Dipole-moment-induced supramolecular assembly of a donor-acceptor-type molecule on a metal surface and in a crystal.

The conformation and alignment of molecules in organic materials are important because they affect the materials' bulk physical properties. Because two-dimensional (2D) materials offer a simpler model of three-dimensional (3D) materials, the conformation and alignment of molecules in 2D assemblies have been investigated at the atomic scale by scanning tunnelling microscopy (STM). However, differences in the conformation and alignment of molecules between 2D and 3D assemblies have not been clarified. In this work, the conformation and alignment of a donor-acceptor-type molecule, 4-(3,3-dimethyl-2,3-dihydro-1H-indol-1-yl)benzonitrile (IBN), are studied in 2D and 3D assemblies. Thus, the 2D assembly of IBN on the Au(111) surface was investigated by STM and the 3D assembly of IBN in a single crystal was investigated by X-ray crystallography. Our survey revealed that the conformation of IBN is planar in both 2D and 3D assemblies because of the electron-delocalised structure resulting from the electron-donating and electron-accepting groups of IBN; thus, the values of the dipole moment of IBN in 2D and 3D assemblies are essentially the same. In both the 2D and 3D assemblies, IBN molecules align to cancel out the dipole moment even though the self-assembled structures differ. In the 2D assemblies, the orientation and self-assembled structure of IBN are changed by the surface density of IBN, and they are affected by the crystal orientation and superstructure of Au(111) because of the strong interaction between IBN and Au(111). In addition, scanning tunnelling spectroscopy revealed that the coordination structure is not included in the self-assembled structure of IBN on Au(111).

Correlation Between Splenectomy and Portal Vein Complications in Living Donor Liver Transplantation.

OBJECTIVES: In adults undergoing living donor liver transplantation (LDLT), the transplanted livers are partial grafts, and the portal venous pressure is higher than that observed with whole liver grafts. In patients undergoing LDLT concomitant with splenomegaly, portal venous flow is often diverted to collateral vessels, leading to a high risk of portal vein thrombosis. In such cases, occlusion of the collateral veins is important; however, complete occlusion of all collaterals without blocking the blood flow through the splenic artery causes portal hypertension and liver failure. We aimed to examine the effect of performing a splenectomy concomitant with LDLT to reduce portal vein complications. METHODS: Between 1991 and 2017, we performed 170 LDLT operations, including 83 in adults. For this cohort study, adult cases were divided into 2 groups. Group I was those who underwent LDLT without splenectomy (n = 60); Group II was those who underwent LDLT with splenectomy for the reduction of portal hypertension (n = 23). We investigated the incident rates of complications, including blood loss, lethal portal vein thrombosis (intrahepatic thrombosis), acute rejection, and so on. We also investigated the survival rates in both groups. RESULTS: The incident rate of lethal portal vein thrombosis in Group II was significantly lower than that observed in Group I (4.4% vs 21.7%, respectively, P = .0363). There were no statistically significant differences observed between the groups with respect to blood loss, survival rates, and other such parameters. CONCLUSION: LDLT concomitant with splenectomy might effectively reduce the occurrence of portal vein complications in adults.

Effect of Middle Hepatic Vein Tributaries Preserving Technique Until Just Before Graft Retrieval on Donors' Surgical Outcomes in Living Donor Liver Transplantation.

