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1.
Sci Rep ; 14(1): 21220, 2024 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261560

RESUMO

One of the most common causes of peritoneal dialysis withdrawal is ultrafiltration failure which is characterized by peritoneal membrane thickening and fibrosis. Although previous studies have demonstrated the inhibitory effect of p38 MAPK inhibitors on peritoneal fibrosis in mice, it was unclear which specific cells contribute to peritoneal fibrosis. To investigate the role of p38 MAPK in peritoneal fibrosis more precisely, we examined the expression of p38 MAPK in human peritoneum and generated systemic inducible p38 MAPK knockout mice and macrophage-specific p38 MAPK knockout mice. Furthermore, the response to lipopolysaccharide (LPS) was assessed in p38 MAPK-knocked down RAW 264.7 cells to further explore the role of p38 MAPK in macrophages. We found that phosphorylated p38 MAPK levels were increased in the thickened peritoneum of both human and mice. Both chlorhexidine gluconate (CG)-treated systemic inducible and macrophage-specific p38 MAPK knockout mice ameliorated peritoneal thickening, mRNA expression related to inflammation and fibrosis, and the number of αSMA- and MAC-2-positive cells in the peritoneum compared to CG control mice. Reduction of p38 MAPK in RAW 264.7 cells suppressed inflammatory mRNA expression induced by LPS. These findings suggest that p38 MAPK in macrophages plays a critical role in peritoneal inflammation and thickening.


Assuntos
Inflamação , Macrófagos , Diálise Peritoneal , Fibrose Peritoneal , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Humanos , Masculino , Camundongos , Clorexidina/análogos & derivados , Clorexidina/farmacologia , Inflamação/patologia , Inflamação/metabolismo , Inflamação/genética , Lipopolissacarídeos , Macrófagos/metabolismo , Camundongos Knockout , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/genética , Fibrose Peritoneal/etiologia , Fibrose Peritoneal/patologia , Peritônio/patologia , Células RAW 264.7
4.
World J Gastroenterol ; 30(32): 3739-3742, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39221070

RESUMO

Gallbladder cancer (GBC) is a rare disease with a poor prognosis. Simple cholecystectomy may be an adequate treatment only for very early disease (Tis, T1a), whereas reoperation is recommended for more advanced disease (T1b and T2). Radical cholecystectomy should have two fundamental objectives: To radically resect the liver parenchyma and to achieve adequate clearance of the lymph nodes. However, recent studies have shown that compared with lymph node dissection alone, liver resection does not improve survival outcomes. The oncological roles of lymphadenectomy and liver resection is distinct. Therefore, for patients with incidental GBC without liver invasion, hepatic resection is not always mandatory.


Assuntos
Colecistectomia , Neoplasias da Vesícula Biliar , Hepatectomia , Excisão de Linfonodo , Humanos , Colecistectomia/efeitos adversos , Colecistectomia/métodos , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/patologia , Hepatectomia/métodos , Hepatectomia/efeitos adversos , Achados Incidentais , Fígado/cirurgia , Fígado/patologia , Fígado/diagnóstico por imagem , Excisão de Linfonodo/métodos , Excisão de Linfonodo/efeitos adversos , Metástase Linfática , Estadiamento de Neoplasias , Peritônio/cirurgia , Peritônio/patologia , Resultado do Tratamento
5.
Sci Rep ; 14(1): 20408, 2024 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223302

RESUMO

Maintaining patients' temperature during surgery is beneficial since hypothermia has been linked with perioperative complications. Laparoscopic surgery involves the insufflation of carbon dioxide (CO2) into the peritoneal cavity and has become the standard in many surgical indications since it is associated with better and faster recovery. However, the use of cold and dry CO2 insufflation can lead to perioperative hypothermia. We aimed to assess the difference between intraperitoneal and core temperatures during laparoscopic surgery and evaluate the influence of duration and CO2 insufflation volume by fitting a mixed generalized additive model. In this prospective observational single-center cohort trial, we included patients aged over 17 with American Society of Anesthesiology risk scores I to III undergoing laparoscopic surgery. Anesthesia, ventilation, and analgesia followed standard protocols, while patients received active warming using blankets and warmed fluids. Temperature data, CO2 ventilation parameters, and intraabdominal pressure were collected. We recruited 51 patients. The core temperature was maintained above 36 °C and progressively raised toward 37 °C as pneumoperitoneum time passed. In contrast, the intraperitoneal temperature decreased, thus creating a widening difference from 0.4 [25th-75th percentile: 0.2-0.8] °C at the beginning to 2.3 [2.1-2.3] °C after 240 min. Pneumoperitoneum duration and CO2 insufflation volume significantly increased this temperature difference (P < 0.001 for both parameters). Core vs. intraperitoneal temperature difference increased linearly by 0.01 T °C per minute of pneumoperitoneum time up to 120 min and then 0.05 T °C per minute. Each insufflated liter per unit of time, i.e. every 10 min, increased the temperature difference by approximately 0.009 T °C. Our findings highlight the impact of pneumoperitoneum duration and CO2 insufflation volume on the difference between core and intraperitoneal temperatures. Implementing adequate external warming during laparoscopic surgery effectively maintains core temperature despite the use of dry and unwarmed CO2 gases, but peritoneal hypothermia remains a concern, suggesting the importance of further research into regional effects.Trial registration: Clinicaltrials.gov: NCT04294758.


