RESUMO
Cardiac fibroblasts are a cell population that controls the homeostasis of the extracellular matrix and orchestrates a damage response to maintain cardiac architecture and performance. Due to these functions, fibroblasts play a central role in cardiac fibrosis development, and there are large differences in matrix protein secretion profiles between fibroblasts from aged versus young animals. Senescence is a multifactorial and complex process that has been associated with inflammatory and fibrotic responses. After damage, transient cellular senescence is usually beneficial, as these cells promote tissue repair. However, the persistent presence of senescent cells within a tissue is linked with fibrosis development and organ dysfunction, leading to aging-related diseases such as cardiovascular pathologies. In the heart, early cardiac fibroblast senescence after myocardial infarction seems to be protective to avoid excessive fibrosis; however, in non-infarcted models of cardiac fibrosis, cardiac fibroblast senescence has been shown to be deleterious. Today, two new classes of drugs, termed senolytics and senostatics, which eliminate senescent cells or modify senescence-associated secretory phenotype, respectively, arise as novel therapeutical strategies to treat aging-related pathologies. However, further studies will be needed to evaluate the extent of the utility of senotherapeutic drugs in cardiac diseases, in which pathological context and temporality of the intervention must be considered.
Assuntos
Senescência Celular , Coração , Animais , Senescência Celular/fisiologia , Envelhecimento/patologia , Fibrose , Fibroblastos/metabolismoRESUMO
Angiotensin II (Ang-II) is a widely studied hypertensive, profibrotic, and pro-inflammatory peptide. In the heart, cardiac fibroblasts (CF) express type 1 angiotensin II receptors (AT1R), Toll-like receptor-4 (TLR4), and the NLRP3 inflammasome complex, which play important roles in pro-inflammatory processes. When activated, the NLRP3 inflammasome triggers proteolytic cleavage of pro-IL-1, resulting in its activation. However, in CF the mechanism by which Ang-II assembles and activates the NLRP3 inflammasome remains not fully known. To elucidate this important point, we stimulated TLR4 receptors in CF and evaluated the signaling pathways by which Ang-II triggers the assembly and activity. In cultured rat CF, pro-IL-1ß levels, NLRP3, ASC, and caspase-1 expression levels were determined by Western blot. NLRP3 inflammasome complex assembly was analyzed by immunocytochemistry, whereas by ELISA, we analyzed NLRP3 inflammasome activity and [Formula: see text] release. In CF, Ang-II triggered NLRP3 inflammasome assembly and caspase-1 activity; and in LPS-pretreated CF, Ang-II also triggered [Formula: see text] secretion. These effects were blocked by losartan (AT1R antagonist), U73221 (PLC inhibitor), 2-APB (IP3R antagonist), and BAPTA-AM (Ca2+ chelator) indicating that the AT1R/PLC/IP3R/Ca2+ pathway is involved. Finally, bafilomycin A1 prevented Ang-II-induced [Formula: see text] secretion, indicating that a non-classical protein secretion mechanism is involved. These findings suggest that in CF, Ang-II by a Ca2+-dependent mechanism triggers NLRP3 inflammasome assembly and activation leading to [Formula: see text] secretion through a non-conventional protein secretion mechanism.
Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Angiotensina II/farmacologia , Receptor 4 Toll-Like , Interleucina-1beta/metabolismo , Caspase 1/metabolismo , Fibroblastos/metabolismoRESUMO
Objective: To describe the management of the distal ureter during radical nephroureterectomy with the transvesical laparoendoscopic single-site surgery (T-LESS) approach. Methods: Between January 2010 and October 2013, five patients underwent laparoscopic radical nephroureterectomy for upper urinary tract carcinoma (UTUC) with the T-LESS approach. Patients were placed in the supine position. A 2.5-cm skin incision was made in the line between the pubis and the umbilicus. The bladder was identified and a multiport was inserted into the bladder. The patients were repositioned to a lateral decubitus position; pneumovesicum was established and the ureteral openings were identified. We marked the bladder cuff with electrocautery all the way through to the extravesical fat. The bladder defect was sealed with sutures. After checking for any leak or bleeding, the multiport was removed and the bladder was closed. At this point, we continued with nephrectomy by standard laparoscopy or LESS. A 18F Foley catheter was placed into the bladder. Results: The mean age was 70 years (range 58-81 years), the mean operative time was 198 minutes (range 115-390 minutes), the mean time for the management of the distal ureter was 35 minutes (range 27-45 minutes), the mean estimated blood loss was 234 mL (range 60-850 mL), and the mean hospital stay was 3.8 days (range 2-8 days). In all patients the bladder cuff was free of disease. Conclusion: The transvesical laparoendoscopic single-site approach to the distal ureter for UTUC appears safe and reproducible, with faster closure of the bladder defect and improved cosmesis.
Assuntos
Carcinoma de Células de Transição , Laparoscopia , Ureter , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/cirurgia , Humanos , Pessoa de Meia-Idade , Nefrectomia , Nefroureterectomia , Ureter/cirurgia , Bexiga Urinária/cirurgiaRESUMO
There has been an increase in the number of urologic procedures performed robotically assisted; this is the case for radical prostatectomy. Currently, in the USA, 67% of prostatectomies are performed robotically assisted. With this increase in robotic urologic surgery it is clear that there are more surgeons in their learning curve, where most of the complications occur. Among the complications that can occur are vascular injuries. These can occur in the initial stages of surgery, such as in accessing the abdominal cavity, as well as in the intraoperative or postoperative setting. We present the most common vascular injuries in robot-assisted radical prostatectomy, as well as their management and prevention. We believe that it is of vital importance to be able to recognize these injuries so that they can be prevented.
RESUMO
Objective To describe a novel technique of repairing the VVF using the transperitoneal-transvaginal approach. Materials and Methods From June 2011 to October 2013, four patients with symptoms of urine leakage in the vagina underwent robotic repair of VVF with the transperitoneal-transvaginal approach. Cystoscopy revealed the fistula opening on the bladder. A ureteral stent was placed through the fistulous tract. After trocar placement, the omental flap was prepared and mobilized robotically. The vagina was identified and incised. The fistulous tract was excised. Cystorrhaphy was performed in two layers in an interrupted fashion. The vaginal opening was closed with running stitches. The omentum was interposed and anchored between the bladder and vagina. Finally, the ureteral catheters were removed in case they have been placed, and an 18 Fr urethral catheter was removed on the 14th postoperative day. Results The mean age was 46 years (range: 41 to 52 years). The mean fistula diameter was 1.5 cm (range 0.3 to 2 cm). The mean operative time was 117.5 min (range: 100 to 150 min). The estimated blood loss was 100 mL (range: 50 to 150 mL). The mean hospital stay was 1.75 days (range: 1 to 3 days). The mean Foley catheter duration was 15.75 days (range: 10 to 25 days). There was no evidence of recurrence in any of the cases. Conclusions The robot-assisted laparoscopic transperitoneal transvaginal approach for VVF is a feasible procedure when the fistula tract is identified by first intentionally opening the vagina, thereby minimizing the bladder incision and with low morbidity. .
Assuntos
Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Laparoscopia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Fístula Vesicovaginal/cirurgia , Tempo de Internação , Duração da Cirurgia , Reprodutibilidade dos Testes , Resultado do Tratamento , Bexiga Urinária/cirurgia , Procedimentos Cirúrgicos Urológicos/métodosRESUMO
OBJECTIVE: To describe a novel technique of repairing the VVF using the transperitoneal-transvaginal approach. MATERIALS AND METHODS: From June 2011 to October 2013, four patients with symptoms of urine leakage in the vagina underwent robotic repair of VVF with the transperitoneal-transvaginal approach. Cystoscopy revealed the fistula opening on the bladder. A ureteral stent was placed through the fistulous tract. After trocar placement, the omental flap was prepared and mobilized robotically. The vagina was identified and incised. The fistulous tract was excised. Cystorrhaphy was performed in two layers in an interrupted fashion. The vaginal opening was closed with running stitches. The omentum was interposed and anchored between the bladder and vagina. Finally, the ureteral catheters were removed in case they have been placed, and an 18 Fr urethral catheter was removed on the 14th postoperative day. RESULTS: The mean age was 46 years (range: 41 to 52 years). The mean fistula diameter was 1.5 cm (range 0.3 to 2 cm). The mean operative time was 117.5 min (range: 100 to 150 min). The estimated blood loss was 100 mL (range: 50 to 150 mL). The mean hospital stay was 1.75 days (range: 1 to 3 days). The mean Foley catheter duration was 15.75 days (range: 10 to 25 days). There was no evidence of recurrence in any of the cases. CONCLUSIONS: The robot-assisted laparoscopic transperitoneal transvaginal approach for VVF is a feasible procedure when the fistula tract is identified by first intentionally opening the vagina, thereby minimizing the bladder incision and with low morbidity.