Effects of FR167653 on ischemia-reperfusion injury in canine lung transplantation models.
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Animals↗
Biomedical subjects
M Aiba
Publications and source records attributed to M Aiba.
FR167653 ameliorates pulmonary damage in ischemia-reperfusion injury in a canine lung transplantation model.
BACKGROUND: Interleukin (IL)-1 and tumor necrosis factor-alpha (TNF-alpha) are recognized as important factors in ischemia-reperfusion (I/R) injury. FR167653 has been characterized as a potent suppressant of IL-1 and TNF-alpha production. We previously reported that FR167653 suppressed the expression of IL-1 beta mRNA after reperfusion and ameliorated pulmonary I/R injury following 3-hour left lung warm ischemia in dogs. The aim of this study was to investigate the effects of FR167653 on I/R injury in a canine left, single, lung transplantation model. METHODS: We used 10 pairs of weight-matched dogs. We assigned 5 pairs to the FR group, in which each animal received FR167653 (1 mg/kg/hr) IV from 30 minutes before ischemia until 2 hours after reperfusion; we treated the transplanted lungs with FR167653 after the onset of reperfusion. The others were assigned to the control group. After 8-hour preservation with 4 degrees C Euro-Collins solution, orthotopic left, single, lung transplantation was performed. During a 5-minute clamping test at the right pulmonary artery of each recipient, the left (transplanted) pulmonary arterial pressure (L-PAP), left (transplanted) pulmonary vascular resistance (L-PVR), arterial oxygen pressure (PaO(2)), and alveolar-arterial oxygen pressure difference (A-aDO(2)) were measured. We harvested transplanted lung specimens for histologic study, and we counted polymorphonuclear neutrophils (PMNs), which were identified by staining with naphthol AS-D cholroacetate esterase. Pulmonary perfusion and ventilation scintigraphy (Tc-99m-MAA and Xe-133) were performed. We observed the animals for 3 days after transplantation. RESULTS: The PAP, L-PVR, PaO(2), and A-aDO(2) revealed significantly (p < 0.05) better function in the FR group than in the control group. Histologically, lung edema was milder, and PMN infiltration was significantly (p < 0.05) lower in the FR group than in the control group. Xe-133 and Tc-99m-MAA were widely distributed throughout the graft lung in the FR group. Three-day survival rates in FR and control groups were 60% and 20%, respectively. CONCLUSIONS: FR167653 appears to generate a protective effect on I/R injury in lung transplantation in dogs.
Animals↗
The effect of FK409-a nitric oxide donor-on canine lung transplantation.
BACKGROUND: Nitric oxide (NO) is known to have beneficial effects in ischemia-reperfusion (I/R) injury through maintaining endothelial integrity, inhibiting leukocyte adhesion and platelet aggregation, and inducing vasodilation. The effect of FK409 (FK), a spontaneous NO donor, was investigated in a canine lung transplantation model. METHODS: Ten pairs of weight-matched dogs were used. Five pairs were assigned to the FK group, to which FK (5 microg/kg/min) was administered intravenously from 30 minutes prior to ischemia until the induction of ischemia in the donor, and from 15 minutes prior to reperfusion until 45 minutes after reperfusion in the recipient. The others were assigned to the control group. After 8-hour preservation in 4 degrees C Euro-Collins solution, orthotopic single-lung transplantation was performed. During a 5-minute clamping test of the right pulmonary artery, left pulmonary arterial pressure (L-PAP), left pulmonary vascular resistance (L-PVR), arterial oxygen pressure (PaO(2)), and alveolar-arterial oxygen pressure difference (A-aDO(2)) were measured. The lung specimens were harvested for histologic study, and polymorphonuclear neutrophils (PMNs) were counted. Pulmonary perfusion and ventilation scintigraphy (Tc-99m-MAA and Xe-133) were performed. RESULTS: PAP, L-PVR, PaO(2), and A-aDO(2) revealed significantly (p < 0.05) better function in the FK group than in the control group. Histologically, edema was more mild, and PMN infiltration was significantly (p < 0.05) lower in the FK group than in the control group. Xe-133 and Tc-99m-MAA were widely distributed throughout the graft lung in the FK group. The 2-day survival rate was 100% in the FK group, which was significantly (p < 0.05) better than the rate (40%) in the control group. CONCLUSIONS: FK appears to generate a protective effect on I/R injury in lung transplantation.