Assuntos
Temperatura Corporal , Dióxido de Carbono , Laparoscopia , Humanos , Laparoscopia/métodos , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Peritônio/cirurgia , Hipotermia/prevenção & controle , Hipotermia/etiologia , Adulto , Insuflação/métodos , Pneumoperitônio Artificial/métodos , Cavidade Peritoneal/cirurgia
6.
Cell Physiol Biochem ; 58(4): 445-457, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39230349

RESUMO

BACKGROUND/AIMS: Lemons (Citrus limon ) contain various nutrients and are among the most popular citrus fruit. Besides their antioxidant, anticancer, antibacterial, and anti-inflammatory properties, clinical studies have indicated their anti-allergic properties. METHODS: Using the differential-interference contrast (DIC) microscopy, we examined the effects of lemon juice and peel constituents, such as citric acid, ascorbic acid, hesperetin and eriodictyol, on the degranulation from rat peritoneal mast cells. Using fluorescence imaging with a water-soluble dye, Lucifer Yellow, we also examined their effects on the deformation of the plasma membrane. RESULTS: Lemon juice dose-dependently decreased the number of degranulated mast cells. At concentrations equal to or higher than 0.25 mM, citric acid, hesperetin, and eriodictyol significantly reduced the number of degranulating mast cells in a dose-dependent manner, while ascorbic acid required much higher doses to exert significant effects. At 1 mM, citric acid, hesperetin, and eriodictyol almost completely inhibited exocytosis and washed out the Lucifer Yellow trapped on the mast cell surface, while ascorbic acid did not. CONCLUSION: This study provides in vitro evidence for the first time that lemon constituents, such as citric acid, hesperetin, and eriodictyol, potently exert mast cell-stabilizing properties. These properties are attributable to their inhibitory effects on plasma membrane deformation in degranulating mast cells.


Assuntos
Ácido Ascórbico , Citrus , Flavanonas , Hesperidina , Mastócitos , Animais , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Citrus/química , Ratos , Ácido Ascórbico/farmacologia , Masculino , Hesperidina/farmacologia , Hesperidina/química , Flavanonas/farmacologia , Flavanonas/química , Ácido Cítrico/farmacologia , Ácido Cítrico/química , Degranulação Celular/efeitos dos fármacos , Sucos de Frutas e Vegetais/análise , Peritônio/citologia , Ratos Sprague-Dawley , Exocitose/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Frutas/química , Isoquinolinas
7.
Radiographics ; 44(8): e230216, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-39088361

RESUMO

Disease spread in the abdomen and pelvis generally occurs in a predictable pattern in relation to anatomic landmarks and fascial planes. Anatomically, the abdominopelvic cavity is subdivided into several smaller spaces or compartments by key ligaments and fascial planes. The abdominal cavity has been traditionally divided into peritoneal, retroperitoneal, and pelvic extraperitoneal spaces. Recently, more clinically relevant classifications have evolved. Many pathologic conditions affect the abdominal cavity, including traumatic, inflammatory, infectious, and neoplastic processes. These abnormalities can extend beyond their sites of origin through various pathways. Identifying the origin of a disease process is the first step in formulating a differential diagnosis and ultimately reaching a final diagnosis. Pathologic conditions differ in terms of pathways of disease spread. For example, simple fluid tracks along fascial planes, respecting anatomic boundaries, while fluid from acute necrotizing pancreatitis can destroy fascial planes, resulting in transfascial spread without regard for anatomic landmarks. Furthermore, neoplastic processes can spread through multiple pathways, with a propensity for spread to noncontiguous sites. When the origin of a disease process is not readily apparent, recognizing the spread pattern can allow the radiologist to work backward and ultimately arrive at the site or source of pathogenesis. As such, a cohesive understanding of the peritoneal anatomy, the typical organ or site of origin for a disease process, and the corresponding pattern of disease spread is critical not only for initial diagnosis but also for establishing a road map for staging, anticipating further disease spread, guiding search patterns and report checklists, determining prognosis, and tailoring appropriate follow-up imaging studies. ©RSNA, 2024 Supplemental material is available for this article.


