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AIM: The study aimed to determine whether pelvic floor muscle (PFM) function before surgery may correlate with the success of surgical interventions for treating stress urinary incontinence (SUI). Our hypothesis was that addressing identified variables in preoperative rehabilitation could potentially improve surgical outcomes. METHODS: This prospective observational study was conducted at a single center and enrolled women qualified to mid-urethral tape insertion for SUI between 2020 and 2022. Digital palpation and manometry (Peritron™ 9300 V) were used to evaluate PFM function. The following parameters were acquired: vaginal resting pressure, vaginal pressure during maximal voluntary contraction (MVC), the area under the curve during a 10-second MVC, moreover the ability to perform correct PFM contraction, reflexive PFM contraction during cough and relaxation were assessed. All measurements were performed before the surgical treatment and during follow-up assessments at 1, 3, and 6 months postoperatively. The primary endpoint of the study was defined as objective cure, characterized by a negative cough stress test (CST), along with a subjective assessment based on the Urogenital Distress Inventory-6 (UDI-6) and Incontinence Impact Questionnaire-7 (IIQ-7). RESULTS: The study involved 57 eligible female participants, all of whom completed the 6-month follow-up. Objective cure was observed in 75.44% of cases, while subjective cure was reported in 33%. There was no association between PFM parameters and surgical outcomes. CONCLUSION: The success of surgical treatment of SUI 6 months postsurgery is not related to preoperative pelvic floor muscle function.
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Diafragma Pélvico , Incontinencia Urinaria de Esfuerzo , Humanos , Femenino , Incontinencia Urinaria de Esfuerzo/cirugía , Incontinencia Urinaria de Esfuerzo/fisiopatología , Diafragma Pélvico/fisiopatología , Diafragma Pélvico/cirugía , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Adulto , Anciano , Contracción Muscular , Manometría , Cabestrillo SuburetralRESUMEN
INTRODUCTION AND HYPOTHESIS: The objective of this study was to identify the potential characteristics of pelvic floor muscles (PFM) in the preoperative assessment that could be associated with post-surgical prolapse severity. We hypothesized that the same variables, if identified, could be addressed in preoperative rehabilitation to improve surgical results. METHODS: This was a single-center prospective observational study that included women who underwent surgical pelvic organ prolapse repair between 2020-2022. Genital prolapse was evaluated according to the Pelvic Organ Prolapse Quantification (POP-Q) system. All the participants underwent a PFM assessment, including a vaginal digital assessment and manometry (Peritron™ 9300 V) before surgery and at 1-, 3-, and 6-month follow-ups. Several PFM variables were recorded: vaginal resting pressure, vaginal pressure during maximal voluntary contraction (MVC), area under the curve during a 10-second MVC, ability to correctly contract the PFMs, and reflexive activation during cough and relaxation. The primary endpoint of the analysis was objective surgical success defined as POP-Q 0 or 1 at the 6-month follow-up. Additionally, a change in pelvic floor muscle function was recorded during postoperative visits. RESULTS: A total of 106 females were included in the study. Fifty-one were lost during the 6-month follow-up, which is a major limitation of the study. None of the examined parameters evaluating PFM were associated with surgical success. No statistically significant difference was found in MVC and PFM endurance before and after surgery. Post-surgery, a significant change was observed in the vaginal resting pressure and the ability to correct PFM activation and relaxation. CONCLUSIONS: Preoperative PFM function is not associated with surgical success 6 months after surgery.