Animals↗
Optimal end point of FR167653 administration and expression of interleukin-8 messenger RNA on extended liver resection with ischemia in dogs.
BACKGROUND: FR167653 is a potent suppressant of interleukin-1 and tumor necrosis factor production. We previously reported that FR167653 inhibited the expression of interleukin-1 messenger RNA (mRNA) after ischemia-reperfusion and provided a protective effect against ischemia-reperfusion injury after extended liver resection. In this study we investigated the optimal end point of FR167653 administration and the inhibition of interleukin-8 (IL-8) mRNA expression caused by the administration of FR167653 during extended liver resection with ischemia in a dog model. STUDY DESIGN: The right portal pedicle was clamped for 60 minutes but the left portal vein was left patent to avoid portal congestion. After reperfusion 75% of the liver was resected. EXPERIMENT I: Adult mongrel dogs were divided into three groups: the control group (n = 9); the FR-2 group (n = 6), which received FR167653 through the portal vein starting 30 minutes before the onset of ischemia until 2 hours after reperfusion; and the FR-6 group (n = 6), which received FR167653 starting 30 minutes before ischemia until 6 hours after reperfusion. Hepatic venous blood was collected to measure liver enzymes. Liver specimens were harvested for histologic study 6 hours after reperfusion and polymorphonuclear neutrophils were counted. EXPERIMENT II: The expression of IL-8 was measured by reverse-transcriptase polymerase chain reaction. RESULTS: Aspartate aminotransferase and alanine aminotransferase levels after reperfusion and hyaluronic acid levels 6 hours after reperfusion were significantly (p < 0.05) lower in the FR-2 and FR-6 groups than in the control group. There were no significant differences between the FR-2 and FR-6 groups after reperfusion. Histologically liver tissue damage was mild in the FR-2 and FR-6 groups, and polymorphonuclear neutrophil infiltration was significantly lower in the FR-2 and FR-6 groups than in the control group. The 3-day survival rate was statistically (p < 0.05) better in the FR-2 and FR-6 groups than in the control group. IL-8 mRNA expression was inhibited in the FR-treated group. CONCLUSIONS: FR167653 should be administered until shortly after reperfusion and need not be administered for many hours after reperfusion. FR167653 inhibits IL-8 mRNA production and inhibits polymorphonuclear neutrophil infiltration.
Alanine Transaminase↗
Relationship between the morphological and biological characteristics of intraductal components accompanying invasive ductal breast carcinoma and patient age.
We divided 324 cases with invasive ductal breast carcinoma into three age groups, and investigated the differences in proliferative activity and extension of the intraductal components among the age cohorts. Proliferative activity was expressed as the number of MIB1-positive nuclei per 1000 cancer cells in the intraductal components (MLI), and the intraductal component extension farthest from the invasive focus was defined as the maximum distance of ductal spread (MXDS). Moreover, analyses were conducted for three grade types, classified according to the classification system of ductal carcinoma in situ. The under-40 age group had significantly higher MXDS values than the other two age groups (p = 0.0280), and this trend was more marked in those with the non-high grade without necrosis type (p = 0.0045). The under-40 age group had higher MLIs, but the differences did not reach statistical significance (p = 0.0793). In regard to those with the high grade type, the under-40 age group had significantly higher MLIs than the other two age groups (p = 0.0269), and this trend was not significant in the cases with any other grade types. Associations between the age group and the margin status of the lumpectomy specimens were investigated in the 143 cases in which breast conserving surgery was tried. The under-40s had a significantly higher margin-positive rate in their lumpectomy specimens than the other two age groups (= 0.0362), and this trend was also seen in the groups with the non-high grade without necrosis type (p = 0.0256). These results confirm the importance of considering patient age when designing surgical procedures for breast conserving therapy.
