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1.
Nihon Ronen Igakkai Zasshi ; 52(4): 411-4, 2015.
Article in Japanese | MEDLINE | ID: mdl-26700781

ABSTRACT

A 79-year-old man with a history of gastrectomy with Billroth II reconstruction 27 years previously was admitted to our hospital due to recurrent pneumonia. Because he had dysphagia and had frequently developed pneumonia over the course of a year, enteral nutrition via nasogastric tube was initiated approximately six months before admission. The clinical and computed tomography findings showed that the cause of pneumonia was aspiration of tube feeding nutrients due to gastroesophageal reflux. To prevent gastroesophageal reflux, he was continuously kept in a 30-degree or greater reclining position. However, gastroesophageal reflux was seen at an injection rate of 50 ml/h or greater. After we inserted a nasogastric-jejunal feeding tube guided by endoscopy, gastroesophageal reflux, dumping syndrome and diarrhea were not seen up to an injection rate of 300 ml/h. Endoscopically guided nasogastric-jejunal feeding tube placement is a simple method and may be useful for patients with aspiration pneumonia due to postgastrectomy. Moreover, long-term postgastrectomy patients appear to tolerate the postopyloric injection of enteral nutrition. Because the number of elderly patients who have dysphagia with postgastrectomy is increasing, these findings provide a basis for treatment in elderly medical settings.


Subject(s)
Enteral Nutrition , Gastrectomy/adverse effects , Pneumonia, Aspiration/etiology , Aged , Deglutition Disorders/etiology , Endoscopy, Gastrointestinal , Humans , Male
2.
Gan To Kagaku Ryoho ; 40(13): 2525-8, 2013 Dec.
Article in Japanese | MEDLINE | ID: mdl-24335363

ABSTRACT

PURPOSE: We have reported, in a randomized, controlled study, that tegafur-uracil(UFT)and protein-bound polysaccharide K(PSK)combination therapy significantly improves the 5-year disease-free survival rate and reduces the risk of recurrence compared to UFT alone for Stage II or III colorectal cancer. In this study, we examined the efficacy of PSK by stratifying patients according to the preoperative lymphocyte ratio(Lym). METHODS: In a randomized, controlled study, 205 patients were eligible(137 in the UFT/PSK group and 68 in the UFT group). Of these, 193 patients with available preoperative Lym data were analysed(131 in the UFT/PSK group and 62 in the UFT group). RESULTS: Among patients with a preoperative Lym of <35%, the relapse-free survival(RFS)rate was 76.5% in the UFT/PSK group and 55.8% in the UFT group(p=0.008). However, in patients with a preoperative Lym of ≥35%, the RFS rate did not differ between the 2 groups. Similarly, overall survival was significantly higher in the UFT/PSK group than in the UFT group in patients with a preoperative Lym of <35%, whereas no intergroup difference was found among patients with a preoperative Lym of ≥35%. CONCLUSION: This study suggests that a low preoperative Lym is a good predictor for response to PSK in patients with Stage II or III colorectal cancer.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Administration, Oral , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Combined Modality Therapy , Humans , Lymphocyte Count , Neoplasm Staging , Polysaccharides/administration & dosage , Prognosis , Tegafur/administration & dosage , Uracil/administration & dosage
3.
Surg Laparosc Endosc Percutan Tech ; 23(6): 536-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24300932

ABSTRACT

BACKGROUND: The mesenteric vessels have many branching patterns. This study clarified the anatomic relationship between the superior mesenteric vein (SMV), the right colic artery (RCA), and the ileocolic artery (ICA) using 3-dimensional computed tomography (3D-CT). The relationship between the RCA and the right colic vein (RCV) was also examined. METHODS: Between April 2006 and July 2011, all patients with colorectal cancer underwent multidetector computed tomography (MDCT) before laparoscopic surgery. The 100 most recent consecutive cases were analyzed. 3D-CT images were made by combining arterial angiography, venous angiography, colonography, tumor, lymph node, and duodenal images. RESULTS: The RCA branched from the SMA in 37 cases (37%); of these, 21 had an ICA that crossed anterior to the SMV and 16 had an ICA that crossed posterior. When the ICA crossed anterior to the SMV, all had an RCA that crossed anterior to the SMV, and no posterior RCA was seen. Furthermore, the RCV joined the SMV in 10 cases (27%) and the gastrocolic trunk in 27 cases (73%). CONCLUSIONS: Our study clarified the anatomic variety of the vessels in right-sided colon cancer. Preoperative 3D-CT is useful for understanding the anatomy to ensure a safe, precise operation.


