocervical Gram-stained bacterioscopy, and Pap-smear before and two months after LNG-IUS insertion. Clinical aspects such as cervical mucus, vaginal discharge, and cervical ectopy were also observed. RESULTS: After LNG-IUS insertion, there was an increase in the following parameters: endocervical pH>4.5 (p=0.02), endocervical neutrophil amount (p<0.0001), vaginal cytolysis (p=0.04). There was a decrease in vaginal discharge (p=0.01). No statistically significant changes were found in vaginal pH, neutrophils amount in the vaginal mucosa, vaginal discharge appearance, vaginal candidiasis, bacterial vaginosis, vaginal coccobacillary microbiota, cervical mucus appearance, or cervical ectopy size. CONCLUSIONS: Short-term LNG-IUS use did not increase vulvovaginal candidiasis or bacterial vaginosis, and led to diminished vaginal discharge. Notwithstanding, this device promoted reactional changes in the vaginal and endocervical environment, without modification on cervical ectopy size.


Assuntos
Colo do Útero/efeitos dos fármacos , Anticoncepcionais Femininos/efeitos adversos , Endométrio/efeitos dos fármacos , Dispositivos Intrauterinos Medicados/efeitos adversos , Levanogestrel/efeitos adversos , Vagina/efeitos dos fármacos , Adolescente , Adulto , Colo do Útero/microbiologia , Endométrio/microbiologia , Feminino , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou , Estatísticas não Paramétricas , Fatores de Tempo , Vagina/química , Vagina/microbiologia , Esfregaço Vaginal , Adulto Jovem
16.
Rev. Assoc. Med. Bras. (1992, Impr.) ; 65(6): 857-863, June 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1012989

RESUMO

SUMMARY OBJECTIVE: To evaluate endocervical and vaginal environment changes in women using a levonorgestrel-releasing intrauterine system (LNG-IUS). METHODS: A quasi-experimental study included sixty women who had an LNG-IUS inserted in the Family Planning Clinic of UNICAMP between April and November of 2016. Women in reproductive age, non-pregnant, without the use of antibiotics and contraceptives seeking for LNG-IUS insertion were selected for this study. All women were evaluated with regard to vaginal and endocervical pH, vaginal and endocervical Gram-stained bacterioscopy, and Pap-smear before and two months after LNG-IUS insertion. Clinical aspects such as cervical mucus, vaginal discharge, and cervical ectopy were also observed. RESULTS: After LNG-IUS insertion, there was an increase in the following parameters: endocervical pH>4.5 (p=0.02), endocervical neutrophil amount (p<0.0001), vaginal cytolysis (p=0.04). There was a decrease in vaginal discharge (p=0.01). No statistically significant changes were found in vaginal pH, neutrophils amount in the vaginal mucosa, vaginal discharge appearance, vaginal candidiasis, bacterial vaginosis, vaginal coccobacillary microbiota, cervical mucus appearance, or cervical ectopy size. CONCLUSIONS: Short-term LNG-IUS use did not increase vulvovaginal candidiasis or bacterial vaginosis, and led to diminished vaginal discharge. Notwithstanding, this device promoted reactional changes in the vaginal and endocervical environment, without modification on cervical ectopy size.


RESUMO OBJETIVO: Avaliar as alterações do ambiente endocervical e vaginal em mulheres usuárias de sistema intrauterino liberador de levonorgestrel (SIU-LNG). MÉTODOS: Um estudo quase-experimental incluiu 60 mulheres que inseriram o SIU-LNG na Clínica de Planejamento Familiar da UNICAMP entre abril e novembro de 2016. Mulheres em idade reprodutiva, não gestantes, sem uso de antibióticos e contraceptivos, em busca pela inserção do SIU-LNG, foram selecionadas para este estudo. Todas as mulheres foram avaliadas quanto ao pH vaginal e endocervical, bacterioscopia vaginal e endocervical por coloração de Gram, exame de Papanicolau antes e dois meses após a inserção de SIU-LNG. Aspectos clínicos como muco cervical, corrimento vaginal e ectopia cervical também foram observados. RESULTADOS: Após a inserção do SIU-LNG houve aumento nos seguintes parâmetros: pH endocervical >4,5 (p=0,02), quantidade de neutrófilos endocervicais (p<0,0001), citolise vaginal (p=0,04). Houve diminuição do conteúdo vaginal (p=0,01). Não foram encontradas alterações estatisticamente significativas no pH vaginal, na quantidade de neutrófilos na mucosa vaginal, apecto do corrimento vaginal, candidíase vaginal, vaginose bacteriana, microbiota cocobacilar vaginal, aparência de muco cervical ou tamanho da ectopia cervical. CONCLUSÃO: O uso do SIU-LNG em curto prazo não aumentou a candidíase vulvovaginal ou a vaginose bacteriana, levou à diminuição do conteúdo vaginal. No entanto, este dispositivo promoveu mudanças reacionais no ambiente vaginal e endocervical, sem modificação no tamanho da ectopia cervical.


