Tooth movement by orthodontic force effects great tissue changes within the periodontium, especially by shifting the blood flow in the pressure side and resulting in a hypoxic state of low oxygen tension. The aim of this study is to elucidate the possible mechanism of apoptosis in response to hypoxia in MC3T3El osteoblasts, the main cells in bone remodeling during orthodontic tooth movement. MC3T3El osteoblasts under hypoxic conditions ($2\%$ orygen) resulted in apoptosis in a time-dependent manner as estimated by DNA fragmentation assay and nuclear morphology stained with fluorescent dye, Hoechst 33258. Pretreatment with Z-VAD-FMK, a pancaspase inhibitor, or Z-DEVD-CHO, a specific caspase-3 inhibitor, completely suppressed the DNA ladder in response to hypoxia. An increase in caspase-3-like protease (DEVDase) activity was observed during apoptosis, but no caspase-1 activity (YVADase) was detected. To confirm what caspases are involved in apoptosis, Western blot analysis was performed using anti-caspase-3 or -6 antibodies. The 10-kDa protein, corresponding to the active products of caspase-3, and the 10-kDa protein of the active protein of caspase-6 were generated in hypoxia-challenged cells in which the processing of the full length form of caspase-3 and -6 was evident. While a time course similar to this caspase-3 and -6 activation was evident, hypoxic stress caused the cleavage of lamin A, which was typical of caspase-6 activity. In addition, the stress elicited the release of cytochrome c into the cytosol during apoptosis. Furthermore, we observed that pre-treatment with SB203580, a selective p38 mitogen activated protein kinase inhibitor, attenuated the hypoxia-induced apoptosis. The addition of SB203S80 suppressed caspase-3 and -6-like protease activity by hypoxia up to $50\%$. In contrast, PD98059 had no effect on the hypoxia-induced apoptosis. To confirm the involvement of MAP kinase, JNK/SAPK, ERK, or p38 kinase assay was performed. Although p38 MAPK was activated in response to hypoxic treatment, the other MAPK -JNK/SAPK or ERK- was either only modestly activated or not at all. These results suggest that p38 MAPK is involved in hypoxia-induced apoptosis in MC3T3El osteoblasts.
Background: Tissue hypoxia is a characteristic of many human malignant neoplasms, and hypoxia inducible factor-1 (HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increased oxygen delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-1 a has been reported in many human malignancies, but in esophageal squamous cell carcinoma, the influence of HIF-1 a on tumor biology, including neovascularization, is not still defined. Material and Method: The influence of HIF-1 a expression on angiogenic factors, correlation between the tumor proliferation and HIF-1 a expression, interaction of HIF-1 a expression and p53, and correlation between HIF-1 a expression and clinicopathological prognostic parameters were investigated, using immunohistochemical stains for HIF-1 a, VEGF, CD34, p53, and Ki-67 on 77 cases of resected esophageal squamous cell carcinoma. Result: HIF-1 a expression in cancer cells was found in 33 of 77 esophageal squamous cell carcinoma cases. The 33 cases (42.9%) showed positive stain for HIF-1 a. High HIF-1 a expression was significantly associated with several pathological parameters, such as histologic grade (p=0.032), pathological TMN stage (p=0.002), the depth of tumor invasion (p=0.022), regional lymph node metastasis (p=0.002), distant metastasis (p=0.049), and lymphatic invasion (p=0.004). High HIF-1 a expression had significant VEGF immunoreactivity (p=0.008) and Ki-67 labeling index (p<0.001), but was not correlated with microvascular density within tumors (p=0.088). The high HIF-1 a expression was correlated with aberrant p53 accumulation with a marginal significance (p=0.056). The overall 5-year survival rate was 34.9%. The survival rate of patients with a high HIF-1 a expression was worse than that of patients with low-expression tumors (log-rank test, p=0.0001). High HIF-1 a expression was independent unfavorable factors although statistical significance is marginal in multivariate analysis. Conclusion: It is suggested that (1) high HIF-1 a expression in esophageal squamous cell carcinoma is associated with tumor hypoxia, or with genetic alteration in early carcinogenesis and progressive stages, (2) high HIF-1 a expression may be associated with intratumoral neovascularization through HIF-VEGF pathway, and (3) high HIF-1 a expression is associated with poor prognosis in patients with esophageal squamous cell carcinoma and may playa role as biomarker for regional lymph node metastasis.
