BACKGROUND/AIMS: Iron overload reportedly increases the risk of colorectal neoplasms, but the distribution of tissue iron in a colorectal neoplasm remains controversial. In this study, we attempted to determine the significance of tissue iron in colorectal adenomas and adenocarcinomas. METHODS: This study investigated 138 colorectal neoplasms (54 adenocarcinomas, 25 adenomas with high-grade dysplasia, and 59 adenomas with low-grade dysplasia) that were removed by surgical or endoscopic resection in Konkuk University Hospital between August 2005 and August 2006. Adjacent normal colon tissues and colorectal neoplasms were stained with Perls' Prussian blue to reveal ferric compounds. RESULTS: Positive Perls' staining was evident in 35.2% (19/54) of the adenocarcinomas and 22.6% (19/84) of the adenomas, and in only 2.2% (3/138) of the samples of adjacent normal colon tissue (p<0.001). Iron appears to reside exclusively in the stroma and outside the gland, rather than in the epithelial cells. Iron expression was strong in larger (p=0.004) and pedunculated (p<0.001) adenomas, and in all types of adenocarcinomas regardless of their size, shape, and location. CONCLUSIONS: The frequent presence of iron in the stroma of large adenomas, pedunculated adenomas, and adenocarcinomas indicates that iron deposition is a secondary phenomenon to intralesional hemorrhage rather than a consequence of epithelial-cell carcinogenesis.
Adenocarcinoma ; Adenoma ; Colon ; Colorectal Neoplasms ; Epithelial Cells ; Ferric Compounds ; Ferrocyanides ; Hemorrhage ; Iron ; Iron Overload

OBJECTIVE: To investigate the efficacy of prussian blue (PB) or its combination with hemoperfusion (HP) in the treatment of acute thallium poisoning. METHODS: Forty-seven patients with acute thallium poisoning with complete data hospitalized in the 307th Hospital of PLA from September 2002 to December 2017 were enrolled, and they were divided into mild poisoning group (blood thallium < 150 μg/L, urinary thallium < 1 000 μg/L) and moderate-severe poisoning group (blood thallium ≥ 150 μg/L, urinary thallium ≥ 1 000 μg/L) according to the toxic degrees. All patients were given symptomatic supportive treatments such as potassium supplementation, catharsis, vital organ protections, neurotrophic drugs, and circulation support. The mild poisoning patients were given PB with an oral dose of 250 mg×kg^-1×d^-1, while moderate-severe poisoning patients were given PB combined HP continued 2-4 hours each time. The PB dose or frequency of HP application was adjusted according to the monitoring results of blood and urine thallium. Data of gender, age, pain grading (numeric rating scale NRS), clinical manifestations, blood and urine thallium before and after treatment, length of hospitalization and prognosis were collected. RESULTS: Of the 47 patients, patients with incomplete blood and urine test results, and used non-single HP treatment such as plasmapheresis and hemodialysis for treatment were excluded, and a total of 29 patients were enrolled in the analysis. (1) Among 29 patients, there were 20 males and 9 females, median age of 40.0 (34.0, 49.0) years old; the main clinical manifestations were nervous system and alopecia, some patients had digestive system symptoms. There were 13 patients (44.8%) in the mild poisoning group with painless (grade 0) or mild pain (grade 1-3) with mild clinical symptoms, the length of hospitalization was 17.0 (14.2, 21.5) days. There were 16 patients (55.2%) in the moderate-severe poisoning group with moderate pain (grade 4-6) or severe pain (grade 7-10) with severe clinical symptoms, the length of hospitalization was 24.0 (18.0, 29.0) days. (2) After treatment, the thallium concentrations in blood and urine in the mild poisoning group were significantly lower than those before treatment [μg/L: blood thallium was 0.80 (0, 8.83) vs. 60.00 (40.00, 120.00), urine thallium was 11.30 (0, 70.10) vs. 370.00 (168.30, 610.00), both P < 0.01], the thallium concentrations in blood and urine in the moderate-severe poisoning group were also significantly lower than those before treatment [μg/L: blood thallium was 6.95 (0, 50.50) vs. 614.50 (245.00, 922.00), urinary thallium was 20.70 (1.95, 283.00) vs. 5 434.00 (4 077.20, 10 273.00), both P < 0.01]. None of the 29 patients died, and their clinical symptoms were improved significantly. All the 27 patients had good prognosis without sequela in half a year follow-up, and 2 patients with severe acute thallium poisoning suffered from nervous system injury. CONCLUSIONS In the acute thallium poisoning patients, on the basis of general treatment, additional PB in mild poisoning group and PB combined with HP in moderate-severe poisoning group can obtain satisfactory curative effects.
Adult ; Female ; Ferrocyanides ; Heavy Metal Poisoning ; Hemoperfusion ; Humans ; Male ; Middle Aged ; Thallium/poisoning*

