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BACKGROUND: Glomerular endothelial cells are recognized to be important for maintaining the glomerular filtration barrier. ADGRF5, an adhesion G protein-coupled receptor, has been suggested to be involved in endothelial cell function. However, the role of ADGRF5 in the glomerular filtration barrier integrity remains elusive. METHODS: Cellular expression of ADGRF5 in mouse glomerulus was determined by histological analyses. The impact of ADGRF5 deletion on the glomerular morphology, kidney function, and glomerular endothelial gene/protein expression was then analyzed using ADGRF5 knockout (Adgrf5-/-) mice and human primary glomerular endothelial cells. RESULTS: ADGRF5 was specifically expressed in the capillary endothelial cells within the glomerulus. Adgrf5-/- mice developed albuminuria and impaired kidney function with morphological defects in the glomeruli, namely glomerular hypertrophy, glomerular basement membrane splitting and thickening, diaphragmed fenestration and detachment of the glomerular endothelial cells, and mesangial interposition. These defects were accompanied by the altered expression of genes responsible for glomerular basement membrane organization (type IV collagens and laminins) and Krüppel-like factor 2 (Klf2) in glomerular endothelial cells. Moreover, ADGRF5 knockdown decreased COL4A3 and COL4A4 expression and increased KLF2 expression in human primary glomerular endothelial cells. CONCLUSIONS: The loss of ADGRF5 resulted in altered gene expression in glomerular endothelial cells, and perturbed the structure and permselectivity of the glomerular filtration barrier.
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BACKGROUND: Endovascular aneurysm repair (EVAR) using a bifurcated stent graft may involve technical challenges when aortic disease (aneurysm or dissection) consists of a length <70 mm between the inferior renal artery and aortic bifurcation or narrow aortic bifurcation that is common in asymmetric distal abdominal aortic aneurysms (AAAs) or iliac artery aneurysms (IAAs). We use EVAR with the double D technique (DDT-EVAR) for such cases, which involves straight type of stent grafts with same diameter in left and right that are deployed parallel to an aortic cuff that has been previously placed. In addition, DDT-EVAR can preserve the inferior mesenteric artery (IMA) for IAA. METHODS: DDT-EVAR was performed for 21 of 910 (2%) cases from April 2007 to April 2019 at our institution. The median patient age was 74 years (range, 52-85). Nineteen patients (90%) were men. Six patients (all saccular; 1 rupture) had AAAs, 12 had IAAs, and 3 had chronic type B aortic dissociation (TBAD) for re-entry closure. AAA and IAA had diameters of 45 mm (range, 34-71) and 34 mm (range, 25-58), respectively. An aortic cuff was used for 19 (90%) cases. Endurant II (Medtronic, Santa Rosa, CA) was used for 12 cases. The Excluder (W.L. Gore & Associates, Inc, Flagstaff, AZ) was used for 7 cases. Endurant II was used for 20 cases, and the VBX (W.L. Gore & Associates, Inc) was used for 1 case as stent-graft limbs. RESULTS: The procedural success rate was 100%. The median operative time was 146 min (range, 88-324). IMA planned for preservation was successful for all 12 cases. Type I and type III endoleaks were not observed. With TBAD, flow to the false lumen decreased or disappeared, and no complications during the hospital stay were associated with the procedure. For 2 patients whose procedure involved Endurant II stent-graft limb, limb occlusions were observed postoperatively, and reintervention was required. No other patients required additional treatment at a median follow-up of 18 months (range, 4-50). CONCLUSIONS: DDT-EVAR is a safe and straightforward technique for the treatment of distal AAA, common iliac artery aneurysm, and TBAD. It may help preserve the IMA and internal iliac artery, even when it is impossible to preserve them with a bifurcated stent graft.