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Diafragma Pélvico , Prolapso de Órgano Pélvico , Femenino , Humanos , Manometría , Prolapso de Órgano Pélvico/cirugía , Descanso , Estudios Prospectivos , Contracción Muscular/fisiologíaRESUMEN
Synthesis of molecular hybrids, obtained by combination of two or more pharmacophoric groups of different bioactive substances in order to produce more efficient drugs, is now a frequently used approach in medicinal chemistry. Following this strategy, we synthetized a library of 3-methylidene-1-tosyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones, combining a 1,8-naphthyridin-4-one motif with an exo-methylidene bond conjugated with a carbonyl group, pharmacophoric units that are present in many natural, biologically active compounds with anticancer potential. We reasoned that such bifunctional conjugates may have enhanced cytotoxic activity. The title compounds were synthesized in a four step reaction sequence. ß-Ketophosphonate, obtained from methyl N-tosylnicotinate and diethyl methylphosphonate, was reacted with various aldehydes giving 3-diethoxyphosphoryl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones as keto-enol tautomers. Later, these compounds were transformed into 3-methylidene-1-tosyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones applying the Horner-Wadsworth-Emmons methodology. Then, the cytotoxicity of the new compounds was assessed on two cancer cell lines, promyelocytic leukemia HL-60 and breast cancer adenocarcinoma MCF-7, and for comparison, on human umbilical vein endothelial cells HUVEC. The most active and selective analog, 2-ethyl-3-methylidene-1-tosyl-2,3-dihydro-1,8-naphthyridin-4(1H)-one 4 a was chosen for more detailed studies on HL-60â cell line, to determine molecular mechanisms of its anticancer activity. It was shown that 4 a strongly inhibited proliferation and induced apoptosis which could be attributed to its ability to cause DNA damage.
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Antineoplásicos , Neoplasias de la Mama , Humanos , Femenino , Estructura Molecular , Relación Estructura-Actividad , Células Endoteliales , Antineoplásicos/química , Células HL-60 , Proliferación CelularRESUMEN
BACKGROUND: The extracellular matrix serves as a scaffold for cardiomyocytes, allowing them to work in accord. In rats, collagen metabolism within a myocardial infarction scar is regulated by melatonin. The present study determines whether melatonin influences matrix metabolism within human cardiac fibroblast cultures and examines the underlying mechanism. METHODS: The experiments were performed on cultures of cardiac fibroblasts. The Woessner method, 1,9-dimethylmethylene blue assay, enzyme-linked immunosorbent assay and quantitative PCR were used in the study. RESULTS: Melatonin treatment lowered the total cell count within the culture, elevated necrotic and apoptotic cell count as well as augmented cardiac fibroblast proliferation, and increased total, intracellular, and extracellular collagen within the fibroblast culture; it also elevated type III procollagen α1 chain expression, without increasing procollagen type I mRNA production. The pineal hormone did not influence matrix metalloproteinase-2 (MMP-2) release or glycosaminoglycan accumulation by cardiac fibroblasts. Melatonin increased the release of Fibroblast Growth Factor-2 (FGF-2) by human cardiac fibroblasts, but cardiotrophin release was not influenced. CONCLUSION: Within human cardiac fibroblast culture, collagen metabolism is regulated by melatonin. The profibrotic effect of melatonin depends on the elevation of procollagen type III gene expression, and this could be modified by FGF-2. Two parallel processes, viz., cell elimination and proliferation, induced by melatonin, lead to excessive replacement of cardiac fibroblasts.
