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1.
Am J Obstet Gynecol ; 225(2): 169.e1-169.e16, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33705749

RESUMO

BACKGROUND: Anatomic terminology in both written and verbal forms has been shown to be inaccurate and imprecise. OBJECTIVE: Here, we aimed to (1) review published anatomic terminology as it relates to the posterior female pelvis, posterior vagina, and vulva; (2) compare these terms to "Terminologia Anatomica," the internationally standardized terminology; and (3) compile standardized anatomic terms for improved communication and understanding. STUDY DESIGN: From inception of the study to April 6, 2018, MEDLINE database was used to search for 40 terms relevant to the posterior female pelvis and vulvar anatomy. Furthermore, 11 investigators reviewed identified abstracts and selected those reporting on posterior female pelvic and vulvar anatomy for full-text review. In addition, 11 textbook chapters were included in the study. Definitions of all pertinent anatomic terms were extracted for review. RESULTS: Overall, 486 anatomic terms were identified describing the vulva and posterior female pelvic anatomy, including the posterior vagina. "Terminologia Anatomica" has previously accepted 186 of these terms. Based on this literature review, we proposed the adoption of 11 new standardized anatomic terms, including 6 regional terms (anal sphincter complex, anorectum, genital-crural fold, interlabial sulcus, posterior vaginal compartment, and sacrospinous-coccygeus complex), 4 structural terms (greater vestibular duct, anal cushions, nerve to the levator ani, and labial fat pad), and 1 anatomic space (deep postanal space). In addition, the currently accepted term rectovaginal fascia or septum was identified as controversial and requires further research and definition before continued acceptance or rejection in medical communication. CONCLUSION: This study highlighted the variability in the anatomic nomenclature used in describing the posterior female pelvis and vulva. Therefore, we recommended the use of standardized terminology to improve communication and education across medical and anatomic disciplines.


Assuntos
Diafragma da Pelve/anatomia & histologia , Terminologia como Assunto , Vagina/anatomia & histologia , Vulva/anatomia & histologia , Vasos Sanguíneos/anatomia & histologia , Fáscia/anatomia & histologia , Feminino , Humanos , Pelve/anatomia & histologia , Nervos Periféricos/anatomia & histologia , Região Sacrococcígea
2.
Int Urogynecol J ; 32(12): 3177-3181, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33128162

RESUMO

INTRODUCTION AND HYPOTHESIS: The aim of this study was to develop a Polish language version of the short form of the Pelvic Floor Impact Questionnaire 7 (PFIQ-7) and to validate it in a sample of Polish-speaking women with pelvic floor disorders (PFDs). METHODS: The PFIQ-7 was initially translated in a stepwise fashion as guided by the International Urogynecological Association (IUGA) Translation Protocol. First, two bilingual physicians in Poland and the USA performed a forward translation of the PFIQ-7. Next, a community review process was undertaken consisting of one-on-one cognitive interviews with 20 patients. The translated questionnaire was then back translated into English. The final Polish version of the PFIQ-7 was subsequently administered to Polish-speaking patients presenting with PFDs at university-based urogynecology clinics in Poland and the USA along with a Polish version of the Pelvic Floor Distress Inventory (PFDI-20). Internal consistency and criterion validity were assessed. RESULTS: A total of 225 women with PFDs enrolled in this multicenter study. Complete data from 185 women in Poland and 40 primarily Polish-speaking women in the USA were analyzed. Participants had a mean age of 60.1 ± 11.1 years and mean body mass index (BMI) 27.9 ± 4.9. The Poland and United States cohorts did not vary significantly in age, BMI, or education level. PFIQ-7 internal consistency as measured by Cronbach's alpha was good (0.93). Criterion validity was adequate between responses on the PFIQ-7 and PFDI-20 prolapse, colorectal, and urinary subscales (0.62-0.69, p < 0.05). CONCLUSIONS: The Polish version of the PFIQ-7 is a reliable tool for evaluating pelvic floor symptoms in Polish-speaking women with PFDs.