BACKGROUND: The technique of preserving the major tributaries of the middle hepatic vein (MHV) (V5 and V8) until just before graft retrieval is beneficial to minimize congestion time of the graft. However, it remains unclear whether this technique exerts a burden on donors in terms of operative time, blood loss, and postoperative hepatic dysfunction. In this study we investigated adverse effects of the MHV tributaries preserving technique until immediately before graft retrieval on donors' surgical outcomes. METHODS: Data from 71 donors who underwent right hepatectomy without MHV for a liver transplantation at our hospital from January 2002 to August 2016 were retrospectively reviewed. Donors were divided into 3 groups as follows: group 1 (n = 12), no MHV tributary reconstruction; group 2 (n = 33), single MHV tributary reconstruction; group 3 (n = 26), 2 or 3 MHV tributaries reconstruction. Donor operation time, blood loss, proportion of the remnant liver, maximum postoperative total bilirubin, aspartate aminotransferase, alanine transaminase, minimum platelets, prothrombin time, albumin level, number of days in hospital from surgery to discharge, and surgical complications were compared. RESULTS: Compared with groups 2 and 3, group 1 exhibited shorter average operational time and less average blood loss, but the difference was not significant. Comparisons of all other factors indicated no significant differences. CONCLUSION: The technique of preserving the major tributaries of the MHV until just immediately before graft retrieval does not appear to impose an apparent burden on donors.

Arterial Complication After Simultaneous Pancreas-Kidney Transplantation From an Abdominal Aortic Aneurysm Donor: A Case Report.

BACKGROUND: With the current disparity between the donor organ availability and recipient needs, various marginal organs with anatomical variations or concomitant diseases have begun to be used. We present a case of simultaneous pancreas-kidney transplantation (SPKTx) from a marginal donor with a giant abdominal aortic aneurysm who was incidentally found to be an organ donor after brain death. CASE PRESENTATION: The donor was a 66-year-old man who died of brain hemorrhage. We performed cannulation of the aorta from the distal part of left common iliac artery because the aneurysm extended from pararenal aorta to the bilateral common iliac artery. Furthermore, we prepared the left common carotid artery as the backup root of cannulation. Fortunately, we could perfuse the organs from the left common iliac artery. Subsequently, we retrieved the heart, liver, pancreas, and kidney grafts and performed SPKTx. The recipient received anatomically and functionally normal organs. At 19 days after transplantation, a rupture of the renal artery occurred on the graft side. We detected the bleeding point and it was managed quickly. CONCLUSIONS: We safely retrieved the organs from a marginal donor and performed the cooperative donation using a creative approach. We dealt with the complications through cautious postoperative management.

A Case of Successful Simultaneous Pancreas-Kidney Transplantation Using the Injured Pancreas Graft.

OBJECTIVE: Graft injuries sometimes occur and may cause complications such as the leakage of pancreatic secretions, which is often lethal. We report our experience of a case of successful simultaneous pancreas-kidney transplantation using injured pancreas graft. PATIENTS AND METHODS: The recipient was a 57-year-old woman with type 1 diabetes mellitus, and the donor was a 30-year-old man with a brain injury. In the donation, the pancreas parenchyma, splenic artery, and gastroduodenal artery were injured iatrogenically. We therefore reconstructed these arteries using vessel grafts and then performed simultaneous pancreas-kidney transplantation. RESULTS: Five days after transplantation, we noted a high titer of amylase in the ascites; therefore, we performed an urgent laparotomy. The origin of the amylase was the injured pancreatic parenchyma, and continued washing and drainage were carried out. We reconstructed the duodenojejunostomy using the Roux-en-Y technique to separate the passage of food from the pancreas graft to prevent injury to other organs due to exposure to pancreatic secretions. Thereafter, we inserted a decompression tube into the anastomosis thorough the blind end of the jejunum. Finally, we inserted 3 drainage tubes for lavage. Following this procedure, the patient recovered gradually and no longer required hemodialysis and insulin therapy. She was discharged from our hospital 56 days after transplantation. CONCLUSION: The restoration of the injured graft was possible by management of pancreatic secretions and use of the donor's vessel grafts. Shortage of donors is a problem throughout the world; thus, it is important to use injured grafts for transplantation if possible.

Splenectomy for Severe Intestinal Bleeding Caused by Portal Hypertensive Enteropathy After Pediatric Living-Donor Liver Transplantation: A Report of Three Cases.