Assuntos
Doenças Peritoneais , Peritônio , Humanos , Peritônio/diagnóstico por imagem , Peritônio/patologia , Peritônio/anatomia & histologia , Doenças Peritoneais/diagnóstico por imagem , Diagnóstico Diferencial
8.
Ren Fail ; 46(2): 2392849, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39165231

RESUMO

AIMS: To investigate the effects and mechanisms of LCZ696, an angiotensin receptor-neprilysin inhibitor (ARNI), on epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells and on macrophage M2 polarization. METHODS: We examined the effects of LCZ696 in a 4.25% high glucose peritoneal dialysis fluid (PDF)-induced peritoneal fibrosis (PF) mouse model, and explored the mechanisms of LCZ696 on human peritoneal mesothelial cells (HPMCs) stimulated by TGF-ß1 (5 ng/mL) and on Raw264.7 cells stimulated by IL-4 (10 ng/mL). To further elucidate the mechanism, we treated HPMCs with the conditioned medium of Raw264.7 cells. RESULTS: LCZ696 effectively improved PF and inhibited the process of EMT in PDF mice. In vitro, LCZ696 also significantly alleviated the EMT of TGF-ß1 induced HPMCs, although there was no statistically significant difference when compared to the Valsartan treatment group. Moreover, LCZ696 ameliorates the increased expression of Snail and Slug, two nuclear transcription factors that drive the EMT. Mechanistically, TGF-ß1 increased the expression of TGFßRI, p-Smad3, p-PDGFRß and p-EGFR, while treatment with LCZ696 abrogated the activation of TGF-ß/Smad3, PDGFRß and EGFR signaling pathways. Additionally, exposure of Raw264.7 to IL-4 results in increasing expression of Arginase-1, CD163 and p-STAT6. Treatment with LCZ696 inhibited IL-4-elicited M2 macrophage polarization by inactivating the STAT6 signaling pathway. Furthermore, we observed that LCZ696 inhibits EMT by blocking TGF-ß1 secretion from M2 macrophages. CONCLUSION: Our study demonstrated that LCZ696 improves PF and ameliorates TGF-ß1-induced EMT of HPMCs by blocking TGF-ß/Smad3, PDGFRß and EGFR pathways. Meanwhile, LCZ696 also inhibits M2 macrophage polarization by regulating STAT6 pathway.


Assuntos
Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo , Transição Epitelial-Mesenquimal , Macrófagos , Fibrose Peritoneal , Tetrazóis , Valsartana , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Camundongos , Animais , Valsartana/farmacologia , Compostos de Bifenilo/farmacologia , Antagonistas de Receptores de Angiotensina/farmacologia , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/patologia , Fibrose Peritoneal/prevenção & controle , Humanos , Tetrazóis/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Aminobutiratos/farmacologia , Células RAW 264.7 , Modelos Animais de Doenças , Combinação de Medicamentos , Neprilisina/antagonistas & inibidores , Neprilisina/metabolismo , Masculino , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Transcrição STAT6/metabolismo , Peritônio/patologia , Peritônio/citologia , Peritônio/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos C57BL
9.
Int J Mol Sci ; 25(16)2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39201294

RESUMO

The characteristic feature of chronic peritoneal damage in peritoneal dialysis (PD) is a decline in ultrafiltration capacity associated with pathological fibrosis and angiogenesis. The pathogenesis of peritoneal fibrosis is attributed to bioincompatible factors of PD fluid and peritonitis. Uremia is associated with peritoneal membrane inflammation that affects fibrosis, neoangiogenesis, and baseline peritoneal membrane function. Net ultrafiltration volume is affected by capillary surface area, vasculopathy, peritoneal fibrosis, and lymphangiogenesis. Many inflammatory cytokines induce fibrogenic growth factors, with crosstalk between macrophages and fibroblasts. Transforming growth factor (TGF)-ß and vascular endothelial growth factor (VEGF)-A are the key mediators of fibrosis and angiogenesis, respectively. Bioincompatible factors of PD fluid upregulate TGF-ß expression by mesothelial cells that contributes to the development of fibrosis. Angiogenesis and lymphangiogenesis can progress during fibrosis via TGF-ß-VEGF-A/C pathways. Complement activation occurs in fungal peritonitis and progresses insidiously during PD. Analyses of the human peritoneal membrane have clarified the mechanisms by which encapsulating peritoneal sclerosis develops. Different effects of dialysates on the peritoneal membrane were also recognized, particularly in terms of vascular damage. Understanding the pathophysiologies of the peritoneal membrane will lead to preservation of peritoneal membrane function and improvements in technical survival, mortality, and quality of life for PD patients.