Assuntos
Distúrbios do Assoalho Pélvico , Prolapso de Órgão Pélvico , Idoso , Feminino , Humanos , Idioma , Pessoa de Meia-Idade , Diafragma da Pelve , Polônia , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários , Traduções
3.
Int Urogynecol J ; 32(8): 2135-2142, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34213599

RESUMO

INTRODUCTION AND HYPOTHESIS: Women with hereditary disorders of connective tissue (HDCT) are at increased risk of pelvic organ prolapse (POP) and stress urinary incontinence (SUI). We hypothesized that patients would have increased incidence and severity of perioperative complications up to 6 weeks after surgeries for POP/SUI. Secondary objectives were to compare pre- and post-operative pelvic floor symptoms and anatomical support as well as pelvic floor disorder recurrence. METHODS: In this multi-center retrospective cohort study, we identified patients with HDCTs by patient history and ICD-9 codes over an 11-year period. Controls without HDCTs were matched 2:1 to the primary POP or SUI procedure and surgeon. Demographic characteristics, perioperative pelvic floor information and complications were collected. A sample size of 65 HDCT patients and 130 controls was calculated to detect a 20% difference in complications with 80% power and alpha of 0.05. RESULTS: We identified 59 HDCT patients and 118 controls. Of the women with HDCTs, 49% had Ehlers-Danlos, 22% joint hypermobility syndrome, 15% Marfan syndrome, and 14% had others. Compared with controls, HDCT patients had more total perioperative complications (46% vs 22%, p = 0.002); an age-adjusted relative risk of complications was 1.4 (CI 0.7-2.6). HDCT patients had more Clavien-Dindo grades I and II complications (p = 0.02, 0.03) and more hospital readmissions (14% vs 3%, p = 0.01) than controls. There was no difference in the incidence of specific complications nor was there a difference in recurrence of POP (10%) or SUI (11%) between groups. CONCLUSIONS: Patients with HDCTs had more Clavien-Dindo grade I and II complications following pelvic floor reconstructive surgery and more readmissions.


Assuntos
Distúrbios do Assoalho Pélvico , Prolapso de Órgão Pélvico , Procedimentos de Cirurgia Plástica , Incontinência Urinária por Estresse , Feminino , Humanos , Diafragma da Pelve/cirurgia , Prolapso de Órgão Pélvico/cirurgia , Estudos Retrospectivos , Incontinência Urinária por Estresse/etiologia , Incontinência Urinária por Estresse/cirurgia
4.
Am J Obstet Gynecol ; 222(3): 204-218, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31805273

RESUMO

The objectives of this study were to review the published literature and selected textbooks, to compare existing usage to that in Terminologia Anatomica, and to compile standardized anatomic nomenclature for the apical structures of the female pelvis. MEDLINE was searched from inception until May 30, 2017, based on 33 search terms generated by group consensus. Resulting abstracts were screened by 11 reviewers to identify pertinent studies reporting on apical female pelvic anatomy. Following additional focused screening for rarer terms and selective representative random sampling of the literature for common terms, accepted full-text manuscripts and relevant textbook chapters were extracted for anatomic terms related to apical structures. From an initial total of 55,448 abstracts, 193 eligible studies were identified for extraction, to which 14 chapters from 9 textbooks were added. In all, 293 separate structural terms were identified, of which 184 had Terminologia Anatomica-accepted terms. Inclusion of several widely used regional terms (vaginal apex, adnexa, cervico-vaginal junction, uretero-vesical junction, and apical segment), structural terms (vesicouterine ligament, paracolpium, mesoteres, mesoureter, ovarian venous plexus, and artery to the round ligament) and spaces (vesicocervical, vesicovaginal, presacral, and pararectal) not included in Terminologia Anatomica is proposed. Furthermore, 2 controversial terms (lower uterine segment and supravaginal septum) were identified that require additional research to support or refute continued use in medical communication. This study confirms and identifies inconsistencies and gaps in the nomenclature of apical structures of the female pelvis. Standardized terminology should be used when describing apical female pelvic structures to facilitate communication and to promote consistency among multiple academic, clinical, and surgical disciplines.