Adult↗
Retroperitoneal epithelioid angiomyolipoma leading to fatal outcome.
Epithelioid angiomyolipoma (AML) is a newly established variant of AML, characterized by monomorphous epithelioid cells that show HMB-45 immunopositivity, and it often displays aggressive behavior. To date, they have mostly appeared in the kidneys; however, the present autopsy case of a 43-year-old female without the stigmata of tuberous sclerosis complex had a huge retroperitoneal mass, accompanied by involvement of the regional lymph nodes. Histopathologically, the tumor was composed of round, polygonal or short spindle-shaped monomorphous cells with abundant eosinophilic cytoplasm and large nuclei with frequent multinucleation. Mitotic figures were scattered. Mature fat cells and thick-walled abnormal blood vessels were totally absent. Immunohistochemically, the tumor cells were reactive with HMB-45 and alpha-smooth muscle actin antibodies. In spite of curative surgery and repeated radio- and chemotherapy, the tumor continued to grow and brought about the patient's death 4 years after the initial symptoms. At autopsy, the peritoneal cavity was filled with the tumor mass exceeding 5.5 kg. Histopathological features were essentially the same as those of biopsy samples, but the cellular pleomorphism and emperipolesis were more easily identified. This report calls attention to this unusual manifestation of AML in the retroperitoneum and the importance of distinguishing it from sarcomas and/or paragangliomas.
Adult↗
[A study of the difficulty of identifying normal intrathoracic structures on CRT images: a search for the optimal luminescence ratio].
This study was concerned with 2 issues: whether there are any normal intrathoracic anatomical structures that are relatively more difficult to identify on CRT (cathode-ray tube) monitor images, and if so, what their features are. Four physicians examined 7 intrathoracic anatomical structures on 50 chest roentgenograms that were displayed on CRT monitors and as conventional X-ray films on a light box. They categorized the visibility of each structure into 5 grades. The 7 structures were the spinal process behind the trachea, right margin of trachea, right main bronchus, left main bronchus, vascular shadow behind right diaphragm, vascular shadow behind cardiac shadow, and right margin of descending aorta. Luminescence ratios were calculated as the ratio of the density of a given viewpoint relative to adjacent areas on the images. We also examined the correlations between luminescence ratio and degree of difficulty in interpreting CRT images at a variety of selected luminescence ratios. Although the spinal process and trachea were easy to identify on CRT images as well as conventional films, other structures were difficult to recognize on CRT images. The luminescence ratio of each structure was higher on conventional film, and relatively low for those structures that were difficult to identify on CRT images. Each structure became gradually easier to identify with increasing luminescence ratios, up to a value of 1.07 maximum. However, this improvement in visibility leveled off beyond 1.07. We concluded that the luminescence ratio should be maintained at more than 1.07 to facilitate optimal identification of overlapping anatomical structures on CRT images.
Aorta, Thoracic↗
The effective dose of FR167653 in pulmonary ischemia-reperfusion injury.
BACKGROUND: Ischemia-reperfusion injury may result in the local release of proinflammatory cytokines. FR167653 is a potent suppressant of interleukin-1 and tumor necrosis factor-alpha. In a previous study, we reported the efficacy of FR167653 in canine ischemia-reperfusion models. In this report we investigated the dose of FR167653 effective in pulmonary ischemia-reperfusion injury in a canine model. METHODS: Adult mongrel dogs, weighing 9 to 13 kg, were allocated into five groups. FR167653 was continuously infused (FR-A (n = 7): 1 mg/kg/hr; FR-B (n = 6): 0.5 mg/kg/hr; FR-C (n = 6): 0.1 mg/kg/hr; FR-D (n = 5): 0.05 mg/kg/hr) from 30 minutes prior to ischemia to 2 hours after reperfusion. In the control group (n = 7), a vehicle was given continuously. Warm ischemia was induced for 3 hours. Arterial oxygen saturation (SaO2), left pulmonary vascular resistance (L-PVR), and cardiac output (CO) were measured. The lung was harvested for histologic study. RESULTS: SaO2 levels after 2 hours of reperfusion were significantly (p < 0.05) higher in groups FR-A, B, C, and D than in the control group. Just after reperfusion, CO deterioration was significantly (p < 0.05) greater in the control group than in the FR-treated groups, and the L-PVR level was significantly (p < 0.05) lower in groups FR-A, B, and C than in the control group. There were statistically significant differences (p < 0.05) in the survival rates of groups FR-A and B and the control group. Histological damage was more severe in the control group than in the FR-treated groups. CONCLUSION: FR 167653 seems to ameliorate ischemia-reperfusion injury of the lung dose-dependently.