Assuntos
Diálise Peritoneal , Fibrose Peritoneal , Peritônio , Humanos , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/etiologia , Fibrose Peritoneal/patologia , Fibrose Peritoneal/metabolismo , Peritônio/patologia , Peritônio/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Neovascularização Patológica , Fator A de Crescimento do Endotélio Vascular/metabolismo , Peritonite/etiologia , Peritonite/patologia , Peritonite/metabolismo
10.
Ren Fail ; 46(2): 2394635, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39192609

RESUMO

BACKGROUND: The quality of life of patients receiving long-term peritoneal dialysis (PD) is significantly impacted by the onset of peritoneal fibrosis (PF), and one of the pathological changes is mesothelial-mesenchymal transition (MMT). In this study, we investigated the potential roles of miR-454-3p and signal transducer and activator of transcription 3 (STAT3) in the progression of peritoneal MMT and the underlying mechanisms. METHODS: Peritoneums were collected to detect morphology via hematoxylin-eosin staining and differentially expressed miRNAs were detected via RT-qPCR. PD effluent-derived cell populations in the peritoneal cavity were isolated from the effluents of 20 PD patients to determine miR-454-3p, STAT3, and MMT markers via Western blotting and RT-qPCR. The relationship between miR-454-3p and STAT3 was examined via a dual-luciferase reporter assay. Western blotting and RT-qPCR were utilized to evaluate the expression of STAT3, MMT markers, and glycolytic enzymes. Immunofluorescence staining revealed the localization and expression of MMT markers and STAT3. RESULTS: MiR-454-3p was downregulated in the peritoneums and PD effluent-derived cell populations of long-term PD patients. High glucose (HG) treatment promoted HMrSV5 cell MMT and glycolysis. MiR-454-3p overexpression alleviated HG-induced MMT and suppressed the expression of STAT3 and glycolytic enzymes. In contrast, the miR-454-3p inhibitor exacerbated HG-induced MMT and promoted the expression of glycolytic enzymes and STAT3. Moreover, STAT3 was the target of miR-454-3p. CONCLUSIONS: This study demonstrated the protective role of miR-454-3p in HG-induced MMT and glycolysis in HMrSv5 cells, suggesting that miR-454-3p may prevent MMT by suppressing glycolytic enzymes via the STAT3/PFKFB3 pathway in the HG environment.


Assuntos
Transição Epitelial-Mesenquimal , Glucose , Glicólise , MicroRNAs , Diálise Peritoneal , Fibrose Peritoneal , Peritônio , Fator de Transcrição STAT3 , MicroRNAs/metabolismo , MicroRNAs/genética , Fator de Transcrição STAT3/metabolismo , Humanos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glucose/metabolismo , Glucose/farmacologia , Glicólise/efeitos dos fármacos , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/patologia , Fibrose Peritoneal/etiologia , Fibrose Peritoneal/genética , Peritônio/patologia , Peritônio/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Linhagem Celular , Regulação para Baixo , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos
11.
Front Immunol ; 15: 1396000, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39192982

RESUMO

Endometriosis is a chronic inflammatory disease that causes debilitating pelvic pain in women. Macrophages are considered to be key players in promoting disease progression, as abundant macrophages are present in ectopic lesions and elevated in the peritoneum. In the present study, we examined the role of GATA6+ peritoneal macrophages on endometriosis-associated hyperalgesia using mice with a specific myeloid deficiency of GATA6. Lesion induction induced the disappearance of TIM4hi MHCIIlo residential macrophages and the influx of increased Ly6C+ monocytes and TIM4lo MHCIIhi macrophages. The recruitment of MHCIIhi inflammatory macrophages was extensive in Mac Gata6 KO mice due to the severe disappearance of TIM4hi MHCIIlo residential macrophages. Ki67 expression confirmed GATA6-dependent proliferative ability, showing different proliferative phenotypes of TIM4+ residential macrophages in Gata6f/f and Mac Gata6 KO mice. Peritoneal proinflammatory cytokines were elevated after lesion induction. When cytokine levels were compared between Gata6f/f and Mac Gata6 KO mice, TNFα at day 21 in Gata6f/f mice was higher than in Mac Gata6 KO mice. Lesion induction increased both abdominal and hind paw sensitivities. Gata6f/f mice tended to show higher sensitivity in the abdomen after day 21. Elevated expression of TRPV1 and CGRP was observed in the dorsal root ganglia after ELL induction in Gata6f/f mice until days 21 and 42, respectively. These results support that peritoneal GATA6+ macrophages are involved in the recruitment and reprogramming of monocyte-derived macrophages. The extensive recruitment of monocyte-derived macrophages in Mac Gata6 KO mice might protect against inflammatory stimuli during the resolution phase, whereas GATA6 deficiency did not affect lesion initiation and establishment at the acute phase of inflammation. GATA6+ residential macrophages act to sustain local inflammation in the peritoneum and sensitivities in the neurons, reflecting endometriosis-associated hyperalgesia.