Assuntos
Genitália Feminina/anatomia & histologia , Pelve/anatomia & histologia , Terminologia como Assunto , Sistema Urinário/anatomia & histologia , Artérias/anatomia & histologia , Feminino , Humanos , Ligamentos/anatomia & histologia , Veias/anatomia & histologia
6.
Molecules ; 25(5)2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32138315

RESUMO

Sphingolipids (SLs), which have structural and biological responsibilities in the human epidermis, are importantly involved in the maintenance of the skin barrier and regulate cellular processes, such as the proliferation, differentiation and apoptosis of keratinocytes (KCs). As many dermatologic diseases, including psoriasis (PsO), intricately characterized by perturbations in these cellular processes, are associated with altered composition and unbalanced metabolism of epidermal SLs, more education to precisely determine the role of SLs, especially in the pathogenesis of skin disorders, is needed. PsO is caused by a complex interplay between skin barrier disruption, immune dysregulation, host genetics and environmental triggers. The contribution of particular cellular compartments and organelles in SL metabolism, a process related to dysfunction of lysosomes in PsO, seems to have a significant impact on lysosomal signalling linked to a modulation of the immune-mediated inflammation accompanying this dermatosis and is not fully understood. It is also worth noting that a prominent skin disorder, such as PsO, has diminished levels of the main epidermal SL ceramide (Cer), reflecting altered SL metabolism, that may contribute not only to pathogenesis but also to disease severity and/or progression. This review provides a brief synopsis of the implications of SLs in PsO, aims to elucidate the roles of these molecules in complex cellular processes deregulated in diseased skin tissue and highlights the need for increased research in the field. The significance of SLs as structural and signalling molecules and their actions in inflammation, in which these components are factors responsible for vascular endothelium abnormalities in the development of PsO, are discussed.


Assuntos
Psoríase/metabolismo , Psoríase/patologia , Pele/metabolismo , Pele/patologia , Esfingolipídeos/metabolismo , Animais , Humanos , Metabolismo dos Lipídeos/fisiologia
7.
Int Urogynecol J ; 30(1): 101-105, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30003284

RESUMO

INTRODUCTION AND HYPOTHESIS: The aim of this study was to develop a Polish language version of the short form of the Pelvic Floor Distress Inventory (PFDI-20) and to validate it in a sample of Polish-speaking women with pelvic floor disorders (PFDs). METHODS: The PFDI-20 was initially translated in a stepwise fashion as guided by the International Urogynecological Association (IUGA) Translation Protocol. After initial forward translation from English to Polish, a community review process consisting of cognitive interviews and confirmation via back translation was performed. The final Polish version of the PFDI-20 was administered to Polish-speaking patients presenting with PFDs at university-based urogynecology clinics in Poland and the United States, along with a Polish version of the King's Health Questionnaire (KHQ). Internal consistency and criterion validity were assessed. Test-retest reliability was assessed in 100 patients after 2 weeks. RESULTS: A total of 254 women with PFDs enrolled in this multicenter study. Complete data from 44 Polish-speaking women in the United States and 200 women in Poland were analyzed. Participants had a mean age of 60.3 ± 11.2 years and mean body mass index (BMI) 27.6 ± 4.7. Internal consistency as measured by Cronbach's alpha was good (0.89). Criterion validity was adequate between responses on the KHQ and PFDI-20 with Pearson correlations in particular domains (0.27-0.50, P < 0.05). Excellent test-retest reliability was demonstrated by intraclass correlation using a two-way mixed-effects model with absolute agreement (0.87). CONCLUSIONS: The Polish version of the PFDI is a reliable tool for evaluating pelvic floor symptoms in Polish-speaking women with PFDs.


Assuntos
Distúrbios do Assoalho Pélvico/psicologia , Inquéritos e Questionários , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Distúrbios do Assoalho Pélvico/diagnóstico , Distúrbios do Assoalho Pélvico/epidemiologia , Polônia/epidemiologia
8.
Int J Mol Sci ; 20(9)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067781

