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PURPOSE: Tumors affecting the female genital tract and their treatments have the potential to induce adverse modifications in vaginal health and impact personal aspects of patient's lives. Vulvovaginal atrophy is one of the morphological changes observed in individuals with a history of gynecological cancer, influenced both by the biological environment of tumors and the main therapeutic modalities employed. Therefore, the purpose of this study was to identify approaches to treat vulvovaginal atrophy while assessing the impact on the emotional and sexual health of women diagnosed with gynecological cancers. METHODS: To achieve this goal, a systematic review was conducted following the methodological guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The databases used for literature research were PubMed and Web of Science. RESULTS: Initially, 886 articles were obtained. After eliminating duplicates and applying inclusion/exclusion criteria, seven articles were selected for analysis. The period of highest publication activity spanned from 2017 to 2020, with the majority conducted in Italy. Five treatment modalities were identified and categorized as vaginal suppository, oral medication, surgical procedure, CO2 laser therapy, and vaginal dilator. Twenty-four outcomes related to vaginal health and 30 outcomes related to overall, sexual, and emotional quality of life were analyzed. CONCLUSION: In general, all interventions demonstrated the ability to improve vaginal health or, at the very least, the sexual health of patients. Thus, despite limitations, all treatments have the potential to address vulvovaginal atrophy in patients with a history of gynecological cancer.
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Atrofia , Neoplasias dos Genitais Femininos , Qualidade de Vida , Vagina , Vulva , Humanos , Feminino , Neoplasias dos Genitais Femininos/terapia , Neoplasias dos Genitais Femininos/psicologia , Neoplasias dos Genitais Femininos/patologia , Vagina/patologia , Vulva/patologia , Doenças Vaginais/terapia , Doenças Vaginais/patologia , Lasers de Gás/uso terapêutico , Supositórios , Administração IntravaginalRESUMO
Fibrosis is one of the main factors that impair the function of many organs. In the heart, fibrosis leads to contractile dysfunction and arrhythmias, which are important in the development of heart failure. Interleukin (IL)-11 is regulated in various heart diseases and has recently been reported to be an important cytokine in fibrosis in this organ. However, this topic has been little explored, and many questions persist. Thus, this systematic review aimed to report on possible IL-11 therapies evaluated in rodent model-induced cardiac fibrosis. Inclusion criteria were experimental in vivo studies that used different rodent models for cardiac fibrosis associated with IL-11 interventions, without year and language restrictions. The search in PubMed, Web of Science, and Embase databases was performed in October 2022. The risk of bias assessment of the studies was based on the guidelines of the SYRCLE tool, and data from the selected articles were also presented in a table as a narrative description. This review was based on eight studies in which five different interventions were used: recombinant human IL-11 (rhIL-11), anti-IL11 (X203), recombinant mouse IL-11 (rmIL-11), lentivirus (LV)-IL-11 + lutein, and anti-IL11RA (X209). Based on the included studies, the results were variable, with IL-11 overexpression inducing cardiac fibrosis, while inhibition protected against this process, preserving the function of this organ. Therefore, IL-11 stands out as a promising therapeutic target for cardiac fibrosis. However, further studies are needed to understand the mechanisms triggered by each treatment, as well as its safety and immunogenicity.
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Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.
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Glomerulonefrite Membranosa , Síndrome Nefrótica , Adulto , Humanos , Pessoa de Meia-Idade , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/etiologia , Glomerulonefrite Membranosa/terapia , Autoanticorpos/uso terapêutico , Glomérulos Renais/patologia , Prognóstico , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/terapiaRESUMO
ABSTRACT Membranous nephropathy is a glomerulopathy, which main affected target is the podocyte, and has consequences on the glomerular basement membrane. It is more common in adults, especially over 50 years of age. The clinical presentation is nephrotic syndrome, but many cases can evolve with asymptomatic non-nephrotic proteinuria. The mechanism consists of the deposition of immune complexes in the subepithelial space of the glomerular capillary loop with subsequent activation of the complement system. Great advances in the identification of potential target antigens have occurred in the last twenty years, and the main one is the protein "M-type phospholipase-A2 receptor" (PLA2R) with the circulating anti-PLA2R antibody, which makes it possible to evaluate the activity and prognosis of this nephropathy. This route of injury corresponds to approximately 70% to 80% of cases of membranous nephropathy characterized as primary. In the last 10 years, several other potential target antigens have been identified. This review proposes to present clinical, etiopathogenic and therapeutic aspects of membranous nephropathy in a didactic manner, including cases that occur during kidney transplantation.
