Sohn, Sang Kyun;Moon, Joon Ho;Lee, In Hee;Ahn, Jae Sook;Kim, Hyeoung Joon;Chung, Joo Seop;Shin, Ho Jin;Park, Sung Woo;Lee, Won Sik;Lee, Sang Min;Kim, Hawk;Lee, Ho Sup;Kim, Yang Soo;Cho, Yoon Young;Bae, Sung Hwa;Lee, Ji Hyun;Kim, Sung Hyun;Song, Ik Chan;Kwon, Ji Hyun;Lee, Yoo Jin
The Korean journal of internal medicine
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v.33
no.6
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pp.1194-1202
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2018
Background/Aims: This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. Methods: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. Results: HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were $53.1%{\pm}10.7%$ for allo-HCT with HMA, $75%{\pm}21.7%$ for allo-HCT without HMA, $17.3%{\pm}3.6%$ for HMA, and $20.8%{\pm}6.9%$ for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ${\geq}65years$ (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS. Conclusions: For the H/VH risk group, very poor cytogenetic risk, age ${\geq}65years$, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.
Toxic effects of 2-bromopropane (2-BP) on the hematopoietic system and testis were investigated in male Srague-Dawley (SD) rats. 80 male SD rats, 5 weeks old, were treated with 2-BP in corn oil at levels of 0, 100, 330 and 1,000 mg/kg/day for 4 weeks orally. 10 animals from each group were maintained for additional 8 weeks following the treatment. In addition, 60 male SD rats were divided into 2 groups and administered 2-BP in corn oil at levels of 0 and 1,000 mg/kg/day orally and sacrificed after 1. 2 and 3 weeks of treatment. Clinical observation. body weight changes, food consumption, organ weight changes. hematology, serum chemistry and histopathology of the testis were performed in the study. No clinical sign and mortality were observed in the study. The body weights were significantly reduced with the treatment but gradually recovered. The relative organ weights of the testis and thymus significantly decreased in both of the groups treated with 1,000 mg/kg/day for 3 and 4 weeks. In the recovery groups, organ weights of the testis and epididymis were significantly reduced in both of the groups treated with 330 and 1,000 mg/kg/day. Platelets and reticulocytes were significantly reduced in both of the group treated with 1.000 mg/kg/day for 3 and 4 weeks. While red blood cells were de-creased but mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were increased in the recovery group. Significant increase of chloride was observed in all of the treatment groups except the recovery groups, and calcium was significantly increased in both of the groups treated with 1,000 mg/kg/ day for 3 and 4 weeks. On the other hand. there were significant decreases in alanine aminotransferase (ALT) and aspatate aminotransferase (AST) in most of groups treated with 1.000 mg/kg/day. In the testis. the spermatogonia in stages I-VI were mostly depleted and the spermatocytes in stages VII-VIII were de-generated or necrotized at week 1 after treatment of 2-BP. The degeneration of germ cells and the a-trophy of seminiferous tubules became more severe in time-dependent and dose-dependent manners. The damaged tubules showed regeneration in part. however. they did not appear to be completely recovered within 8 weeks of the recovery period. On the basis of the results. it is suggested that 2-BP would cause toxicities in hematopoiesis by possibly interfering the production of red blood cells and platelets and in spermatogenesis by the destruction oj spermatogonia in SD male rats.
High-tech medical equipment has increased the utilization of radiation in the medical field. As a result, research on radiation protection using natural materials has become an important social issue. Selenium is a natural substance that is highly expressed in prostate known that an essential role in prostate cells. Selenium was orally administered to Rat and irradiated with 10 Gy of radiation. Then, the prostate tissue w as used as a target organ for 1 day, 7 days and 21 days to investigate the radiation protection effect of selenium through changes of blood components, Superoxide Dismutase and histological changes. As a result, there was a significant protective effect of hematopoietic immune system(hemoglobin concentration, neutrophil, platelet) in the group irradiated with selenium(p<0.05). the observation of tissue changes selenium is an effective component to increase Superoxide Dismutase activity, and it was confirmed that it has an effect of inhibiting the expression of hypertrophy of prostate by irradiation. Therefore, it is considered that selenium can be utilized as a radioprotective agent by inducing prevention of prostate-related diseases.