RESUMO

Despite the constantly updated knowledge regarding the alterations occurring in the cells of patients with psoriasis, the status and the role of the lysosome, a control center of cell metabolism, remain to be elucidated. The architecture of the epidermis is largely regulated by the action of lysosomes, possibly activating signaling pathways in the cellular crosstalk of keratinocytes-epidermal cells-with infiltrating immune cells. Thus, in the present study, lysosome alterations were examined in vitro and in situ using a two-dimensional (2D) keratinocyte model of HaCaT cells with "psoriasis-like" inflammation and skin specimens, respectively. Specific fluorescence and immunohistochemical staining showed an augmented level of acidic organelles in response to keratinocyte activation (mimicking a psoriatic condition while maintaining the membrane integrity of these structures) as compared with the control, similar to that seen in skin samples taken from patients. Interestingly, patients with the most pronounced PASI (Psoriasis Area and Severity Index), BSA (Body Surface Area), and DLQI (Dermatology Life Quality Index) scores suffered a high incidence of positive lysosomal-associated membrane protein 1 (LAMP1) expression. Moreover, it was found that the gene deregulation pattern was comparable in lesioned (PP) and non-lesioned (PN) patient-derived skin tissue, which may indicate that these alterations occur prior to the onset of the characteristic phenotype of the disease. Changes in the activity of genes encoding the microphthalmia family (MiT family) of transcription factors and mammalian target of rapamycin complex 1 (MTORC1) were also observed in the in vitro psoriasis model, indicating that the biogenesis pathway of this arm is inhibited. Interestingly, in contrast to the keratinocytes of HaCaT with "psoriasis-like" inflammation, LAMP1 was up-regulated in both PP and PN skin, which can be a potential sign of an alternative mechanism of lysosome formation. Defining the molecular profile of psoriasis in the context of "the awesome lysosome" is not only interesting, but also desired; therefore, it is believed that this paper will serve to encourage other researchers to conduct further studies on this subject.


Assuntos
Queratinócitos/metabolismo , Lisossomos/metabolismo , Psoríase/metabolismo , Pele/metabolismo , Adulto , Idoso , Linhagem Celular , Feminino , Humanos , Queratinócitos/ultraestrutura , Proteínas de Membrana Lisossomal/genética , Proteínas de Membrana Lisossomal/metabolismo , Lisossomos/ultraestrutura , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Pessoa de Meia-Idade , Psoríase/patologia , Pele/ultraestrutura
9.
Int J Mol Sci ; 19(1)2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29342918

RESUMO

Research in recent years has shown that sphingolipids are essential signalling molecules for the proper biological and structural functioning of cells. Long-term studies on the metabolism of sphingolipids have provided evidence for their role in the pathogenesis of a number of diseases. As many inflammatory diseases, such as lysosomal storage disorders and some dermatologic diseases, including psoriasis, atopic dermatitis and ichthyoses, are associated with the altered composition and metabolism of sphingolipids, more studies precisely determining the responsibilities of these compounds for disease states are required to develop novel pharmacological treatment opportunities. It is worth emphasizing that knowledge from the study of inflammatory metabolic diseases and especially the possibility of their treatment may lead to insight into related metabolic pathways, including those involved in the formation of the epidermal barrier and providing new approaches towards workable therapies.


Assuntos
Metabolismo dos Lipídeos , Doenças por Armazenamento dos Lisossomos/etiologia , Doenças por Armazenamento dos Lisossomos/metabolismo , Dermatopatias/etiologia , Dermatopatias/metabolismo , Animais , Suscetibilidade a Doenças , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Doenças por Armazenamento dos Lisossomos/terapia , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Transdução de Sinais , Dermatopatias/terapia , Esfingolipídeos/metabolismo
10.
Int Urogynecol J ; 28(11): 1671-1675, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28470415

RESUMO

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse is common in the elderly population and may be surgically treated with colpocleisis. We aimed to identify and compare surgical characteristics and 30-day perioperative complications in patients who underwent colpocleisis with and without concomitant vaginal hysterectomy (VH) using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. METHODS: Women who underwent vaginal closure procedures from 2006 to 2014 were identified utilizing Current Procedural Terminology (CPT) codes for LeFort colpocleisis (57120) and vaginectomy (57110). Patients undergoing a concomitant VH were identified by CPT codes ranging from 58260 to 58294. Variables including patient demographics, operative time, hospital length of stay, transfusion' and reoperation were evaluated. Specific medical complications, surgical site infection' and urinary tract infection (UTI) rates were calculated. Variables were analyzed using chi-squared, Fisher's exact, student's t tests and logistic regression. RESULTS: We identified 1,027 women in the ACS-NSQIP database who underwent vaginal closure procedures. The majority of patients (893, 87.0%) underwent colpocleisis alone, and the remainder (134, 13.0%) underwent concomitant VH. Operative times were shorter in patients undergoing colpocleisis alone. UTI was the most common postoperative complication affecting 4.3% of the entire cohort. Twelve women (1.2%) had a serious medical complication, seven who underwent colpocleisis alone and five who underwent colpocleisis with concomitant VH. In backward logistic regression' serious medical complications were the only variable independently associated with VH at the time of colpocleisis (p < 0.05). CONCLUSIONS: Colpocleisis is a safe procedure with rare serious adverse events.