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Melatonina , Humanos , Células Cultivadas , Colágeno/genética , Colágeno/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Factor 2 de Crecimiento de Fibroblastos/farmacología , Fibroblastos , Metaloproteinasa 2 de la Matriz/metabolismo , Melatonina/farmacología , Melatonina/metabolismoRESUMEN
OBJECTIVES: Angiogenesis is engaged in endometriosis. It is regulated by regulatory factors and cytokines, transported in microvesicles. The purpose was to investigate the presence of MVs with vascular endothelial growth factor (VEGF) and metalloproteinase-9 (MMP-9) in peripheral blood and peritoneal fluid of women operated on for endometrioma or teratoma Material and methods:Microvesicles (MVs) were determined in blood samples and peritoneal fluid samples collected from women aged 20-60 years operated on for endometriosis (test group) and teratoma (control group). The final investigations were performed on 47 patients, who qualified for the study based on the meticulous inclusion criteria. MVs were analyzed by flow cytometry (FACS) using annexin V, antibodies for molecules characteristic of cells from endometriosis foci (keratin 18 (K18), CD105, CD146), and antibodies for intraepithelial vascular growth factor VEGF and metalloproteinase-9 (MMP-9). The sample was double "reading" using flow cytometry (FACSCantoII). RESULTS: Cytometry analysis confirmed MVs' presence in plasma and peritoneal fluid collected from patients with both endometriosis and teratomas. A statistically significant higher level of AnnexinV (+) MVs were observed in plasma samples of endometriosis patients. In the control group, there was a higher percentage of double-positive VEGF (+)/MMP-9 (+) and single MMP-9 (+) positive MVs in the serum. In the peritoneal fluid higher frequency of double-positive VEGF (+)/MMP-9 (+) MVs were found in the control group. However, the amount of VEGF (+) / MMP-9 (+) MVs object did not enable to differentiate between the test and control groups. The study was the first, in which MVs were confirmed in plasma and peritoneal fluid in benign adnexa tumors. CONCLUSIONS: Microvesicles are present in peripheral blood and peritoneal fluid samples collected from patients with endometriosis and teratomas. Microvesicles with proangiogenic factors (VEGF and MMP-9) are more abundant in blood and peritoneal fluid samples from patients with teratomas.
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Endometriosis , Teratoma , Humanos , Femenino , Factor A de Crecimiento Endotelial Vascular/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Endometrio/patología , Líquido AscíticoRESUMEN
Millions of women around the world suffer from an overactive bladder and urinary retention. A significant number of them are of reproductive age. For 25 years, SNM has been an effective therapy for treatment-resistant hyperactive bladder and idiopathic urinary retention. The paper presents a case of a 35-year-old pregnant woman with an overactive bladder resistant to pharmacological treatment, who responded positively to sacral neuromodulation. The patient decided against deactivating the neuromodulator and, after an uneventful course of pregnancy, she gave birth by a caesarean section to a healthy female infant. The use of SNM in pregnant patients remains a constant clinical challenge. The current literature was reviewed, but published studies do not provide a clear answer. Further studies with a long follow-up period are necessary to determine more accurately the effects of SNM therapy on the fetus and the course of pregnancy. Currently, it is recommended to deactivate SNM during pregnancy. However, it seems that an individual approach to the patient with information on the risks and benefits of continuing or discontinuing therapy should be the current procedure.
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Terapia por Estimulación Eléctrica , Vejiga Urinaria Hiperactiva , Retención Urinaria , Adulto , Cesárea , Terapia por Estimulación Eléctrica/métodos , Femenino , Humanos , Embarazo , Mujeres Embarazadas , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Retención Urinaria/terapiaRESUMEN
The E3 ubiquitin ligase TRIM25 is a key factor in the innate immune response to RNA viruses. TRIM25 has been shown to play a role in the retinoic-acid-inducible gene-1 (RIG-I) pathway, which triggers expression of type 1 interferons upon viral infection. We and others have shown that TRIM25 is an RNA-binding protein; however, the role of TRIM25 RNA-binding in the innate immune response to RNA viruses is unclear. Here, we demonstrate that influenza A virus (IAV A/PR/8/34_NS1(R38A/K41A)) infection is inhibited by TRIM25. Surprisingly, previously identified RNA-binding deficient mutant TRIM25ΔRBD and E3 ubiquitin ligase mutant TRIM25ΔRING, which lack E3 ubiquitin ligase activity, still inhibited IAV replication. Furthermore, we show that in human-derived cultured cells, activation of the RIG-I/interferon type 1 pathway mediated by either an IAV-derived 5'-triphosphate RNA or by IAV itself does not require TRIM25 activity. Additionally, we present new evidence that instead of TRIM25 directly inhibiting IAV transcription it binds and destabilizes IAV mRNAs. Finally, we show that direct tethering of TRIM25 to RNA is sufficient to downregulate the targeted RNA. In summary, our results uncover a potential mechanism that TRIM25 uses to inhibit IAV infection and regulate RNA metabolism.