Assuntos
Endometriose , Fator de Transcrição GATA6 , Macrófagos Peritoneais , Animais , Feminino , Camundongos , Citocinas/metabolismo , Modelos Animais de Doenças , Endometriose/imunologia , Endometriose/patologia , Endometriose/metabolismo , Gânglios Espinais/metabolismo , Gânglios Espinais/imunologia , Fator de Transcrição GATA6/metabolismo , Fator de Transcrição GATA6/genética , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Hiperalgesia/imunologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Peritônio/patologia , Peritônio/imunologia , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/genética
12.
J Robot Surg ; 18(1): 330, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39196300

RESUMO

We present the trial-and-error process of standardizing robot-assisted radical nephroureterectomy (RANU) at a high-volume center in Japan. Our urology team performed 53 RANU cases using the Da Vinci Xi system, undergoing five major evolutionary stages. We performed RANU via transperitoneal approach in all cases and lymph-node dissection in selected cases. During the evolution, we adopted a lithotomy position and significantly modified port placement to facilitate lower ureter management. However, we ultimately arrived at a method that minimizes port and patient repositioning during lower ureter processing. By strategically placing ProGrasp™ forceps in the most caudal port, we effectively retracted the bladder and grasped the opened bladder wall during lower ureter manipulation. This approach also allowed us to perform pelvic, para-aortic, and renal portal lymph-node dissection without major changes in patient positioning or port placement. Nevertheless, we acknowledge that some variations in positioning and techniques may be necessary depending on specific case requirements.


Assuntos
Excisão de Linfonodo , Nefroureterectomia , Procedimentos Cirúrgicos Robóticos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hospitais com Alto Volume de Atendimentos , Japão , Excisão de Linfonodo/métodos , Nefroureterectomia/métodos , Posicionamento do Paciente/métodos , Peritônio/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/normas , Ureter/cirurgia
13.
Pathol Res Pract ; 262: 155538, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39191196

RESUMO

The mesothelium is a non-adhesive protective surface that lines the serosal cavities and organs within the body. The glycocalyx is a complex structure that coats the outer layer of the mesothelium. However, due to the limitations of conventional fixation techniques, studies on glycans are limited. In this study, lectin staining of frozen tissues was performed to investigate the diversity of glycans in the glycocalyx of mesothelial cells in mice. Datura stramonium lectin (DSL), which recognizes lactosamine and binds to Galectin-3 and -1, was broadly bound to the mesothelial cells of the visceral and parietal peritoneum but not to the pancreas, liver, intestine, or heart. Furthermore, human mesothelial cells in the omentum and parietal peritoneum were positive for DSL. Erythrina cristagalli lectin binding was specific to mesothelial cells in the parietal peritoneum, that is, the pleura, diaphragm, and peritoneum. Intriguingly, surface sialylation, the key element in reducing peritoneal dissemination and implantation, and promoting ascites formation by ovarian carcinoma cells, was much higher in the parietal peritoneum than in the omentum. These findings revealed slight differences in the glycans of mesothelial cells of different organs, which may be related to clinical diseases. These results also suggest that there may be differences in the functions of parietal and visceral mesothelial cells.


Assuntos
Glicocálix , Lectinas , Glicocálix/metabolismo , Animais , Camundongos , Lectinas/metabolismo , Epitélio/metabolismo , Humanos , Peritônio/metabolismo , Peritônio/patologia , Feminino , Coloração e Rotulagem/métodos , Omento/metabolismo , Omento/patologia
14.
BMC Nephrol ; 25(1): 268, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39179976