Assuntos
Procedimentos Cirúrgicos em Ginecologia/estatística & dados numéricos , Prolapso de Órgão Pélvico/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Estados Unidos/epidemiologia
11.
Int J Mol Sci ; 18(12)2017 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-29186769

RESUMO

Psoriasis is an ancient, universal chronic skin disease with a significant geographical variability, with the lowest incidence rate at the equator, increasing towards the poles. Insights into the mechanisms responsible for psoriasis have generated an increasing number of druggable targets and molecular drugs. The development of relevant in vitro and in vivo models of psoriasis is now a priority and an important step towards its cure. In this review, we summarize the current cellular and animal systems suited to the study of psoriasis. We discuss the strengths and limitations of the various models and the lessons learned. We conclude that, so far, there is no one model that can meet all of the research needs. Therefore, the choice model system will depend on the questions being addressed.


Assuntos
Modelos Animais de Doenças , Psoríase/patologia , Animais , Humanos , Camundongos , Psoríase/genética , Psoríase/metabolismo
12.
Clin Colon Rectal Surg ; 29(3): 264-70, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27582653

RESUMO

Fecal incontinence (FI) is a chronic and debilitating condition that carries a significant health, economic, and social burden. FI has a considerable psychosocial and financial impact on patients and their families. A variety of treatment modalities are available for FI including behavioral and dietary modifications, pharmacotherapy, pelvic floor physical therapy, bulking agents, anal sphincteroplasty, sacral nerve stimulation, artificial sphincters, magnetic sphincters, posterior anal sling, and colostomy.

13.
Int Urogynecol J ; 25(12): 1709-14, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24964762

RESUMO

INTRODUCTION AND HYPOTHESIS: To determine the incidence of lower urinary tract (LUT) injury at the time of Cesarean delivery (CD) and to identify factors associated with LUT injury. METHODS: Cases of LUT injury at delivery between 2001 and 2012, were identified by ICD-9 code. Chart review was utilized for verification and descriptive data collection. LUT injury incidence rates were calculated using annual delivery totals and trends over time were calculated using simple linear regression. LUT injury was classified as full-thickness bladder injury (including ureteral injury) or partial-thickness bladder injury based on degree of injury and post-operative intervention. Each case was year-matched to generate two CD controls. Logistic regression analysis was performed using maternal, delivery, and health system characteristics to identify factors associated with full or partial injury. Appropriate statistical analyses were performed with significance at p < 0.05. RESULTS: Overall delivery and CD rates increased during the study time period, but despite the increase in CD rates, annual rates of LUT injury did not vary significantly (p = 0.658). Of the 72 LUT injuries reported, 39 (54 %) were full-thickness bladder, 2 (3 %) ureteral, and 31 (43 %) were partial-thickness bladder injuries. Full injury, controlling for repeat CD, was associated with increasing maternal age, transfusion, and active second stage of labor. Partial injury, was associated with increasing maternal age and delivery in the first half of the academic year. CONCLUSIONS: Despite an increasing volume of CDs, LUT injury remained relatively uncommon (0.3 % of all CDs). Full and partial bladder injuries have unique risk profiles.


Assuntos
Cesárea/efeitos adversos , Bem-Estar Materno , Doenças da Bexiga Urinária/epidemiologia , Doenças da Bexiga Urinária/etiologia , Sistema Urinário/lesões , Adulto , Estudos de Casos e Controles , Codificação Clínica , Cistoscopia , Gerenciamento Clínico , Feminino , Humanos , Incidência , Modelos Lineares , Gravidez , Estudos Retrospectivos , Fatores de Risco , Doenças da Bexiga Urinária/classificação
14.
Proc Natl Acad Sci U S A ; 105(41): 15848-53, 2008 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-18840682