PURPOSE: This study was performed to evaluate the characteristics of rat mesenchymal stem cells (RMSCs) transduced with human ferritin gene and investigate in vitro MRI detectability of ferritin-transduced RMSCs. MATERIALS AND METHODS: The RMSCs expressing both myc-tagged human ferritin heavy chain subunit (myc-FTH) and green fluorescence protein (GFP) were transduced with lentiviurs. Transduced cells were sorted by GFP expression using a fluorescence-activated cell sorter. Myc-FTH and GFP expression in transduced cells were detected by immunofluorescence staining. The cell proliferative ability and viability were assessed by MTT assay. The RMSC surface markers (CD29+/CD45-) were analyzed by flow cytometry. The intracellular iron amount was measured spectrophotometically and the presence of ferritin-iron accumulation was detected by Prussian blue staining. In vitro magnetic resonance imaging (MRI) study of cell phantoms was done on 9.4 T MR scanner to evaluate the feasibility of imaging the ferritin-transduced RMSCs. RESULTS: The myc-FTH and GFP genes were stably transduced into RMSCs. No significant differences were observed in terms of biologic properties in transduced RMSCs compared with non-transduced RMSCs. Ferritin-transduced RMSCs exhibited increased iron accumulation ability and showed significantly lower T2 relaxation time than non-transduced RMSCs. CONCLUSION: Ferritin gene as MR reporter gene could be used for non-invasive tracking and visualization of therapeutic mesenchymal stem cells by MRI.
Animals ; Apoferritins ; Ferritins ; Ferrocyanides ; Flow Cytometry ; Fluorescence ; Fluorescent Antibody Technique ; Genes, Reporter ; Humans ; Iron ; Magnetic Resonance Imaging ; Mesenchymal Stromal Cells ; Rats ; Relaxation ; Track and Field

PURPOSE: A molecular magnetic resonance (MR) imaging technique using superparamagnetic iron oxide (SPIO) nanocrystals was developed for monitoring stem cells noninvasively. This study was performed to investigate whether the presence of transplanted human mesenchymal stem cells in the penile cavernosum of a diabetic rat model could be evaluated noninvasively using molecular MR imaging. MATERIALS AND METHODS: SPIO nanocrystals (Feridex; AMI, Cambridge, USA) were transferred to human mesenchymal stem cells (hMSCs) using GenePORTER. The SPIO-transferred hMSCs were examined with Prussian blue staining. SPIO-labeled hMSCs were transplanted to the penile cavernosum of a diabetic rat model and MR images were examined in vivo using 1.5 T MR. RESULTS: SPIO was transferred to hMSCs successfully. MR signal intensity at the areas of the SPIO-transferred hMSCs decreased in the penile cavernosum of the diabetic rat model. SPIO particles were confirmed in the transplanted penile cavernosum with Prussian blue staining. CONCLUSIONS: The SPIO-labelled hMSCs in the penile cavernosum of a diabetic rat model can be monitored noninvasively using molecular MR imaging.
Animals ; Diabetes Mellitus ; Ferric Compounds ; Ferrocyanides ; Humans ; Iron ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Magnetics ; Magnets ; Mesenchymal Stromal Cells ; Nanoparticles ; Rats ; Stem Cells ; Transplants

OBJECTIVETo explore the feasibility and fluorescence characteristics of CFSE negative staining for in vivo cell imaging of super paramagnetic iron oxide nanoparticles (SPIO) phagocytosed by mouse mononuclear macrophage leukemia cells-RAW264.7.

METHODSAfter labeled with SPIO, the RAW264.7 macrophages were stained with Prussian blue stain and CFSE fluorescence negative stain step by step. Furthermore, trypan blue staining was used to evaluate cell viability of cells which stained with CFSE. At last, laser scanning confocal microscope was used to measure SPIO in cells through CFSE fluorescence negative stain method.

RESULTSSPIO within RAW264.7 macrophages showed blue in Prussian's blue staining, while showed negative area in CFSE negative staining. Good consistencies between Prussian's blue staining and CFSE negative staining were observed. In addition, RAW264.7 macrophages showed high viability after SPIO/CFSE dual-labeled method, proved by typan stain.

CONCLUSIONThe CFSE fluorescence negative staining may be used for detecting SPIO that phagocytosed by RAW264.7 macrophages and it is showed good consistency that confirmed one another when compared to classic Prussian' blue staining.

