• Biomolecules & Therapeutics
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• 제29권1호
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• pp.41-51
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• 2021

Src family kinases (SFKs), an important group of non-receptor tyrosine kinases, are suggested to be excessively activated during various types of tissue fibrosis. The present study investigated the effect of KF-1607, an orally active and a newly synthesized Src kinase inhibitor (SKI) with proposed low toxicity, in preventing the progression of renal interstitial fibrosis. Unilateral ureteral obstruction (UUO) surgery was performed in 6-week-old male C57BL/6 mice to induce renal interstitial fibrosis. Either KF-1607 (30 mg/kg, oral gavage) or PP2 (2 mg/kg, intraperitoneal injection), a common experimental SKI, was administered to mice for seven days, started one day prior to surgery. UUO injury-induced SFK expression, including Src, Fyn, and Lyn kinase. SFK inhibition by KF-1607 prevented the progression of tubular injury in UUO mice, as indicated by decreases in albuminuria, urinary KIM-1 excretion, and kidney NGAL protein expression. Renal tubulointerstitial fibrosis was attenuated in response to KF-1607, as shown by decreases in α-SMA, collagen I and IV protein expression, along with reduced Masson's trichrome and collagen-I staining in kidneys. KF-1607 also inhibited inflammation in the UUO kidney, as exhibited by reductions in F4/80 positive-staining and protein expression of p-NFκB and ICAM. Importantly, the observed effects of KF-1607 were similar to those of PP2. A new pan Src kinase inhibitor, KF-1607, is a potential pharmaceutical agent to prevent the progression of renal interstitial fibrosis.

• Journal of Trauma and Injury
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• 제19권2호
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• pp.192-195
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• 2006

Degenerative vascular disease, previous arterial surgery, long-term ureteral stenting, pelvis surgery, and radiotheraphy are reported as causes of artery-to-collecting-system communication.. Artery-to-collecting-system- communication associated with blunt trauma is rare, but potentially fatal. The diagnosis is very difficult and requires a high degree of suspicion. We were able to make the diagnosis based on the characteristic finding of contrast-enhanced computed tomography (CT) obtained in the early phase, equivalent to the finding obtained in the corticomedullary phase of the kidney. We report a case of artery to collecting system communication due to blunt abdominal trauma following a fall, which was treated by embolization.

• Biomolecules & Therapeutics
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• 제31권6호
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• pp.599-610
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• 2023

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis. Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.

• Journal of Yeungnam Medical Science
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• 제9권2호
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• pp.416-421
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• 1992

저자들은 결석이 동반된 남성에서의 요도게실 2례를 치험하였기에 그 회귀성에 비추어 문헌고찰과 함께 보고하는 바이다.

• Journal of Chest Surgery
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• 제20권4호
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• pp.839-846
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• 1987

The records of 10 patients with traumatic diaphragmatic hernia seen from November 1977 through July 1987 were reviewed. All the patients had a transdiaphragmatic evisceration of abdominal contents into the thorax. We treated 7 male and 3 female patients ranging in age from 3 to 62 years. In 8 patients, diaphragmatic hernia followed blunt trauma and in 2 patients, stab wounds to the chest. The herniation occurred on the right side in 3 patients and on the left side in 7. All the patients sustained additional injuries: rib fractures [7 patients], additional limb, pelvic and vertebral fractures [6], closed head injury [2], lung laceration [1], liver laceration [1], renal contusion [1], ureteral rupture [1], and splenic rupture [1]. Organs herniated through the diaphragmatic rent included the omentum [6 patients], stomach [4], liver [4], colon [3], small intestine [1], and spleen [1]. For right-sided injuries, the liver was herniated in all 3 patients and the colon, in 1. in the initial or latent phase, dyspnea, diminished breath sounds, bowel sounds in the chest were noted in 4 patients, and in the obstructive phase, nausea, vomiting, and abdominal pain were found in all 3 patients. Two patients had a diagnostic chest radiograph with findings of bowel gas patterns, and an additional 8 had abnormal but nondiagnostic studies. Hemothorax, pleural effusion or abnormal diaphragmatic contour were common abnormal findings. Three patients were operated on during the initial or acute phase [immediately after injury], 4 patients were operated on during the latent or intermediate phase [3 to 210 days], and 3 patients were operated on during the obstructive phase [10 to 290 days]. Six patients underwent thoracotomy, 2 required thoracoabdominal incision, and 2 had combined thoracotomy and laparotomy. Primary suture was used to repair the diaphragmatic hernia in 9 cases. One patient required plastic repair by a Teflon felt. Empyema was the main complication in 2 patients. In 1 patient, the empyema was treated by closed thoracostomy and in 1, by decortication and open drainage. There were no deaths.

• Childhood Kidney Diseases
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• 제17권2호
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• pp.127-131
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• 2013

요낭종이란 신장 및 비뇨기계로부터 누출된 소변이 신장 및 신우 주위에 캡슐상의 낭종을 형성하는 드문 질환으로 자연발생적인 신우의 파열로 인한 누출은 매우 드물며, 대부분 요로와 신우 내강의 압력 증가에 의해 발생한다. 본 증례에서 18세 여자 환아는 내원 7일 전부터 시작된 고열과 핍뇨 및 호흡곤란을 주소로 내원하였다. 환아는 출생시 다운 증후군을 진단받았으며 평소 배뇨는 원활하였다. 입원 후 환아는 패혈증 쇼크 및 급성 신손상, 급성 호흡 곤란 증후군 진단 하에 항생제 및 스테로이드 충격 요법 시행 후 핍뇨, 호흡곤란 및 혈액검사 호전 소견 보였으나 7일 동안 유치된 도뇨관 제거 후 환아는 요 폐색 소견이 관찰되었다. 복부 전산화 단층 촬영상 좌측 신장 주위에 요낭종이 확인되어 좌측 요관에 Double-J catheter가 삽입 되었으며 신우의 파열 부위에 조영제 누출이 확인되었다. 시술 후 요 폐색 소견은 호전되었고, 배뇨성 방광 요도 조영술 상 좌측 신장의 4단계 방광 요관 역류가 관찰되었다. Double-J catheter 제거 3개월 후 좌측 신장 주변의 요낭종은 대부분 소실되었고, 좌측 신장의 방광 요관 역류는 보이지 않았다. 저자들은 급성 신부전 환아에서 유치 도뇨관 제거 후 배뇨곤란 및 요 폐색 소견을 보인 신 주위 요낭종 1례를 경험하였기에 보고하는 바이다.