Subject(s)
Colonic Neoplasms/blood supply , Colonic Neoplasms/surgery , Imaging, Three-Dimensional , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Colonic Neoplasms/diagnostic imaging , Female , Humans , Male , Mesenteric Artery, Superior/anatomy & histology , Mesenteric Veins/anatomy & histology , Middle Aged
4.
Gan To Kagaku Ryoho ; 40(1): 91-3, 2013 Jan.
Article in Japanese | MEDLINE | ID: mdl-23306926

ABSTRACT

A 70-year-old female presented with epigastralgia. Gastrointestinal endoscopic examination showed advanced gastric cancer type 2. Computed tomography(CT)showed a liver tumor of 37mm in segment 6. She was treated with oral S-1, 80 mg/body for 14 days, followed by a 7-day rest, and CDDP 20mg/m2(day 1 and 8). After ten courses of treatment, CT showed reduction of the primary cancer, the liver tumor, and the affected lymph nodes. Then, distal gastrectomy, lymph node dissection, and partial liver resection were performed. The histological diagnosis was no viable cancer cells found in stomach, liver or lymph nodes. One year and 1 month postoperatively, the patient is alive without recurrence.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Liver Neoplasms/drug therapy , Stomach Neoplasms/drug therapy , Aged , Cisplatin/administration & dosage , Combined Modality Therapy , Drug Combinations , Female , Humans , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Oxonic Acid/administration & dosage , Remission Induction , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Tegafur/administration & dosage
5.
Gan To Kagaku Ryoho ; 39(6): 993-5, 2012 Jun.
Article in Japanese | MEDLINE | ID: mdl-22705700

ABSTRACT

A 50-year-old woman was diagnosed with ascending colon cancer with bilateral ovarian metastases, carcinomatous peritonitis, and carcinomatous pleurisy. Nine courses of mFOLFOX6 treatment resulted in the disappearance of her ascites and pleural effusion and a marked decrease in her serum CEA and CA19-9 levels. Additionally, the primary tumor and ovarian metastases became smaller. Therefore, a right hemicolectomy with D3 lymph node dissection, total hysterectomy, and bilateral salpingo-oophorectomy were performed. Postoperatively, we changed the chemotherapy from mFOLFOX6 to bevacizumab+FOLFIRI because the patient had an allergic reaction to oxaliplatin, and we suspected lung metastasis. Because the lung metastasis grew after ten courses of bevacizumab+FOLFIRI, we changed to cetuximab+FOLFIRI. Unfortunately, 28 months after her diagnosis, the patient died of carcinomatous pleurisy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Colonic Neoplasms/pathology , Fatal Outcome , Female , Fluorouracil/therapeutic use , Humans , Leucovorin/therapeutic use , Middle Aged , Neoplasm Grading , Organoplatinum Compounds/therapeutic use , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/secondary , Peritoneal Neoplasms/secondary
6.
Gan To Kagaku Ryoho ; 39(2): 273-5, 2012 Feb.
Article in Japanese | MEDLINE | ID: mdl-22333642

ABSTRACT

We present a case of a 59-year-old female who was admitted to our hospital for upper abdominal pain. She was diagnosed with pancreatic body carcinoma by computed tomography and magnetic resonance imaging. We started gemcitabine+S-1 chemotherapy because the tumor had invaded the celiac trunk, common hepatic artery, superior mesenteric vein, and splenic vein. We reduced the S-1 to 100mg/body after the third course of gemcitabine(1, 000mg/m2 on days 1 and 8, every 21 days)+S-1(120mg/body on days 1-14, every 21 days)because of side effects. The tumor became smaller, and the celiac trunk and common hepatic artery were released. Thus, we conducted a distal pancreatectomy with a D2 lymph node dissection.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Celiac Artery/pathology , Hepatic Artery/pathology , Liver/blood supply , Pancreatic Neoplasms/drug therapy , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Drug Combinations , Female , Humans , Middle Aged , Neoadjuvant Therapy , Neoplasm Invasiveness , Oxonic Acid/administration & dosage , Pancreatic Neoplasms/blood supply , Pancreatic Neoplasms/surgery , Tegafur/administration & dosage , Tomography, X-Ray Computed , Gemcitabine
7.
Nihon Shokakibyo Gakkai Zasshi ; 108(8): 1413-9, 2011 08.
Article in Japanese | MEDLINE | ID: mdl-21817845