To estimate the cancer mortality rates among Koreans, a mortality survey was carried out in the province of $Ky{\breve{o}}ngsangnam-do$. The study population are the beneficiaries of Korea Medical Insurance Corporation(KMIC), $Ky{\breve{o}}ngsangnam-do$ area, among which the 3,867 deaths occurred from January, 1989 to December, 1990, were reviewed to confirm the cancer deaths. These were based upon the death certificates and medical utilization records before dying which were available through the computerized databases on medical care utility of KMIC. The survey was conducted along three steps. At first, the death certificates were examined, as a second step medical utilization records were reviewed, and finally direct contacts to the family members of the deceased were done. As a result, 990 deaths were found due to cancer. Using them, age and sex specific cancer(all sites and several sites) mortality rates were estimated. Overall cancer mortality rate in the area was estimated 138.7 per 100,000 person-years in males, and 65.7 in females, respectively. And the orders of site-specific cancer mortality rates were the cancers of stomach, liver, lung, esophagus, and cancers of the hematopoietic system among males, In females, followed by gastric cancer, cancers of lung and liver are the 2nd and 3rd in rank, respectively and cancers of breast and uterine cervix are the 4th and the 5th in rank.
This study is desinged to examine the effects of Taheebo(Tabebuia avellanedae) extract on the prostate of male rats as a natural radiation protection agent. Taheebo extract is well known to inhibit cell growth for the cell lines of breast and prostate cancer. In this study, the X-ray 7 Gy was irradiated in the prostate of male rat to identify radiation protection effects by Taheebo Extracts, 1, 7, and 21 Days later, hematological changes, external toxicity assessments(LDH), antioxidant enzyme(SOD) activity changes and tissue change were observed. IR+TH group showed greater lymphocyte levels than the irradiation group, which is believed to affect the hematopoietic immune system's resilience. As a results of the external toxicity assessment, Taheebo extract's toxicity is maximum 18.128±5.16%, minimum 13.6945±4.43%. Taheebo is considered to be of little toxicity. The composition of prostate cell nuclei and cytoplasm in Control and TH group was honogeneous, whereas the cell nucleus cohesion in the prostate in irradiation group and inflammatory reactions in cytoplasm were shown. IR+TH group showed less inflammatory reactions of cytoplasm in the prostate than in the radiation irradiation group, but showed a cohesive phenomenon of cell nuclei. It is judged that Taheebo extract has radiation protection against prostate cells.
Selenium (Se), which is natural materials existing was known as an important component of selenoprotein, one of the important proteins responsible for the redox pump of a living body. Selenium was orally administered to Rat and irradiated with 10 Gy of radiation. Then, the thyroid gland was used as a target organ for 1 day, 7 days and 21 days to investigate the radiation protection effect of selenium (Se) through changes of blood components, thyroid hormones (T3, T4), antioxidant enzyme (GPx) activity and thyroid tissue changes. As a result, there was a significant protective effect of hematopoietic immune system(hemoglobin concentration, neutrophil, platelet)(p<0.05). The activity of Glutathione Peroxidase (GPx), the antioxidant enzyme, and the activity of the target organ, thyroid hormone (T3, T4), also showed significant activity changes (p<0.05). In the observation of tissue changes, it was confirmed that there was a protective effect of thyroid cell damage which caused the cell necrosis by radiation treatment. Therefore, it is considered that selenium(Se) can be utilized as a radiation defense agent by inducing immunogenic activity effect of a living body.
The Journal of Korea Assosiation for Disability and Oral Health
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v.12
no.2
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pp.96-100
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2016
Metachromatic leukodystrophy (MLD) is a progressive and degenerative neurological disease caused by a deficiency of the catabolic enzyme arylsulfatase A. Deficiency of arylsulfatase A results in accumulation of sulfatide in the white matter of the peripheral and central nervous system and it occurs demyelination as a result. The patient gradually goes through mental and motor failure. General symptoms of MLD include gait disturbance, mental deterioration, muscle rigidity and impaired swallowing. Inheritance of the disease is autosomal recessive. We report a dental caries treatment of a 3-year old boy with MLD. The patient underwent hematopoietic stem cell transplantation (HSCT) to slow the progression of the disease. He was suffered from difficulties of mastication and swallowing from the degenerative neurological symptom. He was ingesting food by both oral feeding and tubal feeding after he took percutaneous endoscopic gastrostomy (PEG). The cause of multiple caries was mainly presumed as patient's prolonged time of meal. The treatment was performed under general anesthesia considering patient's incompliance. Severely affected lower primary molars were treated with pulp treatment and restored with stainless steel crown. Others were restored with composite resin. There were no postoperative complications. MLD is life threatening progressive disease and also has an impact on unfavorable condition for oral health. Routine home oral care and periodic professional dental care should be emphasized to the caregiver of patient considering the susceptibility of dental caries. Not only the medical care, but periodic dental office visit would benefit the quality of life of the patient.
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.
