• Journal of Trauma and Injury
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• v.19 no.1
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• pp.14-20
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• 2006

Purpose: Although hypothermia has been used in many clinical situations, such as post cardiopulmonary resuscitation, stroke, traumatic brain injury, septic shock, and hemorrhagic shock, the mechanism by which it works has not been clearly elucidated. We aimed to evaluate the effect of hypothermia on the plasma nitric oxide (NO) concentration, lung iNOS expression, and histologic changes in intestinal ischemia-reperfusion (IR). Method: Male Sprague-Dawley rats were randomly divided into the hypothermia group (HT, n=8, $27{\sim}30^{\circ}C$) and the normothermia group (NT, n=8, $36{\sim}37^{\circ}C$). They underwent 30 min of intestinal ischemia by clamping the superior mesenteric artery, which was followed by 1.5 h of reperfusion. They were then sacrificed. The acute lung injury (ALI) score, the plasma NO concentration, and lung iNOS gene expression were measured. Results: Compared with the HT group, the NT group showed severe infiltrations of inflammatrory cells, alveolar hemorrhages, and interstitial hypertrophies in lung tissues. There were significant differences in the ALI scores between the NT and the HT groups ($8.7{\pm}1.5/HPF$ in NT vs $5.8{\pm}1.2/HPF$ in HT, p=0.008). Although the plasma NO concentration was slightly lower in the HT group, there was no significant difference between the two groups ($0.80{\pm}0.24{\mu}mol/L$ in NT vs $0.75{\pm}0.30{\mu}mol/L$ in HT, p=0.917). Lung iNOS gene expression was stronger in the NT group than in the HT group. The band density of the expression of iNOS in lung tissues was significantly increased in the NT group compared to the HT group ($5.54{\pm}2.75$ in NT vs$0.08{\pm}0.52$ in HT, p=0.002). Conclusions: This study showed that hypothermia in intestinal IR reduces inflammatory responses, ALI scores, and iNOS gene expression in lung tissues. There was no significant effect of hypothermia on the plasma NO concentration.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.263-273
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• 1999

The role of phospholipase $A_2\;(PLA_2)$ in acute lung leak induced by intestinal ischemia was investigated in association with neutrophilic respiratory burst. To induce lung leak, we generated intestinal ischemia for 60 min prior to the 120 min reperfusion by clamping superior mesenteric artery in Sprague-Dawley rats. Acute lung leak was confirmed by the increased lung leak index and protein content in bronchoalveolar fluid. These changes were inhibited by mepacrine, the non-specific $PLA_2$ inhibitor. The lung myeloperoxidase (MPO) activity denoting the pulmonary recruitment of neutrophils was increased by intestinal I/R, but decreased by mepacrine. Simultaneously, the number of leukocytes in bronchoalveolar fluid was increased by intestinal ischemia/reperfusion (I/R) and decreased by mepacrine. Gamma glutamyl transferase activity, an index of oxidative stress in the lung, was increased after intestinal I/R but decreased by mepacrine, which implicates that $PLA_2$ increases oxidative stress caused by intestinal I/R. The $PLA_2$ activity was increased after intestinal I/R not only in the intestine but also in the lung. These changes were diminished by mepacrine. In the cytochemical electron microscopy to detect hydrogen peroxide, intestinal I/R increased the generation of the hydrogen peroxide in the lung as well as in the intestine. Expression of interleukin-1 (IL-1) in the lung was investigated through RT-PCR. The expression of IL-1 after intestinal I/R was enhanced, and again, the inhibition of $PLA_2$ suppressed the expression of IL-1 in the lung. Taken together, intestinal I/R seems to induce acute lung leak through the activation of $PLA_2$, the increase of IL-1 expression associated with increased oxidative stress by neutrophilic respiratory burst.

• Journal of Digestive Cancer Reports
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• v.7 no.1
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• pp.26-30
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• 2019

Pancreatic cancer has a very poor prognosis. Complete surgical resection remains the only current curative treatment. Locally advanced pancreatic cancer (LAPC) is considered as unresectable because of involvement of celiac and/or mesenteric vessels. The treatment of LAPC is a challenge. Current guidelines suggest systemic therapy. However, the majority of patients will never experience conversion to surgical resection. Thus, in these patients, ablation is an alternative therapy for local control, which causes local destruction while ideally avoiding injury to surrounding healthy tissue. Irreversible electroporation (IRE) is an energy delivery system, effective in ablating tumors by inducing irreversible membrane destruction of cells. IRE demonstrated to be safe in previous studies. However, it is not free from complications, even serious. Here, we reported two cases of the IRE in LAPC patients.

