Cheongsoo Park

Cetuximab-conjugated magneto-fluorescent silica nanoparticles for in vivo colon cancer targeting and imaging

Magneto-fluorescent silica nanoparticles were conjugated with cetuximab for the targeting and imaging of colon cancer. In this study, cetuximab-conjugated magneto-fluorescent nanoparticles (MFSN-Ctx) could specifically target colon cancer cells that expressed EGFR on their cell membranes, and specific fluorescence was detected. MFSN-Ctx produced significant MRI signal changes in a human colon cancer xenograft mouse model. Intravenous injection of MFSN-Ctx resulted in faster uptake as compared to intraperitoneal injection, indicating that MFSN-Ctx had different kinetic properties in tumors based on the method of injection. The local concentration of MFSN-Ctx in a tumor was amplified by the use of an external magnetic field. These results demonstrate the potential application of MFSN-Ctx for the detection of EGFR-expressing colon cancer using in vivo imaging approaches.

Longitudinal changes of left ventricular filling pressure and N-terminal pro-brain natriuretic peptide on chronic hemodialysis.

BACKGROUND Left ventricular filling pressure (LVFP) is related to the long-term prognosis in end-stage renal disease. The aims of this study were to evaluate the time course of the changes in LVFP, the predictors for the changes of LVFP, and the plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels as indicators for the changes of LVFP in chronic hemodialysis (HD). METHODS This study was designed prospectively. Doppler echocardiographic examinations and measurement of plasma NT-proBNP levels were performed in 37 consecutive patients on chronic HD and repeated at median of 43 months later. A ratio of peak early transmitral flow velocity to peak early diastolic mitral annular velocity (E/Em), an estimate of LVFP, was calculated. RESULTS E/Em ratios were significantly increased during the follow-up period. In multivariate analysis, age and changes of LVMI were independently associated with the changes of E/Em ratios. The plasma NT-proBNP levels were independently associated with E/Em at baseline and at the end of follow-up. The changes of plasma NT-proBNP levels were independently associated with changes of E/Em ratios (b-coefficient 0.453, p = 0.003). CONCLUSIONS Our data suggest that the deterioration of LVFP parallels with the progression of LV hypertrophy. Monitoring the plasma NT-proBNP levels might be useful for the detection of the LVFP changes in chronic HD.

Perioperative Assessment of Terlipressin Infusion during Living Donor Liver Transplantation

OBJECTIVE: To investigate the safety and efficacy of infusion of terlipressin during living donor liver transplantation (LDLT). METHODS: Patients undergoing LDLT with low systemic vascular resistance index (SVRI) and pulmonary vascular resistance index (PVRI) (n = 41) were randomly allocated into control (n = 20) and terlipressin groups (n = 21). Terlipressin was infused at 1.0 – 4.0 μg/kg per h in the terlipressin group during surgery. Controls received generally accepted inotropic and vasopressor agents. RESULTS: Terlipressin infusion induced significantly higher SVRI and PVRI at 60 min after drug infusion, produced significantly greater hourly urine output during the anhepatic phase, and was related to significantly shorter stays in the postoperative intensive care unit (ICU) compared with control treatment (mean ± SD ICU stay 5.7 ± 1.5 versus 6.9 ± 1.5 days, respectively). Patients given a terlipressin infusion > 2.0 μg/kg per h during the preanhepatic phase had a median ICU stay of < 6 days (sensitivity 90.0%; specificity 89.0%). CONCLUSIONS: Terlipressin infusion improved low SVRI and PVRI during LDLT and may have contributed to better renal function and shorter ICU stays.

Infarcted Myocardium-Primed Dendritic Cells Improve Remodeling and Cardiac Function After Myocardial Infarction by Modulating the Regulatory T Cell and Macrophage PolarizationClinical Perspective

Background: Inflammatory responses play a critical role in left ventricular remodeling after myocardial infarction (MI). Tolerogenic dendritic cells (tDCs) can modulate immune responses, inducing regulatory T cells in a number of inflammatory diseases. Methods: We generated tDCs by treating bone marrow–derived dendritic cells with tumor necrosis factor-&agr; and cardiac lysate from MI mice. We injected MI mice, induced by a ligation of the left anterior descending coronary artery in C57BL/6 mice, twice with tDCs within 24 hours and at 7 days after the ligation. Results: In vivo cardiac magnetic resonance imaging and ex vivo histology confirmed the beneficial effect on postinfarct left ventricular remodeling in MI mice treated with tDCs. Subcutaneously administered infarct lysate–primed tDCs near the inguinal lymph node migrated to the regional lymph node and induced infarct tissue–specific regulatory T-cell populations in the inguinal and mediastinal lymph nodes, spleen, and infarcted myocardium, indicating that a local injection of tDCs induces a systemic activation of MI-specific regulatory T cells. These events elicited an inflammatory-to-reparative macrophage shift. The altered immune environment in the infarcted heart resulted in a better wound remodeling, preserved left ventricular systolic function after myocardial tissue damage, and improved survival. Conclusions: This study showed that tDC therapy in a preclinical model of MI was potentially translatable into an antiremodeling therapy for ischemic tissue repair.