BACKGROUND: The incidence of portal vein thrombosis after pediatric living-donor liver transplantation (LDLT) is reported to be higher than that after deceased-donor or adult liver transplantation. Portal vein thrombosis can cause portal hypertension and related complications, including portal hypertensive gastropathy or portal hypertensive enteropathy (PHE). PHE, in particular, can lead to severe intestinal bleeding, which is extremely difficult to treat. However, the pathogenesis of and appropriate treatment for PHE are not clearly defined, especially after pediatric LDLT. METHODS: Herein, we report three cases of refractory intestinal bleeding caused by PHE after pediatric LDLT, which were treated with splenectomy. RESULTS: The time between LDLT and splenectomy was 43, 92, and 161 months, respectively. All 3 patients were discharged from the hospital without any peri-operative complications and were doing well, with no adverse effects at 174, 81, and 12 months after splenectomy, respectively. Although shunt surgeries, including the use of a meso-Rex shunt, are reported to be a useful option when the portal vein is completely occluded, adhesiotomy around the liver graft would be required, which could damage the hepatopetal collateral vessels that maintain portal vein flow to the graft. Therefore, shunt surgeries, which can lead to re-transplantation, are considered to be highly risky as a first-line treatment option, particularly considering the limited accessibility to deceased donor organs in our country. CONCLUSIONS: Our data demonstrate that simple splenectomy, although considered a palliative treatment, can be a safe and effective method to control severe intestinal bleeding caused by PHE after pediatric LDLT.

Edaravone, a free radical scavenger, improves the graft viability on liver transplantation from non-heart-beating donors in pigs.

BACKGROUND: Although liver transplantation from non-heart-beating donors (NHBDs) is an effective way to overcome shortage of donors, primary graft nonfunction is often noted in these grafts. We have previously reported that edaravone, a free radical scavenger, has a cytoprotective effect on warm ischemia-reperfusion injury and improves the function of liver grafts from NHBDs in a rat model of ischemia-reperfusion. The purpose of this study was to investigate the effects of edaravone on liver transplantations from NHBDs. METHODS: Pigs were divided into three groups: (1) a heart-beating (HB) group (n = 5), in which liver grafts were retrieved from HB donors; (2) a non-heart-beating (NHB) group (n = 4), in which liver grafts were retrieved under apnea-induced NHB conditions; and (3) an edaravone-treated (ED) group (n = 5), in which liver grafts were retrieved in the same manner as the NHB group and treated with edaravone at the time of perfusion (3 mg/L in University of Wisconsin [UW] solution), cold preservation (1 mg/L in UW solution), and after surgery (1 mg/kg/d). The grafts from all groups were transplanted after 4 hours of cold preservation. RESULTS: In the ED group, the 7-day survival rate was significantly higher than that in the NHB group (80% versus 0%, P = .0042, Kaplan-Meier log-rank test). Furthermore, on histologic examination, the structure of sinusoids in the ED group was well preserved and similar to that in the HB group. CONCLUSIONS: Edaravone may improve the viability of liver grafts from NHBDs.

Risk factors for portal vein stenosis in living-donor liver transplantation.

BACKGROUND: In living-donor liver transplantation (LDLT), the recipient's portal vein is short. Furthermore, portal vein thrombosis and stenosis can be lethal complications. We had begun the systemic administration of gabexate mesilate, a strong serine protease inhibitor, which has cytoprotective effects of endothelial cells. It is often effective on disseminated intravascular coagulation. The purpose of this study was to examine the effects of gabexate mesilate and to reveal risk factors for portal vein stenosis in LDLT. METHODS: From 1991 to 2012, we performed 153 LDLTs. For the present cohort study, patients were divided into 2 groups. In group I, we treated with gabexate mesilate mildly (0-20 mg/kg/d; n = 29). In group II, we treated with gabexate mesilate at full dose (40 mg/kg/d; n = 124). We investigated the survival rates of both groups and performed univariate and multivariate analyses to identify the independent risk factors for portal vein stenosis. RESULTS: The survival rate of group II was significantly better than that of group I (P < .05). On univariate analysis, the risk factors identified to be associated with a P value of <.20 were old age (P = .0385), heavy body weight (P = .1840), tall height (P = .1122), small lumen diameter of portal vein (P = .1379), high volume of blood loss (P = .0589), small amount of gabexate mesilate infusion (P = .0103), and large graft weight (P = .1326). On multiple logistic regression analysis we identified old age (P = .0073) and small amount of gabexate mesilate infusion (P = .0339) to be the independent risk factors for portal vein stenosis. CONCLUSIONS: On multivariate analysis, we found that gabexate mesilate infusion contributed to the reduction of portal vein stenosis.