RESUMO

RAD51 and other members of the RecA family of strand exchange proteins assemble on ssDNA to form presynaptic filaments, which carry out the central steps of homologous recombination. A microplate-based assay was developed for high-throughput measurement of hRAD51 filament formation on ssDNA. With this method, a 10,000 compound library was screened, leading to the identification of a small molecule (RS-1) that enhances hRAD51 binding in a wide range of biochemical conditions. Salt titration experiments showed that RS-1 can enhance filament stability. Ultrastructural analysis of filaments formed on ssDNA showed that RS-1 can increase both protein-DNA complex lengths and the pitch of helical filament turns. RS-1 stimulated hRAD51-mediated homologous strand assimilation (D-loop) activity by at least 5- to 11-fold, depending on the condition. This D-loop stimulation occurred even in the presence of Ca(2+) or adenylyl-imidodiphosphate, indicating that the mechanism of stimulation was distinct from that conferred by Ca(2+) and/or inhibition of ATPase. No D-loop activity was observed in the absence of a nucleotide triphosphate cofactor, indicating that the compound does not substitute for this requirement. These results indicate that RS-1 enhances the homologous recombination activity of hRAD51 by promoting the formation of active presynaptic filaments. Cell survival assays in normal neonatal human dermal fibroblasts demonstrated that RS-1 promotes a dose-dependent resistance to the cross-linking chemotherapeutic drug cisplatin. Given that RAD51-dependent recombination is a major determinant of cisplatin resistance, RS-1 seems to function in vivo to stimulate homologous recombination repair proficiency. RS-1 has many potential applications in both research and medical settings.


Assuntos
Benzamidas/farmacologia , Rad51 Recombinase/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Sulfonamidas/farmacologia , Sobrevivência Celular , Cisplatino , DNA de Cadeia Simples/metabolismo , Resistencia a Medicamentos Antineoplásicos , Estabilidade Enzimática/efeitos dos fármacos , Fibroblastos/citologia , Humanos , Recém-Nascido , Ligantes
15.
Cells ; 10(11)2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34831208

RESUMO

Psoriasis (Ps), commonly perceived as a skin and joint disorder, has a complex basis and results from disturbances in the sophisticated network between skin and the immune system. This makes it difficult to properly depict the complete pathomechanism on an in vitro scale. Deciphering the complicated or even subtle modulation of intra- and intercellular factors, assisted by the implementation of in vitro human skin models, may provide the opportunity to dissect the disease background step by step. In addition to reconstructed artificial skin substitutes, which mimic the native physiological context, in vitro models are conducive to the broad "3 Rs" philosophy (reduce, refine, and replace) and represent important tools for basic and applied skin research. To meet the need for a more comprehensive in vitro Ps model, a set of various experimental conditions was applied in this study. The selection of in vitro treatment that mimicked the Ps phenotype was illustrated by analyses of discriminating biomarker genes involved in the pathogenesis of the disease, i.e., keratinocyte differentiation markers, antimicrobial peptides, chemokines, and proliferation markers. This resulted in a reproducible protocol for the use of the primary skin keratinocyte (pKC) monoculture treated with a cytokine cocktail (5MIX, i.e., interleukin (IL) 1 alpha (IL-1α), IL-17A, IL-22, oncostatin M (OSM), and tumour necrosis factor alpha (TNF-α)) at a calcium (Ca2+) concentration (i.e., 2 mM) in an applied medium, which best mirrored the in vitro Ps-like inflammatory model. In addition, based on waste skin material, the method has the potential for extensive experimentation, both in detailed molecular studies and preclinical tests.


Assuntos
Citocinas/farmacologia , Imiquimode/farmacologia , Inflamação/patologia , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Modelos Biológicos , Psoríase/patologia , Soro/metabolismo , Adulto , Células Cultivadas , Técnicas de Cocultura , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Marcadores Genéticos , Células HaCaT , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Acetato de Tetradecanoilforbol/farmacologia
16.
Female Pelvic Med Reconstr Surg ; 27(8): 521-526, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34261104