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Virus de la Influenza A , Humanos , ARN Mensajero/genética , Virus de la Influenza A/genética , Ubiquitina-Proteína Ligasas/genética , Proteínas de Motivos Tripartitos/genética , Factores de TranscripciónRESUMEN
In this report, we present efficient and stereoselective syntheses of 2,6-disubstituted trans-3-methylidenetetrahydropyran-4-ones and 2-(4-methoxyphenyl)-5-methylidenetetrahydropyran-4-one that significantly broaden the spectrum of the available methylidenetetrahydropyran-4-ones with various substitution patterns. Target compounds were obtained using Horner-Wadsworth-Emmons methodology for the introduction of methylidene group onto the pyranone ring. 3-Diethoxyphosphoryltetrahydropyran-4-ones, which were key intermediates in this synthesis, were prepared by fully or highly stereoselective addition of Gilman or Grignard reagents to 3-diethoxyphosphoryldihydropyran-4-ones. Addition occurred preferentially by axial attack of the Michael donors on the dihydropyranone ring. Relative configurations and conformations of the obtained adducts were assigned using a detailed analysis of the NMR spectra. The obtained methylidenepyran-4-ones were evaluated for cytotoxic activity against two cancer cell lines (HL-60 and MCF-7). 2,6-Disubstituted 3-methylidenetetrahydropyran-4-ones with isopropyl and phenyl substituents in position 2 were more cytotoxic than analogs with n-butyl substituent. Two of the most cytotoxic analogs were then selected for further investigation on the HL-60 cell line. Both analogs induced morphological changes characteristic of apoptosis in cancer cells, significantly inhibited proliferation and induced apoptotic cell death. Both compounds also generated DNA damage, and one of the analogs arrested the cell cycle of HL-60 cells in the G2/M phase. In addition, both analogs were able to inhibit the activity of topoisomerase IIα. Based on these findings, the investigated analogs may be further optimized for the development of new and effective topoisomerase II inhibitors.
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There is uncertainty regarding the association between abdominal morphology, pelvic floor function, and psychological factors in women with postpartum pelvic girdle pain (PGP). The aim of this case-control study was to evaluate the differences between women with and without persistent PGP regarding pelvic floor function, diastasis recti, and psychological factors 6−24 weeks postpartum. Pelvic floor manometry, palpation examination of abdominal muscles, the International Consultation on Incontinence Questionnaire Short Form, The Depression, Anxiety and Stress Scale21, and the Pain Catastrophizing Scale were used. The PGP group presented with lower vaginal resting pressure (p < 0.001), more tenderness (p = 0.018) and impaired voluntary activation of pelvic floor muscles (p ≤ 0.001). Women with pain also had more distortion on the level of the anterior abdominal wall (p = 0.001) and more severe diastasis recti (p = 0.046) when compared to pain-free controls. Lower vaginal resting pressure was the strongest factor explaining PGP (OR 0.702, 95%CI 0.502−0.981). There were no differences in terms of the pelvic floor strength, endurance, severity of urinary incontinence and reported distress between the groups. Women with PGP 6−24 weeks postpartum differ in pelvic floor and abdominal muscle function from the pain-free controls. Vaginal resting pressure may be an important factor in pelvic girdle pain shortly postpartum. Further studies are needed to see a trend in changes over time.