Animals ; Cell Line, Tumor ; Cell Survival ; Contrast Media ; Ferric Compounds ; Ferrocyanides ; Fluoresceins ; Fluorescence ; Leukemia ; Macrophages ; Magnetic Resonance Imaging ; Magnetite Nanoparticles ; Mice ; Negative Staining ; Phagocytosis ; Succinimides

We investigated the effect of zinc on the formation of colonic aberrant crypt foci induced by azoxymethane (AOM) followed by dextran sodium sulfate (DSS) in mice with high iron diet (HFe; 450 ppm iron). Six-week old ICR mice were fed on high iron diets with combination of three different levels of zinc in diets, low-zinc (LZn; 0.01 ppm), medium-zinc (MZn; 0.1 ppm), and high-zinc (HZn; 1 ppm) for 12 weeks. Animals were received weekly intraperitoneal injections of AOM (10 mg/kg B.W. in saline) for 3 weeks followed by 2% DSS (molecular weight 36,000~50,000) in the drinking water for a week. To confirm the iron storage in the body, the hepatic iron concentration has been determine chemically and compared with histological assessment visualized by Prussian blue reaction. Aberrant crypt (AC) and aberrant crypt foci (ACF) were analyzed in the colonic mucosa of mouse fed high dietary iron. Superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) level were also investigated. Apoptosis in the preneoplastic lesion was determined by terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL). In addition, immunohistochemistry of beta-catenin was also performed on the mucous membrane of colon. The number of large ACF (> or = 4 AC/ACF), which possess greater tumorigenic potential, was significantly lower in MZn and HZn groups compared with LZn group. Cytosolic SOD activity in the liver was significantly higher in HZn group compared with LZn group. Hepatic MDA level was decreased significantly in HZn group compared with MZn and LZn groups. Apoptotic index was significantly higher in HZn group. Taken together, these findings indicate that dietary zinc might exert a protective effect against colonic preneoplastic lesion induced by AOM/DSS in ICR mice with high iron status, and suggest that dietary supplement of zinc might play a role in suppressing colon carcinogenesis in mice.
Aberrant Crypt Foci ; Animals ; Apoptosis ; Azoxymethane ; beta Catenin ; Colon ; Cytosol ; Dextrans ; Diet ; Dietary Supplements ; Drinking Water ; Ferrocyanides ; Immunohistochemistry ; Injections, Intraperitoneal ; Iron ; Iron Overload ; Iron, Dietary ; Liver ; Mice ; Mice, Inbred ICR ; Mucous Membrane ; Prussian Blue Reaction ; Sodium ; Sulfates ; Superoxide Dismutase ; Zinc

PURPOSE: To evaluate the usefulness of in vivo magnetic resonance (MR) imaging for tracking intravenously injected superparamagnetic iron oxide (SPIO)-labeled human umbilical vein endothelial cells (HUVECs) in an acute renal failure (ARF) rat model. MATERIALS AND METHODS: HUVECs were labeled with SPIO and poly-L-lysine (PLL) complex. Relaxation rates at 1.5-T MR, cell viability, and labeling stability were assessed. HUVECs were injected into the tail vein of ARF rats (labeled cells in 10 rats, unlabeled cells in 2 rats). Follow-up serial T2*-weighted gradient-echo MR imaging was performed at 1, 3, 5 and 7 days after injection, and the MR findings were compared with histologic findings. RESULTS: There was an average of 98.4+/-2.4% Prussian blue stain-positive cells after labeling with SPIO-PLL complex. Relaxation rates (R2*) of all cultured HUVECs at day 3 and 5 were not markedly decreased compared with that at day 1. The stability of SPIO in HUVECs was maintained during the proliferation of HUVECs in culture media. In the presence of left unilateral renal artery ischemia, T2*-weighted MR imaging performed 1 day after the intravenous injection of labeled HUVECs revealed a significant signal intensity (SI) loss exclusively in the left renal outer medulla regions, but not in the right kidney. The MR imaging findings at days 3, 5 and 7 after intravenous injection of HUVECs showed a SI loss in the outer medulla regions of the ischemically injured kidney, but the SI progressively recovered with time and the right kidney did not have a significant change in SI in the same period. Upon histologic analysis, the SI loss on MR images was correspondent to the presence of Prussian blue stained cells, primarily in the renal outer medulla. CONCLUSION: MR imaging appears to be useful for in vivo monitoring of intravenously injected SPIO-labeled HUVECs in an ischemically injured rat kidney.
Acute Kidney Injury ; Animals ; Cell Survival ; Cell Tracking ; Culture Media ; Endothelial Cells ; Ferric Compounds ; Ferrocyanides ; Follow-Up Studies ; Human Umbilical Vein Endothelial Cells ; Injections, Intravenous ; Iron ; Ischemia ; Kidney ; Magnetic Resonance Spectroscopy ; Magnets ; Rats ; Relaxation ; Renal Artery ; Track and Field ; Umbilical Veins ; Veins