RESUMO A nefropatia membranosa é uma glomerulopatia, cujo principal alvo acometido é o podócito, e acarreta consequências na membrana basal glomerular. Tem maior frequência em adultos, principalmente acima dos 50 anos. A apresentação clínica é a síndrome nefrótica, mas muitos casos podem evoluir com proteinúria não nefrótica assintomática. O mecanismo consiste na deposição de complexos imunes no espaço subepitelial da alça capilar glomerular com subsequente ativação do sistema do complemento. Grandes avanços na identificação de potenciais antígenos alvo têm ocorrido nos últimos vinte anos, e o principal é a proteína "M-type phospholipase-A2 receptor" (PLA2R) com o anticorpo anti-PLA2R circulante, o que possibilita avaliar a atividade e o prognóstico dessa nefropatia. Essa via de lesão corresponde aproximadamente a 70% a 80% dos casos da nefropatia membranosa caracterizada como primária. Nos últimos 10 anos vários outros antígenos alvo potenciais têm sido identificados. Esta revisão se propõe a apresentar de modo didático aspectos clínicos, etiopatogênicos e terapêuticos da nefropatia membranosa, incluídos os casos com ocorrência no transplante renal.
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Diabetic nephropathy (DN) is the leading cause of chronic kidney disease and end-stage renal failure worldwide. Several mechanisms are involved in the pathogenesis of this disease, which culminate in morphological changes such as podocyte injury. Despite the complex diagnosis and pathogenesis, limited attempts have been made to establish new biomarkers for DN. The higher concentration of Mindin protein in the urine of patients with type 2 diabetes mellitus suggests that it plays a role in DN. Therefore, this study investigated whether in situ protein expression of Mindin can be considered a potential DN biomarker. Fifty renal biopsies from patients diagnosed with DN, 57 with nondiabetic glomerular diseases, including 17 with focal segmental glomerulosclerosis (FSGS), 14 with minimal lesion disease (MLD) and 27 with immunoglobulin A nephropathy (IgAN), and 23 adult kidney samples from autopsies (control group) were evaluated for Mindin expression by immunohistochemistry. Podocyte density was inferred by Wilms' tumor 1 (WT1) immunostaining, while foot process effacement was assessed by transmission electron microscopy. Receiver operative characteristic (ROC) analysis was performed to determine the biomarker sensitivity/specificity. Low podocyte density and increased Mindin expression were observed in all cases of DN, regardless of their class. In the DN group, Mindin expression was significantly higher than that in the FSGS, MCD, IgAN and control groups. Higher Mindin expression was significantly positively correlated with foot process effacement only in class III DN cases. Furthermore, Mindin protein presented high specificity in the biopsies of patients with DN (p < 0.0001). Our data suggest that Mindin may play a role in DN pathogenesis and is a promising biomarker of podocyte lesions.