Animals↗
Induction of a critical elevation of povidone-iodine absorption in the treatment of a burn patient: report of a case.
A critical elevation of povidone-iodine absorption which occurred in a burn patient who was topically treated with 10% povidone-iodine (PI) gel is herein reported. A 65-year-old man was admitted to our hospital for deep second- and third-degree burns covering 26% of his total body surface area. The intravenous administration with lactated Ringer's solution and topical treatment with silver sulfadiazine were applied in addition to such treatments as debridement and skin grafting. However, wound infection occurred due to Pseudomonas aeruginosa. Topical treatment with PI gel was effective for this condition. Persistent nodal bradycardia with hypotension, metabolic acidosis, and renal failure occurred 16 days after the start of PI gel treatment. Iodine toxicosis caused by PI gel was suspected with a serum iodine level of 20600 microg/dl (normal range 2-9 microg/dl). The PI gel treatment was therefore discontinued immediately, and hemodialysis was scheduled. However, the patient's family refused hemodialysis and he died 44 days after admission. To our knowledge, only eight patients with iodine toxicosis have been reported in burn patients treated with PI gel.
Absorption↗
The effects of FK409 on pulmonary ischemia-reperfusion injury in dogs.
FK409 is the first spontaneous nitric oxide (NO) donor known to increase plasma cyclic guanosine 3',5'monophosphate levels. In this study, we evaluated the effect of FK409 on pulmonary ischemia-reperfusion injury in an in situ warm ischemia canine model. Fourteen dogs were divided into two groups, and the FK409-treated group was given 5 micrograms/kg per min FK409. Warm ischemia was induced for 3 h. The arterial partial pressure of oxygen (PaO2), arterial oxygen saturation (SaO2), cardiac output (CO), left pulmonary vascular resistance (L-PVR), and endothelin-I (ET-I) were measured. A histologic study was performed, and polymorphonuclear neutrophils (PMNs) were also counted. The PaO2, SaO2, and L-PVR levels and PMNs after 30 min of reperfusion, ET-I after 2 h of reperfusion, and the 7-day survival rate were significantly (P < 0.05) better in the FK409-treated group than in the control group. The histologic damage was reduced in the FK409-treated group compared to the control group. FK409 appears to have a protective effect in ischemia-reperfusion injury of the lung.
Animals↗
Effect of FR167653 on small bowel ischemia-reperfusion injury in dogs.
IL-1 and TNF-alpha are known to be pleiotropic cytokines associated with various inflammatory conditions such as small intestinal injury after ischemia-reperfusion. FR167653 has been characterized as a potent suppressant of IL-1 and TNF-alpha production. The effect of FR167653 on intestinal reperfusion injury was investigated in a warm ischemia model of the canine gut. Sixteen mongrel dogs were divided into two groups: a control group and a FR group to which FR167653 was administered. Both the superior mesenteric artery and vein were clamped for 2 hr. Arterial pH, hepatic venous hemoglobin oxygen saturation, intramucosal pH, and the survival rate were well maintained in the FR group in comparison with the control group after reperfusion. FR167653 inhibited the expression of IL-1beta mRNA. Histologically, ischemia-reperfusion injury was more severe in the control group than the FR group. This study suggests that FR167653 inhibits proinflammatory cytokines and ameliorates ischemia-reperfusion injury of the small intestine.
Animals↗
Prognostic significance of MIB1-determined proliferative activities in intraductal components and invasive foci associated with invasive ductal breast carcinoma.
