• Journal of Korean Neurosurgical Society
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• v.54 no.6
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• pp.467-476
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• 2013

Objective : This study aimed to evaluate the hypotheses that administration routes [intra-arterial (IA) vs. intravenous (IV)] affect the early stage migration of transplanted human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in acute brain infarction. Methods : Male Sprague-Dawley rats (n=40) were subjected to photothrombotic infarction. Three days after photothrombotic infarction, rats were randomly allocated to one of four experimental groups [IA group : n=12, IV group : n=12, superparamagnetic iron oxide (SPIO) group : n=8, control group : n=8]. All groups were subdivided into 1, 6, 24, and 48 hours groups according to time point of sacrifice. Magnetic resonance imaging (MRI) consisting of T2 weighted image (T2WI), $T2^*$ weighted image ($T2^*WI$), susceptibility weighted image (SWI), and diffusion weighted image of rat brain were obtained prior to and at 1, 6, 24, and 48 hours post-implantation. After final MRI, rats were sacrificed and grafted cells were analyzed in brain and lung specimen using Prussian blue and immunohistochemical staining. Results : Grafted cells appeared as dark signal intensity regions at the peri-lesional zone. In IA group, dark signals in peri-lesional zone were more prominent compared with IV group. SWI showed largest dark signal followed by $T2^*WI$ and T2WI in both IA and IV groups. On Prussian blue staining, IA administration showed substantially increased migration and a large number of transplanted hBM-MSCs in the target brain than IV administration. The Prussian blue-positive cells were not detected in SPIO and control groups. Conclusion : In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration. MRI and histological analyses revealed the time course of cell migration, and the numbers and distribution of hBM-MSCs delivered into the brain.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.19 no.2
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• pp.147-151
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• 2016

Neonatal hemochromatosis (NH) is a severe neonatal liver injury that is confirmed by extra-hepatic iron accumulation. Although a recent study described treating NH with exchange transfusions and intravenous immunoglobulin, liver transplantation should be considered for patients with severe liver failure that does not respond to other medical treatment. Herein, we report the case of a two-month-old female infant who presented with persistent ascites and hyperbilirubinemia. Her laboratory findings demonstrated severe coagulopathy, high indirect and direct bilirubin levels, and high ferritin levels. Abdominal magnetic resonance imaging presented low signal intensity in the liver on T2-weighted images, suggesting iron deposition. The infant was diagnosed with NH as a result of the clinical findings and after congenital infection and metabolic diseases were excluded. The infant was successfully treated with a living-donor liver transplantation. Living related liver transplantation should be considered as a treatment option for NH in infants.

• Investigative Magnetic Resonance Imaging
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• v.17 no.3
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• pp.181-191
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• 2013

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 $98.4{\pm}2.4%$ Prussian blue stain-positive cells after labeling with SPIOPLL 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.

• Journal of Pharmacopuncture
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• v.7 no.3
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• pp.5-25
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• 2004