• Journal of Digestive Cancer Research
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• v.5 no.1
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• pp.23-27
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• 2017

Although laparoscopic pancreaticoduodenectomy (LPD) is considered as minimally invasive surgery, an advanced level of laparoscopic skill is still required. LPD comprises various procedures including reconstruction. Therefore, establishment of a safe approach at each step is needed. Prevention of intraoperative bleeding is the most important factor in safe completion of LPD. The establishment of effective retraction methods is also important at each site to prevent vascular injury. I also recommend the "uncinate process first" approach during initial cases of LPD, in which the branches of the inferior pancreaticoduodenal artery are dissected first, at points where they enter the uncinate process. This approach is performed at the left side of the superior mesenteric artery (SMA) before isolating the pancreatic head from the right aspect of the SMA, which allows safe dissection without bleeding. Safe and reliable reconstruction is also important to prevent postoperative complications. Laparoscopic pancreatojejunostomy requires highly skilled suturing technique. Pancreatojejunostomy through a small abdominal incision, as in hybrid-LPD, facilitates reconstruction. In LPD, the surgical view is limited. Therefore, we must carefully verify the position of the pancreaticobiliary limb. A twisted mesentery may cause severe congestion of the pancreaticobiliary limb following reconstruction, resulting in severe complications. We must secure the appropriate position of the pancreaticobiliary limb before starting reconstruction. We describe the incidence of intraoperative and postoperative complications and appropriate technique for safe performance of LPD.

• Tuberculosis and Respiratory Diseases
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• v.54 no.5
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• pp.532-541
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• 2003

Background : Phospholipase $A_2$ ($PLA_2$) has been known to be involved in the pathogenesis of acute lung injury (ALI) including ARDS. Since doxycycline has the property of inhibiting secretory group II $PLA_2$, the therapeutic effect of doxycycline hyclate was investigated for gut ischemia/reperfusion (I/R)-induced ALI in Sprague-Dawley rats. Methods : ALI was induced in Sprague-Dawley rats by clamping of the superior mesenteric artery for 60 min, followed by 120 min of reperfusion. To confirm the pathogenetic mechanisms of this ALI associated with neutrophilic oxidative stress, we measured bronchoalveolar lavage (BAL) protein content and lung MPO, and performed cyto-chemical electron microscopy for detection of free radicals, assay of $PLA_2$ activity and cytochrome-c reduction assay. Results : In gut I/R-induced ALI rats, protein leakage, pulmonary neutrophil accumulation, free radical production and lung $PLA_2$ activity were all increased. These effects were reversed by doxycycline hyclate. Conclusion : Doxycycline appears to be effective in ameliorating the gut I/R-induced ALI by inhibiting $PLA_2$, thereby decreasing the production of free radicals from neutrophils.

• Animal Bioscience
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• v.35 no.8
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• pp.1235-1249
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• 2022

Objective: The purpose of this study was to evaluate the protection of glutamate (GLU) against the impairment in intestinal barrier function induced by lipopolysaccharide (LPS) stress in weaned pigs. Methods: Twenty-four weaned pigs were divided into four treatments containing: i) non-challenged control, ii) LPS-challenged control, iii) LPS+1.0% GLU, and iv) LPS+2.0% GLU. On day 28, pigs were treated with LPS or saline. Blood samples were collected at 0, 2, and 4 h post-injection. After blood samples collection at 4 h, all pigs were slaughtered, and spleen, mesenteric lymph nodes, liver and intestinal samples were obtained. Results: Dietary GLU supplementation inhibited the LPS-induced oxidative stress in pigs, as demonstrated by reduced malondialdehyde level and increased glutathione level in jejunum. Diets supplemented with GLU enhanced villus height, villus height/crypt depth and claudin-1 expression, attenuated intestinal histology and ultrastructure impairment induced by LPS. Moreover, GLU supplementation reversed intestinal intraepithelial lymphocyte number decrease and mast cell number increase induced by LPS stress. GLU reduced serum cortisol concentration at 4 h after LPS stress and downregulated the mRNA expression of intestinal corticotropin-releasing factor signal (corticotrophin-releasing factor [CRF], CRF receptor 1 [CRFR1], glucocorticoid receptor, tryptase, nerve growth factor, tyrosine kinase receptor A), and prevented mast cell activation. GLU upregulated the mRNA expression of intestinal transforming growth factor β. Conclusion: These findings indicate that GLU attenuates LPS-induced intestinal mucosal barrier injury, which is associated with modulating CRF signaling pathway.