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Dolor de Cintura Pélvica , Incontinencia Urinaria , Estudios de Casos y Controles , Femenino , Humanos , Contracción Muscular/fisiología , Diafragma Pélvico/fisiología , Periodo Posparto/fisiologíaRESUMEN
The time-sensitive GABA shift from excitatory to inhibitory is critical in early neural circuits development and depends upon developmentally regulated expression of cation-chloride cotransporters NKCC1 and KCC2. NKCC1, encoded by the SLC12A2 gene, regulates neuronal Cl- homeostasis by chloride import working opposite KCC2. The high NKCC1/KCC2 expression ratio decreases in early neural development contributing to GABA shift. Human SLC12A2 loss-of-function mutations were recently associated with a multisystem disorder affecting neural development. However, the multisystem phenotype of rodent Nkcc1 knockout models makes neurodevelopment challenging to study. Brain-Derived Neurotrophic Factor (BDNF)-NTRK2/TrkB signalling controls KCC2 expression during neural development, but its impact on NKCC1 is still controversial. Here, we discuss recent evidence supporting BDNF-TrkB signalling controlling Nkcc1 expression and the GABA shift during hippocampal circuit formation. Namely, specific deletion of Ntrk2/Trkb from immature mouse hippocampal dentate granule cells (DGCs) affects their integration and maturation in the hippocampal circuitry and reduces Nkcc1 expression in their target region, the CA3 principal cells, leading to premature GABA shift, ultimately influencing the establishment of functional hippocampal circuitry and animal behaviour in adulthood. Thus, immature DGCs emerge as a potential therapeutic target as GABAergic transmission is vital for specific neural progenitors generating dentate neurogenesis in early development and the mature brain.
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OBJECTIVE: Pregnancy-related pelvic girdle pain (PGP) may persist or occur postpartum and negatively affects women's lives. There is uncertainty regarding the association between the structures of the bony pelvis, diastasis recti abdominis (DRA), pain processing, and PGP and to what extent these factors should be considered during physical therapy. This study aimed to evaluate the differences between women with and without PGP shortly after delivery regarding the separation of a pubic symphysis, DRA, and pain catastrophizing. METHODS: Women diagnosed with PGP 24 to 72 hours after vaginal delivery were matched to pain-free controls according to age and parity. Ultrasound evaluations of diastasis recti (interrecti distance [IRD]) during rest and curl-up task and pubic symphysis (interpubic width) were performed. The Pain Catastrophizing Scale was used to assess the level of catastrophizing. A special Cox regression model was used to fit a conditional logistic regression for a 1:2 matched case-control study. RESULTS: Thirty-five women with clinically diagnosed PGP and 70 matched controls were included in the study. The PGP group had a significantly higher pre-pregnancy body mass index than the control group. After adjusting for body mass index in multiple conditional logistic regression, the interpubic distance (odds ratio = 1.64; 95% CI = 1.22 to 2.20) and IRD during curl-up (odds ratio = 2.01; 95% CI = 1.08 to 3.74) were significantly associated with PGP. Pain catastrophizing and IRD at rest were not associated with PGP in univariable or multivariable analysis. CONCLUSIONS: Pain catastrophizing is similar for women with and without PGP early postpartum. However, the degree of the pubic symphysis and rectus abdominis separation during the curl-up task are positively associated with PGP shortly after delivery. IMPACT: This study indicates that a reconsideration of the way we look at DRA is warranted. The development of a more comprehensive assessment including objective measurements and a biopsychosocial understanding is needed to inform directions for further postpartum physical therapy.
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Diástasis Muscular , Dolor de Cintura Pélvica , Sínfisis Pubiana , Estudios de Casos y Controles , Catastrofización , Femenino , Humanos , Dolor de Cintura Pélvica/diagnóstico , Embarazo , Sínfisis Pubiana/diagnóstico por imagen , Recto del AbdomenRESUMEN
The current lack of reliable methods for quantifying extracellular vesicles (EVs) isolated from complex biofluids significantly hinders translational applications in EV research. The recently developed fluorescence nanoparticle tracking analysis (FL-NTA) allows for the detection of EV-associated proteins, enabling EV content determination. In this study, we present the first comprehensive phenotyping of bronchopulmonary lavage fluid (BALF)-derived EVs from non-small cell lung cancer (NSCLC) patients using classical EV-characterization methods as well as the FL-NTA method. We found that EV immunolabeling for the specific EV marker combined with the use of the fluorescent mode NTA analysis can provide the concentration, size, distribution, and surface phenotype of EVs in a heterogeneous solution. However, by performing FL-NTA analysis of BALF-derived EVs in comparison to plasma-derived EVs, we reveal the limitations of this method, which is suitable only for relatively pure EV isolates. For more complex fluids such as plasma, this method appears to not be sensitive enough and the measurements can be compromised. Our parallel presentation of NTA-based phenotyping of plasma and BALF EVs emphasizes the great impact of sample composition and purity on FL-NTA analysis that has to be taken into account in the further development of FL-NTA toward the detection of EV-associated cancer biomarkers.