Risk factors for hepatic artery thrombosis after microsurgical vascular reconstruction in liver transplantation.

OBJECTIVE: In liver transplantation, microsurgical reconstruction of a hepatic artery is essential but requires challenging techniques. Especially in living-donor liver transplantation, the recipient artery is short and located deep in the abdominal cavity. Furthermore, hepatic artery thrombosis (HAT) can be a lethal complication. This study sought to uncover the risk factors for HAT after microsurgical vascular reconstruction. METHODS: From 1991 to 2011, we performed 151 microsurgical vascular reconstructions, including 3 deceased-donor liver transplantations. We retrospectively investigated the cases, performing univariate and multivariate analyses to identify independent risk factors for HAT. The patients had undergone ultrasonographic examinations for HAT over the first 14 days after transplantation. RESULTS: Upon univariate analysis, the risk factors identified to be associated with P < .20 were young age (P = .0484), low body weight (P = .0466), short height (P = .0128), high graft-to-recipient weight ratio (P = .0031), small liver graft volume (P = .0416), small amounts of gabexate mesilate infusion (P = .0516), and the conventional technique (without a back-wall support suture; P = .1326). A multiple logistic regression analysis identified low body weight to be the only independent risk factor for HAT. CONCLUSION: On the univariate analysis, we found that using the back-wall support suture technique contributed to the reduction of HAT, whereas on multivariate analysis, the only independent risk factor for HAT was low body weight.

Expression of receptors for anaphylatoxins C3a and C5a on rat islet preparations.

BACKGROUND: Complement activation has been implicated in the development of the instant blood-mediated inflammatory reaction (IBMIR). In particular, anaphylatoxins C3a and C5a elicit a broad range of proinflammatory effects, including chemotaxis of inflammatory cells and cytokine release. We have previously shown that 2 types of receptors for C5a are expressed on isolated islets. In the present study, we investigated this component in detail. METHODS: C3aR, C5aR, and C5L2, together with CD11b and CD31, on freshly isolated islets (fresh group) and islets cultured with (cytokine group) or without (culture group) TNF-α, IL-1ß, and IFN-γ for ∼12 hours were analyzed by flow cytometry. In addition, these 3 kinds of receptors were analyzed on nonendocrine cells. RESULTS: C5aR and C5L2 were expressed on the isolated islets (C5aR: 7.91 ± 2.83%; C5L2: 2.45 ± 1.34%) and the expression of both C5a receptors was markedly attenuated by culture for 12 hours (C5aR: P < .005; C5L2: P < .05). Compared with the culture group, the expression was significantly up-regulated in the cytokine group (C5aR: P < .05; C5L2: P = .05). C5aR-positive cells expressed CD11b but not CD31. In contrast to islets, nonendocrine cells expressed C5L2 predominantly. C3aR was scarcely expressed on isolated islets or nonendocrine cells. CONCLUSIONS: These data suggest that C5aR and C5L2 are expressed on CD11b-positive leukocytes in islet preparations. Depletion of C5a receptors by culturing appropriately could be an attractive therapeutic strategy in clinical islet transplantation.

A precise analysis of C5a inhibitory peptide on inflammatory mediators induced after islet transplantation.