ABSTRACT

A 26-year-old man was admitted to our hospital because of a high-grade fever and abdominal pain. A blood test showed marked inflammation. Enhanced computed tomography (CT) showed an 8.0×6.0cm cystic lesion in the left hepatic lobe. Esophagogastroduodenoscopy showed a huge egg-yolk-like mass in the gastric submucosa in the lesser curvature of the gastric body from the gastric angle. There were 3 ulcers on the mass, out of which milky pus flowed. Trophozoites of Entamoeba histolytica were detected from cultures of the liver abscess and a biopsy of the gastric ulcers. The amoebic dysentery antibody titer was increased 1600 times. An amoebic liver abscess complicated by a gastric fistula was diagnosed. As therapy, oral metronidazole was administered for 2 weeks without percutaneous drainage. The systemic inflammatory findings improved immediately and the abscess decreased markedly in size.


Subject(s)
Antiprotozoal Agents/administration & dosage , Gastric Fistula/drug therapy , Gastric Fistula/etiology , Liver Abscess, Amebic/complications , Liver Abscess, Amebic/drug therapy , Metronidazole/administration & dosage , Administration, Oral , Adult , Humans , Male
8.
Gan To Kagaku Ryoho ; 38(7): 1187-9, 2011 Jul.
Article in Japanese | MEDLINE | ID: mdl-21772109

ABSTRACT

A n 83-year-old male presented with a leg edema. Gastrointestinal endoscopic examination showed advanced gastric cancer type 2, which was diagnosed as mod~well-differentiated adenocarcinoma. Computed tomography (CT) showed enlarged multiple lymph nodes. He was treated with oral S-1, 80 mg/day for 14 days, followed by a 7-day rest. After two courses of treatment, CT showed reduction of the lymph nodes. After 8 courses of treatment, total gastrectomy and lymph node dissection were performed. The histological diagnoses were tub 2>tub 1, pSS, pN0, pStage I B. One year and 10 months postoperatively, the patient is alive without recurrence.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Oxonic Acid/therapeutic use , Stomach Neoplasms/drug therapy , Tegafur/therapeutic use , Aged , Biopsy , Combined Modality Therapy , Drug Combinations , Humans , Lymphatic Metastasis , Male , Remission Induction , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery
9.
Gan To Kagaku Ryoho ; 38(4): 659-62, 2011 Apr.
Article in Japanese | MEDLINE | ID: mdl-21499000

ABSTRACT

A 6 3-year-old male presented with dysphagia. Gastrointestinal endoscopic examination showed advanced gastric cancer type 3, which was diagnosed as well-differentiated adenocarcinoma. Computed tomography(CT)showed bilateral lung tumors, hugely enlarged Virchow and para-aortic lymph nodes. He was treated with combination chemotherapy of weekly paclitaxel(PTX)and doxifluridine(5'-DFUR). PTX was administered at a dose of 80mg/m2 on day 1, 8 and 15, and 5'- DFUR was orally administered at a dose of 533mg/m / 2day for 5 days followed by withdrawal for 2 days. After four courses of treatment, CT showed an almost complete disappearance of the lung and lymph node metastases. After 13 courses of treatment, total gastrectomy and lymph node dissection were performed. One year postoperatively, the patient died of a recur- rence.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Aorta/pathology , Floxuridine/therapeutic use , Lung Neoplasms/drug therapy , Paclitaxel/therapeutic use , Stomach Neoplasms/drug therapy , Combined Modality Therapy , Fatal Outcome , Floxuridine/administration & dosage , Gastrectomy , Humans , Lung Neoplasms/secondary , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Paclitaxel/administration & dosage , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Tomography, X-Ray Computed
10.
Gan To Kagaku Ryoho ; 37(3): 517-20, 2010 Mar.
Article in Japanese | MEDLINE | ID: mdl-20332695