RESUMO

BACKGROUND: Urinary Dickkopf 3 (DKK3) excretion is a recently established biomarker of renal functional development. Its excretion into the peritoneal cavity has not been reported. We here studied DKK3 in peritoneal dialysis. METHODS: DKK3 was assessed in serum, urine and dialysate in a prevalent adult peritoneal dialysis cohort and its concentration analyzed in relation to creatinine and clinical characteristics. RESULTS: Highest DKK3 concentrations were found in serum, followed by urine. Dialysate concentrations were significantly lower. Dialysate DKK3 correlated with both other compartments. Serum, dialysate and urine values were stable during three months of follow-up. Continuous ambulatory dialysis (CAPD) but not cycler-assisted peritoneal dialysis (CCPD) volume-dependently increased peritoneal DKK3 in relation to creatinine. RAAS blockade significantly decreased urinary, but not serum or peritoneal DKK3. CONCLUSION: Our data provide a detailed characterization of DKK3 in peritoneal dialysis. They support the notion that the RAAS system is essential for renal DKK3 handling.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Diálise Peritoneal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Quimiocinas/sangue , Quimiocinas/metabolismo , Idoso , Adulto , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Falência Renal Crônica/terapia , Falência Renal Crônica/metabolismo , Biomarcadores/sangue , Soluções para Diálise/metabolismo , Rim/metabolismo , Peritônio/metabolismo , Diálise Peritoneal Ambulatorial Contínua , Sistema Renina-Angiotensina/fisiologia , Creatinina/urina , Creatinina/sangue , Creatinina/metabolismo
15.
Am J Physiol Renal Physiol ; 327(3): F363-F372, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38961839

RESUMO

Epithelial-to-mesenchymal transition (EMT) is considered as one of the senescence processes; reportedly, antisenescence therapies effectively reduce EMT. Some models have shown antisenescence effects with the use of sodium-glucose cotransporter 2 (SGLT2) inhibitor. Therefore, our study investigated the antisenescence effects of empagliflozin as an SGLT2 inhibitor in a peritoneal fibrosis model and their impact on EMT inhibition. For in vitro study, human peritoneal mesothelial cells (HPMCs) were isolated and grown in a 96-well plate. The cell media were exchanged with serum-free M199 medium with d-glucose, with or without empagliflozin. All animal experiments were carried out in male mice. Mice were randomly classified into three treatment groups based on peritoneal dialysis (PD) or empagliflozin. We evaluated changes in senescence and EMT markers in HPMCs and PD model. HPMCs treated with glucose transformed from cobblestone to spindle shape, resulting in EMT. Empagliflozin attenuated these morphological changes. Reactive oxygen species production, DNA damage, senescence, and EMT markers were increased by glucose treatment; however, cotreatment with glucose and empagliflozin attenuated these changes. For the mice with PD, an increase in thickness, collagen deposition, staining for senescence, or EMT markers of the parietal peritoneum was observed, which, however, was attenuated by cotreatment with empagliflozin. p53, p21, and p16 increased in mice with PD compared with those in the control group; however, these changes were decreased by empagliflozin. In conclusion, empagliflozin effectively attenuated glucose-induced EMT in HPMCs through a decrease in senescence. Cotreatment with empagliflozin improved peritoneal thickness and fibrosis in PD.NEW & NOTEWORTHY Epithelial-to-mesenchymal transition (EMT) is considered one of the senescence processes. Antisenescence therapies may effectively reduce EMT in peritoneal dialysis models. Human peritoneal mesothelial cells treated with glucose show an increase in senescence and EMT markers; however, empagliflozin attenuates these changes. Mice undergoing peritoneal dialysis exhibit increased senescence and EMT markers, which are decreased by empagliflozin. These findings suggest that empagliflozin may emerge as a novel strategy for prevention or treatment of peritoneal fibrosis.


Assuntos
Compostos Benzidrílicos , Senescência Celular , Transição Epitelial-Mesenquimal , Glucosídeos , Diálise Peritoneal , Fibrose Peritoneal , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glucosídeos/farmacologia , Compostos Benzidrílicos/farmacologia , Diálise Peritoneal/efeitos adversos , Senescência Celular/efeitos dos fármacos , Masculino , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Fibrose Peritoneal/patologia , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/prevenção & controle , Peritônio/patologia , Peritônio/efeitos dos fármacos , Peritônio/metabolismo , Camundongos , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Glucose/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL , Células Cultivadas , Dano ao DNA/efeitos dos fármacos
16.
Pediatr Surg Int ; 40(1): 187, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003422