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Aneurisma de la Aorta Abdominal/cirugía , Disección Aórtica/cirugía , Rotura de la Aorta/cirugía , Implantación de Prótesis Vascular/instrumentación , Prótesis Vascular , Procedimientos Endovasculares/instrumentación , Aneurisma Ilíaco/cirugía , Stents , Anciano , Anciano de 80 o más Años , Disección Aórtica/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Rotura de la Aorta/diagnóstico por imagen , Implantación de Prótesis Vascular/efectos adversos , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Aneurisma Ilíaco/diagnóstico por imagen , Tiempo de Internación , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/terapia , Retratamiento , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: This study aimed to determine the factors that affect the extracellular fluid (ECF) content in the legs of patients with chronic venous disease (CVD). METHODS: Bioimpedance analysis and air plethysmography (APG) were performed in 79 patients with CVD who visited our clinic between September 2016 and March 2019. The normal right legs (N) of 14 healthy volunteers were also reviewed for comparison. The ratio of ECF resistance (Re) of the leg to that of the arm (ReL/ReA) was used to express the ECF content in the tested leg. The severity of CVD was expressed using the clinical, etiological, anatomical, and pathophysiological (CEAP) classification. RESULTS: The ReL/ReA decreased as the CEAP class increased (N: median; 0.81 [range 0.66-0.95], C0-1: 0.79 [0.60-0.98], C2: 0.77 [0.56-1.08], C3: 0.67 [0.57-0.85], C4: 0.64 [0.44-0.89]). Older age, female sex, and CEAP class affected the ReL/ReA, but body mass index did not. The ReL/ReA did not correlate with the parameters that were derived from APG, including the venous filling index. CONCLUSIONS: We found that the ECF content in legs of patients with CVD might be primarily affected by patient-related factors and CEAP class, as opposed to venous hemodynamics.
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Líquido Extracelular/metabolismo , Hemodinámica , Extremidad Inferior/irrigación sanguínea , Enfermedades Vasculares/fisiopatología , Venas/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Enfermedad Crónica , Impedancia Eléctrica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pletismografía , Prohibitinas , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Enfermedades Vasculares/diagnóstico , Enfermedades Vasculares/metabolismoRESUMEN
OBJECTIVE: This study aimed to evaluate the effect of inferior mesenteric artery (IMA) embolization during endovascular aneurysm repair (EVAR) in patients at high risk of type II endoleak (T2EL) in randomized controlled trial (RCT). SUMMARY BACKGROUND DATA: Several studies have demonstrated a reduction of T2EL by IMA embolization before EVAR. However, there have been no RCT confirming the efficacy of IMA embolization. METHODS: Patients scheduled for elective EVAR between April 2014 and March 2018 were eligible. Patients at high risk of T2EL (IMA patency with IMA ≥3âmm, LAs ≥2âmm, or an aortoiliac-type aneurysm) were prospectively randomized to receive EVAR with or without IMA embolization. The primary endpoint was occurrence of T2EL during follow-up. Secondary endpoints included aneurysmal sac changes, adverse events from IMA embolization, and reintervention rate due to T2EL. This trial is registered with the University Hospital Medical Information Network, number UMIN000022147. RESULTS: One hundred thirteen patients had high risk and 106 were randomized. In the intention-to-treat analysis, the incidence of T2EL was significantly lower in the embolization group [24.5% vs 49.1%; P = 0.009, absolute risk reduction = 24.5%; 95% confidence interval (CI), 6.2-40.5, number needed to treat = 4.1; 95% CI, 2.5-16.1]. The aneurysmal sac shrunk significantly more in the embolization group (-5.7â±â7.3âmm vs -2.8â±â6.6âmm; P = 0.037), and the incidence of aneurysmal sac growth related to T2EL was significantly lower in the embolization group (3.8% vs 17.0%; P = 0.030). There were no complications related to IMA embolization or reinterventions associated with T2EL. CONCLUSIONS: Our results demonstrated the effectiveness of IMA embolization during EVAR in high-risk patients for the prevention of T2EL, which is suggested for avoiding aneurysmal sac enlargement related to T2EL.