ABSTRACT

A 64-year-old female presented with a left cervical tumor. Gastrointestinal endoscopic examination showed advanced gastric cancer type 3, which was diagnosed as poorly-differentiated adenocarcinoma. Computed tomography (CT) showed hugely enlarged Virchow and para-aortic lymph nodes. She was treated with oral S-1, 100 mg/day for 28 days, followed by a 2-week rest. After two courses, S-1 was administered for 14 days followed by a 7-day rest because of side effects. After five courses of treatment, CT showed complete disappearance of the lymph node metastases. Total gastrectomy and lymph node dissection were performed. The histology was judged as Grade 2. The residual cancer in the stomach was only 2mm in size, and there were no viable cancer cells in any lymph nodes. One year postoperatively, the patient is alive without recurrence.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Lymphatic Metastasis/pathology , Oxonic Acid/therapeutic use , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Tegafur/therapeutic use , Drug Combinations , Female , Gastrectomy , Humans , Lymph Node Excision , Lymphatic Metastasis/diagnostic imaging , Middle Aged , Radiography
11.
Gan To Kagaku Ryoho ; 36(1): 115-8, 2009 Jan.
Article in Japanese | MEDLINE | ID: mdl-19151575

ABSTRACT

A 68-year-old man underwent total gastrectomy for Type 3 gastric cancer with liver metastasis. The final finding was T3(SE), N1, H1, P0, CY0(class IV), Stage IV, Cur C. After surgery, he was treated with combination chemotherapy of weekly paclitaxel(PTX)/doxifluridine(5'-DFUR). Paclitaxel was administered at a dose of 80 mg/m(2) on day 1, 8 and 15, and doxifluridine was orally administered at a dose of 533 mg/m(2) day for five days followed by withdrawal for two days. This regimen was repeated every four weeks. After 2 courses, the tumor marker level normalized, and the size of the liver metastasis was remarkably decreased. After 5 courses, a CT scan revealed the liver metastasis had disappeared, and he has now survived without recurrence after the disappearance of the liver metastasis. No severe adverse reactions were observed, and the man can be treated as an outpatient. This therapy may thus be effective in the treatment of advanced gastric cancer following non-curative operation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Floxuridine/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Paclitaxel/therapeutic use , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers, Tumor/blood , Floxuridine/adverse effects , Humans , Liver Neoplasms/blood , Liver Neoplasms/diagnostic imaging , Male , Neoplasm Staging , Paclitaxel/adverse effects , Remission Induction , Stomach Neoplasms/blood , Stomach Neoplasms/surgery , Tomography, X-Ray Computed , Treatment Outcome
12.
World J Gastroenterol ; 13(25): 3487-92, 2007 Jul 07.
Article in English | MEDLINE | ID: mdl-17659696

ABSTRACT

AIM: To evaluate the effect of ANP on warm I/R injury in a porcine THVE model. METHODS: Miniature pigs (mini-pigs) weighing 16-24 kg were observed for 120 min after reperfusion following 120 min of THVE. The animals were divided into two groups. ANP (0.1 mug/kg per min) was administered to the ANP group (n = 7), and vehicle was administered to the control group (n = 7). Either vehicle or ANP was intravenously administered from 30 min before the THVE to the end of the experiment. Arterial blood was collected to measure AST, LDH, and TNF-alpha. Hepatic tissue blood flow (HTBF) was also measured. Liver specimens were harvested for p38 MAPK analysis and histological study. Those results were compared between the two groups. RESULTS: The AST and LDH levels were lower in the ANP group than in the control group; the AST levels were significantly different between the two groups (60 min: 568.7 +/- 113.3 vs 321.6 +/- 60.1, P = 0.038 < 0.05, 120 min: 673.6 +/- 148.2 vs 281.1 +/- 44.8, P = 0.004 < 0.01). No significant difference was observed in the TNF-alpha levels between the two groups. HTBF was higher in the ANP group, but the difference was not significant. A significantly higher level of phosphorylated p38 MAPK was observed in the ANP group compared to the control group (0 min: 2.92 +/- 1.1 vs 6.38 +/- 1.1, P = 0.011 < 0.05). Histological tissue damage was milder in the ANP group than in the control group. CONCLUSION: Our results show that ANP has a protective role in I/R injury with p38 MAPK activation in a porcine THVE model.


