• Radiation Oncology Journal
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• v.9 no.1
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• pp.7-15
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• 1991

Pentoxifylline (PENTO) has been known to improve RBC fluidity, and thus improve the flux of RBC through narrow capillaries. Additionally, PENTO also decreases the $O_2$ affinity of hemoglobin by increasing 2,3-DPG levels, thereby increasing the $O_2$ release from RBC. Nicotinamide (NA) has been reported to decrease the number of acutely hypoxic cells in tumors by temporarily increasing tumor blood flow. Therefore, the purpose of this study was to examine whether the combination of PENTO and NA (PENTO+NA) would reduce the radioresistance of the Fsall murine fibrosarcoma by oxygenating the hypoxic cells. We obsewed a significantly enhanced radiation-induced growth delay of the FSaII tumors by PENTO+NA. Thus the enhancement ratio was between 2.5 and 2.8 in growth delay assay. The $TCD_{50}$ of control tumors was about 57 Gy, but that of PENTO+NA treated tumors was about 32Gy. Thus $TCD_{50}$ was modified by a factor of 1.8. We also observed that PENTO+NA exerted no effect on the radiation-induced skin damage after the legs without bearing tumors were exposed to X-irradiation. In order to clarify radiosensitizing effects of PENTO+ NA, changes in tumor blood flow and intratumor pOf were measured using laser Doppler flowmetry and $O_2$ microelectrode methods. The tumor blood flow significantly increased at 10 min. after injection of PENTO+ NA. Furthermore, we also found that PENTO+ NA significantly increased intratumor $pO_2$ from 8 to 19 mmHg. We concluded that PENTO+MA was far more effective than NA alone or PENTO alone. The increase in the response of tumors in vivo to X-irradiation appeared to be due mainly to an increase in the tumor oxygenation. Further studies using various concentrations of PENTO alone and in combination with NA to obtain better sequencing and maximal radiosensitization are warranted.

• The Korean Journal of Physiology
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• v.23 no.1
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• pp.13-21
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• 1989

The present study was designed to investigate i) the action of various nucleotides on membrane permeability of rat red blood cell and hepatocyte for $Na^{+}$ and $Rb^{+}$ ii) the characteristics of purinoceptors on these cell membranes. Blood from Sprague-Dawley rats was obtained by carotid arterial cannulation. Red blood cells were then washed 3 times with saline at $4{\circ}C$. Hepatic parenchymal cells were isolated from rat livers by using a modification of the Berry and Friend (1969) method. For the $Na^{+}$ influx studies, isolated RBC and hepatocyte were incubated in incubation medium containing $^{22}Na^{+}0.2\;{\mu}Ci/ml$ at $37^{\circ}C$. After various time intervals samples were removed from the incubation flask and washed out 3 times with ice-cold washing solutions. Cells were destroyed by adding Triton X-100 and TCA solution. After centrifugation, the supernatants were assayed for $^{22}Na^{+}$ by gamma counter. $^{86}Rb^{+}$ was used to simulate $K^{+}$ in these $K^{+}efflux$ studies. Isolated hepatocytes were incubated for 60 min in the loading solution containing $^{86}Rb^{+}\;10\;{\mu}Ci/ml$ at $37^{\circ}C$. After loading, the cells washed out 3 times by centrifugation with washing solution. The cells were incubated in buffer solution at $37^{\circ}C$. At intervals thereafter, samples were removed and centrifuged. The supernatants were analyzed for $^{86}Rb^{+}$ by liquid scintillation counter. The main results of the experiments were: 1) ATP and ATPP increased in both $^{22}Na^{+}$ influx and $^{86}Rb^{+}$ efflux in the red blood cell. Although ADP showed a tendency to increase in RBC membrane permeability for $^{22}Na^{+}$ and $^{86}Rb^{+}$, the changes were not significantly different from the control. 2) The Significant changes in $^{22}Na^{+}$ and $^{86}Rb^{+}$ flux by ATP were also demonstrated in hepatocyte. ATPP and ADP showed a tendency to increase in hepatocyte membrane permeability for both ions. 3) Other nucleoside triphosphates-ITP, GTP and CTP-did not change in membrane permeability for $^{22}Na^{+}$ and $^{86}Rb^{+}$ in RBC and hepatocyte. In conclusion, not only ATP but also ATPP activate purinoceptors and change in membrane permeability for $Na^{+}$ and $K^{+}$. In order to activate purinoceptors on the cell membrane, the nucleotides have to possess intact adenine moiety and three phosphates or more in its molecule.

• Journal of Korean Society of Water and Wastewater
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• v.12 no.2
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• pp.42-49
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• 1998

By checking the variations of the raw water quality and MLSS, the effects of the membrane materials on permeable flux and quality of the treated water were investigated in this study. Due to the stability for high variations of MLSS, tubular type membranes were selected. