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1.
BMC Gastroenterol ; 24(1): 203, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886646

RESUMO

Transanal total mesorectal excision (taTME) has improved the laparoscopic dissection for rectal cancer in the narrow pelvis. Although taTME has more clinical benefits than laparoscopic surgery, such as a better view of the distal rectum and direct determination of distal resection margin, an intraoperative urethral injury could occur in excision ta-TME. This study aimed to determine the feasibility and efficacy of the ta-TME with IRIS U kit surgery. This retrospective study enrolled 10 rectal cancer patients who underwent a taTME with an IRIS U kit. The study endpoints were the safety of access (intra- or postoperative morbidity). The detectability of the IRIS U kit catheter was investigated by using a laparoscope-ICG fluorescence camera system. Their mean age was 71.4±6.4 (58-78) years; 80 were men, and 2 were women. The mean operative time was 534.6 ± 94.5 min. The coloanal anastomosis was performed in 80%, and 20% underwent abdominal peritoneal resection. Two patients encountered postoperative complications graded as Clavien-Dindo grade 2. The transanal approach with IRIS U kit assistance is feasible, safe for patients with lower rectal cancer, and may prevent intraoperative urethral injury.


Assuntos
Estudos de Viabilidade , Complicações Pós-Operatórias , Neoplasias Retais , Cirurgia Endoscópica Transanal , Uretra , Humanos , Neoplasias Retais/cirurgia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Uretra/lesões , Uretra/cirurgia , Cirurgia Endoscópica Transanal/métodos , Cirurgia Endoscópica Transanal/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Duração da Cirurgia , Protectomia/métodos , Protectomia/efeitos adversos , Complicações Intraoperatórias/prevenção & controle , Complicações Intraoperatórias/etiologia , Reto/cirurgia , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Laparoscopia/métodos , Laparoscopia/efeitos adversos
2.
World J Surg Oncol ; 22(1): 119, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702732

RESUMO

BACKGROUND: Coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA) is a well-established, safe procedure. However, problems with RGEA grafts in subsequent abdominal surgeries can lead to fatal complications. This report presents the first case of right hepatectomy for hepatocellular carcinoma after CABG using the RGEA. CASE PRESENTATION: We describe a case in which a right hepatectomy for an 81-year-old male patient with hepatocellular carcinoma was safely performed after CABG using a RGEA graft. Preoperatively, three-dimensional computed tomography (3D- CT) images were constructed to confirm the run of the RGEA graft. The operation was conducted with the standby of a cardiovascular surgeon if there was a problem with the RGEA graft. The RGEA graft had formed adhesions with the hepatic falciform ligament, necessitating meticulous dissection. After the right hepatectomy, the left hepatic lobe descended into the vacated space, exerting traction on the RGEA. However, this traction was mitigated by suturing the hepatic falciform ligament to the abdominal wall, ensuring stability of the RGEA. There were no intraoperative or postoperative complications. CONCLUSION: It is crucial to confirm the functionality and anatomy of the RGEA graft preoperatively, handle it gently intraoperatively, and collaborate with cardiovascular surgeons.


Assuntos
Carcinoma Hepatocelular , Ponte de Artéria Coronária , Artéria Gastroepiploica , Hepatectomia , Neoplasias Hepáticas , Humanos , Masculino , Artéria Gastroepiploica/cirurgia , Hepatectomia/métodos , Idoso de 80 Anos ou mais , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Ponte de Artéria Coronária/métodos , Tomografia Computadorizada por Raios X , Prognóstico , Imageamento Tridimensional , Complicações Pós-Operatórias/cirurgia
3.
Ann Med Surg (Lond) ; 85(9): 4589-4592, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37663743

RESUMO

Introduction and Importance: Lateral lymph node dissection (LLND) for recurrent lateral pelvic lymph node metastasis could be the only surgical treatment to improve its prognosis, but is difficult and challenging technically. Case Presentation: A 75-year-old Japanese man who underwent a radical laparoscopic intersphincteric resection to treat double lower rectal cancer. Computed tomography and MRI showed lower rectal wall thickening and bilateral lateral lymph node swelling. The authors scheduled and performed the LLND for recurrent lateral pelvic lymph nodes after ISR by the totally extraperitoneal (TEP) approach. The bottom of the obturators lymph node (#263D) were positive for metastasis histologically. Clinical Discussion: The TEP approach is an especially effective option for the treatment of bilateral LLND. Conclusion: Herein, the authors introduce our surgical technique: successful challenging treatment of the LLND by the TEP approach after intersphincteric resection of the lower rectum.

4.
Ann Med Surg (Lond) ; 84: 104954, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36582910

RESUMO

Introduction: and importance: TEP might be one of options for treating such a sports hernia. Case presentation: An 18-year-old Japanese male presented with right groin pain for approximately two years. The pain was initially felt on the right side only, especially on kicking. We assessed the patient using laparoscopic examination with an intra-abdominal scope and subsequently diagnosed a sports hernia with a bilateral internal inguinal hernia. We then performed total extraperitoneal repair (TEP) for its treatment. The patient had a good postoperative course and was discharged from our hospital in remission after 3 days. Finally, the patient was able to play soccer without groin pain. Clinical discussion: Chronic groin pain in athletes can be caused by a bulge in the posterior inguinal wall, consistent with an incipient direct inguinal hernia. Conclusion: We show that intraperitoneal examination with TEP might be one of options for treating such a sports hernia. Endoscopic placement of the retropubic mesh must be considered an important option for this type of hernia.

5.
Ann Med Surg (Lond) ; 73: 103173, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34976391

RESUMO

INTRODUCTION: Low and mid rectal cancer cells have the tendency to spread in the lateral pelvic lymph node (LPLN). The Japanese guidelines recommend systematic lymph node dissection when a positive LPLN is suspected or in stages II-III rectal cancer. However, laparoscopic lymph node dissection is complex and challenging. We introduce transanal LPLN dissection using an abdominal approach. PRESENTATION OF CASE: A 78-year-old man was diagnosed with advanced rectal cancer. Computed tomography and magnetic resonance imaging showed lower rectal wall thickening and bilateral lateral lymph node swelling. We performed laparoscopic abdominal peritoneal resection with combined bilateral LPLN dissection using abdominal and transanal approaches. He had an uneventful postoperative course with no signs of recurrence at the 5-month follow-up. DISCUSSION: LPLN metastases for low rectal cancer especially occur at the bottom of the deep pelvic spaces. As laparoscopic LPLND for low rectal cancer can be complicated, we adopted abdominal and transanal approaches, which provide the advantage of an anatomical view. This procedure may improve lateral pelvic anatomical structure viewing, and may offer advantages over laparoscopic abdominal approaches for visualizing and dissecting LPLNs. CONCLUSION: Curative resection has become available for rectal cancer with transanal LPLN dissection. LPLN dissection with combined abdominal and transanal approaches is a feasible treatment for advanced rectal cancer.

6.
Ann Med Surg (Lond) ; 72: 103005, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34849217

RESUMO

INTRODUCTION: Dysfunctions such as mucosal prolapse occur after intersphincteric resection (ISR) to treat lower rectal cancer, even when it is possible to preserve the anus. METHOD: We analyzed the data of 12 patients with rectal or colonic prolapse who underwent the Gant-Miwa-Thiersch procedure between March 2017 and May 2021. RESULT: There were no severe postoperative complications or recurrences. CASE PRESENTATION: A 75-year-old Japanese man initially underwent ISR and had mucosal prolapse nine months after his initial operation. We performed the Gant-Miwa-Thiersch procedure for colonic mucosal prolapse after ISR. SURGICAL PROCEDURE: Our procedure is a perineal plication method of prolapsed colonic mucosa with nylon wiring (The Gant-Miwa procedure), using a 1-nylon wire encircled three times to straighten the anal canal, with a cord inserted above the internal sphincter muscle (Thiersch procedure). DISCUSSION: Mucosal plication is performed via the Gant-Mowa or Delorme procedure to reduce the risk of recurrence. However, mucosal plication can be performed many times. Our Thiersch procedure involves encircling and straightening the anal canal with a 1-nylon wire to fix the new internal anal sphincter. In conclusion, the Gant-Miwa-Thiersch procedure for rectal and colonic mucosal prolapse, especially after ISR, is a viable treatment option.