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Aneurisma de la Aorta Abdominal/terapia , Embolización Terapéutica/métodos , Endofuga/prevención & control , Procedimientos Endovasculares , Arteria Mesentérica Inferior , Anciano , Femenino , Humanos , Análisis de Intención de Tratar , Masculino , Estudios Prospectivos , Dispositivo Oclusor SeptalRESUMEN
BACKGROUND: To study the effect of prolonged complex decongestive therapy (CDT) on lymphedema in arms without a subcutaneous echo-free space (SEFS) on subcutaneous tissue ultrasonography. METHODS: Fifty-one patients with arm lymphedema treated for longer than 1 year using CDT in our clinic were retrospectively evaluated. Before starting CDT, subcutaneous tissue ultrasonography was performed to examine for the presence of an SEFS. Two-stage CDT was performed as recommended by the International Society of Lymphology. Limb circumference was measured, and limb volume was calculated at the initial and latest visits. RESULTS: In patients with lymphedema in which SEFS was observed anywhere in the arm on the initial visit (n = 25), the edema ratio was significantly reduced by a median of -15% (range, -106% to 17%; P < 0.001). On the other hand, in the arms with lymphedema in which SEFS was not observed (SEFS[-], n = 26), the edema ratio was not changed significantly by CDT (median, 1% [range, -30% to 23%]). In arms without an SEFS that were not treated using arm sleeves regularly (n = 15), no increase in edema ratio was observed (median, 1% [range, -29% to 16%]). CONCLUSIONS: In arms with lymphedema without SEFS, the effect of CDT on the reduction of arm volume is limited.
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Brazo/diagnóstico por imagen , Vendajes de Compresión , Linfedema/terapia , Adulto , Anciano , Anciano de 80 o más Años , Brazo/fisiopatología , Femenino , Humanos , Linfedema/diagnóstico por imagen , Linfedema/fisiopatología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Presión , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , UltrasonografíaRESUMEN
OBJECTIVE: Concurrent abdominal aortic aneurysm (AAA) and unilateral iliac occlusion is a challenge in the implantation of bifurcated stent grafts (BFGs). The endovascular approach is less invasive than open surgery; the aortouni-iliac (AUI) graft with crossover femorofemoral bypass (CFFB) has many problems associated with extra-anatomic reconstruction. We attempted endovascular aneurysm repair (EVAR) using BFGs in such cases and evaluated the outcomes. METHODS: This was a retrospective study. Between October 2012 and December 2017, there were 649 patients who underwent surgery for AAA, of whom 32 patients underwent open reconstruction and 617 patients underwent endovascular aneurysm repair; 15 patients with unilateral occluded iliac arteries and AAA were included. The analysis included patients with unilateral iliac chronic total occlusion (CTO). The intraoperative, postoperative, and follow-up variables were reviewed. RESULTS: The occluded lesions were the common iliac artery in 5 patients, the common iliac artery-external iliac artery (EIA) in 2 patients, the EIA in 7 patients, and the EIA-common femoral artery in 1 patient. The mean occlusive length was 89.7 ± 43.6 mm, and the mean AAA size was 54.6 ± 5.6 mm. Technical success was achieved in 13 patients (87%). All patients underwent recanalization through the true lumen and stent placement. The only procedure-related complication was distal embolism, which was treated with intraoperative thrombectomy. Recanalization of CTO lesions was not possible in two patients (13%), who underwent AUI graft placement with CFFB. The 30-day mortality and morbidity rates were 0%. The mean follow-up periods were 12 and 32 months for patients who underwent BFG placement and AUI graft placement with CFFB, respectively. During follow-up, the primary patency rate of successfully recanalized arteries was 100%. Aneurysm size decreased in four patients who underwent BFG placement; no change was seen in the other 11 patients. Freedom from aneurysm-related events was 100%; no patient needed secondary interventions. All patients with claudication pain preoperatively reported improvement in their symptoms during follow-up. In addition, the ankle-brachial index improved significantly from 0.51 ± 0.25 preoperatively to 0.88 ± 0.20 postoperatively (P < .001) in patients who underwent BFG placement. CONCLUSIONS: Recanalization of unilateral iliac CTO lesions and placement of BFG in cases with concomitant aneurysmal disease and unilateral iliac occlusive disease demonstrated a significant primary patency rate with improvements in claudication and ankle-brachial index.
