In anesthetized normocapnic and normotensive dogs, the effect of arterial hypoxemia on cerebral blood flow and oxidative carbohydrate metabolism was studied. The results are as follows: 1) The hypoxic vasodilatory effect on cerevral vessels is intact even at profound systemic hypoxemia(Pao2 30 torr) if Paco2 is controlled within normal limits. 2) CMRO2 did not significantly increase above the normal even during profound arterial hopoxemis, indicating that CMRO2 levels are poor indices of hypoxia. 3) A disporportinately high glycolysis at Pao2 of 50 torr suggested early cerebral metabolic changes which became more marked with further decrease in Pao2. 4) One hour after restitution of normoxia, however, carebral blood flow and metabolism manifested complete recovery. 6) It is concluded that a transient(20 minutes) profoun systemic arterial hypoxemia does not produce prolonged disorder of cerebral blood flow and oxidative carbohydrate metabolism provided that the cerebral perfusion pressure is kept normal.
Animals ; Anoxia* ; Carbohydrate Metabolism ; Cerebrovascular Circulation* ; Dogs ; Glycolysis ; Metabolism*

The isolated dog brain was perfused for a period of 4 minutes with blood normal in all constituents, but pathologically low in oxygen in order to follow the metabolic response of the brain to anoxia. During anoxic perfusion, the brain appears to subsist on the free amino acids in the brain and on glucose taken up from the perfusion blood. Oxygen uptake is relatively constant increasing temporarily immediately after anoxia. The lactic acid formed within the brain during anoxia is not released in any quantity; instead it appears to be metabolized in the brain following the period of anoxia causing a lower than norma1 uptake of glucose. Brain ATP and GrP levels decrease significantly, but not markedly indicating that the brain's energy requirements are being partially met during anoxic perfusion.
Amino Acids/*metabolism ; Animals ; Anoxia/*metabolism ; Brain/*metabolism ; Dogs ; Electroencephalography ; Glucose/*metabolism ; Lactates/*metabolism ; Oxygen Consumption

Tumor PET imaging with radiopharmaceuticals plays a major role in the understanding of tumor biological information and for diagnosis of tumorswith non-invasive methods. These radiopharmaceuticals can be divided into two categories radiopharmaceuticals for metabolic process imaging and for specific receptor imaging. Most tumor imaging radiopharmaceuticals such as [18F]FDG, [18F]FLT, and [11C]choline can be trapped in tumor cells by specific metabolic processes of each radiopharmaceutical and show an increase in metabolism of tumor regions. Unlike these compounds, the hypoxia imaging adiopharmaceuticals such as [18F]FMISO and [64Cu]ATSM are trapped by oxidative metabolic mechanisms under only hypoxic conditions of tumor cells. For tumor specific receptor imaging, [18F]FES for estrogen receptor positive breast cancer may be used and recent clinical results showed the possibility of evaluating tumor therapy responseby estrogen receptor imaging with [18F]FES. This paper gives an overview of the current status of tumor PET imaging adiopharmaceuticals and the development of new lead compounds as potential radiopharmaceuticals by medicinal chemistry.
Anoxia ; Breast Neoplasms ; Chemistry, Pharmaceutical ; Diagnosis ; Estrogens ; Metabolism ; Radiopharmaceuticals*

BACKGROUND: This study was purposed to study the effect of reoxygenation with room air as compared to FiO2 1.0 in a feline model subjected to hypoxemia followed by reoxygenation. Changes in the brain energy metabolism were investigated by 31P magnetic resonance spectroscopy(31P MRS). METHODS: Twelve cats were employed for this study and divided into two groups(6 cats each). Both groups were subjected to hypoxemia for 1 hr with FiO2 0.07 followed by reoxygenation for 2hrs. For group I, the reoxygenation was done by FiO2 1.0 and for group 2, by room air. Brain intracellular pH and the ratio of Pcr/Pi(phosphocreatine/inorganic phosphate) were calculated from the spectra acquired every 15 mimutes of the hypoxemia and reoxygenation periods. RESULTS: The intracellular pH of the baseline were 7.07+/-0.01 and 7.04+/-0.01 for group 1 and group 2, respectively, and dropped to 6.89+/-0.04 and 6.83+/-0.06 during hypoxemia. For both groups, the intracellular pH returned to baseline values after 30 minutes of reoxygenation. The ratios of Pcr/Pi of the baseline were 2.41+/-0.21 and 2.47+/-0.15, for group 1 and group 2, and dropped to 0.77+/-0.10 and 0.70+/-0.11, respectively, during hypoxemia and recovered to the baseline values after 30 minutes of reoxygenation for both groups. For both pH and the ratios of Pcr/Pi, the differences between the groups were statistically insignificant. CONCLUSION: From this study, we can conclude that reoxygenation by room air is as effective as FiO2 1.0 in the feline model of hypoxemia investigated by 31P MRS.
Animals ; Anoxia* ; Brain* ; Cats* ; Energy Metabolism* ; Hydrogen-Ion Concentration ; Metabolism ; Oxygen* ; Ventilation