RESUMO

OBJECTIVE: The aims of this study were to evaluate the biomolecular properties of vaginal and perineal granulation tissue in postpartum women and assess the potential impact of vaginal estrogen application. METHODS: We prospectively identified women referred to a subspecialty peripartum clinic between September 2016 and April 2018 who developed symptomatic perineal or vaginal granulation tissue. As part of routine clinical care, granulation tissue was excised from each participant by a urogynecologist and subjected to RNA extraction, real-time quantitative polymerase chain reaction, histologic evaluation, and immunohistochemistry. Serum steroid hormone levels were measured. Comparisons were made between participants who used topical vaginal estradiol (E2) and those who did not (non-E2 controls). RESULTS: Sixteen postpartum women were recruited for this pilot study. More than 30% of patients (n = 5, 31%) had used topical vaginal estradiol (E2) during their postpartum recovery. Histological appearance of granulation tissue evaluated by hematoxylin and eosin staining was similar in women treated with vaginal E2 and non-E2 controls. Both estrogen receptor α (ERα) and ERß mRNA and ERα protein were readily detectable in the granulation tissue of E2-treated women. Although not statistically significant, participants who used topical E2 developed granulation tissue that exhibited local estrogen-responsive gene upregulation. Serum levels of estrone, E2, dehydroepiandrosterone, progesterone, and testosterone did not differ between vaginal E2-treated patients and controls. CONCLUSIONS: Estrogen receptor α seems to be the predominant receptor mediating estrogen action in postpartum perineal and vaginal granulation tissue. Vaginal E2 use does not seem to affect serum levels of estrone, E2, dehydroepiandrosterone, progesterone, and testosterone in postpartum women.


Assuntos
Estradiol/farmacologia , Estrogênios/farmacologia , Tecido de Granulação/efeitos dos fármacos , Vagina/patologia , Administração Tópica , Estradiol/administração & dosagem , Receptor alfa de Estrogênio , Estrogênios/administração & dosagem , Feminino , Humanos , Projetos Piloto , Período Pós-Parto
17.
Sci Rep ; 11(1): 18297, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521933

RESUMO

Genistein is applied worldwide as an alternative medicament for psoriasis (Ps) because of its anti-inflammatory activity and perceived beneficial impact on the skin. Hereby, we report our in vivo and in vitro investigations to supplement scientific research in this area. The reduction of clinical and biochemical scores in mild to moderate Ps patients taking genistein, its safety, good tolerability with no serious adverse events or discontinuations of treatment, no dose-limiting toxicities, negligible changes in pharmacodynamic parameters and remarkable serum interleukin level alterations were documented in this study. A certain regression of the Ps phenotype was visible, based on photo-documented Ps lesion evaluation. Through in vitro experiments, we found that genistein reduced IL-17A and TNF-α induced MAPK, NF-κB, and PI3K activation in normal human epidermal keratinocytes. Moreover, at the mRNA level of genes associated with the early inflammatory response characteristic for Ps (CAMP, CCL20, DEFB4A, PIK3CA, S100A7, and S100A9) and key cellular signalling (MTORC1 and TFEB), we showed that this isoflavone attenuated the increased response of IL-17A- and TNF-α-related pathways. This allows us to conclude that genistein is a good candidate for Ps treatment, being attractive for co-pharmacotherapy with other drugs.


Assuntos
Anti-Inflamatórios/uso terapêutico , Genisteína/uso terapêutico , Psoríase/tratamento farmacológico , Adulto , Anti-Inflamatórios/efeitos adversos , Linhagem Celular , Citocinas/sangue , Feminino , Imunofluorescência , Genisteína/efeitos adversos , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Psoríase/sangue , Reação em Cadeia da Polimerase em Tempo Real
18.
Female Pelvic Med Reconstr Surg ; 27(7): 462-467, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33208651

RESUMO

OBJECTIVE: In women with obstetric anal sphincter injuries, we compared the rate of major levator ani avulsion after forceps-assisted delivery versus spontaneous vaginal delivery. METHODS: Prospective cohort of primiparous women with obstetric anal sphincter injuries. The primary outcome was the rate of major levator ani avulsion as measured by 3-dimensional transvaginal ultrasonography performed between 1 and 2 weeks postpartum. Secondary outcomes included ultrasonographic anteroposterior hiatal diameter, levator hiatal area, and levator-urethra gap, and differences in validated pelvic disorder questionnaires scores at 1 to 2 and 13 weeks postpartum. RESULTS: Sixty-two women (30 spontaneous deliveries, 32 forceps deliveries) were included in the final analysis. After controlling for delivery variables, women who underwent forceps-assisted delivery were more likely to experience a major avulsion as compared with those who underwent spontaneous delivery (21/32, [65.6%] vs 8/30 [26.7%]; odds ratio, 5.9; 95% confidence interval, 1.5-24.5; P = 0.014). They were also more likely to have larger levator-urethra gaps bilaterally (P = 0.012, 0.016). After controlling for potential confounders, levator ani avulsion was independently associated with persistent anal incontinence symptoms at 13 weeks postpartum (P = 0.02). CONCLUSIONS: In women with obstetric anal sphincter injuries, the risk of levator ani avulsion is almost 6 times higher after forceps-assisted vaginal delivery as compared with spontaneous vaginal delivery. In those with avulsion, recovery of anal continence is compromised, suggesting that adding insult (avulsion) to injury (obstetric anal sphincter injury) may have negative functional consequences.