• Journal of Chest Surgery
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• v.35 no.7
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• pp.501-510
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• 2002

Background: The various pathogeneses of acute respiratory distress syndrome have been suggested but not established yet. In the present study, the role of group II phospholipase $A_2$($PLA_2$) in the pathogenesis of gut ischemia-reperfusion(I/R) induced acute lung injury (ALI), especially in the pulmonary oxidative stress with infiltration of neutrophils was investigated. Material and Method: To induce ALI, reperfusion of mesentery was done for 120 min after clamping of superior mesenteric artery for 60 min in Sprague-Dawley rats that weighed about 300g. To exmaine the role of group II $PLA_2$ in ALI, especially endothelial injury associated with the action of neutrophils, lung myeloperoxidase activity, lung leak index, bronchoalveolar lavage fluid protein were measured, and pulmonary $PLA_2$ activity changes in gut I/R were also measured. The role of group II $PLA_2$in the neutrophilic generation of free radicals was assessed by inhibiting group II $PLA_2$ with rutin, manoalide and scalaradial. Furthermore, to verify the oxidative stress in the lung, histologic and free radical detecting cytochemical electron microscopy were done. Result: After reperfusion, ALI was developed with accumulation of neutrophils in the lung, which was confirmed by the increase of myeloperoxidase activity, lung leak index and bronchoalveolar lavage protein (p<0.001). The pulmonary and intestinal group II $PLA_2$ activities significantly increased after gut I/R which were reversed by rutin(p<0.001). In vitro, cytochrome-c reduction assay denoted the inhibitory effects of rutin, scalaradial and manoalide on the production of free radicals from isolated human neutrophils. Histologically, neutrophilic accumulation and pericapillary edema in the lung after gut I/R was detected by light microscopy which was suppressed by rutin. In $CeCl_3$ cytochemical electron microscopy, the increased production of hydrogen peroxide in the lung after gut I/R was confirmed and also the production of hydrogen peroxide was decreased by rutin. Conclusion: On the basis of these experimental results, the inhibition of group II $PLA_2$ seemed to mitigate gut I/R-induced ALI by suppressing the production of free radicals from the infiltrated neutrophils. Collectively, group II $PLA_2$ seems to play a crucial role in gut I/R-induced ALI by neutrophilic oxidative stress.

• Advances in pediatric surgery
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• v.10 no.1
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• pp.1-8
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• 2004

A re-pull-through operation for Hirschsprung's disease is performed when the primary operation has failed because of the remnant or acquired aganglionosis, anastomotic stricture and/or fistula. The purpose of this study is to review our experience of the re-pull-through procedure for Hirschsprung's disease. From May 1978 to July 2003, 26 patients who underwent re-pull-through operations at the Department of Pediatric Surgery, Seoul National University Children's Hospital, were studied retrospectively by means of chart review as well as telephone interview. The mean age at primary operation and re-operation were llmonths (2 months - 10 years) and 43 months (1 year - 23 years 3 months), respectively. Initial operation for Hirschsprung's disease was Duhamel's procedure in 17, Swenson's in 6 and Soave's 3. Causes of failure of primary operation were remains of secondary aganglionic segment (n=23), vascular arcade injury (n= 1), rectoperineal fistula (n=2, due to mesenteric torsion and poor blood supply), Mean interval between the primary operation and the re-operation was 34 months (6 months-22 years). Reoperation methods were Soave's in 12, Duhamel's in 8, APSP (abdomino-posterosagittal pull-through procedure) in 5, and Swenson's in 1 case. In 2 cases of repeated rectoperineal fistula or rectourethral fistula, re-APSP were performed 3 times, respectively. A total of 29 re-pull-through operations were performed. Postoperative complications were wound infection (n=1), adhesive ileus (n=1), rectoperineal fistula (n=3), rectourethral fistula (n=2), and death due to pulmonary embolism (n=1). Mean follow up period of reoperation was 78 months (1 month-23years). In current state, 2 patients have an ileostomy because of repeated rectoperineal fistula and rectourethral fistula. Of the remaining 23 patients, 21(91 %) are totally continent with or without minimal soiling. Reoperation for Hirschsprung's disease was effective and safe for the patients complicated to the initial pull-through operation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.1
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• pp.32-42
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• 2007

This study was conducted on the immunoregulatory effect of Saengshik on gut-associated lymphoid tissue with inflammatory bowel disease. Although the contents of IgA increased in mesenteric lymph node, IgE content was suppressed by Saengshik. The same results were found in spleen, but IgA and IgE responses were very weak. Concentration of fecal IgA was high from the first day through the third day in Saengshik group. In DSS + Saengshik group, concentration of IgA was high till the 2nd day and it maintained the highest level among the test groups on 5th day. Concentration of IFN-gamma and IL-2 was the highest in the Saengshik group, but the concentration of TNF-alpha was lower in DSS + Saengshik compared to DSS. The expressions of STAT1 in Saengshik group were high, while those of STAT6 were low According to these findings, Saengshik exhibited effectiveness via increasing the IgA production, suppressing the IgE production, followed by inhibiting the production of IL-4 and IL-10. Saengshik also strengthened the immune system and alleviated injury in DSS -induced inflammation.