Subject(s)
Atrial Natriuretic Factor/therapeutic use , Ischemia/drug therapy , Liver/blood supply , Reperfusion Injury/prevention & control , Alanine Transaminase/blood , Animals , Female , Ischemia/metabolism , Ischemia/pathology , L-Lactate Dehydrogenase/blood , Male , Swine , Tumor Necrosis Factor-alpha/blood , p38 Mitogen-Activated Protein Kinases/analysis , p38 Mitogen-Activated Protein Kinases/physiology
13.
J Heart Lung Transplant ; 25(8): 965-71, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16890118

ABSTRACT

BACKGROUND: Free radical scavengers and superoxide dismutase have been found to protect against cerebral ischemic damage, and it was suggested that oxygen free radicals contribute to ischemia-reperfusion injury induced by cerebral ischemic damage. MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent scavenger and inhibitor of hydroxyl radicals and protective agent of peroxidative injury. The purpose of this study was to evaluate the effects of MCI-186 on pulmonary ischemia-reperfusion injury in a simulated transplanted lung model. METHODS: Fourteen dogs were divided into two groups (n = 7 each). In the MCI group, MCI-186 was continuously administered at 3 mg/kg/hour intravenously (IV) from 30 minutes before reperfusion until 30 minutes after reperfusion (total administration time 1 hour). Vehicle was administered in the control group. Warm ischemia was induced for 3 hours by clamping the left pulmonary artery and veins. Simultaneously, the left stem bronchus was bisected and then anastomosed before reperfusion. The right pulmonary artery was ligated 15 minutes after reperfusion, and the right stem bronchus was then bisected. RESULTS: The respiratory gas exchange, hemodynamic changes, wet-to-dry weight ratio (WDR) and malondialdehyde (MDA) concentration in the tissue were significantly improved (p < 0.05) in the MCI group. The histologic damage was more severe in the control group and polymorphonuclear neutrophil (PMN) infiltration was reduced in the MCI group. CONCLUSION: MCI-186 has a protective effect on pulmonary ischemia-reperfusion injury through the inhibition of lipid peroxidation.


Subject(s)
Antipyrine/analogs & derivatives , Free Radical Scavengers/therapeutic use , Lung Transplantation/adverse effects , Lung/blood supply , Reperfusion Injury/drug therapy , Reperfusion Injury/etiology , Animals , Antipyrine/therapeutic use , Dogs , Edaravone
14.
Hepatogastroenterology ; 52(65): 1545-8, 2005.
Article in English | MEDLINE | ID: mdl-16201115

ABSTRACT

BACKGROUND/AIMS: In liver surgery, total clamping of the portal triad (Pringle's procedure) is commonly used, and this sometimes causes liver failure. This study evaluated the effects of a free radical scavenger, MCI-186, on ischemia-reperfusion injury during liver resection in dogs. METHODOLOGY: The experimental animals were divided into two groups. In the MCI group (n = 6), MCI-186 (6mg/kg/h) was administered twice, through a catheter placed in the right hepatic vein: the first time was from 0.5 hours before the onset of ischemia until ischemia by partial inflow occlusion, and the second was from 0.5-hours before reperfusion until reperfusion. In the control group (n = 6), vehicle (physiological saline) was administered in the same manner. RESULTS: The serum AST, ALT, and LDH levels were significantly (P < 0.05) lower in the MCI group than in the control group. Hepatic tissue blood flow 0.5 hours after reperfusion was significantly (P < 0.05) higher in the MCI group than in the control group. Histological tissue damage was mild, and tissue MDA levels were significantly (P < 0.05) lower in the MCI group than in the control group. CONCLUSIONS: MCI-186 ameliorates the ischemia-reperfusion injury caused by Pringle's procedure during extended liver resection.


Subject(s)
Antipyrine/analogs & derivatives , Free Radical Scavengers/therapeutic use , Hepatectomy , Reperfusion Injury/drug therapy , Animals , Antipyrine/therapeutic use , Dogs , Edaravone , Lipid Peroxidation , Liver/blood supply , Microcirculation , Reperfusion Injury/physiopathology
15.
Hepatogastroenterology ; 52(64): 1143-6, 2005.
Article in English | MEDLINE | ID: mdl-16001648

ABSTRACT

Protein-losing gastropathy due to diffuse varioliform gastritis is a rare condition, and its occurrence accompanying ampullary carcinoma is particularly rare. We report here a case of ampullary carcinoma accompanied with protein-losing gastroenteropathy due to diffuse varioliform gastritis. A 39-year-old Japanese woman was admitted to our hospital because of general fatigue and generalized edema. Her total protein level was 3.1g/dL, with an albumin level of 1.4g/dL, and hemoglobin level of 6.9g/dL. Upper gastrointestinal endoscopic examination showed diffuse varioliform gastritis and carcinoma of the papilla of Vater. A diagnosis of protein-losing gastropathy was made based on the results of scintigraphy using technetium 99m-labeled human albumin. Continuous bleeding from ampullary carcinoma caused anemia and deteriorated hypoproteinemia. Pancreaticoduodenectomy was performed for ampullary carcinoma prior to Helicobacter pylori eradication. The tumor was a papillary adenocarcinoma, which had invaded the lamina muscularis propria over the sphincter of Oddi; the resected stomach revealed typical hyperplastic lymphocytic gastritis. H. pylori were detected on microscopic analysis. Scintigraphy after surgery showed no accumulation of the tracer in the bowel. Anemia, hypoalbuminemia and diffuse varioliform gastritis are improved 6 months after surgery and H. pylori eradication, and the patient is currently free from disease.


