Pharmacologic preconditioning effects: Prostaglandin E1 induces heat-shock proteins immediately after ischemia/reperfusion of the mouse liver

Prostaglandin E1 (PGE1) has several potential therapeutic effects, including cytoprotection, vasodilation, and inhibition of platelet aggregation. This study investigates the protective action of PGE1 against hepatic ischemia/reperfusion injury in vivo using a complementary DNA microarray. PGE1 or saline was continuously administered intravenously to mice in which the left lobe of the liver was made ischemic for 30 minutes and then reperfused. Livers were harvested 0, 10, and 30 minutes postreperfusion. Messenger RNA was extracted, and the samples were labeled with two different fluorescent dyes and hybridized to the RIKEN set of 18,816 full-length enriched mouse complementary DNA microarrays. Serum alanine aminotransferase and aspartate aminotransferase levels at 180 minutes postreperfusion were significantly lower in the PGE1-treated group than in the saline-treated group. The cDNA microarray analysis revealed that the genes encoding heat-shock protein (HSP) 70, glucose-regulated protein 78, HSP86, and glutathione S-transferase were upregulated at the end of the ischemic period (0 minutes postreperfusion) in the PGE1 group. Our results suggested that PGE1 induces HSPs immediately after ischemia reperfusion. HSPs might therefore play an important role in the protective effects of PGE1 against ischemia/reperfusion injury of the liver.     

Antiproliferative effects of NKH477, a forskolin derivative, on cytokine profile in rat lung allografts.

OBJECTIVE: NKH477 was recently identified as a water-soluble forskolin derivative and was reported to prolong survival of murine cardiac allografts. However, the mechanism of the efficacy is not clear in vivo. The aim of this study was to investigate the immunosuppressive effects of NKH477 on acute lung allograft rejection in the rat model and its mechanism of action in vivo. METHODS: Left lungs were transplanted orthotopically from Brown-Norway donors to Lewis recipients. Recipient rats were untreated or treated daily with different doses of NKH477. Grafts were excised on Day 3 or Day 5 to determine histopathological rejection and expressions of interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-gamma by enzyme-linked immunosorbent assay. The cytokine expression at Day 3 or Day 5 was also evaluated in recipient spleens by immunohistochemistry. Furthermore, mesenteric lymph node cells from recipients at Day 5 were cultured alone or stimulated with donor antigens for 72 hours to determine cell proliferation by means of thymidine incorporation. RESULTS: NKH477 significantly extended allograft survival time in a dose-dependent manner and reduced histopathological rejection. Treatment with NKH477 inhibited IFN-gamma and IL-10 expression, whereas expression of these cytokines were markedly upregulated in the untreated allografts. Expression of IL-2 and IL-10 also increased in the spleen of untreated allorecipients. NKH477 suppressed expression of both cytokines in the spleen. In addition, lymphocyte proliferation was inhibited in NKH477-treated recipients as compared with untreated recipients. CONCLUSION: These results suggest that NKH477 exerts an antiproliferative effect on lymphocytes in vivo with an altered cytokine profile in rat recipients of lung allografts.     

Endogenous bone-marrow-derived stem cells contribute only a small proportion of regenerated myocardium in the acute infarction model.

BACKGROUND: Our recent study showed that granulocyte-colony stimulating factor (G-CSF) promoted bone-marrow cells (BMC) to migrate into the infarcted heart and that they differentiated into cardiomyocytes. However, we still do not know to what degree bone-marrow-derived cardiomyocytes contribute to myocardial regeneration after injury. In this study, we verified the proportional contribution of cells from bone marrow (BM) and from non-bone marrow (n-BM) in regenerating neomyocardium after myocardial infarction. METHODS: Eight C57BL/6 mice were irradiated (900 cGy), and green fluorescent protein (GFP) mouse-derived BMCs (GFP-BMC, 1 x 10(6) cells) were injected. Four weeks later, the left descending coronary artery was ligated. Recombinant human G-CSF (200 microg/kg/day, 8 days) was injected. At 4 weeks after ligation, hearts were fixed for histology. We calculated the proportions of cardiomyocytes derived from BM and n-BM after taking the chimeric rate into consideration. RESULTS: The chimeric rate was 54.6% +/- 5.9%. At the infarcted border area, the total cell number was 1000.3 +/- 56.5/mm(2), and mobilized BM-derived GFP-BMC was 103.3 +/- 13.1/mm(2). After compensation with the chimeric rate, we found BM-derived troponin I-positive cells at 23.9 +/- 4.1/mm(2), nestin-positive cells at 12.9 +/- 2.6/mm(2), and Ki67-positive cells at 18.3 +/- 2.6/mm(2), respectively. We found significant differences in the contribution of troponin I-(6.7% +/- 1.7% vs 93.3% +/- 1.7%), nestin- (2.4 +/- 0.5 vs 97.6 +/- 0.5), and Ki67-positive (3.9 +/- 1.0 vs 96.1 +/- 1.0) cells derived from BM and n-BM. CONCLUSIONS: Bone marrow was one of the origins of regenerated cardiomyocytes; however, the contribution of cells from BM was very small compared with those of n-BM origin in the infarction model.     

A nonspecific colonic ulcer occurring after hepatectomy: Report of a Case

We herein report the case of a 53-year-old man with a nonspecific acute colonic ulcer whose liver function deteriorated after he had undergone hepatectomy. He was referred to our hospital for a hepatoma caused by hepatitis B virus and a right hemihepatectomy was performed. His liver function was poor after the operation, and minor complications such as pleural effusion and biliary fistula developed. A large amount of melena was seen 29 days after the hepatectomy and he developed hemorrhagic shock. Superior mesenteric arteriography revealed pooling of blood in both the hepatic flexure of the ascending colon and the cecum. An emergency right hemicolectomy was performed. There was a 5 x 1-mm ulcer 18 cm distal to the ileocecal valve. Numerous erosions were observed to be scattered throughout the colonic mucosa. The patient recovered slowly and was discharged 6 months after the hepatectomy. This is the first report of an acute colonic ulcer that could have been caused by liver dysfunction.     