7.
Ann Med Surg (Lond) ; 72: 103139, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34925824

RESUMO

INTRODUCTION AND IMPORTANCE: Ventral hernial repair extensively requires the use of surgical meshes to cover the abdominal wall. Patients with a history of laparoscopic ventral hernial repair are predisposed to secondary mesh infections. However, strategies to avoid these mesh infections have not yet been reported. Herein, we report the safety of laparoscopic cholecystectomy in a patient with cholecystitis following extended totally extraperitoneal repair of a ventral hernia. CASE PRESENTATION: A 69-year-old man presented with a five-day history of right hypochondrial pain and severe epigastric pain since the previous day. He had undergone ventral hernial repair. With a diagnosis of acute cholecystitis, laparoscopic cholecystectomy was performed. During laparoscopic cholecystectomy, we inserted the first trocar from the right lower quadrant of the abdomen. Subsequently, we completed the surgery without penetrating the mesh by the ports and observing the other ports in the abdominal cavity. The patient recovered without any complications or short-term mesh infections. CLINICAL DISCUSSION: When performing abdominal surgery in a patient after ventral hernial repair, the presence of the mesh limits the approachability of the abdominal cavity without mesh penetration. Although it remains unclear whether mesh damage during abdominal surgery causes secondary mesh infection, avoiding any damage to the mesh may be recommended, especially in patients who are highly susceptible to intra-abdominal infection. CONCLUSION: We concluded that if the surgery is completed without damaging the mesh site, mesh infection after abdominal contamination surgery may be avoided.

8.
Case Rep Gastroenterol ; 15(1): 379-388, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33976615

RESUMO

We describe the case of a 78-year-old man with collision tumor from the primary malignant lymphoma and adenocarcinoma in the ascending colon. He suffered anemia from sigmoid colon cancer, and colonoscopy revealed early-stage colorectal cancer with a diameter of 20 mm in the cecum, the biopsy specimen showed moderately differentiated adenocarcinoma. Contrast-enhanced computed tomography (CT) revealed bowel wall thickening with contrast enhancement at the cecum; however, no lymph node and organ metastases were found. As above, we performed laparoscopic ileocecal resection with D3 lymph node dissection. The postoperative course was uneventful, and he was discharged from the hospital on postoperative day 11. Histopathological findings were moderately differentiated adenocarcinoma which invaded the muscularis propria and serosa from the submucosa, while the adjacent serosa showed a highly diffuse proliferation of atypical cells with an irregular nuclear-to-cytoplasmic ratio. Besides, immunohistochemical staining findings were diffuse large B-cell lymphoma, and diffuse large B-cell lymphoma was coexistent with moderately differentiated adenocarcinoma. We treated the patient with cyclophosphamide, doxorubicin, vincristine, and prednisolone in combination with rituximab (R-CHOP therapy) during 3 months postoperatively. When the 8 courses had been completed, postoperative positron emission tomography-CT (PET-CT) confirmed complete response, and the disease control has been doing well. Malignant lymphoma of the colorectal region is relative rare, and the occurrence of synchronous lymphoma and adenocarcinoma of the colon is also rare. Furthermore, collision tumor by these different entities is very unusual. We presented here such a case. The accurate clinical determination of the dominant tumor and a close follow-up is required for proper treatment in these cases.

9.
Ann Med Surg (Lond) ; 65: 102271, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33996044

RESUMO

INTRODUCTION: and importance: Granular cell tumor (GCT) is a benign, mesenchymal tumor that originates from Schwann cells. CASE PRESENTATION: A 75-year-old Japanese woman was referred to our hospital due to epigastric discomfort. Upper gastrointestinal endoscopy revealed an ulcerated cancer lesion, approximately 1.2 cm in diameter, at the angle of the stomach in the posterior gastric wall and a yellowish submucosal tumor, 5 mm in diameter, near an anal ulcerated lesion. Based on these findings, the patient was scheduled for laparoscopic distal gastrectomy and lymph node dissection. The pathological diagnosis was a moderately differentiated tubular adenocarcinoma invading mucosal stroma without lymph node metastasis and GCT in the stomach. Tumor cells were positive for S-100 and were consistent with the characteristics of GCT. CLINICAL DISCUSSION: To the best of our knowledge, this is an extremely rare case with reports of only 6 cases of such a combination, including our case. CONCLUSIONS: We believe that the coexistence of a GCT and gastric cancer in our patient was accidental and that there was no relation between them.