Subject(s)
Adenocarcinoma, Papillary/complications , Ampulla of Vater , Common Bile Duct Neoplasms/complications , Gastritis, Hypertrophic/pathology , Protein-Losing Enteropathies/etiology , Adenocarcinoma, Papillary/diagnosis , Adenocarcinoma, Papillary/surgery , Adult , Common Bile Duct Neoplasms/diagnosis , Common Bile Duct Neoplasms/surgery , Female , Gastritis, Hypertrophic/complications , Gastritis, Hypertrophic/microbiology , Helicobacter Infections/diagnosis , Helicobacter Infections/therapy , Helicobacter pylori , Humans , Pancreaticoduodenectomy , Protein-Losing Enteropathies/diagnosis
16.
Dig Dis Sci ; 50(1): 27-36, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15712633

ABSTRACT

Bradykinin mediates acute inflammation by increasing microvascular permeability, vasodilation, leukocyte migration and accumulation, and the production of arachidonic acid via phospholipase A2 activation. Arachidonic acid metabolites, or eicosanoids, are potent modulators of biological functions, particularly inflammation. Bradykinin exerts its inflammatory effects via the bradykinin B2 receptor. The aim of this study was to evaluate the effect of a bradykinin B2 receptor antagonist, FR173657 (FR), on intestinal ischemia-reperfusion (I/R) injury. Twenty-eight mongrel dogs were divided into four groups (n = 7 per group). Group I underwent I/R alone, Group II underwent I/R and received FR treatment, Group III was sham operated, and Group IV was sham operated and received FR treatment. The FR treatment consisted of FR continuously from 30 min prior to ischemia to 2 hr after reperfusion. In the I/R procedure, the superior mesenteric artery (SMA) and vein were clamped for 2 hr and then released to permit reperfusion for 12 hr. The intramucosal pH (pHi), SMA blood flow, and mucosal tissue blood flow were measured during the reperfusion period. The serum thromboxane B2 and 6-keto-prostaglandin F1alpha levels were determined, and tissue samples were examined histologically. Results showed that tissue blood flow, pHi, and SMA blood flow after reperfusion were maintained in Group II in comparison with Group I. Histopathological examination showed less severe mucosal damage after reperfusion in Group II than in Group I. The serum thromboxane B2 and 6-keto-prostagland in F1alpha levels were significantly lower in Group II than in Group I (P < 0.05). We conclude that FR treatment appears to have clear protective effects on small bowel I/R injury by inhibiting the release of eicosanoids.


Subject(s)
Bradykinin B2 Receptor Antagonists , Intestine, Small/blood supply , Quinolines/pharmacology , Reperfusion Injury/physiopathology , 6-Ketoprostaglandin F1 alpha/blood , Animals , Dogs , Female , Hemodynamics/drug effects , Hydrogen-Ion Concentration , Intestinal Mucosa/blood supply , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Intestine, Small/pathology , Male , Mesenteric Artery, Superior/physiopathology , Regional Blood Flow/drug effects , Reperfusion Injury/blood , Thromboxane B2/blood
17.
Hepatogastroenterology ; 51(60): 1771-5, 2004.
Article in English | MEDLINE | ID: mdl-15532823

ABSTRACT

BACKGROUND/AIMS: In liver surgery, total clamping of the portal triad (Pringle's procedure) is commonly used, and sometimes causes liver failure. This study evaluated the effects of a bradykinin B2 receptor antagonist, FR173657 (FR), on ischemia-reperfusion injury during liver resection in dogs. METHODOLOGY: Experimental animals were divided into two groups. In the FR group (n=6), FR (100 nmol/kg/hr) was administered continuously via the portal vein from 30 min before the onset of ischemia until 2 hr after reperfusion. In the control group (n=6), vehicle was injected in the same manner. The right portal pedicle was clamped for 60 min, while the left portal branch was left patent to avoid portal congestion. Following reperfusion, the non-ischemic lobes were resected, and remnant liver function was evaluated. RESULTS: AST and ALT were significantly (p<0.05) lower in the FR group than in the control group. Hepatic tissue blood flow 30 min after reperfusion was significantly (p<0.05) higher in the FR group than in the control group. Histological tissue damage was mild, and polymorphonuclear neutrophil infiltration was significantly (p<0.05) reduced in the FR group compared with the control group. CONCLUSIONS: A bradykinin B2 receptor antagonist ameliorated the ischemia-reperfusion injury caused by Pringle's procedure during extended liver resection.