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Aneurisma de la Aorta Abdominal/cirugía , Arteriopatías Oclusivas/cirugía , Implantación de Prótesis Vascular/instrumentación , Prótesis Vascular , Procedimientos Endovasculares/instrumentación , Arteria Ilíaca/cirugía , Anciano , Anciano de 80 o más Años , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/fisiopatología , Arteriopatías Oclusivas/complicaciones , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/fisiopatología , Implantación de Prótesis Vascular/efectos adversos , Enfermedad Crónica , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Arteria Ilíaca/diagnóstico por imagen , Arteria Ilíaca/fisiopatología , Masculino , Complicaciones Posoperatorias/etiología , Diseño de Prótesis , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
PURPOSE: To evaluate the advantages of chimney endovascular aneurysm repair (chEVAR) using an Endurant stent-graft with uncovered balloon-expandable stents (BES) for patients with juxtarenal aortic aneurysms. MATERIALS AND METHODS: Twenty-two patients (mean age 78.5±9.0 years; 13 men) who underwent chEVAR using Endurant and uncovered BES between January 2014 and December 2017 were analyzed retrospectively. The maximum aneurysm diameter was 59.1±11.9 mm, and the proximal neck length was 5.2±2.9 mm. Of the 22 cases, 9 (40%) involved proximal neck angulation and 9 (40%) had a conical neck. Single and double chimneys were performed using BES in 19 and 3 cases, respectively. In 2 cases, an additional self-expanding covered stent was used inside the uncovered BES. RESULTS: The technical success was 91% (20/22) as 2 (9%) cases showed minor type Ia endoleak. No postoperative systemic complications or acute renal dysfunction (Acute Kidney Injury Network classification stage 2 or higher) were observed. The mean radiologic observation period was 16.1±9.6 months, and no aneurysm expansion (>5 mm) was observed during this time. The mean maximum aneurysm diameter decreased to 52.9±10.2 mm (p<0.001 vs preoperative), with an individual mean sac regression of 6.2±5.9 mm. Overall primary chimney stent patency was 100%. One of the 2 cases of intraoperative type Ia endoleak resolved at the 6-month imaging, and no new type Ia endoleaks developed in any cases at follow-up. No additional treatment- or aneurysm-related events were observed. CONCLUSION: Short-term outcomes of chEVAR using Endurant with uncovered BES have been favorable when covered stents were unavailable, and it can be useful for high-risk patients with juxtarenal aortic aneurysms.
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Angioplastia de Balón/instrumentación , Aneurisma de la Aorta Abdominal/cirugía , Implantación de Prótesis Vascular/instrumentación , Prótesis Vascular , Stents , Anciano , Anciano de 80 o más Años , Angioplastia de Balón/efectos adversos , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/fisiopatología , Implantación de Prótesis Vascular/efectos adversos , Endofuga/etiología , Femenino , Humanos , Masculino , Diseño de Prótesis , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
This study was conducted to identify specific abnormalities using the results from air plethysmography in legs with lymphedema. A routine air plethysmography exercise protocol was performed in 31 patients with unilateral leg lymphedema, and the results were compared with those of 53 patients with unilateral great saphenous vein reflux and 15 normal subjects. The venous filling index in legs with lymphedema (2.1 ± 1.2 mL/sec) was smaller than in legs with great saphenous vein reflux (6.4 ± 4.1 mL/sec, p < 0.05), but was not different from that in normal legs (1.9 ± 1.2 mL/sec). The ejection fraction was similar in all groups. The residual volume fraction in legs with lymphedema (35 ± 32%) was larger than that in normal subjects (13 ± 23%, p < 0.05), but was not significantly different from that in the contralateral leg of the lymphedema patients (32 ± 27%). In conclusion, we found no specific air plethysmography findings in uncomplicated lymphedema.
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Hemodinámica/fisiología , Linfedema/fisiopatología , Pletismografía , Insuficiencia Venosa/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Pierna/irrigación sanguínea , Linfedema/complicaciones , Masculino , Persona de Mediana Edad , Pletismografía/métodos , Vena Safena/diagnóstico por imagen , Vena Safena/fisiopatología , Ultrasonografía Doppler Dúplex/métodos , Várices/complicaciones , Várices/fisiopatologíaRESUMEN
A congenital abnormality of the inferior vena cava is said to be an anatomical risk factor for venous thromboembolism. In this report, we present a case of a patient with a left duplicated common iliac vein who developed a venous thromboembolism following total abdominal hysterectomy and bilateral salpingo-oophorectomy. Only 2 items were risk factors for thromboembolism: age of ≥40 years and open surgery duration of ≥30 min; no congenital abnormalities of the inferior vena cava or thrombotic factors were observed. Thus, it was suspected that the duplicated common iliac vein could have caused the venous thromboembolism.