Chung, Won Sik;Cha, Kyung Man;Kim, Hyung Min;Jeong, Won Jung;So, Byung Hak
Journal of The Korean Society of Clinical Toxicology
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v.14
no.1
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pp.26-32
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2016
Purpose: Aspiration pneumonia is an important complication of drug intoxication with decreased mental status. The purpose of the study is to investigate the risk factors of aspiration pneumonia in the patients of benzodiazepine overdose with or without co-ingestion of other drugs. Methods: A retrospective chart review of patients who visited the emergency department between January 2012 and December 2014 was conducted. Demographic data, time from ingestion to visit, initial vital signs, symptoms, mental status, medical history, laboratory results, chest radiological findings and co-ingested medications were recorded. Multiple logistic analyses were performed to verify the association between variables and the development of aspiration pneumonia. Results: A total of 249 patients presented to the emergency department with benzodiazepine overdose. Aspiration pneumonia had developed in 24 patients (9.6%). Univariate analysis revealed time from ingestion to visit was longer, Glasgow coma scale score was lower, hypoxia was presented, leukocytosis was shown, types of ingested drugs was high, less activated charcoal was applied and tricyclic antidepressants was taken in patients that developed aspiration pneumonia. Time from ingestion to visit (odds ratio (OR) 1.121, 95% confidence interval (CI), 1.057-1.189, p=0.000), GCS score (OR 0.724. 95% CI, 0.624-0.839, p=0.000), oxygen saturation (OR 0.895, 95% CI, 0.835-0.959, p=0.002), and co-ingestion of TCA (OR 4.595, 95% CI, 1.169-18.063, p=0.029) were identified as risk factors of morbidity of aspiration pneumonia upon multiple logistic regression analysis. Conclusion: Time from ingestion to visit, low GCS score, low oxygen saturation and co-ingestion of TCA were risk factors of the development of aspiration pneumonia in benzodiazepine overdose patients.
During the period of Sep. 1981 to Feb. 1983, a program of measuring the blood gases and pH of 19 varicocele patients was taken. These patients were classified into 2 groups based upon their semen analyses; Group A consisted of 9 patients who demonstrated normal findings and group B consisted of 10 patients who demonstrated seminal stress pattern. The blood pH: $PO_2$ , and $PCO_2$ were measured in the internal spermatic vein and the radial vein of all the patients. The results obtained were as follows; 1. In Group A, no difference was detected in the value of the pH, $PO_2$ and $PCO_2$ between the internal spermatic vein and the radial vein. 2. In group B, a similar lack of difference in blood gases found between the internal spermatic vein and the radial vein. 3. The blood gases between the internal spermatic veins of Group A and B were compared. No difference was discovered between the 2 group also. It has been hypothesized that the pathogenesis of spermatogenic depression in patients with varicocele is testicular hypoxia due to low oxygen tension of the internal spermatic vein. However, our results do not bear out this proposed mechanism.
Seo, Tae-Cheol;Rhee, Han-Cheol;Rho, Mi-Young;Choi, Kyeong-Lee;Yun, Hyung-Kwon;Chun, Chang-Hoo
Journal of Bio-Environment Control
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v.18
no.2
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pp.112-118
/
2009
To determine the effects of circulation frequency of nutrient solution, three frequencies of 10min. on/10min. off; 10min. on/110min. off; and 10min. on/1,430min. off. treatments were applied to leafy vegetable production using deep flow technique (DFT) systems and their growth and phytonutrient content were investigated. In the 10min. on/I,430min. off treatment, dissolved oxygen concentration (DOC) 17 days after treatment decreased to 2.8mg. $L^{-1}$, known to be a low DOC that causes hypoxia, and thereafter decreased to 1.5mg. $L^{-1}$ 20 days after treatment. Fresh weight of 7 leafy vegetables in the 10min. on/1,430min. off treatment was lower by 0${\sim}$24% than those in the 10min. on/110min. off treatment, and those in the 10min. on/10min. off was higher by -2${\sim}$34% than those in the 10min. on/110min. off treatment as control. As the more frequent circulation was applied, the higher phosphorous content and the lower carbon to nitrogen ratio (C/N ratio) and total ascorbic acid contents were resulted. Results indicate that the circulation frequency of 110min, on/110min. off could be recommended for the production of the tested leafy vegetables in DFT systems.