The prognostic significance of the proliferative activities in intraductal components and invasive foci was investigated using 157 cases of invasive ductal breast carcinoma in which intraductal components predominated. Proliferative activity was expressed as the number of MIB1-positive nuclei per 1000 cancer cells in the most active areas of intraductal components (MLI-DCIS) or invasive foci (MLI-INV). MLI-DCIS correlated closely with MLI-INV (r = 0.710, 95% confidence interval, 0.623-0.780; P < 0.0001). Both MLI-DCIS and MLI-INV were related to oestrogen receptor (ER) (P = 0.0006, P = 0.0028 respectively), grade of invasive tumour (P < 0.0001, P < 0.0001 respectively) and classification of intraductal components (P < 0.0001, P < 0.0001 respectively). In the univariate disease-free survival analysis, both MLI-DCIS and MLI-INV were found to be significant (P < 0.0001, P = 0.0003 respectively). However, in node-negative cases, only MLI-DCIS was significant (P = 0.0416). Multivariate analysis revealed that MLI-DCIS was significant not only in all cases, but also in node-negative cases (P = 0.0223, P = 0.0426 respectively), whereas MLI-INV was not. These findings indicate that MIB1-determined proliferative activity of intraductal components is a significant prognostic determinant of invasive ductal breast carcinoma in which intraductal components predominate.
Adult↗
[Risk assessment in urgent or emergent coronary artery bypass grafting for acute coronary syndrome].
Emergent coronary artery bypass grafting (CABG) for the treatment of acute coronary syndrome has increased the operative mortality. Forty-nine patients underwent urgent or emergent CABG for the treatment of medically refractory unstable angina in 10 patients, and for acute myocardial infarction (AMI) in 39 patients. Ten operative deaths were occurred in the AMI patients, and the mortality was 20 percent. The preoperative risk factors were evaluated in 10 patients who died in the operative period. Cardiopulmonary resuscitation before operation, intra aortic balloon pumping, the use of catecholamine, and intubation with or without percutaneous cardiopulmonary support revealed operative risk factor. Because the patients who have preoperatively shock, it seemed to be needed that the rescue of the patients should improve the clinical results for urgent or emergent CABG.
Adult↗
The effect of Lazaroid U-74389G on extended liver resection with ischemia in dogs.
BACKGROUND: In liver surgery, total clamping of the portal triad (Pringle's procedure) is commonly used, and it sometimes causes liver failure. This study was designed to evaluate the effect of Lazaroid U-74389G (LAZ-G), which inhibits iron-dependent lipid peroxidation, on ischemia-reperfusion injury during liver resection in dogs. METHODS: The experiment animals were divided into 2 groups. The control group was subjected to 60 minutes of warm ischemia by partial inflow occlusion. The LAZ-G-treated group received LAZ-G before ischemia and then underwent liver ischemia. After reperfusion, the nonischemic lobes were resected, and the remnant liver function was evaluated. RESULTS: The LAZ-G-treated group showed a significantly improved animal survival rate. Biochemical analysis and morphologic evaluation by electron microscopy suggest that LAZ-G pretreatment protects both hepatic parenchymal cells and sinusoidal endothelial cells from ischemia-reperfusion injury. Expression of IL-1 beta messenger RNA in hepatic venous blood was measured by a reverse transcriptase-polymerase chain reaction; it was shown to be inhibited in the LAZ-G-treated group after reperfusion. This suggests that LAZ-G decreases the activation of proinflammatory cytokine expression. CONCLUSIONS: Lazaroid U-74389G ameliorates ischemia-reperfusion injury caused by Pringle's procedure during extensive liver resection. This agent may therefore be clinically applicable for extended liver surgery involving vascular isolation.
Animals↗
Acinic Cell Adenocarcinoma Arising in the Breast of a Young Male: A Clinicopathological, Immunohistochemical and Ultrastructural Study.