RESUMO

PURPOSE: To present our technical modifications of single incision laparoscopic percutaneous extraperitoneal closure (SILPEC) of the internal inguinal ring (IIR) for pediatric inguinal hernia (PIH). METHODS: The prospectively collected data of all children diagnosed with PIH undergoing SILPEC at our center from 2016 to 2023 were reviewed and divided into two groups for result comparison: Group A: before and Group B: after the implementation of full modifications. Our modifications included using a nonabsorbable monofilament suture, creating a peritoneal thermal injury at the internal inguinal ring (IIR), employing a cannula to ensure the suture at the IIR ligates only the peritoneum, and double ligation of the IIR in selected cases. RESULTS: 1755 patients in group A and in group B (1 month to 14 years old) were enrolled. There were no significant differences regarding baseline patient characteristics between the two groups. At a median follow-up of 40 months, the rate of recurrent CIH and subcutaneous stitch granuloma (SSG) was 2.3% and 1.5% in group A vs. 0% and 0% in group B (p < 0.001). There were no hydroceles, no ascended or atrophic testis. CONCLUSIONS: Our SILPEC technical modifications can achieve zero recurrence and zero SSG for PIH.


Assuntos
Hérnia Inguinal , Herniorrafia , Laparoscopia , Recidiva , Técnicas de Sutura , Humanos , Hérnia Inguinal/cirurgia , Laparoscopia/métodos , Criança , Lactente , Masculino , Pré-Escolar , Adolescente , Feminino , Herniorrafia/métodos , Granuloma/cirurgia , Estudos Prospectivos , Resultado do Tratamento , Estudos Retrospectivos , Canal Inguinal/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Peritônio/cirurgia
17.
FASEB J ; 38(13): e23819, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38984942

RESUMO

Peritoneal dialysis is a common treatment for end-stage renal disease, but complications often force its discontinuation. Preventive treatments for peritoneal inflammation and fibrosis are currently lacking. Cyclo(His-Pro) (CHP), a naturally occurring cyclic dipeptide, has demonstrated protective effects in various fibrotic diseases, yet its potential role in peritoneal fibrosis (PF) remains uncertain. In a mouse model of induced PF, CHP was administered, and quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry was employed to identify PF-related protein signaling pathways. The results were further validated using human primary cultured mesothelial cells. This analysis revealed the involvement of histone deacetylase 3 (HDAC3) in the PF signaling pathway. CHP administration effectively mitigated PF in both peritoneal tissue and human primary cultured mesothelial cells, concurrently regulating fibrosis-related markers and HDAC3 expression. Moreover, CHP enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while suppressing forkhead box protein M1 (FOXM1), known to inhibit Nrf2 transcription through its interaction with HDAC3. CHP also displayed an impact on spleen myeloid-derived suppressor cells, suggesting an immunomodulatory effect. Notably, CHP improved mitochondrial function in peritoneal tissue, resulting in increased mitochondrial membrane potential and adenosine triphosphate production. This study suggests that CHP can significantly prevent PF in peritoneal dialysis patients by modulating HDAC3 expression and associated signaling pathways, reducing fibrosis and inflammation markers, and improving mitochondrial function.


Assuntos
Histona Desacetilases , Fibrose Peritoneal , Animais , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/prevenção & controle , Fibrose Peritoneal/patologia , Camundongos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos , Diálise Peritoneal/efeitos adversos , Peritônio/patologia , Peritônio/metabolismo
18.
World J Urol ; 42(1): 387, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958744

RESUMO

PURPOSE: Single-Port Robot-Assisted Partial Nephrectomy (SP-RAPN) can be performed by transperitoneal and retroperitoneal approaches. However, there is a lack of surgical outcomes for novel Retroperitoneal Low Anterior Access (LAA) in SP-RAPN. The study compared outcomes of the standard approach (SA), considering transperitoneal (TP) and posterior retroperitoneal (RP) access vs LAA in SP-RAPN series. METHODS: 102 consecutive patients underwent SP-RAPN between 2019 and 2023 at a tertiary referral robotic center were identified. Baseline characteristics, peri- and post-operative outcomes were collected. Patients were stratified according to surgical approach into standard (RP or TP) vs LAA and, subsequently, RP vs LAA. Multivariable logistic regression analysis was used to test the probability of the same-day discharge adjusting for comorbidity indexes. RESULTS: Overall, 102 consecutive patients were included in this study (68 SA - 26 TP and 42 posterior RP vs 34 LAA). Median age was 60 (IQR 51.5-66) years and median BMI was 31 (IQR 26.3-37.6). No baseline differences were observed. LAA exhibited significantly shorter length of stay (LOS) (median 10 [IQR 8-12] vs 24 [IQR 12-30.2.] hours, p < .0001), reduced post-operative pain (p < .0001) and decreased narcotic use on 0-1 PO Day (p < .001) compared to SA and RP only. Multivariate analysis, adjusting for comorbidities, identified LAA as a strong predictor for Same-Day Discharge. CONCLUSION: LAA is an effective approach as well as RP and TP, regardless of the renal mass location, whether it is anterior or posterior, upper/mid or lower pole, yielding favorable outcomes in LOS, post-operative pain and decreased narcotics use compared to SA in SP-RAPN.


