In previous studies we reported that the levels of RBC, hemoglobulin (HGB) and hematocrit (HCT) in SAM P6 were increased significantly from 7 day after oral administration of the pilose antler extract, 5 g/kg/day, and were lasted during the study. Thus, this study was performed to elucidate mechanism of erythropoietic action by the extract administration. SAM R1 and SAM P6 were chosen as experimental animals. At age of 12 weeks, pilose antler extract were given 0.3 and 5 g/kg/day (p.o.) each for 0, 7 and 14 days in both animals. Complete blood cells such as RBC, HGB, and HCT were counted. And plasma concentration of erythropoietin (EPO) which is the major regulator of erythropoiesis was measured using $^{125}I-antierythropoietin$ IgG. Total iron concentration in plasma was also analyzed. The levels of RBC and HCT were increased significantly after administration at both doses of 0.3 and 5 g/kg/day in SAM P6, however, these were increased only at dose of 5 g/kg/day in SAM R1. The plasma EPO concentration was increased significantly after administration in SAM P6. The plasma concentrations of total iron were significantly decreased after administration of the extract in SAM P6. These results suggest that the changes in erythropoietic effects after the administration of pilose antler extract may be mediated, at least in part, through the change in the plasma EPO.
In this research we proceeded experiments to find the basis which make it possible to explain the physical and pathological process of Sasang constitutional medicine, in the way substituting hematopoietic-immune system(essence of life, blood, Ki and mental faculties : 精血氣神) Under these suppositions, the essence of life(精) is the multipotent stem cell which has the possibility to be specialized to any cell, the Ki(氣), blood(血) and mental faculties(神) are inferred that they are formed from specialized the essence of life(精), the blood(血) is the red blood cells and etc. that appears as the result of the genesis of circulation system. The Ki(氣) is from specialized basic immunity, the mental faculties(神) means long-term memories or combined immunity. Cytokines can act as specilaizing, growing factors and particiate in extremly combined procedure being controlled by both positive and negative specializing signals. Blood gathering was carried out in the morning and on empty stomach. The plasma was seperated and Erythropoietin, Stem cell factor, Granulocyte-colony stimulaing factor, Tumor necrosis factor, interlukin-3, Interleukin-6 were measured with ELISA kit. According to the result of post analysis by Duncan, each constitution is different in SCF(stem cell factor), IL-6(interleukin-6), EPO(erythropoietin). The value of Stem cell factor is high in order of Soumin(少陰人), Soyangin(少陽人), and Taeumin(太陰人), The value of interleukin-6 is high in Taeumin, Soumin, and Soyangin. Erythropoietin is high in order of Soumin, Soyangin, and Taeumin.
Six week-old ICR mice were divided into four groups including NC, RC, RR and RS, then they were injected with sun ginseng (RS), red ginseng (RR) and saline (RC) intraperitoneally as an amount of 60mg/kg body weight at 1 hour, 12 hours and 36 hours before the whole body irradiation with 6.5Gy of X-ray. And the mice were sacrificed at nine days after the irradiation. The RS group were significant increase in the weight of spleen (p<0.05) and the numbers of endogenous spleen colony (p<0.001) and WBC (p<0.05) especially neutrophils, lymphocytes and monocytes in comparison with the RC group. The RR group were significant increase in the numbers of endogenous spleen colony (p<0.01) and WBC (p<0.05) especially neutrophils, lymphocytes and eosinophils in comparison with the RC group. The RS group exhibited a more increase in the weight of spleen and the number of endogenous spleen colony than the RR group. The values of ALT (alanine transaminase) and AST (aspartate transaminase) were significantly elevated (p<0.05) by radiation and they were significantly decreased (p<0.05) in the RS group to the values of the NC group. The value of TBARS(thiobarbituric acid reactive substance) was significantly elevated (p<0.01) by radiation and it was significantly decreased (p<0.05) in the RS group. And the values of SOD (superoxide dismutase) and CAT (catalase) were significantly increased (p<0.05) in the RS group in comparison with the RC group. Taken together the above results, sun ginseng demonstrated the protective effects on hepatocytes and immune and hematopoietic cells in mice exposed to medium dose of irradiation, and those radioprotective effects were a little higher or similar to the red ginseng.