10.
Minim Invasive Ther Allied Technol ; 30(6): 369-376, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32196402

RESUMO

INTRODUCTION: There are several reports on the use of the over-the-scope clip (OTSC) for gastrointestinal bleeding/fistula and endoscopic iatrogenic perforation. However, there are almost no reports on OTSC use for anastomotic leakage (AL) after colorectal cancer surgery. The purpose of this study was to evaluate the outcome of AL closure using the OTSC. MATERIAL AND METHODS: Five patients who had undergone AL after laparoscopic surgery for colorectal cancer from April 2017 to April 2019 were evaluated. RESULTS: The average distance from the anal verge of the anastomosis site was 12 (5-18) cm. The average diameter of the dehiscent part was 10.9 (9.3-14.4) mm. The average number of OTSC days after the occurrence of AL was 11 (5-22). On the contrast examination immediately after OTSC, all cases were completely closed, but in the later contrast examination, only one case remained completely closed. The average incompletely closed diameter was 3.6 (2.9-5.1) mm, and the diameter of the dehiscent part was reduced in all cases. Only one patient ultimately underwent colostomy; the rest were cured with OTSC alone. CONCLUSION: AL site closure using the OTSC after colorectal cancer surgery is a useful minimally invasive treatment when combined with appropriate drain management.


Assuntos
Cirurgia Colorretal , Procedimentos Cirúrgicos do Sistema Digestório , Laparoscopia , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Endoscopia Gastrointestinal , Humanos
11.
Ann Med Surg (Lond) ; 57: 218-222, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32793342

RESUMO

: Laparoscopic cholecystectomy is the treatment of choice for almost all biliary diseases. We present a novel technique using near-infrared fluorescence imaging for laparoscopic cholecystectomy. : A 78-year-old woman diagnosed with acute cholecystitis (Grade II) was scheduled for emergency laparoscopy according to Tokyo Guidelines 2018. We performed a direct percutaneous drainage of the gallbladder to grasp the gallbladder itself. Subsequently, indocyanine green was administered into the gallbladder through the same tube, and the cystic and common bile ducts could be easily detected. The postoperative course was good, and the patient was discharged in remission nine days after the surgery. : Real-time fluorescence cholangiography with indocyanine green is reliable for biliary anatomy visualization before the dissection of the Calot's triangle. Our method of indocyanine green injection into the same drainage catheter does not require pre-preparation and can be simultaneously performed with drainage intraoperatively. This surgical technique is simple, straightforward, and effective and can be useful in intraoperative decision-making, especially during laparoscopic cholecystectomy.

12.
Wideochir Inne Tech Maloinwazyjne ; 15(2): 268-275, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32489486

RESUMO

INTRODUCTION: In recent years, laparoscopic surgery (LS) has been performed for small bowel obstruction (SBO). However, the indications and short-term and long-term outcomes of LS for SBO have not yet been established. AIM: To evaluate the usefulness of LS for SBO compared to open surgery (OS), as well as to identify risk factors for poor outcomes after LS. MATERIAL AND METHODS: A total of 105 patients who underwent surgery for SBO were divided into OS (n = 64) and LS (n = 41) groups, and propensity score-matched analysis was used to compare the short-term and long-term outcomes of the groups. Risk factors for conversion to OS, postoperative complications, and intraoperative bowel injury in LS were also identified. RESULTS: The incidences of surgical site infection and postoperative ileus were significantly lower in the LS group. The incidence of recurrent bowel did not differ significantly between the two groups. Prior bowel obstruction was a risk factor for conversion of LS to OS (odds ratio (OR) = 24.79, p = 0.0025). Bowel diameter was a risk factor for postoperative complications (OR = 1.50, 95% CI: 1.01-2.22) and for bowel injury (OR = 1.33, 95% CI: 1.05-1.67). CONCLUSIONS: LS for SBO had better postoperative short-term outcomes than OS. The outcomes of LS for SBO were significantly affected by prior bowel obstruction and bowel diameter.

13.
Anticancer Res ; 39(11): 6393-6401, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704873

RESUMO

BACKGROUND/AIM: Intracorporeal anastomosis (IA) in laparoscopic colectomy for colon cancer is technically difficult, and there is a lack of consensus on the risk of bacterial contamination and cancer cell dissemination. In this study, short- and long-term outcomes of IA were examined. PATIENTS AND METHODS: Short and long-term outcomes of those who underwent IA (n=44) or extracorporeal anastomosis (EA) (n=61) were compared. RESULTS: IA was better than EA for blood loss, incision length, and first stool. Maximum temperature and C-reactive protein on postoperative day 1 were higher for the IA group. The rate of positive cultures from intraoperative lavage was higher for IA. The rate of positive cultures improved to an equivalent level by replacing mechanical pretreatment with chemical pretreatment. IA and EA were equivalent for the results of ascites cytology from lavage. CONCLUSION: With the use of appropriate preoperative treatment, IA takes advantage of the minimally invasive nature of laparoscopic surgery.