Clinical effects of percutaneous cardiopulmonary support in severe heart failure: early results and analysis of complications.

Between January 1993 and December 2001, we employed percutaneous cardiopulmonary support (PCPS) in 35 patients. PCPS was used for postcardiotomy in 25 of these patients who could not be weaned from cardiopulmonary bypass (CPB) because of severe cardiogenic shock. In the other 10 patients, PCPS was used for a non-surgical disease. Twenty-nine patients (82.9%) were weaned from PCPS, and 28 (80.0%) survived. The other 7 patients (20.0%) died due to postoperative complications. The causes of death were multiple organ failure (MOF) due to wound bleeding, low cardiac output syndrome (LOS), myonephropathic metabolic syndrome (MNMS) with severe lower limbs ischemia, cerebrovascular accident (CVA), and sepsis. The first cause for the complications was postoperative sustained severe heart failure. To improve the survival rate, it was necessary to prevent bleeding and begin PCPS at an earlier stage.     

Efficacy of continuous cleansing with teicoplanin on post-CABG methicillin-resistant staphylococcus aureus (MRSA) mediastinitis: report of a case.

The patient was a 48-year-old male who was diagnosed with unstable angina. He had worsening cardiogenic shock during coronary angiography. Emergency coronary artery bypass grafting (CABG) was performed. He had a methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis on day 22 after CABG. Drains were placed in the anterior mediastinum, left thoracic cavity, and abscess cavity, and another drain was placed in the mediastinal space for continuous cleansing with povidone iodine, oxydol. For antibiotics, teicoplanin (TEIC) was administered intravenously and to the local site via the cleansing drain for about one month. No MRSA was detected by culture in discharges from the mediastinal drain. Inflammatory findings were improved, and the patient was discharged and resumed everyday life without recurrence of inflammation as of eight months. Although the number of cases of MRSA mediastinitis is small and accumulation of cases is necessary to investigate therapeutic methods and selection of antibiotics, our department will select closed continuous cleansing and TEIC for antibiotics as the first choice for MRSA mediastinitis, and accumulate cases to investigate its efficacy.     

Spontaneous and isolated dissection of the main trunk of the superior mesenteric artery.

A 42-year-old man was admitted to another hospital complaining of acute abdominal pain that was induced by eating. Abdominal computed tomography and selective angiography revealed an intimal flap separating true and false lumens that was located 3 cm from the origin of the superior mesenteric artery (SMA). Emergency surgery was performed because of the sudden recurrence of diffuse abdominal pain after eating and abdominal aorta-SMA bypass grafting was done using a radial artery graft. Postoperative angiography revealed that the graft showed good patency. The postoperative course was uneventful and abdominal pain no longer occurred after eating. This excellent result was achieved by early diagnosis using CT scanning and angiography plus an aggressive surgical repair with a radial artery bypass graft for isolated dissection of the superior mesenteric artery.     

Surgical repair of a common atrium in an adult.

We report a rare successful surgical repair of a common atrium (CA) with mild tricuspid valve (TV) regurgitation due to valvular annulus enlargement in a 39-year-old man, who had a complete atrial septum defect (ASD) without the characteristic of an endocardial cushion defect. The left-to-right shunt ratio was 85 percent and the Qp/Qs was 6.7 due to the CA. Left ventriculogram revealed no evidence of typical goose-neck deformity and no mitral valve regurgitation. The operation consisted of making a new atrial septum with an autologous pericardial patch and tricuspid annuloplasty (DeVega) using extracorporeal circulation. There was no evidence of a cleft on the anterior leaflet of the mitral valve or the septal leaflet of the TV. The postoperative echocardiogram showed no residual shunt flow through a new atrial septum and no TV regurgitation, and atrioventricular (AV) dissociation did not occur. We consider this procedure to be widely applicable in consideration of the favorable results obtained after surgical treatment.     

Treatment strategies for hepatic metastasis from colorectal cancer

Hepatic micrometastases of the parenchyma adjacent to a macroscopic lesion were detected in 17 of 31 resected liver metastases. Fifty-nine micrometastatic lesions were detected in total; 26 lesions were situated in the portal vein (PV), 22 in the central vein (CV), 5 in the bile duct (BD), and 6 in the sinusoid (SS). A histological study confirmed the direct invasion of the macrometastatic cancer cells into the adjacent PV, CV, BD, and SS. According to the tumor doubling time, the mean diameter of the macrometastases in 19 remnant livers was calculated to have been 0.57±0.87 cm at the time of the primary resection. The calculated diameter of 3 of these 19 macrometastases was found to be less than 0.01 cm, the minimum implantable size, indicating that the cancer recurrence in these specimens may have developed from macroscopic metastatic lesions as a satellite, and not from the primary tumor. In 13 patients who received doses of 5250 mg or more of 5 fluorouracil (FU) via the hepatic artery, the cumulative disease-free rate 2 years postoperatively was 100%; this value was 47.6% in 11 patients who received less than 5250 mg of 5 FU via the hepatic artery, and 0% in 39 patients who received no chemotherapy (P<0.005). These results suggest that anatomical hepatic resection for satellite lesions, combined with prophylactic hepatic arterial chemotherapy for micrometastases, decreases the recurrence rate of hepatic metastases in the remnant liver.