Subject(s)
Hepatectomy/adverse effects , Ischemia/prevention & control , Liver/blood supply , Receptor, Bradykinin B2/administration & dosage , Reperfusion Injury/prevention & control , Analysis of Variance , Animals , Biopsy, Needle , Disease Models, Animal , Dogs , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Hepatectomy/methods , Immunohistochemistry , Infusions, Intravenous , Intraoperative Care , Ischemia/pathology , Liver Circulation/drug effects , Male , Probability , Random Allocation , Reference Values , Risk Factors , Sensitivity and Specificity , Statistics, Nonparametric
18.
J Heart Lung Transplant ; 23(5): 606-13, 2004 May.
Article in English | MEDLINE | ID: mdl-15135378

ABSTRACT

BACKGROUND: This study investigated the effects of a bradykinin B(2) receptor antagonist, FR173657 (FR), on ischemia-reperfusion (I/R) injury in a canine lung transplantation model. METHODS: Eighteen pairs of weight-matched dogs were randomly divided into 3 groups. Six pairs were assigned to the FR(D+R) group, in which FR (100 nmol/kg/h) was administered to the transplant donor continuously beginning 30 minutes before ischemia until the onset of ischemia, and FR was administered to the transplant recipient beginning 30 minutes before reperfusion and continuing for 2 hours after reperfusion. Another 6 pairs of dogs were assigned to the FR(R) group, in which FR was administered only to the recipient in the same manner as in the FR(D+R) group. The other pairs were assigned to the control group, in which vehicle alone was administered. Orthotopic left lung transplantation was performed after 12-hour cold storage in Euro-Collins solution. Fifteen minutes after reperfusion, the right pulmonary artery and the right stem bronchus were ligated. The animals were measured for 4 hours after reperfusion for left pulmonary vascular resistance (L-PVR), cardiac output (CO), arterial oxygen pressure (PaO(2)) and alveolar-arterial oxygen pressure difference (A-aD(O(2))). Lung specimens were harvested for measurement of the wet-to-dry lung weight ratio (WDR), histopathologic studies and polymorphonuclear neutrophil (PMN) count. RESULTS: Compared with the control group, PaO(2), A-aDO(2), L-PVR and CO were all significantly (p < 0.05) improved and WDR significantly (p < 0.05) lower in both the FR(D+R) and FR(R) groups. Moreover, in the FR-treated groups, histologic tissue edema was mild, and PMN infiltration was significantly (p < 0.05) reduced. CONCLUSIONS: The bradykinin B(2) receptor antagonist, FR173657, ameliorates I/R injury in lung grafts, indicating that protection of lung grafts can be achieved by the administration of FR solely to the transplant recipient.


Subject(s)
Bradykinin B2 Receptor Antagonists , Lung Transplantation , Lung/blood supply , Quinolines/pharmacology , Reperfusion Injury/physiopathology , Animals , Carbon Dioxide/analysis , Cardiac Output , Dogs , Hypertonic Solutions/pharmacology , Neutrophils/cytology , Organ Size , Partial Pressure , Quinolines/administration & dosage , Random Allocation
19.
J Heart Lung Transplant ; 21(9): 1022-9, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12231374