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Vena Ilíaca/anomalías , Malformaciones Vasculares/complicaciones , Trombosis de la Vena/etiología , Factores de Edad , Anticoagulantes/uso terapéutico , Angiografía por Tomografía Computarizada , Femenino , Humanos , Histerectomía/efectos adversos , Vena Ilíaca/diagnóstico por imagen , Persona de Mediana Edad , Tempo Operativo , Flebografía/métodos , Factores de Riesgo , Salpingooforectomía/efectos adversos , Terapia Trombolítica , Resultado del Tratamiento , Malformaciones Vasculares/diagnóstico por imagen , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/tratamiento farmacológicoRESUMEN
BACKGROUND: To study the impact of aggressive decongestion in limbs with lymphedema without subcutaneous echo-free space (SEFS) in subcutaneous tissue ultrasonography. METHODS: In 13 patients with arm lymphedema (ALE) (13 arms) and 16 patients with leg lymphedema (LLE) (18 legs) without SEFS, an aggressive decongestion was performed as the first phase of complex decongestive therapy. Measurements of circumference and calculation of limb volume were performed before and after the treatment. RESULTS: In ALE, no significant reduction in arm volume (median -63 [range -251 to 176] mL) or edema ratio (-4 [-15 to 12]%) was confirmed. On the other hand, a small but significant reduction in leg volume (-207 [-834 to 131] mL, P < 0.001) and edema ratio (-4 [-14 to 2]%, P < 0.01) was confirmed in LLE. CONCLUSION: In limbs with lymphedema without SEFS, the impact of aggressive decongestion seemed limited.
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Vendajes de Compresión , Extremidad Inferior/diagnóstico por imagen , Linfedema/diagnóstico por imagen , Linfedema/terapia , Tejido Subcutáneo/diagnóstico por imagen , Ultrasonografía/métodos , Extremidad Superior/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Antropometría , Femenino , Humanos , Extremidad Inferior/patología , Linfedema/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tejido Subcutáneo/patología , Resultado del Tratamiento , Extremidad Superior/patología , Adulto JovenRESUMEN
OBJECTIVES: To examine the correlations between elements of feet-washing behavior, presence of tinea pedis (TP), and patients' background characteristics in order to identify a concrete intervention method to prevent TP. DESIGN AND PARTICIPANTS: A cross-sectional study of 30 patients with diabetes (16 with TP) who were admitted to or visited the university hospital. MAIN OUTCOME MEASURES: The presence of TP was confirmed by the detection of dermatophytes by direct microscopy. Data on elements of feet-washing behavior, such as scrubbing between the toes, were collected by observing recorded videos of participants normally washing their feet as they do at home. The patients' background characteristics included demographic data; diabetes-related factors; patient knowledge regarding diabetes, foot problems, and TP prevention; purpose for feet washing; and any difficulties in feet washing. MAIN RESULTS: The number of times patients scrubbed between their toes while washing with soap was significantly lower in patients with TP (odds ratio, 0.95; P = .036; with a cutoff value of 35 times) and those who had difficulty in reaching their feet with their hands (B = -14.42, P = .041). CONCLUSIONS: An effective foot-washing protocol should include specific instructions for patients to scrub between their toes at least 35 times in all 8 spaces while washing with soap. Appropriate advice is also needed for individuals who have difficulty reaching their feet with their hands. Education about appropriate foot-washing behavior may potentially prevent TP.
