Effects of a p38 mitogen-activated protein kinase inhibitor as an additive to Euro-Collins solution on reperfusion injury in canine lung transplantation1

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.     

The effect of Celsior solution on 12-hour cardiac preservation in comparison with University of Wisconsin solution

BACKGROUND: Celsior is a new extracellular-type preservation solution which has been developed to act not only as a storage medium but also as a perfusion fluid during initial donor heart arrest, poststorage graft reimplantation and early reperfusion. We designed this experimental study to evaluate the effect of the Celsior solution in comparison with the University of Wisconsin solution from the viewpoint of energy depletion. METHODS: Adult mongrel dogs weighing 9 to 13 kg were divided into two groups. In the UW group (n=7), a 4 degrees C University of Wisconsin solution was used for coronary vascular washout and storage following cardiac arrest using a glucose-insulin-potassium solution. In the Celsior group (n=7), the Celsior solution was used to obtain cardiac arrest, coronary vascular washout and storage. High energy phosphate levels and myocardial pH were measured using (31)P-nuclear magnetic resonance spectroscopy immediately after preservation and at 3, 6 and 12 hours after preservation. After 12-hour cold storage, left ventricular free wall tissues were harvested for histological examination. RESULTS: High energy phosphate levels and myocardial pH were significantly better preserved in the Celsior group than in the UW group. In the histological findings, glycogen granules were preserved well in the Celsior group. CONCLUSIONS: We conclude from our study that the Celsior solution is comparable to the University of Wisconsin solution for use in 12-hour heart preservation in canine models.     

Immunohistochemical study on primary and recurrent tumors in patients with local recurrence in the conserved breast

One hundred and seventy patients received breast-conserving therapy in the Second Department of Surgery, Gunma University School of Medicine. Six (3.5%) out of the 170 patients showed breast recurrence. We investigated the breast recurrent cases clinicopathologically. The age at the initial operation ranged from 38 to 78 (mean 57) years. One patient was clinical stage I and the others were clinical stage II. Surgical margin at the initial operation was negative in two patients and positive in four. Histological type was invasive ductal cancer in all cases. Three patients had lymph node involvement. The interval from the initial operation to breast recurrence ranged from 19 to 68 months. Five cases were nodular type and one was diffuse type of breast recurrence. Histological type of breast recurrence was the same as the initial one. We performed salvage surgery for all breast recurrent patients, mastectomy for four patients and local resection for two. One patient who showed diffuse type of recurrence could not be controlled with any surgical treatment, and later died of breast cancer. We investigated the expression of estrogen receptor, progesterone receptor, pS2, c-erbB-2 and p53 on both initial and recurrent specimens of the six patients. The expression of each protein on the recurrent specimens was the same as the initial one. We conclude that breast recurrence after breast-conserving therapy has its origin in the residue of cancer cells at the initial operation, even if surgical margins are histopathologically negative.     

Flow Visualization Study on Centrifugal Blood Pump Using a High Speed Video Camera

Abstract: Flow visualization is widely applied to evaluate rotary blood pumps; however, it is very difficult to visualize flow near the vanes of centrifugal blood pumps because the rotational speed of the impeller is usually several thousand rpm. In this study, a tracer method with a high speed video camera that can take more than 2,000 frames/s was utilized for flow visualization together with computer-assisted image measurement. This method visualized the complex secondary flow pattern near the vanes of the impeller, such as the vortex and recircula-tion. It also visualized the enhanced washout effect by the secondary washout vanes on the backside of the impeller. The proposed method was effective to analyze the flow pattern in the centrifugal blood pump by providing useful information for better design of the pump hemolysis and thrombus formation.     