Objectives : To observe changes in the serum proteins before and after intravenous injection of wild ginseng herbal acupuncture. Methods : Blood was collected before and after the administration of wild ginseng herbal acupuncture and only the serum was centrifuged. Then differences in the spots on the scanned image after running 2-Dimensionl electrophoresis were located and conducted mass analysis and protein identification. Results : Following results were obtained from the comparative analysis of serum proteins before and after the administration of wild ginseng herbal acupuncture. 1. 28 spots were identified before and after the administration. 2. In confirming manifestation degree, spots with more than two-times increase were 204, 803, 1505, 2205, 3105, 7104, 9001 spots, with more than one-time increase were 1101, 1302, 2013, 3009, 3010, 4002, 4009, 6706, 7103, 8006, 8101, and spots with decrease were 205, 801, 3205, 5202, 6105. 3. After conducting protein identification, proteins 205, 804, 1302, 4009, 6105, 6106 are unidentified yet, and 1101 is unnamed protein. Protein 204 is identified as complement receptor CR2-C3d, 801 as YAP1 protein, 803 as antitrypsin polymer, 1505 as PRO0684, 2013 and 3010 as proapolipoprotein, 2205 as USP48, 2403 as vitamin D binding protein, 3009 as complement component 4A preprotein, 3105 as immunoglobulin lambda chain, 3205 as transthyretin, 4002 as Ras-related protein Ral-A, 4204 as beta actin, 5202 and 7104 as apolipoprotein L1, 6704 as alpha 2 macroglobulin precursor, 7103 as complement component 3 precursor, 8006 as testis-specific protein Y, 8101 as Transferrin, 9001 as(Alpha-Oxy, Beta-(C112g)deoxy) T-State Human Hemoglobin, and 9003 as human hemoglobin. 4. Immune protein CR2-C3d, which acts against microbes and pathogenic organisms, and Antitrypsin(803), which is secreted with inflammatory response in the lungs, were increased by more than 200% after the administration of herbal acupuncture. 5. Immunoglobulin lambda chain(3105), Alpha-Oxy, Beta-(C112g)deoxy T-State Human Hemoglobin(9001), and human hemoglobin(9003) were increased by more than two-times after the administration of herbal acupuncture. 6. Proapolipoprotein(2013, 3010) and apolipoprotein(7104), key components of the HDL-cholesterol which plays an important role in preventing arteriosclerosis, were increased after the administration of herbal acupuncture. 7. Vitamin D binding protein(DBP, 2403), protecting the lung at the time of inflammatory response, was increased after the administration of herbal acupuncture. 8. Transthyretin(TTR, 3205), which is the main protein causing familial aimyloid polyneuropathy(FAP), was decreased after the administration of herbal acupuncture. 9. Ras-related protein Ral-A(4002) that controls phospholipid metabolism, cytoskeletal formation, and membrane traffic, was increased after the administration of herbal acupuncture. 10. Testis-specific protein Y(8006), which takes part in determination of the gender, was increased by more than two-times after the administration of herbal acupuncture. 11. Transferrin(8101), T-State Human Hemoblobin(9001), and Human Hemoblobin(9003) which balances the iron level in the body, were increased after the administration of herbal acupuncture. Conousion : Above results support the notion that intravenous injection of cultivated wild ginseng herbal acupuncture induce changes in serum proteins and this research can be a pioneer work in finding biomarkers.

• Clinical and Experimental Pediatrics
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• v.59 no.2
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• pp.100-103
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• 2016

Patients with hemolytic-uremic syndrome (HUS) can rapidly develop profound anemia as the disease progresses, as a consequence of red blood cell (RBC) hemolysis and inadequate erythropoietin synthesis. Therefore, RBC transfusion should be considered in HUS patients with severe anemia to avoid cardiac or pulmonary complications. Most patients who are Jehovah's Witnesses refuse blood transfusion, even in the face of life-threatening medical conditions due to their religious convictions. These patients require management alternatives to blood transfusions. Erythropoietin is a glycopeptide that enhances endogenous erythropoiesis in the bone marrow. With the availability of recombinant human erythropoietin (rHuEPO), several authors have reported its successful use in patients refusing blood transfusion. However, the optimal dose and duration of treatment with rHuEPO are not established. We report a case of a 2-year-old boy with diarrhea-associated HUS whose family members are Jehovah's Witnesses. He had severe anemia with acute kidney injury. His lowest hemoglobin level was 3.6 g/dL, but his parents refused treatment with packed RBC transfusion due to their religious beliefs. Therefore, we treated him with high-dose rHuEPO (300 IU/kg/day) as well as folic acid, vitamin B12, and intravenous iron. The hemoglobin level increased steadily to 7.4 g/dL after 10 days of treatment and his renal function improved without any complications. To our knowledge, this is the first case of successful rHuEPO treatment in a Jehovah's Witness child with severe anemia due to HUS.