ABSTRACT

BACKGROUND: This study investigated the effects of a bradykinin B(2) receptor antagonist, FR173657 (FR), on pulmonary ischemia-reperfusion (I/R) injury. METHODS: Twenty-four mongrel dogs were divided into four groups (n = 6 each). In Groups I, II and III, FR doses of 33, 100 and 300 nmol/kg per hour, respectively, were administered continuously beginning 30 minutes before ischemia and continuing for 2 hours after reperfusion. In Group IV, vehicle alone was administered. Warm ischemia was induced for 3 hours by clamping the left pulmonary artery and veins. Simultaneously, the left stem bronchus was bisected and then anastomosed before reperfusion. Fifteen minutes after reperfusion, the right pulmonary artery and bronchus were ligated. Left pulmonary vascular resistance (L-PVR), cardiac output (CO), arterial oxygen pressure (PaO(2)) and the alveolar - arterial oxygen pressure difference (A-aDO2) were measured for 4 hours after reperfusion. Lung tissue was harvested for wet-to-dry weight ratio (WDR) measurements, histopathologic studies and polymorphonuclear neutrophil (PMN) counts. Serum thromboxane (TX) B(2), 6-keto-prostaglandin (PG) F(1alpha) and leukotriene (LT) B(4) levels were also measured. RESULTS: PaO(2), A-aDO2, L-PVR and CO were significantly (p < 0.05) improved and WDR was significantly (p < 0.05) lower in Groups II and III than in Group IV. Histologic tissue edema was mild, and PMN infiltration was significantly (p < 0.05) reduced in Groups I, II and III compared with Group IV. TXB(2) levels were significantly (p < 0.05) lower in Group II than in Group IV, whereas 6-keto-PGF(1alpha) levels were not significantly different. LTB(4) levels were significantly (p < 0.05) lower in Groups II and III than in Group IV. CONCLUSIONS: FR appears to have a protective effect on pulmonary I/R injury stemming from the inhibition of eicosanoid release.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Bradykinin Receptor Antagonists , Lung Diseases/immunology , Lung/drug effects , Quinolines/pharmacology , Reperfusion Injury/immunology , Animals , Dogs , Eicosanoids/metabolism , Lung Diseases/metabolism , Lung Diseases/pathology , Pulmonary Circulation/drug effects , Pulmonary Circulation/physiology , Pulmonary Gas Exchange/drug effects , Pulmonary Gas Exchange/physiology , Receptor, Bradykinin B2 , Reperfusion Injury/metabolism , Reperfusion Injury/pathology
20.
Transplantation ; 74(3): 320-6, 2002 Aug 15.
Article in English | MEDLINE | ID: mdl-12177609

ABSTRACT

BACKGROUND: The activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in the development of ischemia/reperfusion injury. FR167653 is a novel p38 MAPK inhibitor. This study evaluated the effects of p38 MAPK inhibition during cold ischemia on subsequent reperfusion injury using FR167653 as an additive to Euro-Collins solution in canine lung transplantation. METHODS: Canine orthotopic left lung transplantation was performed after 12-hr cold storage using Euro-Collins solution, with or without FR167653. Fifteen minutes after reperfusion, the right pulmonary artery and the right stem bronchus were ligated, and the animals were observed for 4 hr after reperfusion. Left pulmonary vascular resistance (L-PVR), cardiac output (CO), arterial oxygen pressure (Pao2), and alveolar-arterial oxygen pressure difference (A-aDo2) were measured. Lung specimens were harvested for wet-to-dry lung weight ratio (WDR) measurements, histopathologic studies, and polymorphonuclear neutrophil (PMN) counts. The activities of p38 MAPK in lung grafts were evaluated. RESULTS: The addition of FR167653 significantly (P<0.05) improved Pao2, A-aDo2, L-PVR, CO, and WDR and suppressed PMN infiltration after transplantation. FR167653 also ameliorated histologic damage to the lung graft. During cold storage, p38 MAPK was not activated in the lung graft, whereas it was markedly activated 30 min after reperfusion. FR167653 significantly (P<0.05) inhibited p38 MAPK activation 30 min after reperfusion. CONCLUSIONS: The addition of FR167653 to Euro-Collins solution improved lung graft viability associated with the inhibition of p38 MAPK activation. These results suggest that inhibiting p38 MAPK activation may attenuate ischemia/reperfusion injury in lung transplantation.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Enzyme Inhibitors/pharmacology , Hypertonic Solutions/pharmacology , Lung Transplantation/physiology , Lung , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Neutrophils/physiology , Organ Preservation Solutions/pharmacology , Pyrazoles/pharmacology , Pyridines/pharmacology , Reperfusion Injury/prevention & control , Transplantation, Homologous/physiology , Animals , Blood Pressure/drug effects , Blood Pressure/physiology , Dogs , Leukocyte Count , Lung/blood supply , Organ Preservation/methods , Oxygen/blood , Partial Pressure , Phosphorylation , Pulmonary Circulation/drug effects , Time Factors , Vascular Resistance/drug effects , p38 Mitogen-Activated Protein Kinases
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