Assuntos
Ascite/microbiologia , Colectomia/métodos , Neoplasias do Colo/cirurgia , Laparoscopia/métodos , Complicações Pós-Operatórias/microbiologia , Grampeamento Cirúrgico/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Feminino , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
14.
BMC Surg ; 19(1): 181, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779610

RESUMO

BACKGROUND: Various body composition indices have been reported as prognostic factors for different cancers. However, whether body composition affects prognosis after lower gastrointestinal tract perforation requiring emergency surgery and multidisciplinary treatment has not been clarified. This study examined whether body composition evaluations that can be measured easily and quickly from computed tomography (CT) are useful for predicting prognosis. METHODS: Subjects comprised 64 patients diagnosed with perforation at final diagnosis after emergency surgery for a preoperative diagnosis of lower gastrointestinal tract perforation and penetration. They were divided into a survival group and a non-survival (in-hospital mortality) group and compared. Body composition indices (psoas muscle index (PMI); psoas muscle attenuation (PMA); subcutaneous adipose tissue index (SATI); visceral adipose tissue index (VATI); visceral-to-subcutaneous fat area ratio (VSR)) were measured from preoperative CT. Cross-sectional psoas muscle area at the level of the 3rd lumbar vertebra was quantified. Optimal cut-off values were calculated using receiver operating characteristic curve analysis. Poor prognostic factors were investigated from multivariate logistic regression analyses that included patient factors, perioperative factors, intraoperative factors, and body composition indices as explanatory variables. RESULTS: The cause of perforation was malignant disease in 12 cases (18.7%), and benign disease in 52 cases (81.2%). The most common cause was diverticulum of the large intestine. Emergency surgery for the 64 patients led to survival in 52 patients and death in 12 patients. On multivariate logistic regression analysis, independent predictors of poor prognosis were Sequential Organ Failure Assessment score (odds ratio 1.908; 95% confidence interval (CI) 1.235-3.681; P = 0.0020) and PMI (odds ratio 13.478; 95%CI 1.342-332.690; P = 0.0252). The cut-off PMI was 4.75 cm2/m2 for males and 2.89 cm2/m2 for females. Among survivors, duration of hospitalization was significantly longer in the low PMI group (29 days) than in the high PMI group (22 days, p = 0.0257). CONCLUSIONS: PMI is easily determined from CT and allows rapid evaluation of prognosis following lower gastrointestinal perforation.


Assuntos
Traumatismos Abdominais/diagnóstico por imagem , Gordura Intra-Abdominal/diagnóstico por imagem , Músculos Psoas/diagnóstico por imagem , Gordura Subcutânea/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
16.
Am J Surg ; 215(1): 58-61, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29029780

RESUMO

PURPOSE: Stoma closure has been associated with a high rate of surgical site infection (SSI) and the optimal skin closure method is still controversial. The aim of this study was to compare the short-term and long-term outcomes between the conventional linear closure (CC) and the persestring closure (PC) using propensity score matching analysis. METHODS: We analysed the data of 360 patients who underwent stoma closure with CC or PC between January 2000 and December 2014. The propensity score was calculated from age, gender, body mass index, primary disease, type of stoma, diabetes mellitus, history of smoking, steroid use, the American Society of Anesthesiologists score, Prognostic Nutritional Index and modified Glasgow Prognostic Score. RESULTS: There was no difference in operative variables between the two groups. The CC group and the PC group were comparable with regards to overall SSI (25.0 vs. 7.8%; P = 0.007), superficial SSI (21.9 vs. 4.7%; P = 0.003). Significant risk factor for SSI was conventional linear closure (OR, 4.14; 95% CI, 1.448-13.91). CONCLUSION: Our study suggests that a pursestring stoma closure leads to less SSI.


Assuntos
Estomas Cirúrgicos , Infecção da Ferida Cirúrgica/etiologia , Técnicas de Sutura , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto Jovem
17.
J Am Soc Nephrol ; 16(5): 1339-49, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15788472

RESUMO

The intracellular polymerization of abnormal serine protease inhibitors (serpins) results in liver or neuronal cell abnormalities recently identified as "serpinopathies." It was demonstrated in transgenic rats that overexpression of megsin, a recently discovered serpin located in the kidney, produces renal and pancreatic lesions characteristic of serpinopathies. Megsin expression is elevated in a variety of organs, including kidney and pancreas. Periodic acid-Schiff-positive, diastase-resistant intracellular inclusions develop only in the kidney and the pancreas. They correspond to electron-dense deposits, shown to contain megsin by immunohistochemistry and immunoelectron microscopy. In the kidney, inclusions are located mainly in the endoplasmic reticulum of glomerular epithelial, distal, and collecting duct cells, and are associated with massive proteinuria and an impaired renal function. In the pancreas, similar inclusions are found in the exocrine and Langerhans islet cells, where islet beta cells are reduced as a result of apoptosis. They are associated with diabetes with low insulin levels. The animals have an impaired growth and die within 10 wk. Rats that overexpress a mutant megsin, characterized by a deficient conformational transition activity, do not develop the serpinopathy, suggesting that some conformational flexibility of the serpin is required for the development of serpinopathy. This model of serpinopathy is the first to involve the kidney and the pancreas.


Assuntos
Nefropatias/fisiopatologia , Pancreatopatias/fisiopatologia , Serpinas/genética , Animais , Animais Geneticamente Modificados , Feminino , Expressão Gênica , Humanos , Hibridização In Situ , Marcação In Situ das Extremidades Cortadas , Rim/patologia , Rim/fisiopatologia , Nefropatias/mortalidade , Nefropatias/patologia , Pâncreas/patologia , Pâncreas/fisiopatologia , Pancreatopatias/mortalidade , Ratos , Ratos Wistar
18.
Nephron Exp Nephrol ; 96(4): e127-33, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15122062

RESUMO

Mesangial cells play a critical role in the maintenance of normal glomerular functions such as matrix remodeling and immune complex disposal. We recently identified a novel human mesangium-predominant gene, megsin, which is a new member of the serine protease inhibitor (serpin) superfamily. While our previous studies demonstrated progressive mesangial matrix expansion and an increase in the number of mesangial cells in megsin transgenic mice, it took 40 weeks to develop these manifestations. Here we performed hemi-nephrectomy to accelerate glomerular injury in megsin transgenic mice. Hemi-nephrectomized transgenic mice developed focal segmental mesangial expansion, which was associated with proteinuria. Megsin has thus a biologically relevant influence on the development of glomerular damage. The hemi-nephrectomized model of this transgenic mouse might serve as a tool to investigate the mechanisms of glomerular disease.


Assuntos
Mesângio Glomerular/patologia , Nefropatias/etiologia , Serpinas/fisiologia , Animais , Proteínas do Sistema Complemento/análise , Mesângio Glomerular/imunologia , Imunoglobulinas/análise , Nefropatias/imunologia , Nefropatias/patologia , Glomérulos Renais/imunologia , Cinética , Camundongos , Camundongos Transgênicos , Nefrectomia , Proteinúria/etiologia , Serpinas/genética
19.
J Am Soc Nephrol ; 14(5): 1212-22, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12707391

RESUMO

Prevention or retardation of diabetic nephropathy (DN) includes anti-hypertensive treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) on the premises that these drugs have an added protective effect beyond their influence on BP. The present study used a strain of spontaneously hypertensive/NIH-corpulent rats [SHR/NDmc-cp (fat/fat)] as a model of type II DN to unravel the renoprotective effects of anti-hypertensive drugs. Olmesartan (1 or 5 mg/kg per d), an ARB, and hydralazine (5mg/kg per d), an anti-hypertensive drug without effect on the renin-angiotensin system (RAS), were given for 20 wk. BP, renal function, glucose and insulin levels, and proteinuria were monitored. Glomerular lesions and kidney pentosidine content were assessed at the end of the study. Olmesartan (1 and 5 mg) significantly reduced BP and kidney pentosidine content and improved histologic renal damage and proteinuria. The changes were dose-dependent. The effect of hydralazine (5 mg) was similar to that of olmesartan (1 mg) but reached statistical significance only for kidney pentosidine content. The similarity of both drugs' effects on kidney damage and proteinuria suggest that renoprotection does not hinge on manipulation of RAS in these rats. By contrast, the inhibition of renal pentosidine formation assessed both by immunohistochemistry and HPLC suggests a critical role of advanced glycation end product (AGE) formation together with hypertension in the genesis of diabetic nephropathy. This view is supported by the correlation found between renal pentosidine content and proteinuria. The unsuspected AGE-lowering effect of hydralazine was further confirmed in vitro and elucidated; it is due to both reactive carbonyl compounds trapping and modifications of the oxidative metabolism. It is concluded that AGE inhibition should be included in the therapeutic strategy of DN.