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Pie Diabético/epidemiología , Conductas Relacionadas con la Salud , Higiene , Tiña del Pie/epidemiología , Anciano , Comorbilidad , Estudios Transversales , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Pie Diabético/diagnóstico , Femenino , Hospitales Universitarios , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto , Valores de Referencia , Medición de Riesgo , Cuidados de la Piel/métodos , Tiña del Pie/diagnósticoRESUMEN
Deep-tissue injury (DTI) is a unique type of pressure ulcer (PU) in which deep-tissue damage expands outwards to the superficial skin. DTI progresses rapidly into a severe PU, despite initially appearing as only a bruise or darkened tissue in the superficial skin. Although some DTI detection methods are available, there is currently no strategy for treating deteriorating DTI. This study investigated the efficacy of vibration therapy for preventing DTI deterioration through down-regulation of the hypoxia-inducible factor-1 matrix metalloproteinase (MMP) axis in rats. We prepared a conventional PU rat model (PU group) and a DTI deterioration rat model (DTI group). The DTI group was further divided into two groups subjected to vibration and control treatments, respectively. Macroscopic and histological features, hypoxia, oxidative stress, apoptosis, and MMP2 and MMP9 activities in compressed skin were analyzed. Hypoxia, oxidative stress, and MMP activity were enhanced in the DTI group compared with the PU group. Vibration remarkably inhibited DTI deterioration, hypoxia, and the expression/activities of MMP2 and MMP9. These results suggest that vibration therapy can effectively attenuate deterioration of DTI. This report provides the first evidence for a therapeutic treatment for deteriorating DTI.
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Factor 1 Inducible por Hipoxia/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Úlcera por Presión/patología , Piel/patología , Vibración , Animales , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar , Piel/lesiones , Cicatrización de HeridasRESUMEN
Quorum sensing is a cell-to-cell communication mechanism, which is responsible for regulating a number of bacterial virulence factors and biofilm maturation and therefore plays an important role for establishing wound infection. Quorum-sensing signals may induce inflammation and predispose wounds to infection by Pseudomonas aeruginosa; however, the interaction has not been well investigated. We examined the effects of the P. aeruginosa las quorum-sensing signal, N-3-oxo-dodecanoyl homoserine lactone (3OC12-HSL), on matrix metalloproteinase (MMP) 9 expression in Rat-1 fibroblasts. 3OC12-HSL upregulated the expression of the MMP9 gene bearing an activator protein-1 (AP-1) binding site in the promoter region. We further investigated the mechanism underlying this effect. c-Fos gene expression increased rapidly after exposure to 3OC12-HSL, and nuclear translocation of c-Fos protein was observed; both effects were reduced by pretreatment with an AP-1 inhibitor. These results suggest that 3OC12-HSL can alter MMP9 gene expression in fibroblasts via the AP-1 signaling pathway.
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4-Butirolactona/análogos & derivados , Fibroblastos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Homoserina/análogos & derivados , Metaloproteinasa 9 de la Matriz/genética , Pseudomonas aeruginosa/química , Factor de Transcripción AP-1/genética , 4-Butirolactona/farmacología , Abietanos/farmacología , Animales , Línea Celular , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Fibroblastos/citología , Fibroblastos/metabolismo , Homoserina/farmacología , Metaloproteinasa 9 de la Matriz/metabolismo , Regiones Promotoras Genéticas , Transporte de Proteínas , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Pseudomonas aeruginosa/metabolismo , Percepción de Quorum , Ratas , Transducción de Señal , Factor de Transcripción AP-1/antagonistas & inhibidores , Factor de Transcripción AP-1/metabolismoRESUMEN
Deep tissue injuries (DTIs) can become significant problems because of their rapid deterioration into deep pressure ulcers. Presently, no animal model of DTI deterioration has been developed. By concentrating pressure and shear stress in deep tissues while minimising pressure and shear stress in the overlying skin, we produced an effective rat model of DTI deterioration. Two-dimensional finite element method (FEM) simulated the distribution of pressure and shear stress under several pressure-loading conditions. FEM showed that concentrated shear stress in deep tissue with minimum shear stress in the overlying skin could be created by using a prominence and a cushion, respectively. On the basis of the results of FEM analysis, we selected suitable conditions for testing the rat DTI deterioration model. The compressed area was macroscopically observed until day 13, and histopathologic analysis via haematoxylin and eosin (H&E) staining was performed on days 3, 7 and 13. H&E staining showed that the distribution of tissue damage was similar to the predicted FEM results. Deep ulceration and tissue damage extending from deep tissues to the overlying skin and surrounding tissues were observed in the DTI deterioration model, which are similar to the clinical manifestations of DTI deterioration. In conclusion, a representative DTI deterioration model was established by concentrating high shear stress in deep tissues while minimising shear stress in the overlying skin. This model will allow a better understanding of the mechanisms behind DTI deterioration and the development of preventative strategies.