Evidence indicates that hypoxia and oxidative stress can control metabolic reprogramming of cancer cells and other cells in tumor microenvironments and that the reprogrammed metabolic pathways in cancer tissue can also alter the redox balance. Thus, important steps toward developing novel cancer therapy approaches would be to identify and modulate critical biochemical nodes that are deregulated in cancer metabolism and determine if the therapeutic efficiency can be influenced by changes in redox homeostasis in cancer tissues. In this review, we will explore the molecular mechanisms responsible for the metabolic reprogramming of tumor microenvironments, the functional modulation of which may disrupt the effects of or may be disrupted by redox homeostasis modulating cancer therapy.
Anoxia ; Homeostasis* ; Metabolic Networks and Pathways ; Metabolism* ; Oxidation-Reduction ; Oxidative Stress ; Tumor Microenvironment

A tracheostomy is the safest and popular method for maintaining airway. Recently, this method is interesting in neurosurgical unit respiratory care in brain damaged patients. Authors had performed a tracheostomy on 20 cases among the brain damaged patients and evaluated it's effect by PaO2 and PaCO2 change, respiratory and Glasgow coma scale change between pretracheostomic and posttracheostomic state. Also, it's complications were evaluated. The results are as follows ; 1) After tracheostomy, significant elevations were noted in mean arterial oxygen tension from 65.55+/-19.34mmHg to 85.83+/-33.53mmHg at 30mins, to 84.48+/-29.12mmHg at 60mins, to 97.00+/-21.25mmHg at 120mins. 2) After tracheostomy, significant changes were not noted in mean arterial carbon dioxide tension. 3) After tracheostomy, progressive decrease in mean respiratory rate per min. were noted from 27.6+6.44 to 21.89+2.79 during 24hrs. 4) After tracheostpmy, slight improvement in mean Glasgow coma scale were noted from 7.7+2.54 to 8.25+2.95 during 24hrs. 5) The complications occured in 5 cases. 4 cases of them were pneumonias and 1 case of them was hemorrhage. From above results, Authors conclude that tracheostomy improves poor clinical status including hypoxemia and tachypnea which have influence on brain metabolism in the brain damaged patients.
Anoxia ; Brain* ; Carbon Dioxide ; Glasgow Coma Scale ; Hemorrhage ; Humans ; Metabolism ; Oxygen ; Pneumonia ; Respiratory Rate ; Tachypnea ; Tracheostomy*

Hypoxia-inducible factor 1 (HIF1) is a master transcription factor that induces the transcription of genes involved in the metabolism and behavior of stem cells. HIF1-mediated adaptation to hypoxia is required to maintain the pluripotency and survival of stem cells under hypoxic conditions. HIF1 activity is well known to be tightly controlled by the alpha subunit of HIF1 (HIF1α). Understanding the regulatory mechanisms that control HIF1 activity in stem cells will provide novel insights into stem cell biology under hypoxia. Recent research has unraveled the mechanistic details of HIF1α regulating processes, suggesting new strategies for regulating stem cells. This review summarizes recent experimental studies on the role of several regulatory factors (including calcium, 2-oxoglutarate-dependent dioxygenase, microtubule network, importin, and coactivators) in regulating HIF1α activity in stem cells.
Anoxia ; Biology ; Calcium ; Hypoxia-Inducible Factor 1 ; Karyopherins ; Metabolism ; Microtubules ; Stem Cells ; Transcription Factors

BACKGROUND: In this study, the putative interactions between apoptosis and heat shock proteins disturbed as a result of ATP depletion were investigated as a hypoxia model. METHODS: The direct cellular damages were assessed by the release of LDH from the cytoplasm of the human tubular epithelial cells (HK-2 cells) following ATP depletion. The Bcl-2/Bax mRNA expression ratio, used as an index to assess to what extent apoptosis contributed to tubular cell damage, and the expressions of HSP 90, 72 and 27 in relation to the Bcl-2/Bax ratio in the ischemic model, as parameters of their functional contributions to tubule cell damage, were also studied. Heat preconditioning (HS) was performed at 43 degrees in a temperature-regulated water bath for 1 h. RESULTS: The release of LDH due to ATP depletion was not significantly increased in HK-2 cells compared to the control, but was slightly increased in heat preconditioned cells compared to non heat preconditioned cells, but the difference was not statistically significant (6.33 +/- 0.57 U/L vs. 8.67 +/- 2.52 U/L, p> 0.05). The Bcl-2/ Bax mRNA expression ratio increased progressively from the control to the heat preconditioned and ATP depleted cells (control; 100%, ATP depletion; 154 +/- 6%, heat preconditioning; 212 +/- 6%, heat preconditioning and ATP depletion; 421 +/- 8%). No contribution of heat preconditioning and ATP depletion was observed on the expressions of HSP90 and HSP27. However, HSP72 expression was prominent by ATP depletion, especially after heat preconditioning. CONCLUSION: There may be a possibility that the preservation of cytolytic damage and an increase in the Bcl-2/Bax mRNA expression ratio is related to the increase of HSP72 in ATP depletion as a hypoxia model.
Adenosine Triphosphate/*deficiency ; Anoxia/metabolism ; Epithelium/*metabolism ; Heat-Shock Proteins/*metabolism ; Humans ; Kidney Tubules/cytology/*metabolism ; L-Lactate Dehydrogenase/metabolism ; RNA, Messenger/metabolism ; Research Support, Non-U.S. Gov't

We report here, that a vector constructed based on ppET-1 gene promoter and 5' untranslated region induced a high level of gene expression in endothelial cells and the specificity is even further enhanced under hypoxia-mimic conditions due to a natural hypoxia responsive element within the promoter region. A naked DNA vector that confers endothelial cell specific gene expression as well as efficient levels of gene expression was constructed with an endothelial cell specific naked DNA vector, pETlong, by using the full length promoter of the preproendothelin-1 gene and the entire 5' untranslated region upstream from the start codon. Inclusion of the entire 5' untranslated region in pETlong increased gene expression 2.96 fold as compared with that from pETshort, which contains only the promoter sequences. Reporter gene expression from pETlong was 7.9 fold higher as compared with that from CMV-driven promoter based vector in calf pulmonary endothelial cells. However, in nonendothelial COS cells, luciferase activity from pETlong was only 0.3 fold as compared with that of CMV-based vector. Similar results were observed in other nonendothelial cells. These results demonstrate that the pETlong drives gene expression in endothelial cells with high efficacy and specificity. We have examined hypoxia responsiveness of pETlong as the promoter region of the preproendothelin-1 gene contains hypoxia responsive elements. The activity of the pETlong vector was increased 1.6 fold under hypoxia-mimic conditions using cobalt chloride. The high levels of hypoxia-inducible expression in endothelial cells relative to the low levels of background expression in other cells shows that pETlong could be a useful tool for vascular targeting of vascular disease and cancer gene therapy.
*5' Untranslated Regions ; Animals ; Anoxia/metabolism ; Cattle ; Endothelial Cells/*metabolism ; Endothelin-1/*genetics/metabolism ; Endothelium, Vascular/metabolism ; Gene Transfer Techniques ; *Genetic Vectors ; Human ; *Promoter Regions (Genetics)

The mechanisms that regulate angiogenesis in hypoxia or hypoxic microenvironment are modulated by several pro- and antiangiogenic factors. Hypoxia-inducible factors (HIFs) have been established as the basic and major inducers of angiogenesis, but understanding the role of interacting proteins is becoming increasingly important to elucidate the angiogenic processes of a hypoxic response. In particular, with regard to wound healing and the novel therapies for vascular disorders such as ischemic brain and heart attack, it is essential to gain insights in the formation and regulation of HIF transcriptional machineries related to angiogenesis. Further, identification of alternative ways of inhibiting tumor growth by disrupting the growth-triggering mechanisms of increasing vascular supply via angiogenesis depends on the knowledge of how tumor cells develop their own vasculature. Here, we review our findings on the interactions of basic HIFs, HIF-1alpha and HIF-2alpha, with their regulatory binding proteins, histone deacetylase 7 (HDAC7) and translation initiation factor 6 (Int6), respectively. The present results and discussion revealed new regulatory interactions of HIF-related mechanisms.
Animals ; Anoxia/genetics/*metabolism ; Gene Expression Regulation ; Histone Deacetylases/genetics/metabolism ; Humans ; Hypoxia-Inducible Factor 1/genetics/*metabolism ; Neovascularization, Pathologic/genetics/*metabolism