Assuntos
Canal Anal/lesões , Extração Obstétrica/efeitos adversos , Lacerações/etiologia , Diafragma da Pelve/lesões , Adulto , Incontinência Fecal/etiologia , Feminino , Humanos , Complicações do Trabalho de Parto , Gravidez , Estudos Prospectivos
19.
Female Pelvic Med Reconstr Surg ; 27(2): e481-e483, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33105342

RESUMO

OBJECTIVE: The aims of the study were to characterize pelvic floor and urinary symptoms in women seeking treatment for uterine fibroids and to explore the association between uterine/fibroid size and pelvic floor symptoms. METHODS: Women seeking treatment for uterine fibroids at a single academic center were enrolled in this cross-sectional study. All participants underwent pelvic imaging and completed the Symptom Severity Subscale of the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) and the Pelvic Floor Distress Inventory (PFDI-20). RESULTS: One hundred ninety-five women with a mean age of 41 ± 6 years and body mass index of 29 ± 7 kg/m2 were included. In this cohort, 58% identified as Black and 38% had at least 1 vaginal delivery. Women attributed pelvic pain (68%), dyspareunia (37%), and urinary incontinence (31%) to their fibroids. The mean ± SD UFS-QOL score was 48.7 ± 25.4, and 63% of participants reported being at least "somewhat bothered" by tightness/pressure in pelvic area, 60% by frequent daytime urination, and 47% by nocturia. The mean PFDI-20 score was 45.5 ± 31.9. Women reported being at least "somewhat bothered" by heaviness/dullness in the pelvis (60%), frequent urination (56%), pelvic pain or discomfort (48%), and sensation of incomplete bladder emptying (43%). The PFDI-20 and UFS-QOL scores were not correlated with uterine volume (r = 0.12, P = 0.12, and r = 0.06, P = 0.44) or fibroid size (r = 0.09, P = 0.26, and r = 0.01, P = 0.92). CONCLUSIONS: Women presenting for evaluation and treatment of fibroids report high rates of pelvic floor symptoms, particularly urinary frequency and pelvic pressure. However, uterine size and fibroid size are not associated with pelvic floor symptom bother.


Assuntos
Dispareunia/etiologia , Leiomioma/complicações , Dor Pélvica/etiologia , Incontinência Urinária/etiologia , Neoplasias Uterinas/complicações , Adulto , Estudos Transversais , Feminino , Humanos , Menorragia/etiologia , Qualidade de Vida
20.
Neuro Endocrinol Lett ; 31(4): 573-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20802445

RESUMO

OBJECTIVE: The dysregulation of adiponectin and leptin is found in insulin resistance. There is evidence that both cytokines and insulin might contribute to the placental development and the fetal growth. The objective of this study was to evaluate the relationship of maternal plasma cytokine and insulin concentrations with the placental dimension in the first trimester of pregnancy. METHODS: 34 women with singleton pregnancy, between 11th and 14th weeks, were included to the study. Plasma levels of adiponectin, leptin, insulin and glucose were quantified with ultrasound measurements of the placenta. HOMA-IR were calculated to assess the insulin sensitivity. RESULTS: Mean concentrations of adiponectin, leptin and insulin were 18,39±13.99 µg/ml; 6.99±5.67 ng/ml and 43.98±23.89 pmol/l respectively. The placenta thickness was positively associated with the maternal adiponectin plasma concentration (r=0.36; p=0.037). There were no associations between placental measurements and leptin, fasting insulin, fasting glucose and HOMA-IR. There was not significant correlation between placental measurements and the fetal Crown Rump Length (CRL). CONCLUSIONS: The results of this study imply that maternal adiponectin plasma concentration may have a role in placental growth.


Assuntos
Adiponectina/sangue , Insulina/sangue , Leptina/sangue , Placenta/anatomia & histologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Resistência à Insulina , Tamanho do Órgão , Placenta/diagnóstico por imagem , Gravidez , Primeiro Trimestre da Gravidez , Ultrassonografia Pré-Natal
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