• Toxicological Research
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• v.22 no.1
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• pp.55-59
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• 2006

The purpose of this study was to investigate the toxicity of hematoporphyrin-coated magnetic ferrofluid (HP-MF) through intravenous administration in Sprague-Dawley rats. Each group was treated with either saline, or the HP-MF at 0.5, 1, 1.5, 2 and 4 ml/kg body weight (b.w.) for the observation of survival rate, clinical symptoms, laboratory values and histopathological findings. In this study, HP-MF was evaluated for the survival rates, symptoms, laboratory values and histopathological examination after treatments. The result revealed that the animals in the group of HP-MF at 2 and 4 ml/kg b.w. showed some lethality. In serum biochemistry, the levels of AST, ALT and ALP were increased in the MF and HP-MF treated groups. However, histopathological examination for the suspected organs showed no evidence of hepatotoxicity and nephrotoxicity of typical iron poisoning. Though the toxicity of HP-MF was higher than that of HP, long retention of hematoporphyrin via HP-MF provides additional benefit over conventional hematoporphyrin. HP-MF could be utilized as a potential photodynamic agent in cancer therapy. It is suggested to develop an efficient external magnetic device to attract hematoporphyrin in the target site, thereby enabling to administering a small amount of HP-MF.

• Journal of The Korean Society of Clinical Toxicology
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• v.15 no.2
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• pp.148-151
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• 2017

Methemoglobinemia is a condition in which the iron portion of hemoglobin, which binds to oxygen, is oxidized to produce methemoglobin, which increases blood concentration. There are many causes of methemoglobinemia, the most common being food, drugs, and chemicals. A 75-year-old male patient who had taken an herbicide did not notice any nonspecific symptoms. However, after 4 hours, his methemoglobin levels increased to 17.1%, while after 7 hours it increased to 26.5%, at which time intravenous administration of methylene blue 1 mg/kg (an antidote) was started. After a total of five doses of methylene blue at 1 mg/kg due to reactive methemoglobinemia for about 36 hours, the methemoglobin levels increased to 23.7%. Because no more methylene blue could be administered, 10 g of ascorbic acid (vitamin C) was administered intravenously. After 82 hours, ascorbic acid 10 g was administered six times for repeated reactive methemoglobinemia. No additional reactive methemoglobinemia was observed. The ventilator and endotracheal tube were successfully removed on day 5 after admission.

• Journal of The Korean Society of Clinical Toxicology
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• v.6 no.2
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• pp.134-137
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• 2008

Methylene blue is the first choice for treating methemoglobinemia, any increase in normal methemoglobin levels. Methemoglobin is an abnormal hemoglobin in which the iron has been oxidized to the ferric(+3) state, making it incapable of oxygen transport. Methemoglobinemia most commonly results from exposure to oxidizing chemicals, but may also arise form genetic, dietary, or even idiopathic etiologies. Patients with low methemoglobin levels are asymptomatic, but high methemoglobin levels can lead to headaches or even death. Methylene blue, the first-line treatment for methemoglobinemia, can also produce hemolytic anemia. Jaundice or dark urine during methylene blue treatment may indicate hemolytic anemia. A 47-year-old female patient with a history of depressive mood disorder developed significant methemoglobinemia after ingesting a Propanil overdose. Twenty-two hours after ingestion, methemoglobin levels in the blood were 73.2%. She was treated with intravenous methylene blue in the therapeutic range (1 mg/kg every 4 h for 3days). The 2nd day after methylene blue use, methemoglobin levels in the blood were 33%, and the 5th day decreased to 10% with better general condition. The patient had hyperbilirubinemia after hemolytic anemia, but she recovered completely.

• Journal of Yeungnam Medical Science
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• v.18 no.2
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• pp.226-238
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• 2001