Benthic environmental parameters were analysed at 40 stations during the period from April 1995 to February 1996. such as water temperature, salinity, and dissolved oxygen (DO)-concentration in the surface and bottom water layers, grain size, chemical oxygen demand (COD), ignition loss, particulate organic carbon (POC) in the sediment of Youngsan River estuary. The water temperature ranged from 4.1 to $29.8^{\circ}C$ in the surface and 4.0 to $20.7^{\circ}C$ in the bottom layers. Salinity ranged from 15.1 to $33.6\%_{\circ}$ in the surface and 31.5 to $33.2\%_{\circ}$ in the bottom layer. The salinity in the outer pan of the study area was higher than that of inner area from autumn to spring, whereas they remained lower in summer. Dissolved oxygen concentration ranged from 5,1 to 11.2 $mg/\ell$ in the surface, and 0.79 to 10,2 $mg/{\ell}$ in the bottom layers. Hypoxic condition ($\le2.0mg/\ell$) was developed in the bottom water layer from Youngsan dike to Mokpo Harhour in summer due to the summer stratification. The surface sediment type was silty clay with a mean grain size of $9.12{\pm}0.45\phi$. The range of COD was from 6.15 to $15.49mgO_2/g$ with a mean of $10.59{\pm}12.64mgO_2/g$. The COD in the inner stations was relatively higher than that of outer stations, and decreased toward the outer part of the study area. Ignition loss (IL) ranged from 3.35 to $15.45\%$ with a mean of $5.96{\pm}1.91\%$. Principal component analysis was carried out from the following five environmental parameters: water temperature, dissolved oxygen in the bottom layer and mean grain size, clay content and COD in the sediment. The forty stations in the study area were classified into three stational groups. Group I was located in the inner part of the estuary characterised by relatively low surface salinity and bottom water temperature, fine sedimemt texture, high organic matter and low dissolved oxygen concentration during the summer. Meanwhile, Group III showing relatively high bottom salinity and water temperature was located in the outer part of the estuary characterising coarse sediment and low organic content in sediment. Group II was between Group I and Group III. The division of the areal groups had high correlations to the DO in the bottom layer and clay content in the sediment.
The level and activity of critical regulatory proteins in cells are tightly controlled by several tiers of post-translational modifications. HIF-1α is maintained at low levels under normoxia conditions by the collaboration between PHD proteins and the VHL-containing E3 ubiquitin ligase complex. We recently identified a new physiologically relevant mechanism that regulates HIF-1α stability in the nucleus in response to cellular oxygen levels. This mechanism is based on the collaboration between the SET7/9 methyltransferase and the LSD1 demethylase. SET7/9 adds a methyl group to HIF-1α, which triggers degradation of the protein by the ubiquitin-proteasome system, whereas LSD1 removes the methyl group, leading to stabilization of HIF-1α under hypoxia conditions. In cells from knock-in mice with a mutation preventing HIF-1α methylation (Hif1αKA/KA), HIF-1α levels were increased in both normoxic and hypoxic conditions. Hif1αKA/KA knock-in mice displayed increased hematological parameters, such as red blood cell count and hemoglobin concentration. They also displayed pathological phenotypes; retinal and tumor-associated angiogenesis as well as tumor growth were increased in Hif1αKA/KA knock-in mice. Certain human cancer cells exhibit mutations that cause defects in HIF-1α methylation. In summary, this newly identified methylation-based regulation of HIF-1α stability constitutes another layer of regulation that is independent of previously identified mechanisms.