Assuntos
Humanos , Feminino , Adolescente , Adulto , Adulto Jovem , Vagina/efeitos dos fármacos , Colo do Útero/efeitos dos fármacos , Levanogestrel/efeitos adversos , Anticoncepcionais Femininos/efeitos adversos , Endométrio/efeitos dos fármacos , Dispositivos Intrauterinos Medicados/efeitos adversos , Fatores de Tempo , Vagina/microbiologia , Vagina/química , Esfregaço Vaginal , Colo do Útero/microbiologia , Estatísticas não Paramétricas , Endométrio/microbiologia , Teste de Papanicolaou , Pessoa de Meia-Idade
17.
Rev Assoc Med Bras (1992) ; 65(2): 171-176, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30892440

RESUMO

INTRODUCTION: Genital hygiene can play an essential role in avoiding vulvovaginal discomfort and preventing infections. The scientific evidence on best practices on genital hygiene is scarce, and without doubt, gynecologists should be the best person to discuss and guide the subject. OBJECTIVE: Evaluate the general genital female gynecologist hygiene. METHODS: This descriptive analytic study identified genital hygiene and sexual practices of 220 female gynecologists, through a questionnaire with 60 self-answered questions. The data were analyzed and presented using frequency, percentage, mean and standard deviation. RESULTS: The studied population was constituted by middle age (37.3 years) and white (71.3%) female gynecologists. More than a half (53.6%) declared spending over 10 hours a day away from home and complained of vaginal discharge in 48.1% of the cases. Regular vulvovaginal hygiene: 17.8% reported washing genitals once a day and 52% twice a day. The use of dry paper alone was reported in 66.4% post urination and 78.5% post-evacuation. Using running water and soap was practiced by 25.9% and 21.5% respectively. Vulvovaginal hygiene related to sex: More than half of them had intercourse 1-3 times a week, and 37.4% and 24.1% had frequent oral sex and eventually anal sexof the participants, respectively. Genital hygiene before sex was positive in 52.7% of the subjects and, post-sex hygiene in 78.5% of them. CONCLUSION: Genital hygiene habits of female gynecologists can be improved, despite the high grade of scientific knowledge they hold.


Assuntos
Genitália , Ginecologia/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Higiene , Adulto , Feminino , Remoção de Cabelo/estatística & dados numéricos , Humanos , Estilo de Vida , Inquéritos e Questionários
18.
Rev. Assoc. Med. Bras. (1992, Impr.) ; 65(2): 171-176, Feb. 2019. tab
Artigo em Inglês | LILACS | ID: biblio-990340

RESUMO

SUMMARY INTRODUCTION: Genital hygiene can play an essential role in avoiding vulvovaginal discomfort and preventing infections. The scientific evidence on best practices on genital hygiene is scarce, and without doubt, gynecologists should be the best person to discuss and guide the subject. OBJECTIVE: Evaluate the general genital female gynecologist hygiene. METHODS: This descriptive analytic study identified genital hygiene and sexual practices of 220 female gynecologists, through a questionnaire with 60 self-answered questions. The data were analyzed and presented using frequency, percentage, mean and standard deviation. RESULTS: The studied population was constituted by middle age (37.3 years) and white (71.3%) female gynecologists. More than a half (53.6%) declared spending over 10 hours a day away from home and complained of vaginal discharge in 48.1% of the cases. Regular vulvovaginal hygiene: 17.8% reported washing genitals once a day and 52% twice a day. The use of dry paper alone was reported in 66.4% post urination and 78.5% post-evacuation. Using running water and soap was practiced by 25.9% and 21.5% respectively. Vulvovaginal hygiene related to sex: More than half of them had intercourse 1-3 times a week, and 37.4% and 24.1% had frequent oral sex and eventually anal sexof the participants, respectively. Genital hygiene before sex was positive in 52.7% of the subjects and, post-sex hygiene in 78.5% of them. Conclusion: Genital hygiene habits of female gynecologists can be improved, despite the high grade of scientific knowledge they hold.