A 23-year-old man with acinic cell adenocarcinoma of the breast is reported. He presented with a 4.8 x 4.2 cm mass in his left breast, and excisional biopsy was performed. Under the light microscope, tumor cells had abundant periodic acid-Schiff-positive secretory granules and eosinophlic cytoplasms. Electron microscopy revealed the granules to have various electron densities, a finding characteristic of acinic cell adenocarcinoma. Immunohistochemically, the tumor cells were stained with salivary-type amylase. Electron microscpic and immunohistochemical investigation greatly facilitated the diagnosis of this acinic cell adenocarcinoma, which was in an unusual location. We believe this is the first case report of acinic cell adenocarcinoma of the mammary gland studied utilizing light microscopic, ultrastructural and immunohistochemical techniques.
Journal Article↗
[Blood flow velocity in the ophthalmic artery measured by Doppler ultrasonography during cardiopulmonary bypass--usefulness for cerebral perfusion monitor].
Brain blood flow is supplied from the internal carotid artery, and the ophthalmic artery is the first branch of the internal carotid artery. We studied how blood flow velocity in the ophthalmic artery (OAV) changes during cardiopulmonary bypass (CPB) and investigated whether it can be used to monitor brain blood flow during CPB. In 13 open heart surgeries in adults, OAV and blood flow velocity in the common carotid artery (CAV) were measured with Doppler ultrasonography, and blood flow volume in the brachiocephalic artery (BA flow) was measured simultaneously with an electromagnetic flow meter. Maximal blood flow velocity in the ophthalmic artery (OAVmax) and the common carotid artery (CAVmax) were 0.27 +/- 0.13 m/sec and 0.64 +/- 0.40 m/sec, BA flow was 486 +/- 226 ml/min before CPB. When CPB pump flow was varied (2.4, 2.2, 2.0, 2.2, 2.4 l/min/m2), the parameters during and after CPB changed as follows (as percentage of pre-CPB levels): OAVmax, 58.1%, 50.9%, 37.6%, 49.4%, 64.7%, 108.4%; CAVmax, 67.0%, 58.0%, 48.2%, 113.6%, 105.5%, 134.3%; and BAflow, 87.3%, 39.8%, 53.9%, 50.5%, 95.0%, 159.8%. Our results indicate that OAVmax more accurately reflects changes in pump flow than does CAVmax and BA flow. Because vessel resistance in the ophthalmic artery was small during CPB, OAVmax was thought to be determined mainly by CPB pump flow. OAVmax was useful for monitoring brain blood flow during CPB.
Adult↗
[Evaluation of highly damaged renal function following extracorporeal circulation--usefulness of alpha 1-microglobulin index].
The patients with highly damaged renal functions following extracorporeal circulation (ECC) were reviewed. Markers such as serum and urine creatinine (SCr, UCr), blood urea nitrogen (BUN), alpha 1-microglobulin in urine (as a marker of renal tubular function, abbreviated as U alpha 1-m), microalbumin in urine (as a marker of renal glomerular function, abbreviated as UA1b) were measured in each cases. Twenty patients were selected with the maximum value of U alpha 1-mover 60 micrograms/dl during or after ECC. The patients were classified into three groups according to preoperative value of alpha 1-m index (alpha 1-m index (I) = U alpha 1-m/UCr x 100 mg/g Cr), and Albumin index (Albumin index (I) = UA1b/UCr x 100 mg/g Cr). Group I (n = 13); alpha 1-m I > 10 and, Alb I > or = 50 (abnormal value of tubular and glomerular function), Group II (n = 3); alpha 1-m I < or = 10, Alb I > or = 50 (abnormal value of glomerular function), Group III (n = 4); alpha 1-m I < or = 10, Alb I < 50 (normal value of tubular and glomerular function). Six patients in Group I required postoperative hemodialysis (HD) and one patient in Group II. No one required HD in Group III. These facts suggest that preoperative damage of tubular and glomerular functions may become prolonged or irreversible damages may occur after operation. HD is required frequently in patients with alpha 1-m I level over 500 mg/g Cr, especially continuous HD may be needed in patient with alpha 1-m I level over 1000 mg/g Cr.
Acute Kidney Injury↗
Comparative study of intramucosal pH in histologic damage from small bowel ischemia-reperfusion injury.
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Animals↗