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Vesículas Extracelulares/genética , Citometría de Flujo , Neoplasias Pulmonares/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/aislamiento & purificación , Líquido del Lavado Bronquioalveolar/química , Vesículas Extracelulares/patología , Fluorescencia , Humanos , Pulmón/patología , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Nanopartículas/química , Nanopartículas/uso terapéuticoRESUMEN
Information about mechanical strain in the extracellular space is conducted along collagen fibers connected with integrins and then transmitted within cells. An aim of the study is to verify the hypothesis that the stiffness of cardiac human fibroblast substrates exerts a regulatory effect on collagen metabolism via integrin α2ß1 and downstream signaling. The experiments were performed on human cardiac fibroblasts cultured on stiff or soft polyacrylamide gels. Extracellular and intracellular collagen content, metalloproteinase-1 (MMP-1), metalloproteinase-9 (MMP-9) and expression of the α1 chain of the procollagen type I gene (Col1A1) were elevated in cultures settled on soft substrate. The substrate stiffness did not modify tissue inhibitors of matrix metalloproteinase capacity (TIMPs 1-4). Integrin α2ß1 inhibition (TC-I 15) or α2 subunit silencing resulted in augmentation of collagen content within the culture. Expression of Col1A1 and Col3A1 genes was increased in TC-I 15-treated fibroblasts. Total and phosphorylated levels of both FAK and Src kinases were elevated in fibroblasts cultured on stiff substrate. Inhibition of FAK (FAK kinase inhibitor 14) or Src kinase (AZM 47527) increased collagen content within the culture. The substrate stiffness exerted a regulatory influence on collagen metabolism via integrin α2ß1 and its downstream signaling (FAK and Src kinases) in cardiac fibroblasts.
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Colágeno/metabolismo , Fibroblastos/metabolismo , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Integrina alfa2beta1/metabolismo , Miocardio/citología , Familia-src Quinasas/metabolismo , Fenómenos Biomecánicos , Línea Celular , Humanos , Metaloproteinasas de la Matriz/metabolismo , Modelos Biológicos , Fosforilación , Subunidades de Proteína/metabolismo , Sistemas de Mensajero Secundario , Especificidad por Sustrato , Inhibidores Tisulares de Metaloproteinasas/metabolismoRESUMEN
Histamine is involved in the regulation of collagen metabolism during healing following a myocardial infarction; however, its effects on the intact heart tissue is unknown. The aim of the present study was to determine whether histamine may influence collagen content in cells isolated from intact heart, and to identify the histamine receptor involved in the regulation of collagen deposition. Cells were isolated from intact rat hearts and subjected to identification by flow cytometry. The effects of histamine and its receptor agonists and antagonists were investigated. The heart cells were found to be actin, desmin and vimentin positive. Histamine (used at a concentrations of 1x10-10-1x10-5 M) increased collagen content within the culture and increased the expression of α1 chain of the procollagen type III gene. The H2, H3 and H4 receptor inhibitors ranitidine, ciproxifan and JNJ 7777120 blocked the effect of histamine on collagen content. All tested histamine receptor agonists, viz. 2-pyridylethylamine dihydrochloride (H1 receptor agonist), amthamine dihydrobromide (H2 receptor agonist), imetit (H3 receptor agonist) and 4-methylhistamine hydrochloride (H4 receptor agonist), elevated collagen content within the heart myofibroblast cultures. The cells isolated from the intact heart were identified as myofibroblasts. Thus, the results of the present study showed that histamine augmented collagen content in the heart myofibroblast culture by activation of three histamine receptors (H2, H3 and H4). The effect of the amine was also dependent on the activation of collagen type III gene expression.