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major reason for stopping or changing anticancer therapy. Among the proposed pathomechanisms underlying CIPN, proinflammatory processes have attracted increasing attention. Here we assessed the role of prostaglandin D2 (PGD2) signaling in cisplatin-induced neuropathic pain. Methods: CIPN was induced by intraperitoneal administration of cisplatin 2 mg/kg for 4 consecutive days using adult male Sprague-Dawley rats. PGD2 receptor DP1 and/or DP2 antagonists were administered intrathecally and the paw withdrawal thresholds were measured using von Frey filaments. Spinal expression of DP1, DP2, hematopoietic PGD synthase (H-PGDS), and lipocalin PGD synthase (L-PGDS) proteins were analyzed by western blotting. Results: The DP1 and DP2 antagonist AMG 853 and the selective DP2 antagonist CAY10471, but not the DP1 antagonist MK0524, significantly increased the paw withdrawal threshold compared to vehicle controls (P = 0.004 and P < 0.001, respectively). Western blotting analyses revealed comparable protein expression levels in DP1 and DP2 in the spinal cord. In the CIPN group the protein expression level of L-PGDS, but not of H-PGDS, was significantly increased compared to the control group (P < 0.001). Conclusions: The findings presented here indicate that enhanced PGD2 signaling, via upregulation of L-PGDS in the spinal cord, contributes to mechanical allodynia via DP2 receptors in a cisplatin-induced neuropathic pain model in rats, and that a blockade of DP2 receptor activation may present a novel therapeutic target for managing CIPN.
Oxygen is the final acceptor of electron transport from fat and carbohydrate oxidation, which is the rate-limiting factor for cellular ATP production. Under altitude hypoxia condition, energy reliance on anaerobic glycolysis increases to compensate for the shortfall caused by reduced fatty acid oxidation [1]. Therefore, training at altitude is expected to strongly influence the human metabolic system, and has the potential to be designed as a non-pharmacological or recreational intervention regimen for correcting diabetes or related metabolic problems. However, most people cannot accommodate high altitude exposure above 4500 M due to acute mountain sickness (AMS) and insulin resistance corresponding to a increased levels of the stress hormones cortisol and catecholamine [2]. Thus, less stringent conditions were evaluated to determine whether glucose tolerance and insulin sensitivity could be improved by moderate altitude exposure (below 4000 M). In 2003, we and another group in Austria reported that short-term moderate altitude exposure plus endurance-related physical activity significantly improves glucose tolerance (not fasting glucose) in humans [3,4], which is associated with the improvement in the whole-body insulin sensitivity [5]. With daily hiking at an altitude of approximately 4000 M, glucose tolerance can still be improved but fasting glucose was slightly elevated. Individuals vary widely in their response to altitude challenge. In particular, the improvement in glucose tolerance and insulin sensitivity by prolonged altitude hiking activity is not apparent in those individuals with low baseline DHEA-S concentration [6]. In addition, hematopoietic adaptation against altitude hypoxia can also be impaired in individuals with low DHEA-S. In short-lived mammals like rodents, the DHEA-S level is barely detectable since their adrenal cortex does not appear to produce this steroid [7]. In this model, exercise training recovery under prolonged hypoxia exposure (14-15% oxygen, 8 h per day for 6 weeks) can still improve insulin sensitivity, secondary to an effective suppression of adiposity [8]. Genetically obese rats exhibit hyperinsulinemia (sign of insulin resistance) with up-regulated baseline levels of AMP-activated protein kinase and AS160 phosphorylation in skeletal muscle compared to lean rats. After prolonged hypoxia training, this abnormality can be reversed concomitant with an approximately 50% increase in GLUT4 protein expression. Additionally, prolonged moderate hypoxia training results in decreased diffusion distance of muscle fiber (reduced cross-sectional area) without affecting muscle weight. In humans, moderate hypoxia increases postprandial blood distribution towards skeletal muscle during a training recovery. This physiological response plays a role in the redistribution of fuel storage among important energy storage sites and may explain its potent effect on changing body composition. Conclusion: Prolonged moderate altitude hypoxia (rangingfrom 1700 to 2400 M), but not acute high attitude hypoxia (above 4000 M), can effectively improve insulin sensitivity and glucose tolerance for humans and antagonizes the obese phenotype in animals with a genetic defect. In humans, the magnitude of the improvementvaries widely and correlates with baseline plasma DHEA-S levels. Compared to training at sea-level, training at altitude effectively decreases fat mass in parallel with increased muscle mass. This change may be associated with increased perfusion of insulin and fuel towards skeletal muscle that favors muscle competing postprandial fuel in circulation against adipose tissues.
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