Assuntos
Nefrectomia , Procedimentos Cirúrgicos Robóticos , Humanos , Nefrectomia/métodos , Pessoa de Meia-Idade , Masculino , Feminino , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Espaço Retroperitoneal , Resultado do Tratamento , Estudos Retrospectivos , Peritônio/cirurgia , Neoplasias Renais/cirurgia
19.
Urolithiasis ; 52(1): 109, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39073726

RESUMO

Impacted proximal ureteral stones (IPUS) present challenging clinical scenarios due to their persistent nature and associated complications. While ureterorenoscopy (URS) lithotripsy is recommended as the primary treatment, controversies exist regarding the optimal management of such stones. In this retrospective analysis, we compared the operative outcomes and long-term results of transperitoneal laparoscopic ureterolithotomy (LU) and percutaneous nephrolithotomy (PCNL) for IPUS larger than 15 mm. Propensity score matching (PSM) was employed to mitigate potential selection biases. Following PSM, 83 patients in each cohort exhibited comparable baseline characteristics. LU demonstrated a superior surgical success rate (100% vs. 96.4%, p = 0.244) and significantly lower perioperative hemoglobin decline (0.6 ± 0.4 g/dL vs. 1.5 ± 0.7 g/dL, p = 0.036) compared to PCNL. Additionally, LU exhibited a higher stone-free rate after 2 months (100% vs. 91.6%, p = 0.043), but a longer duration of catheterization (7.4 ± 1.2 days vs. 3.5 ± 2.2 days vs., p = 0.011). Conversely, PCNL was associated with a higher incidence of total complications (21.7% vs. 9.6%, p = 0.033) and stone recurrence during a mean period of 40-month follow-up (20.5% vs. 8.4%, p = 0.027). Transperitoneal LU and PCNL represent effective interventions for managing IPUS exceeding 15 mm. Notably, LU emerges as a preferable option over PCNL, offering superior stone clearance rates, reduced perioperative complications, and lower recurrence rates.


Assuntos
Laparoscopia , Nefrolitotomia Percutânea , Pontuação de Propensão , Cálculos Ureterais , Humanos , Nefrolitotomia Percutânea/métodos , Nefrolitotomia Percutânea/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Cálculos Ureterais/cirurgia , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Pessoa de Meia-Idade , Adulto , Seguimentos , Resultado do Tratamento , Fatores de Tempo , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Peritônio/cirurgia
20.
Asian J Endosc Surg ; 17(4): e13362, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39045770

RESUMO

INTRODUCTION: Practical simulation training with proper haptic feedback and the fragility of the human body is required to overcome the long learning curve associated with laparoscopic inguinal hernia repair (LIHR). However, few hernia models accurately reflect the texture and fragility of the human body. Therefore, in this study, we developed a novel model for transabdominal preperitoneal (TAPP) LIHR training and evaluated its validity. METHODS: We developed a high-quality mock peritoneum with a hydrated polyvinyl alcohol layer and a unique two-way crossing cellulose fiber layer. To complete the simulation, the peritoneum was adhered to a urethane foam inguinal base with surgical landmarks. Participants could perform all the procedures required for the TAPP LIHR. Twenty-four surgeons performed TAPP LIHR simulation using a novel simulator. Their opinions were rated on a 5-point Likert scale. Additionally, 6 surgical residents and 10 surgical experts performed the procedure. Their performance was evaluated using the TAPP checklist score and procedure time. RESULTS: Most participants strongly agreed that the TAPP LIHR simulator with an exchangeable peritoneum model was useful. The participants agreed on the model fidelity for tactile sensation, forceps handling, and humanlike anatomy. In comparisons between surgical residents and experts, the experts had significantly higher scores (10.6 vs. 17.2, p < 0.05) and shorter procedure times (92.3 vs. 55.9 min; p < .05) than did surgical residents. CONCLUSIONS: We developed a high-quality exchangeable peritoneal model that mimics the human peritoneum's texture and fragility. This model enhances laparoscopic simulation training, potentially shortening TAPP LIHR learning curves.


Assuntos
Competência Clínica , Hérnia Inguinal , Herniorrafia , Laparoscopia , Peritônio , Treinamento por Simulação , Hérnia Inguinal/cirurgia , Laparoscopia/educação , Humanos , Herniorrafia/educação , Herniorrafia/métodos , Peritônio/cirurgia , Treinamento por Simulação/métodos , Modelos Anatômicos , Internato e Residência , Masculino
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