Endometrioid adenocarcinoma arising from endometriosis of the mesenterium of the sigmoid colon

This report presents a case of endometrioid adenocarcinoma arising from endometriosis of the mesenterium of the sigmoid colon following total abdominal hysterectomy and bilateral salpingo-oophorectomy for leiomyoma of the uterus and infiltrating pelvic endometriosis, and hormone replacement therapy. A 62-year-old woman presented with an abdominal tumor. Based on the diagnosis of mesocolonic tumor, sigmoidectomy with lymph node resection was performed. The tumor cells were immunopositive for cytokeratin 7, but negative for cytokeratin 20, and the tumor was histologically diagnosed as endometrioid adenocarcinoma of the mesocolon. Hyperestrogenism has been implicated as a risk factor for the development of cancer from endometriosis. The patient had been receiving high-dose unopposed estrogens for 14 years after a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Physicians should recognize that endometriosis-associated neoplasms are able to cause symptoms or signs such as abdominal and/or pelvic pain, pelvic mass, and vaginal bleeding, especially if the patient has been treated with hormone replacement therapy. It is important to recognize the possibility of tumors arising from endometriosis when evaluating intestinal or mesenteric neoplasms in women, even in the patient who has previously undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy, particularly if the patient has a history of endometriosis and has received hormone replacement therapy.     

The effects of anesthetics and ethanol on alpha2 adrenoceptor subtypes expressed with G protein-coupled inwardly rectifying potassium channels in Xenopus oocytes

A wide range of physiological effects are mediated by alpha2-adrenoceptors (ARs) through their association with G protein-coupled inwardly rectifying potassium (GIRK) channels. Although alpha2-ARs are divided into three subtypes (alpha2A-C), a pharmacological distinction among the subtypes is difficult to establish because of the lack of a selective agonist and antagonist; therefore, little is known about the effects of anesthetics on the alpha2-AR subtypes. We expressed each subtype together with GIRK1/GIRK2 subunits in Xenopus oocytes and observed alpha2-AR-mediated GIRK1/GIRK2 currents to test the effects of ethanol, halothane, and several IV anesthetics at clinical concentrations. UK 14,304, a selective alpha2-AR agonist, evoked GIRK1/GIRK2 currents in every subtype. None of the IV anesthetics, which included pentobarbital, propofol, ketamine, and alphaxalone, influenced UK 14,304-evoked potassium currents in any of the receptor subtypes. Ethanol enhanced the UK 14,304-evoked potassium currents, whereas halothane inhibited the currents. However, these effects were not significantly different from those on the baseline-GIRK1/GIRK2 current, suggesting that neither ethanol nor halothane acts directly on the alpha2-AR subtypes. Although none of the drugs examined had any effect on the alpha2-ARs, the physiological actions of the alpha2-ARs mediated by the GIRK1/GIRK2 channels may be affected by ethanol and halothane.     

Complications related to anesthesia method in the University of Occupational and Environmental Health Hospital

BACKGROUND: Complications related to anesthesia remain a problem. We studied the incidence of complications during anesthesia in 2758 patients who had undergone anesthesia in the University of Occupational and Environmental Health Hospital. METHODS: We checked the anesthesia records retrospectively and analyzed the collected data for the incidence of complications during anesthesia. RESULTS: The total incidence of complications during anesthesia was 12.2%. The incidences of complication are estimated to be 13.4% in inhalation anesthesia, 11.9% in inhalation anesthesia plus epidural, spinal or conduction block, 8.9% in CSEA, zero % in epidural anesthesia and 7.5% in spinal anesthesia. CONCLUSIONS: The incidence of complications in inhalation anesthesia was almost as same as that in inhalation anesthesia plus epidural, spinal or conduction block. More study should be necessary to prevent complications related to anesthesia.     

N-acetyl-cysteine attenuates endotoxin-induced adhesion molecule expression in human whole blood

Leukocyte adhesion to endothelial cells plays a pivotal role in the early stage of endotoxin shock. The attenuation of the leukocyte response to endotoxin may contribute to the prevention of further organ dysfunction. Recent evidence implies that N-acetyl-cysteine (NAC) attenuates endotoxin-induced pathophysiological changes. We investigated the effect of NAC on the expression of CD11b and CD62L in endotoxin-stimulated human whole blood. NAC (>10 mM) significantly inhibited the lipopolysaccharide (LPS)-induced upregulation of CD11b in a concentration-dependent manner. However, NAC did not affect the LPS-induced downregulation of CD62L. We also analyzed the effect of NAC on interleukin-8 (IL-8)-induced expression of CD11b in human whole blood. IL-8 (10 ng/mL) significantly upregulated the expression of CD11b, and the IL-8-induced upregulation was significantly attenuated by NAC (>10 mM) in a dose-dependent manner. We conclude that NAC attenuates the increased expression of CD11b in either LPS or IL-8-stimulated human whole blood.