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Modelos Animales de Enfermedad , Úlcera por Presión/etiología , Úlcera por Presión/patología , Animales , Fuerza Compresiva , Módulo de Elasticidad , Análisis de Elementos Finitos , Masculino , Ratas , Ratas Wistar , Resistencia al Corte , Estrés MecánicoAsunto(s)
Aneurisma de la Aorta Abdominal/cirugía , Procedimientos Endovasculares/efectos adversos , Fibrosis Retroperitoneal/etiología , Anciano , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Glucocorticoides/administración & dosificación , Humanos , Masculino , Metilprednisolona/administración & dosificación , Recurrencia , Fibrosis Retroperitoneal/diagnóstico por imagen , Fibrosis Retroperitoneal/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Recent advances in mechanobiology and the discovery of mechanosensitive ion channels have opened a new era of research on hypertension and related diseases. Piezo1 and Piezo2, first reported in 2010, are regarded as bona fide mechanochannels that mediate various biological and pathophysiological phenomena in multiple tissues and organs. For example, Piezo channels have pivotal roles in blood pressure control, triggering shear stress-induced nitric oxide synthesis and vasodilation, regulating baroreflex in the carotid sinus and aorta, and releasing renin from renal juxtaglomerular cells. Herein, we provide an overview of recent literature on the roles of Piezo channels in the pathogenesis of hypertension and related kidney damage, including our experimental data on the involvement of Piezo1 in podocyte injury and that of Piezo2 in renin expression and renal fibrosis in animal models of hypertensive nephropathy. The mechanosensitive ion channels Piezo1 and Piezo2 play various roles in the pathogenesis of systemic hypertension by acting on vascular endothelial cells, baroreceptors in the carotid artery and aorta, and the juxtaglomerular apparatus. Piezo channels also contribute to hypertensive nephropathy by acting on mesangial cells, podocytes, and perivascular mesenchymal cells.
RESUMEN
Glomerular podocyte injury plays an essential role in proteinuria pathogenesis, a hallmark of chronic kidney disease, including hypertensive nephropathy. Although podocytes are susceptible to mechanical stimuli, their mechanotransduction pathways remain elusive. Piezo proteins, including Piezo1 and 2, are mechanosensing ion channels that mediate various biological phenomena. Although renal Piezo2 expression and its alteration in rodent dehydration and hypertension models have been reported, the role of Piezo1 in hypertensive nephropathy and podocyte injury is unclear. In this study, we examined Piezo1 expression and localization in the kidneys of control mice and in those of mice with hypertensive nephrosclerosis. Uninephrectomized, aldosterone-infused, salt-loaded mice developed hypertension, albuminuria, podocyte injury, and glomerulosclerosis. RNAscope in situ hybridization revealed that Piezo1 expression was enhanced in the podocytes, mesangial cells, and distal tubular cells of these mice compared to those of the uninephrectomized, vehicle-infused control group. Piezo1 upregulation in the glomeruli was accompanied by the induction of podocyte injury-related markers, plasminogen activator inhibitor-1 and serum/glucocorticoid regulated kinase 1. These changes were reversed by antihypertensive drug. Exposure of Piezo1-expressing cultured podocytes to mechanical stretch activated Rac1 and upregulated the above-mentioned markers, which was antagonized by the Piezo1 blocker grammostola mechanotoxin #4 (GsMTx4). Administration of Piezo1-specific agonist Yoda1 mimicked the effects of mechanical stretch, which was minimized by the Yoda1-specific inhibitor Dooku1 and Rac inhibitor. Rac1 was also activated in the above-mentioned hypertensive mice, and Rac inhibitor downregulated gene expression of podocyte injury-related markers in vivo. Our results suggest that Piezo1 plays a role in mechanical stress-induced podocyte injury.