OBJECTIVE: We recently reported that C5a inhibitory peptide (C5aIP) prevents the instant blood-mediated inflammatory reaction by attenuating cross talk between complement and coagulation cascades. C5aIP has also been shown to possess a broad range of anti-inflammatory effects. Due to methodological limitations, it is difficult to perform detailed analyses on wide range of inflammatory mediators in rat model. Therefore, we examined whether C5aIP suppressed various inflammatory cytokines induced after islet transplantation using a mouse model. METHODS: Six islet equivalents per gram of syngeneic mouse islet grafts were transplanted intraportally into two groups of streptozotocin-induced diabetic mice: control group (n = 8) and C5aIP group (n = 6). The C5aIP group was treated with a bolus of 4 mg/kg just after islet infusion and a continuous infusion of 0.4 mg/kg/h, whereas the control group was injected with equivalent amounts of saline. Serum samples were collected at 0, 6, and 24 hours after transplantation. We analyzed 23 types of cytokines: interleukins-1a, -1b, -3, -4, -5, -6, -9, -10, -12, -13, and -17; eotaxin; G-CSF; GM-CSF; interferon (INF) gamma; KC; MCP-1; MIP-1 and -1b, RANTES and tumor necrosis factor-alpha. Leukocytes in the recipient liver were isolated at 6 hours after transplantation to examine IFN gamma production by fluorescence activated cell sorting (FACS). RESULTS: No significant difference was detected in terms of the major inflammatory cytokines between the two groups. INF gamma production on CD11b(+)Gr-1(+) cells in the liver was not significantly inhibited by C5aIP (control 30.0% vs C5aIP 24.1%). CONCLUSIONS: These data suggested that beneficial effects of C5aIP on islet engraftment are mainly due to blockade of cross talk between complement and coagulation cascades, rather than the suppression of inflammatory mediators.

C5a-inhibitory peptide combined with gabexate mesilate prevents the instant blood-mediated inflammatory reaction in a rat model of islet transplantation.

BACKGROUND: The instant blood-mediated inflammatory reaction (IBMIR), in which the activation of both the coagulation and the complement cascades plays a key role, is one of the main obstacles to successful islet transplantation. At present, however, no useful protocol is clinically available. Therefore the aim of this study was to examine whether complementary peptides against an active region of C5a were safe to suppress IBMIR, owing to their extremely low molecular mass, when combined with a clinically available anticoagulant. METHODS: Complement receptors on pancreatic tissues and isolated islets were analyzed by immunohistochemical staining and flow cytometry. Two-and-a-half islet equivalents per gram of syngeneic rat islet grafts were transplanted intraportally into 4 groups of 10-13 animals each after streptozotocin induction of diabetes: control, gabexate (Gab), C5a-inhibitory peptide (C5aINH), and C5aINH plus Gab. Recipients injected with equivalent amounts of saline solution served as control subjects. Plasma samples were collected at 0, 0.5, 1, 3, 6, and 24 h after transplantation for analysis. We also evaluated the curative rate, intravenous glucose tolerance test, and insulin amounts in the liver of the recipients. RESULTS: C3a receptor (C3aR) was scarcely expressed on the isolated islets with relatively strong expression of C5a receptor (C5aR): C3aR: 0.44 +/- 0.38%; C5aR: 7.91 +/- 2.83%). However, C5aR was not expressed on pancreatic tissues before the isolation procedures. Thrombin-antithrombin complex was significantly suppressed in the 3 treated groups (P = .0015). The curative rate was also significantly improved (0% vs 33% vs 67% vs 100%, respectively; P = .03). Glucose tolerance was significantly improved among the 3 treated groups (P < .0005). Insulin amounts in the liver were considerably higher among treated versus control hosts. Notably, the treatment did not affect the increased body weight of the recipient. CONCLUSIONS: This study suggested that C5a-inhibitory peptide combined with gabexate mesilate may be a useful approach to control the IBMIR induced in clinical islet transplantation and one that is free of side effects.