Variation of the choline signal intensity in the dorsolateral prefrontal cortex of rats exposed to the forced swimming test as detected by in vivo 1H MR spectroscopy

BACKGROUND (1)H magnetic resonance spectroscopy (MRS) has documented an increased Cho/Cr ratio in the dorsolateral prefrontal cortex (DLPFC) in major depressive disorder (MDD). The aim of this study was to investigate neurochemical alterations in the left DLPFC, considered a main area of pathogenesis in depression, using rats exposed to the forced swimming test (FST). MATERIALS AND METHODS Twenty-four male rats were used for the MRI and in vivo(1)H MRS studies. Rats exposed to the FST to induce a depressed mental status. Using in vivo(1)H MRS, the metabolite ratios of the rats with a depressed mental status and the controls, were measured and the values of the two groups were compared. RESULTS The Cho/Cr and Cho/NAA ratios in the DLPFC of the rats with a depressed mental status were significantly higher than that in the controls. CONCLUSIONS The present study demonstrates a significantly increased Cho/Cr ratio in the DLPFC of rats with depression compared with controls. This result may suggest an accelerated turnover of membrane without neuronal loss is occurring in the DLPFC of the rats with depression.

Intraoperative Calcium-Related Risk Factors for Biochemical Acute Pancreatitis After Living-Donor Liver Transplantation

Laboratory-based biochemical acute pancreatitis (BAP) is considered to be a benign but common complication after liver transplantation (LT), which to compensate for transfusion-related hypocalcemia, usually demands a large quantity of exogenous calcium which may be associated with pancreatic injury. We sought to investigate the relationship between intraoperative calcium-related factors and BAP occurrence after living-donor LT. Perioperative data, including intraoperative calcium chloride administration and serum calcium levels, were reviewed from 217 patients who underwent living-donor LT. Hyperamylasemia (≥ 458 U/L) was used to define posttransplantation BAP according to previous reports. Posttransplantation BAP was identified among 37 patients (17.3%), who showed a greater death rate than those in the non-BAP group (21.6% vs 8.6%; P = .013). Compared to with calcium-related parameters, the 2 groups showed differences in the amount of calcium chloride administered during the preanhepatic phase, the serum calcium surge during the initial 2 h after the liver graft reperfusion, the last serum calcium level, and the amount of transfused pack red blood cells (P < .05). However, after multivariate adjustment, only the amount of administered calcium chloride during the preanhepatic phase (odds ratios, 2.11-5.87, depending an amount) and the serum calcium surge during the initial 2 hours after liver graft reperfusion (odds ratio, 2.34) were selected as risk factors for posttransplantation BAP. The risk ratio of posttransplantation BAP increased in proportion to the administered amount of calcium chloride. In conclusion, limiting excessive calcium administration during the preanhepatic phase and close monitoring of the serum calcium surge after reperfusion may be required to prevent posttransplantation BAP in living-donor LT.

MR Assessment of Acute Pathologic Process after Myocardial Infarction in a Permanent Ligation Mouse Model: Role of Magnetic Nanoparticle-Contrasted MRI

We evaluated the relationship between myocardial infarct size and inflammatory response using cardiac magnetic resonance imaging (CMR) in an acute myocardial infarction (AMI) mouse model. Myocardial infarction (MI) was induced in 14 mice by permanent ligation of the left anterior descending artery. Late gadolinium enhancement (LGE), manganese-enhanced MRI (MEMRI), and magnetofluorescent nanoparticle MRI (MNP-MRI) were performed 1, 2, and 3 days after MI, respectively. The size of the enhanced lesion was quantitatively determined using Otsus thresholding method in area-based and sector-based approaches and was compared statistically. Linear correlation between the enhanced lesion sizes was evaluated by Pearsons correlation coefficients. Differences were compared using Bland-Altman analysis. The size of the inflammatory area determined by MNP-MRI (57.1 ± 10.1%) was significantly larger than that of the infarct area measured by LGE (40.8 ± 11.7%, P < 0.0001) and MEMRI (44.1 ± 14.9%, P < 0.0001). There were significant correlations between the sizes of the infarct and inflammatory lesions (MNP-MRI versus LGE: r = 0.3418, P = 0.0099; MNP-MRI versus MEMRI: r = 0.4764, P = 0.0002). MNP-MRI provides information about inflammatory responses in a mouse model of AMI. Thus, MNP-MRI associated with LGE and MEMRI may play an important role in monitoring the disease progression in MI.

Comparison of Intraoperative Changes in Blood Glucose According to Model for End-stage Liver Disease Score During Living Donor Liver Transplantation.

BACKGROUND Recipients of liver transplantation (LT) may experience disturbance of blood glucose balance, which is aggravated by various exogenous factors. The Model for End-stage Liver Disease (MELD) score is an indicator of the severity of pretransplantation liver disease. In this study, we investigated the role of the MELD score in intraoperative changes in blood glucose in patients undergoing living donor LT (LDLT). METHODS Perioperative data from 280 patients undergoing LDLT were reviewed, including glucose-related data. Intraoperatively, blood glucose levels were checked every hour, and the mean values at each phase of LDLT were calculated. Patients were divided into high and low MELD groups. An unpaired t-test and repeated measures analysis of variance (RMANOVA) were used in intergroup and intragroup comparisons of perioperative blood glucose. RESULTS The high MELD group consisted of 79 patients. Both the time sequential change during LDLT and the interaction between perioperative blood glucose and MELD score were significant (RMANOVA with multivariate adjustment; P < .05). Pretransplant blood glucose levels did not differ between the 2 groups, but the mean levels of blood glucose were lower and the incidence of hypoglycemia was higher in the high compared with the low MELD group during all phases of LDLT (P < .05). CONCLUSIONS Blood glucose levels progressively increased during LDLT with an interaction with the MELD score. Patients with a high MELD score had low blood glucose levels and a greater incidence of intraoperative hypoglycemia. MELD score is a useful determinant of intraoperative blood glucose levels in LDLT patients.