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Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Glomerulonefrite por IGA , Glomerulosclerose Segmentar e Focal , Podócitos , Adulto , Humanos , Nefropatias Diabéticas/diagnóstico , BiomarcadoresRESUMO
INTRODUCTION: Chikungunya virus was detected in cases of acute chikungunya fever in renal tissue. However, chikungunya virus-related kidney injury still lacks characterization, and it is unknown whether the kidneys are reservoirs for the virus. We sought to detect histopathological changes and viral antigens in renal tissue, and to evaluate kidney injury markers in different phases of chikungunya fever. METHODS: Two groups were evaluated in this exploratory study: patients with biopsy-proven kidney injury established after chikungunya fever, and patients with post-chikungunya fever chronic joint manifestations without known kidney injury, in whom we actively searched for kidney injury markers. RESULTS: In the first group, 15 patients had kidney injury 0.5-24 months after chikungunya fever. The most frequent histopathological diagnoses were glomerular lesions. No viral antigens were detected in renal tissue. High-risk genotypes were detected in patients with atypical hemolytic uremic syndrome and focal and segmental glomerulosclerosis. In the second group, 114 patients had post-chikungunya fever joint manifestations on average for 35.6 months. Mean creatinine and proteinuria were 0.9 mg/dl and 71.5 mg/day, respectively. One patient had isolated hematuria. There was no indication for renal biopsy in this group. CONCLUSIONS: Several histopathological features were found after chikungunya fever, without virus detection in renal tissue. These findings suggest that chikungunya virus may trigger kidney lesions with varying degrees of severity at different stages of infection. However, the probability that this virus replicates in the renal tissue seems unlikely.
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Febre de Chikungunya , Vírus Chikungunya , Glomerulosclerose Segmentar e Focal , Nefropatias , Febre de Chikungunya/complicações , Febre de Chikungunya/diagnóstico , Vírus Chikungunya/genética , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Nefropatias/diagnóstico , Nefropatias/etiologia , Nefropatias/patologia , Glomérulos Renais/patologiaRESUMO
The objective of this study was to evaluate the histopathological changes caused by infection with the Colombian strain of Trypanosoma cruzi (T. cruzi) in the acute and chronic experimental phases. C57Bl/6 mice were infected with 1000 trypomastigote forms of the Colombian strain of T. cruzi. After 30 days (acute phase) and 90 days (early chronic phase) of infection, the animals were euthanized, and the colon was collected and divided into two parts: proximal and distal. The distal portion was used for histopathological analysis, whereas the proximal portion was used for quantification of pro- and anti-inflammatory cytokines. In addition, the weight of the animals and parasitemia were assessed. The infection induced gradual weight loss in the animals. In addition, the infection induced an increase in interferon gamma (IFNγ) and tumor necrosis factor-alpha (TNF-α) in the intestine in the acute phase, in which this increase continued until the early chronic phase. The same was observed in relation to the presence of intestinal inflammatory infiltrates. In relation to interleukin (IL)-10, there was an increase only in the early chronic phase. The Colombian strain infection was also able to induce neuronal loss in the myenteric plexus and deposition of the collagen fibers during the acute phase. The Colombian strain of T. cruzi is capable of causing histopathological changes in the intestine of infected mice, especially in inducing neuronal destructions. Thus, this strain can also be used to study the intestinal form of Chagas disease in experimental models.
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Doença de Chagas , Trypanosoma cruzi , Animais , Colágeno , Colômbia , Intestinos/patologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The association between inflammatory processes and intestinal neuronal destruction during the progression of Chagasic megacolon is well established. However, many other components play essential roles, both in the long-term progression and control of the clinical status of patients infected with Trypanosoma cruzi. Components such as neuronal subpopulations, enteric glial cells, mast cells and their proteases, and homeostasis-related proteins from several organic systems (serotonin and galectins) are differentially involved in the progression of Chagasic megacolon. This review is aimed at revealing the characteristics of the intestinal microenvironment found in Chagasic megacolon by using different types of already used biomarkers. Information regarding these components may provide new therapeutic alternatives and improve the understanding of the association between T. cruzi infection and immune, endocrine, and neurological system changes.