Background: Anemia in chronic renal failure plays an important role in increasing morbidity of dialysis patients. The causes of the anemia are multifactorial. With using of erythropoietin(EPO) most of uremia-induced anemia can be overcome. However, about 10% of renal failure patients shows EPO-resistant anemia. Hyporesponsiveness to EPO has been related to many factors: iron deficiency, aluminum intoxication, inflammations, malignancies and secondary hyperparathyroidism. So I evaluated the improvement of EPO responsiveness after correction of above several factors. Materials and Methods: Seventy-two patients on hemodialysis over 6 months were treated with intravenous ascorbic acid(IVAA, 300 mg t.i.w. for 12 weeks), After administration of IVAA for 12 weeks, patients were classified into several groups according to iron status, serum aluminum levels and i-PTH levels. Indivisualized treatments were performed: increased iron supplement for absolute iron deficiency, active vitamin D3 for secondary hyperparathyroidism and desferrioxamine(DFO, 5 mg/kg t.i.w.) for aluminum intoxication or hyperferritinemia. Results: 1) Result of IVAA therapy for 12 weeks on all patients(n=72). Hemoglobin levels at 2, 4, 6 week were significantly elevated compared to baseline, but those of hemoglobin at 8, 10, 12 week were not significantly different. 2) Result of IVAA therapy for 20 weeks on patients with 100 ${\mu}g/l$ ${\leq}$ ferritin < 500 ${\mu}g/l$ and transferrin saturation(Tsat) below 30%(n=30). After treatment of IV AA for 12 weeks, patients were evaluated the response of therapy according to iron status. Patients with 100 ${\mu}g/l$ ${\leq}$ ferritin < 500 ${\mu}g/l$ and Tsat below 30% showed the most effective response. These patients were treated further for 8 weeks. Hemoglobin levels at 2, 4 week were significantly increased compared to baseline with significantly reduced doses of EPO at 2, 4, 6, 10, 12, 16, 20 week. Concomitantly significantly improvement of Tsat at 2, 6, 16, 20 week compared to baseline were identified. 3) Result of IVAA therapy for 12 weeks followed by DFO therapy for 8 weeks on patients with serum aluminum above 4 ${\mu}g/l$(n=12) Hemoglobin levels were not significantly increased during IVAA therapy for 12 weeks but dosages of EPO were significantly decreased at 2, 4, 6, 8 week during DFO therapy compared to pre-treatment status. Conclusion: IVAA can be helpful for the treatment of the anemia caused by functional iron deficiency and can reduce the dosage of EPO for anemia correction. And administration of low dose DFO, in cases of increased serum aluminum level, can reduce the requirement of EPO.

• Journal of Ginseng Research
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• v.3 no.1
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• pp.66-93
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• 1979

Panax ginseng C. A. Meyer, which has been known for more than EWO years. occupies a Particular prince in folk medicine as so called tonic remedy. The pharmacolgical investigations of ginseng, based on the scientific concepts and methodology, have been performed by many researchers through the past 50∼60 years at different parts of the world. The pharmacological action of Panax ginseng compiled from the numerous reports can be summarized as follows: 1. On central nervous system, the effect of Panax ginseng is timulatory in smaller doses and somewhat depressive in larger doses. From the psychopharmacological aspect, ginseng seems to increase the mental efficiency of man. 2. Ginseng has the effect tending to Protect organism from various physical and chemical stresses. 3. The growth and basal metabolic rates of experimental animals are stimulated by ginseng. Ginseng also prolongs the survival time of animals under adverse influences. 4. Increasing the physical and mental efficiency, ginseng postpones the onset of fatigue and increases the working capacities. 5. In the case of the intravenous administration of ginseng, a transitory and slight hypotensive effect is observed. These hypotensive effects seems to include that of a direct action and actions related to the release of histamine and/or serotonin by ginseng. 6. It is Presumed that ginseng lowers the elevated bleed ingar and cholesterol level. 7. Ginseng tends to increase the gastrointestinal motizity and tone 8. It is presumed that ginseng Promotes the iron metabolism and activates the hematopoietic factors. 9. Ginseng tends to stimulate the biosynthesis of nucleic acid and release of histamine and serotonin. 10. The toxicity end adverse reactions of ginseng appear to be nothing that warrants apprehension. 11. Anticancer erects of ginseng seem to be due to indirect action rather than direct action on cancer cell, by improving the host condition 12. Recent clinical trials of ginseng harts obtained sent good results, but Present trial is still limited in its range, so it is necessary to broaden the scope of trial covering many kinds of organs and diseases. From the above, although it appears that substantial advancements have been achieved in the studies on the Pharmacological actions of Panax ginseng there are many discrepancies noticed in the reported data. Furthermore the precise mechanisms of actions of ginseng are sometimes obscure, even unknown in other actions as the students stand now. The main reasons for this are considered to be that even though saponin has been identified at one of the active substances of ginseng, other components have not fully been identified and that the experimental approaches of the investigations varied with different researchers. Thus a thorough analysis of the chemical components and newer standardized concepts and metohds appear to be the pre-requisites for further study of the pharmacolgical effects and mechaisms of Panax ginseng.