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The aging of the organism is a complex and multifactorial process. It can be viewed in the context of the whole organism, but also of individual tissues and organs. The problem of vaginal aging and the related genitourinary syndrome of menopause significantly reduces the quality of women's lives. The aging process of the vagina includes estrogen deficiencies, changes in the microbiome, and changes at the genetic level associated with DNA methylation. During the menopause, the number of Lactobacillus colonies decreases, and the number of pathological bacteria colonies increases. The decrease in estrogen levels results in a decrease in vaginal epithelial permeability, perfusion, and elastin levels, resulting in vaginal dryness and atrophy. Changes at the molecular level are the least clear. It can also be assumed that, similarly to the tissues studied so far, there are changes in cytosine methylation and TET (ten-eleven translocation) expression. The interrelationships between DNA methylation, hormonal changes, and the vaginal microbiome have not yet been fully elucidated.
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Enfermedades Vaginales , Envejecimiento , Estrógenos , Femenino , Humanos , MenopausiaRESUMEN
Extracellular vesicles (EVs) have been identified as key messengers of intracellular communication in health and disease, including the lung. EVs that can be found in bronchoalveolar lavage fluid (BALF) are released by multiple cells of the airways including bronchial epithelial cells, endothelial cells, alveolar macrophages, and other immune cells, and they have been shown to mediate proinflammatory signals in many inflammatory lung diseases. They transfer complex molecular cargo, including proteins, cytokines, lipids, and nucleic acids such as microRNA, between structural cells such as pulmonary epithelial cells and innate immune cells such as alveolar macrophages, shaping mutually their functions and affecting the alveolar microenvironment homeostasis. Here, we discuss this distinct molecular cargo of BALF-EVs in the context of inducing and propagating inflammatory responses in particular acute and chronic lung disorders. We present different identified cellular interactions in the inflammatory lung via EVs and their role in lung pathogenesis. We also summarize the latest studies on the potential use of BALF-EVs as diagnostic and prognostic biomarkers of lung diseases, especially of lung cancer.
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Líquido del Lavado Bronquioalveolar/inmunología , Vesículas Extracelulares/inmunología , Enfermedades Pulmonares/inmunología , Animales , Biomarcadores/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Enfermedades Pulmonares/metabolismoRESUMEN
Urinary retention in young women is a relatively rare clinical problem and is often underdiagnosed. In particular, functional causes of urinary retention pose a diagnostic challenge. One of them is Fowler's syndrome, which is associated with impaired urethral relaxation. Fowler's syndrome is characterized by a large bladder capacity, reduced sensation, increased maximal urethral closure pressure, and detrusor underactivity. Several hypotheses have arisen to explain the cause of urethral relaxation disorders: hormonal changes characteristic of Polycystic Ovary Syndrome (PCOS), causing abnormal stabilization of the muscle membrane, primary failure of relaxation of the striated muscle of the urethra sphincter, and increased urethral afferent activity, inhibiting the bladder afferent signals from reaching the brain by potentiating a spinal mechanism of urinary continence. Currently, sacral neuromodulation is the only intervention that can restore an atypical voiding pattern in women with Fowler's syndrome. The therapeutic effectiveness exceeds 70%, although the revision rate is relatively high, exceeding 50%. Well-designed, long-term prospective studies comparing sacral neuromodulation (SNM) with other therapies such as pelvic floor muscle physiotherapy are warranted to offer the best patient-tailored treatment.