Background: Chronic myeloproliferative diseases are clonal stem cell diseases which occur as a result of uncontrollable growth and reproduction of hematopoietic stem cells, which are the myeloid series source in bone marrow. Recent studies have suggested that chronic inflammation can be a triggering factor in the clonal change in chronic myeloproliferative neoplasia (CMPN). In our study, we evaluated the existence of a chronic inflammation process in our Philadelphia negative (Ph-)CMPN patients using inflammation parameters in combination with demographic, laboratory and clinical characteristics of the patients. Materials and Methods: Demographic characteristics, clinical and laboratorial data, and thrombosis histories of 99 Ph-CMPN patients, who were diagnosed at our outpatient clinic of hematology in accordance with WHO 2008 criteria, were analyzed retrospectively,with 80 healthy individuals of matching gender and age included as controls. Complete blood counts, sedimentation, C reactive protein (CRP), JAK V617F gene mutations, abdomen ultrasound images and previous thrombosis histories of these patients were retrospectively analyzed. Results: Ph-CMPN and healthy control groups included 99 and 80 cases, respectively. PV, ET and MF diagnoses of patients were 43 (%43.4), 44 (44.4%) and 12 (12.1%), respectively. JAK V617F gene mutation was found to be positive in 64 (71.1%) of all cases and in 27(65.8%), 32 (82%), 5 (50%) of the cases in PV, ET and PMF groups, respectively. Thrombosis was determined as 12 (12%) in the entire group, 12.5% in the JAK V617F negative and 15.3% in the positive patients, with no statistical significance (p=0.758). No significant difference was observed between patients with and without previous thrombosis history in respect to hemogram parameters, sedimentation and CRP (p>0.05), neutrophil to lymphocyte ratio (NLR), erythrocyte distribution width (RDW), mean platelet volume (MPV) and sedimentation levels of the patient.
Objective: Explore the feasibility of allo-hemopietic stem cell transplants in treating patients with B cell acute lymphocytic leukemia. Methods: Between september 2006 and February 2011, fifteen patients with B cell acute lymphocytic leukemia (ALL) were treated by allo-hemopietic stem cell transplants (HSCT). Stem cell sources were peripheral blood. Six patients were conditioned by busulfan (BU) and cyclophosphamide (CY) and nine patients were conditioned with TBI and cyclophosphamide (CY). Graft versus host disease (GVHD) prophylaxis regimen consisted of cyclosporine A (CSA), methotrex ate (MTX) and mycophenolatemofetil (MMF). Results: Patients received a median of $7.98{\times}10^8{\cdot}kg^{-1}$ ($5.36-12.30{\times}10^8{\cdot}kg^{-1}$) mononuclear cells (MNC). The median time of ANC> $0.5{\times}10^9/L$ was day 12 (10-15), and PLT> $20.0{\times}10^9/L$ was day 13 (11-16). Extensive acute GVHD occurred in 6 (40.0%) patients, and extensive chronic GVHD was recorded in 6 (40.0%) patients. Nine patients were alive after 2.5-65 months follow-up. Conclusion: Allogeneic stem cell transplant could be effective in treating patients with B cell acute lymphocytic leukemia.
Formaldehyde (FA) is an economically important chemical, and has been found to cause various types of toxic damage to the body. Formaldehyde-induced toxic damage involves reactive oxygen species (ROS) that trigger subsequent toxic effects and inflammatory responses, which may increase risk of cancer. Therefore, in the present study, we aimed to investigate the possible toxic mechanism in bone marrow caused by formaldehyde. In accordance with the principle of randomization, the mice were divided into four groups of 6 mice per group. One group was exposed to ambient air and the other three groups were exposed to different concentrations of formaldehyde (20, 40, $80mg/m^3$) for 15 days in the respective inhalation chambers, 2h a day. At the end of the 15-day experimental period, all mice were killed. Bone marrow cells were obtained. Some of those were used for the determination of blood cell numbers, bone marrow karyote numbers, CFU-F, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content; others were used for the determination of mitochondrial membrane potential (MMP), cell cycle and Bcl-2, Bax, CytC protein expression. WBC and PLT numbers in median and high dose groups were obvious reduced, but there was no change on RBC numbers. There was also reduced numbers of bone marrow karyotes and CFU-F in the high dose group. SOD activity was decreased, but MDA content was increased. MMP and Bcl-2 expression were decreased with increasing formaldehyde concentration, while expression of Bax and Cyt C was increased. We also observed change in cell cycling, and found that there was S phase arrest in the high dose group. Our study suggested that a certain concentration of formaldehyde could have toxic effects on the hematopoietic system, with oxidative stress as a critical effect.