RESUMO INTRODUÇÃO: A higiene genital pode desempenhar um papel importante na prevenção de desconfortos vulvovaginais e infecções. Evidências científicas sobre as melhores práticas em higiene genital são escassas, e o ginecologista, sem dúvida, é a melhor pessoa para discutir e orientar o assunto. OBJETIVO: Avaliar a higiene genital feminina usual de médicas ginecologistas. MÉTODOS: Estudo analítico descritivo que identificou higiene genital e práticas sexuais de 220 ginecologistas por meio de um questionário com 60 perguntas autorrespondidas. Os dados foram analisados e apresentados por frequência, porcentagem, média e desvio padrão. Resultados: A população estudada consistiu de médicas ginecologistas femininas brancas (71,3%) com idade média de 37,3 anos. Mais da metade (53,6%) relatou ficar fora de suas casas por períodos superiores a 10 horas por dia e queixaram-se de descarga vaginal em 48,1% dos casos. Higiene vulvovaginal regular: 17,8% relataram lavar os genitais uma vez por dia e 52%, duas vezes por dia. O uso apenas de papel (seco) foi relatado em 66,4% dos casos após micção e em 78,5% após a evacuação. A higiene ideal com água corrente e sabão foi praticada apenas em 25,9% e 21,5%, respectivamente. Higiene vulvovaginal relacionada ao sexo: mais da metade delas relatou relações sexuais 1-3 vezes por semana, sexo oral frequente e anal eventual em 37,4% e 24,1%, respectivamente. A higiene genital pré-sexo foi relatada por 52,7% das pessoas e em 78,5% após o coito. Conclusão: Os hábitos de higiene genital dos ginecologistas femininos estão sujeitos a melhorias, mesmo considerando o alto grau de conhecimento científico que possuem.


Assuntos
Humanos , Feminino , Adulto , Conhecimentos, Atitudes e Prática em Saúde , Higiene , Genitália , Ginecologia/estatística & dados numéricos , Inquéritos e Questionários , Remoção de Cabelo/estatística & dados numéricos , Estilo de Vida
19.
PLoS One ; 13(8): e0202401, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30133508

RESUMO

OBJECTIVE: To characterize the lipid profile in vaginal discharge of women with vulvovaginal candidiasis, cytolytic vaginosis, or no vaginal infection or dysbiosis. DESIGN: Cross-sectional study. SETTING: Genital Infections Ambulatory, Department of Tocogynecology, University of Campinas, Campinas, São Paulo-Brazil. SAMPLE: Twenty-four women were included in this study: eight with vulvovaginal candidiasis, eight with cytolytic vaginosis and eight with no vaginal infections or dysbiosis (control group). METHODS: The lipid profile in vaginal discharge of the different study groups was determined by liquid chromatography-mass spectrometry and further analyzed with MetaboAnalyst 3.0 platform. MAIN OUTCOME MEASURES: Vaginal lipids concentration and its correlation with vulvovaginal candidiasis and cytolytic vaginosis. RESULTS: PCA, PLS-DA and hierarchical clustering analyses indicated 38 potential lipid biomarkers for the different groups, correlating with oxidative stress, inflammation, apoptosis and integrity of the vaginal epithelial tissue. Among these, greater concentrations were found for Glycochenodeoxycholic acid-7-sulfate, O-adipoylcarnitine, 1-eicosyl-2-heptadecanoyl-glycero-3-phosphoserine, undecanoic acid, formyl dodecanoate and lipoic acid in the vulvovaginal candidiasis group; N-(tetradecanoyl)-sphinganine, DL-PPMP, 1-oleoyl-cyclic phosphatidic, palmitic acid and 5-aminopentanoic acid in the cytolytic vaginosis group; and 1-nonadecanoyl-glycero-3-phosphate, eicosadienoic acid, 1-stearoyl-cyclic-phosphatidic acid, 1-(9Z,12Z-heptadecadienoyl)-glycero-3-phosphate, formyl 9Z-tetradecenoate and 7Z,10Z-hexadecadienoic acid in the control group. CONCLUSIONS: Lipids related to oxidative stress and apoptosis were found in higher concentrations in women with vulvovaginal candidiasis and cytolytic vaginosis, while lipids related to epithelial tissue integrity were more pronounced in the control group. Furthermore, in women with cytolytic vaginosis, we observed higher concentrations of lipids related to bacterial overgrowth.


Assuntos
Apoptose , Candidíase Vulvovaginal , Metabolismo dos Lipídeos , Estresse Oxidativo , Vagina/metabolismo , Adolescente , Adulto , Candidíase Vulvovaginal/diagnóstico , Candidíase Vulvovaginal/metabolismo , Candidíase Vulvovaginal/patologia , Cromatografia Líquida , Estudos Transversais , Citodiagnóstico , Feminino , Humanos , Espectrometria de Massas , Projetos Piloto , Vagina/microbiologia
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