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Biomarcadores/metabolismo , Doença de Chagas/diagnóstico , Inflamação/diagnóstico , Megacolo/diagnóstico , Trypanosoma cruzi/fisiologia , Animais , Microambiente Celular , Doença de Chagas/imunologia , Sistema Endócrino , Humanos , Sistema Imunitário , Inflamação/imunologia , Megacolo/imunologia , Sistema Nervoso , NeuroimunomodulaçãoRESUMO
PURPOSE OF REVIEW: In this narrative review, we describe general aspects, histological alterations, treatment, and implications of Fabry disease (FD) nephropathy. This information should be used to guide physicians and patients in a shared decision-making process. SOURCE OF INFORMATION: Original peer-reviewed articles, review articles, and opinion pieces were identified from PubMed and Google Scholar databases. Only sources in English were accessed. METHODS: We performed a focused narrative review assessing the main aspects of FD nephropathy. The literature was critically analyzed from a theoretical and contextual perspective, and thematic analysis was performed. KEY FINDINGS: FD nephropathy is related to the progressive accumulation of GL3, which occurs in all types of renal cells. It is more prominent in podocytes, which seem to play an important role in the pathogenesis of this nephropathy. A precise detection of renal disorders is of fundamental importance because the specific treatment of FD is usually delayed, making reversibility unlikely and leading to a worse prognosis. LIMITATIONS: As no formal tool was applied to assess the quality of the included studies, selection bias may have occurred. Nonetheless, we have attempted to provide a comprehensive review on the topic using current studies from experts in FD and extensive review of the literature.
OBJET DE LA REVUE: Dans cette revue narrative, nous discutons des aspects généraux, des modifications histologiques, du traitement et des implications de la néphropathie liée à la Maladie de Fabry. Des informations qui serviront à guider les médecins et les patients dans un processus commun de prise de décision. SOURCES: Les originaux d'articles évalués par les pairs, d'articles-synthèses et d'articles d'opinion ont été répertoriés dans les bases de données Pubmed et Google Scholar. Seuls les articles en anglais ont été consultés. MÉTHODOLOGIE: Nous avons procédé à une revue narrative ciblée examinant les principaux aspects de la néphropathie liés à la maladie de Fabry. La documentation a fait l'objet d'une critique rigoureuse du point de vue théorique et contextuel, et une analyse thématique a été effectuée. PRINCIPAUX RÉSULTATS: La néphropathie liée à la maladie de Fabry est associée à l'accumulation progressive de GL3, qui se produit dans tous les types de cellules rénales. Elle est plus présente dans les podocytes, qui semblent jouer un rôle important dans la pathogenèse de la néphropathie. Un dépistage précis des troubles rénaux est d'une importance capitale puisque le traitement spécifique de la maladie de Fabry est généralement retardé, ce qui rend la réversibilité peu probable et conduit à un pronostic plus défavorable. LIMITES: Des biais de sélection pourraient s'être introduits puisqu'aucun outil formel n'a été utilisé pour évaluer les études incluses. Nous avons néanmoins tenté de procéder à un examen complet du sujet grâce aux études actuelles menées par des experts de la maladie de Fabry et à une revue approfondie de la documentation.
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Podocyte injury in focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) results from the imbalance between adaptive responses that maintain homeostasis and cellular dysfunction that can culminate in cell death. Therefore, an in situ analysis was performed to detect morphological changes related to cell death and autophagy in renal biopsies from adult patients with podocytopathies. Forty-nine renal biopsies from patients with FSGS (n = 22) and MCD (n = 27) were selected. In situ expression of Wilms Tumor 1 protein (WT1), light chain microtubule 1-associated protein (LC3) and caspase-3 protein were evaluated by immunohistochemistry. The foot process effacement and morphological alterations related to podocyte cell death and autophagy were analyzed with transmission electronic microscopy. Reduction in the density of WT1-labeled podocytes was observed for FSGS and MCD cases as compared to controls. Foot process width (FPW) in control group was lower than in cases of podocytopathies. In FSGS group, FPW was significantly higher than in MCD group and correlated with proteinuria. A density of LC3-labeled podocytes and the number of autophagosomes in podocytes/ pedicels were higher in the MCD group than in the FSGS group. The number of autophagosomes correlated positively with the estimated glomerular filtration rate in cases of MCD. The density of caspase-3-labeled podocytes in FSGS and MCD was higher than control group, and a higher number of podocytes with an evidence of necrosis was detected in FSGS cases than in MCD and control cases. Podocytes from patients diagnosed with FSGS showed more morphological and functional alterations resulting from a larger number of lesions and reduced cell adaptation.