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Síndrome del Ovario Poliquístico , Retención Urinaria , Femenino , Humanos , Masculino , Estudios Prospectivos , Uretra , Vejiga Urinaria , Retención Urinaria/etiología , Retención Urinaria/terapiaRESUMEN
(1) Background: Caesarean sections in obese patients are associated with an increased risk of surgical wound complications, including hematomas, seromas, abscesses, dehiscence, and surgical site infections. The aim of the present study is to perform a meta-analysis and systematic review of the current literature focusing on the strategies available to decrease wound complications in this population. (2) Methods: We reviewed the data available from the PubMed and the Science Direct databases concerning wound complications after caesarean sections in obese women. The following key words were used: "caesarean section", "cesarean section", "wound complication", "wound morbidity", and "wound infection". A total of 540 papers were retrieved, 40 of which were selected for the final systematic review and whereas 21 articles provided data for meta-analysis. (3) Results: The conducted meta-analyses revealed that the use of prophylactic drainage does not increase the risk of wound complications in obese women after a caesarean sections (pooled OR = 1.32; 95% CI 0.64-2.70, p = 0.45) and that vertical skin incisions increase wound complications (pooled OR = 2.48; 95% CI 1.85-3.32, p < 0.01) in obese women, including extremely obese women. (4) Conclusions: Subcutaneous drainage does not reduce the risk of a wound complications, wound infections, and fever in obese women after caesarean sections. Negative prophylactic pressure wound therapy (NPWT) may reduce the risk of surgical site infections. The evidence of using a prophylactic dose of an antibiotic before the caesarean section is still lacking.
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The inflammatory reaction influences the deposition of collagen within wound granulation tissue. The aim of the present study is to determine whether histamine acting directly on myofibroblasts derived from wound granulation tissue may influence collagen deposition. It also identifies the histamine receptor involved in this process. The experiments were carried out on cells isolated from the granulation tissue of a wound model (a polypropylene net inserted subcutaneously to rats) or intact rat skin. Collagen content was measured following the addition of different concentrations of histamine and treatment with histamine receptor antagonists (ketotifen - H1 inhibitor, ranitidine - H2 inhibitor) and a histamine receptor H1 agonist (2-pyridylethylamine dihydrochloride).The cells were identified as myofibroblasts: alpha-smooth muscle actin, vimentin, and desmin positive in all experimental conditions. Histamine increased the collagen level within both cell cultures, i.e., those isolated from granulation tissue or intact skin. It did not, however, influence the expression of either the collagen type I or III genes within the cultured myofibroblasts. Histamine activity was reduced by ketotifen (the H1 receptor inhibitor) and increased by the H1 receptor agonist, as demonstrated by changes in the levels of collagen in the myofibroblast culture. Histamine increased collagen content within the cultures, acting directly on myofibroblasts via H1 receptor stimulation.
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Colágeno/metabolismo , Tejido de Granulación/efectos de los fármacos , Histamina/farmacología , Miofibroblastos/efectos de los fármacos , Receptores Histamínicos H1/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Animales , Células Cultivadas , Tejido de Granulación/metabolismo , Histamina/metabolismo , Agonistas de los Receptores Histamínicos/metabolismo , Agonistas de los Receptores Histamínicos/farmacología , Masculino , Miofibroblastos/metabolismo , Ratas , Ratas Wistar , Cicatrización de Heridas/fisiologíaRESUMEN
Chronic pelvic pain is a common health problem that afflicts 39% of women at some time in their life. It is a common challenge for gynecologists, internists, surgeons, gastroenterologists, and pain management physicians. Pelvic venous insufficiency (PVI) accounts for 16-31% of cases of chronic pain but it seems to be often overlooked in differential diagnosis. The aim of this article was to summarize current data concerning PVI. The embolization of insufficient ovarian veins remains the gold standard of therapy but the optimal procedure is yet to be determined. Well-designed randomized trials are required to establish the best treatment modalities.