Asunto(s)
Hipertensión Renal , Hipertensión , Nefritis , Podocitos , Ratones , Animales , Podocitos/metabolismo , Mecanotransducción Celular , Riñón , Hipertensión/metabolismo , Canales Iónicos/metabolismo , Canales Iónicos/farmacologíaRESUMEN
OBJECTIVES: After staged reconstruction for hypoplastic left heart syndrome, the neoaortic root tends to dilate, and the incidence of significant neoaortic valve insufficiency increases with time. This study aimed to evaluate the mid-term outcomes of the neoaortic root geometries and valve function after chimney reconstruction in the Norwood procedure. METHODS: Between 2013 and 2021, 20 consecutive patients who underwent chimney reconstruction during the Norwood procedure for hypoplastic left heart syndrome and its variants in our institution were enrolled. The actual diameters of the following points were measured, and Z-scores were calculated based on the normal aortic root geometries using the long axis view of echocardiography at the pre-Norwood stage and the lateral view of angiography at pre-Glenn, pre-Fontan, post-Fontan and follow-up (age 5-6 years) stages: neoaortic valve annulus; sinus of Valsalva; sinotubular junction; and ascending aorta just proximal to the anastomosis to the aortic arch. The degree of neoaortic valve regurgitation was evaluated by echocardiography at each stage. RESULTS: The median follow-up period was 3.9 years. Neoaortic roots after chimney reconstruction were spared from progressive dilation over time. With growth, the conical configuration of the neoaortic roots was preserved without geometrical distortion. The Z-scores of the annulus, sinus of Valsalva, sinotubular junction and ascending aorta ranged roughly from 4 to 6, 4 to 6, 2 to 4 and 0 to 2, respectively. All neoaortic valves at each stage had mild or no regurgitation. CONCLUSIONS: Chimney reconstruction prevented neoaortic root dilation and avoided significant neoaortic valve regurgitation in the mid-term. These neoaortic dimensions with smooth flow profiles in the neoaorta after chimney reconstruction may have contributed to the current results. Further studies are needed to clarify the long-term outcomes.
Asunto(s)
Insuficiencia de la Válvula Aórtica , Síndrome del Corazón Izquierdo Hipoplásico , Procedimientos de Norwood , Humanos , Preescolar , Niño , Síndrome del Corazón Izquierdo Hipoplásico/cirugía , Resultado del Tratamiento , Procedimientos de Norwood/efectos adversos , Aorta/cirugía , Ecocardiografía , Insuficiencia de la Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/etiología , Estudios de Seguimiento , Estudios RetrospectivosRESUMEN
Undermining is one of the most challenging complications of deep pressure ulcers. Recommendations in most guidelines are based only on expert opinions. Here, we examined the relationship between surgical incision of the undermined space and pressure ulcer healing through a Japanese multicenter prospective cohort study. A total of 162 patients with undermining in 40 national hospitals in Japan were enrolled from July 2007 to June 2009. The incision group included 39 patients (24.1%) whose undermining was surgically incised during the observational period. Their 4-week follow-up data on pressure ulcer severity and areas of healthy granulation tissue were recorded as outcome variables using the DESIGN-R pressure ulcer assessment tool. The 4-week follow-up was restarted after the incision in the incision group. The outcome variables over time were compared between the two groups using a linear mixed model with or without adjustment for demographic and other variables. The incision group showed more rapid improvement in the total and granulation DESIGN-R scores compared with the nonincision group (p < 0.001 and p = 0.007, respectively, in the crude models). This study may provide the first considerable evidence to support that surgical incision of undermining may promote healing of deep pressure ulcers.
Asunto(s)
Úlcera por Presión/cirugía , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Úlcera por Presión/patología , Estudios Prospectivos , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
Because wound exudate includes secreted proteins that affect wound healing, its biochemical analysis is useful for objective assessment of chronic wounds. Wound blotting allows for collection of fresh exudate by attaching a nitrocellulose membrane onto the wound surface. To determine its applicability for several analysis methods and its executability in clinical wound assessment, this study comprised an animal experiment and clinical case reports. In the animal experiment, full-thickness wounds were created on the dorsal skin of mice, and exudate samples were collected daily by a conventional method and by wound blotting. Extremely small but adequate volumes of exudate were collected by wound blotting for subsequent analysis in the animal experiments. Immunostaining showed the concentration and distribution of tumor necrosis factor (TNF) α. The activity of alkaline phosphatase was visualized by reaction with chemiluminescent substrate. The TNF distribution analysis indicated three different patterns: wound edge distribution, wound bed distribution, and a mostly negative pattern in both the animal and clinical studies, suggesting association between the TNF distribution pattern and wound healing. Our results indicate that wound blotting is a convenient method for biochemical analysis of exudate and a candidate tool with which to predict the healing/deterioration of chronic ulcers.