Assuntos
Anti-Hipertensivos/farmacologia , Arginina/análogos & derivados , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/complicações , Produtos Finais de Glicação Avançada/metabolismo , Hipertensão Renal/tratamento farmacológico , Imidazóis/farmacologia , Lisina/análogos & derivados , Tetrazóis/farmacologia , Animais , Arginina/análise , Glicemia , Pressão Sanguínea , Peso Corporal , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Hidralazina/farmacologia , Hipertensão Renal/metabolismo , Hipertensão Renal/patologia , Imuno-Histoquímica , Técnicas In Vitro , Rim/química , Rim/metabolismo , Rim/patologia , Lipídeos/sangue , Lisina/análise , Masculino , Olmesartana Medoxomila , Oxirredução , Proteinúria/tratamento farmacológico , Proteinúria/metabolismo , Proteinúria/patologia , Ratos
20.
Kidney Int ; 63(1): 331-9, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12472800

RESUMO

BACKGROUND: Reactive carbonyl compounds (RCOs) present in peritoneal dialysis (PD) fluid have been incriminated in the progressive deterioration of the peritoneal membrane in long-term PD patients. They are initially present in fresh conventional heat-sterilized glucose PD fluid and are supplemented during dwell time by the diffusion of blood RCOs within the peritoneal cavity. In the present study, RCO entrapping agents were immobilized on affinity beads to adsorb RCOs both in fresh PD fluid and in PD effluent. METHODS: The RCO trapping potential of various compounds was assessed in vitro first by dissolving them in the tested fluid and subsequently after coupling with either epoxy- or amino-beads. The tested fluids include fresh heat-sterilized glucose and non-glucose PD fluids, and PD effluent. Their RCOs contents, that is, glyoxal (GO), methylglyoxal (MGO), 3-deoxyglucosone (3-DG), formaldehyde, 5-hydroxymethylfuraldehyde, acetaldehyde, and 2-furaldehyde were monitored by reverse-phase high-pressure liquid chromatography. The biocompatibility of PD fluid was assessed by a cytotoxic assay with either human epidermoid cell line A431 cells or with primary cultured human peritoneal mesothelial cells. RESULTS: Among the tested RCO entrapping agents, hydrazine coupled to epoxy-beads proved the most efficient. It lowered the concentrations of three dicarbonyl compounds (GO, MGO, and 3-DG) and those of aldehydes present in fresh heat-sterilized glucose PD fluid toward the low levels observed in filter-sterilized glucose PD fluid. It did not change the glucose and electrolytes concentration of the PD fluid but raised its pH from 5.2 to 5.9. Hydrazine-coupled epoxy-bead also lowered the PD effluent content of total RCOs, measured by the 2,4-dinitrophenylhydrazone (DNPH) method. The cytotoxicity of heat-sterilized PD fluid incubated with hydrazine-coupled epoxy-beads was decreased to the level observed in filter-sterilized PD fluid as the result of the raised pH and the lowered RCOs levels. CONCLUSION: Hydrazine-coupled epoxy-beads reduce the levels of a variety of dicarbonyls and aldehydes present in heat-sterilized glucose PD fluid to those in filter-sterilized PD fluid, without altering glucose, lactate, and electrolytes contents but with a rise in pH. Incubated with PD effluents, it is equally effective in reducing the levels of serum-derived RCOs. RCO entrapping agents immobilized on affinity beads improve in vitro the biocompatibility of conventional heat-sterilized glucose PD fluid. Their clinical applicability requires further studies.


Assuntos
Glucose/metabolismo , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Diálise Peritoneal/efeitos adversos , Desintoxicação por Sorção , Aldeídos/metabolismo , Compostos de Epóxi , Guanidinas/farmacologia , Humanos , Hidrazinas/farmacologia , Técnicas In Vitro , Teste de Materiais , Microesferas , Peritônio/metabolismo
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