This study was carried out to investigate the effects of induced wet-injury conditions on barley seedling growth. Barley seedlings at the three leaf stage were grown in culture solutions with various combinations of dissolved oxygen (DO), nutrients and citric acid (CA) concentrations. Seedling growth was reduced by hypoxia. Root length and root fresh weight were most severely reduced under 1 ppm DO. Shoot growth was slightly reduced but not root growth under low nutrient condition. Seedling growth was reduced by CA in a concentration-dependant manner, Response of seedling growth was efficiently differentiated in a solution containing 1 ppm DO, one tenth of the normal P, K and Mg concentration and 3 mM CA. Under this induced wet-injury condition, overall seedling growth of 6 cultivars was reduced by 11 to 19% compared to the control condition. The results suggest that the induced wet-injury condition can be used for the screening of resistant genotypes at the seedling stage.
[Purpose] The present study investigated the effect of endurance exercise with blood flow restriction (BFR) performed at either 25% maximal oxygen uptake (${\dot{V}}O_2$ max) or 40% ${\dot{V}}O_2$ max) on muscle oxygenation, energy metabolism, and endocrine responses. [Methods] Ten males were recruited in the present study. The subjects performed three trials: (1) endurance exercise at 40% ${\dot{V}}O_2$ max without BFR (NBFR40), (2) endurance exercise at 25% ${\dot{V}}O_2$ max with BFR (BFR25), and (3) endurance exercise at 40% ${\dot{V}}O_2$ max with BFR (BFR40). The exercises were performed for 15 min during which the pedaling frequency was set at 70 rpm. In BFR25 and BFR40, 2 min of pressure phase (equivalent to 160 mmHg) followed by 1 min of release phase were repeated five times (5 × 3 min) throughout 15 minutes of exercise. During exercise, muscle oxygenation and concentration of respiratory gases were measured. The blood samples were collected before exercise, immediately after 15 min of exercise, and at 15, 30, and 60 minutes after completion of exercise. [Results] Deoxygenated hemoglobin (deoxy-Hb) level during exercise was significantly higher with BFR25 and BFR40 than that with NBFR40. BFR40 showed significantly higher total-hemoglobin (total-Hb) than NBFR40 during 2 min of pressure phase. Moreover, exercise-induced lactate elevation and pH reduction were significantly augmented in BFR40, with concomitant increase in serum cortisol concentration after exercise. Carbohydrate (CHO) oxidation was significantly higher with BFR40 than that with NBFR40 and BFR25, whereas fat oxidation was lower with BFR40. [Conclusion] Deoxy-Hb and total Hb levels were significantly increased during 15 min of pedaling exercise in BFR25 and BFR40, indicating augmented local hypoxia and blood volume (blood perfusion) in the muscle. Moreover, low-and moderate-intensity exercise with BFR facilitated CHO oxidation.
Journal of the Korean Society for Marine Environment & Energy
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v.18
no.2
/
pp.51-63
/
2015
In order to investigation long-term variations of water qualities in the Saemangeum Salt-Water Lake formed after the sea-dike construction, the survey has carried out over 40 time from 2002 to 2010. The decreased salinity in surface water immediately after the dike construction has maintained on equal terms for years. After the dike construction, the early concentration of SPM in surface water has decreased but then it showed the tendency to move up and down due to the changes of water level in the lake. The elevated concentration of Chl-a in surface water initially after the dike construction was kept at the same conditions for years. The concentration of DIN in surface water has not changed before and shortly after the dike construction. However, the concentration of $NH_4-N$ in surface water has increased steadily after the dike construction. Consequently the concentration of DIN in the lake water after years has raised compared to pre-dike construction. The reduced concentration of DIP in surface water soon after the dike construction has increased after years as well as $NH_4-N$ due to the accumulation of organic matter to inside lake. Unlike with the unvaried $NO_3-N$, the concentration of DISi in surface water after the dike construction has immediately increased and maintained the enhanced level indicating the supply from other sources except the freshwater. Since the dike construction, the spatial characteristics of water quality was divided river sides and rest of the lake markedly. Stratification of river sides was more strong than the dike sides. In the warm seasons, hypoxia causing the release of nutrients and metals from sediment was observed downward about 1 m from surface of river sides. We strongly suggest to make some urgent measure to prevent low dissolved oxygen condition in the bottom layer of the river sides.
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