Background: In normal cells, activated epidermal growth factor receptor (EGFR) molecules are subjected to ubiquitination-mediated proteasome degradation pathway by c-Cbl, an ubiquitin ligase that checks uncontrolled proliferation. Hence expression of wild type c-Cbl molecule is essential to keep this degradation machinery in a functional state. Loss of expression or function of c-Cbl may consequently lead to sustained activation of EGFR and promote carcinogenesis, loss of function mutations in the c-Cbl gene already being reported in lung and hematopoietic cancers. However, the genetic status of c-Cbl in oral squamous cell carcinoma (OSCC) is not known. Hence in the present study we investigated the genomic DNA isolated from OSCC tissue biopsy samples for mutations in the RING finger domain coding region of c-Cbl gene, which has also been reported to be most frequently mutated in other cancers. Materials and Methods: Total genomic DNA isolated from thirty two post surgical OSCC tissue samples were amplified using primers flanking the exon 8 of c-Cbl gene that codes for the RING finger domain. The PCR amplicons were then resolved in a 1.2% agarose gel, purified and subjected to direct sequencing to screen for mutations. Results: The sequencing data of the thirty two OSCC samples did not identify mutations in the RING finger domain coding region of c-Cbl gene. Conclusions: To the best of our knowledge, this is the first time that the genetic status of c-Cbl gene in OSCC samples has been investigated. The present data indicates that genetic alteration of RING finger domain coding region of c-Cbl gene is relatively infrequent in OSCC samples.
Park, Dongsun;Jo, In Geun;Jang, Ja Young;Kwak, Tae Hwan;Yoo, Sang Ku;Jeon, Jeong Hee;Choi, Ehn-Kyoung;Joo, Seong Soo;Kim, Okjin;Kim, Yun-Bae
Biomolecules & Therapeutics
/
제23권5호
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pp.449-457
/
2015
The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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제27권5호
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pp.464-467
/
2001
Aplastic anemia is a hematopoietic disorder characterized by marked reduction or absence of erythoid, granulocytic, and megakariocytic cells in the bone marrow with resultant pancytopenia. To control of infection & bleeding secondary to leukopenia and thrombocytopenia, the inflammatory lesions in oral & maxillofacial area should be removed. Material & Method: The extractions were performed on 21 patients with severe aplastic anemia. The initial, pre-operative and postoperative CBCs were checked up. Amount and kind of transfused platelet in each patient and increment of platelet level were recorded. The complications were documented. Result : A mean of 2.9 teeth were extracted from each patient(ranging between 1 and 13). Furthermore, surgical extractions including ostectomy and odontectomy of the third molar were performed on 11 patients. The preoperative WBC levels presented between $600/{\mu}L$ and $5000/{\mu}L$(mean $2376/{\mu}L$). The WBC values decreased by an average of $145/{\mu}L$ per patient after extractions had been performed. The teeth of 16 patients were extracted under 10.0g/dL, and the mean change in postoperative hemoglobin levels in comparison with preoperative hemoglobin levels was -0.06 per patient. The initial platelet levels were between 1000/(L and $81,000/{\mu}L$(mean $20,174/{\mu}L$). In five patients, extractions were performed with platelet levels less than $50,000/{\mu}L$. Conclusion : The results suggest that more active and preventive treatments in the oral and maxillofacial area are possible and are necessary to remove the infectious foci on the patients with severe aplastic anemia. We report the results of our experiences and literature reviews in treatment of the patients with severe aplastic anemia in our department.
Kim, Ha-Neui;Ha, Hyun-Il;Lee, Jong-Ho;Kwak, Han-Bok;Kim, Hong-Hee;Lee, Zang-Hee
International Journal of Oral Biology
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제30권4호
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pp.143-148
/
2005
Osteoclasts are multinucleated cells with bone resorbing activity and differentiated from hematopoietic cell lineages of monocyte/macrophages in the presence of receptor activator of NF-${\kappa}B$ ligand (RANKL) and M-CSF. However, the exact molecular mechanisms through which RANKL stimulates osteoclastogenesis remain to be elucidated. Here we report that activation of cAMP-response elementbinding protein (CREB) is not involved in osteoclastogenesis from osteoclast precursors in response to RANKL. RANKL induced CREB activation in osteoclast precursors. Using pharmacological inhibitors, we found that RANKL-induced CREB activation is dependent on p38 MAPK pathways. We also found that ectopic expressions of wild type and dominant negative forms of CREB in osteoclast precursors did not affect RANKL-induced osteoclast formation and bone resorbing activity. Furthermore, dominant negative forms of CREB did not alter the expression levels of osteoclast-specific marker genes. Taken together, these data suggest that CREB is dispensable for differentiation and resorbing activity of osteoclasts.
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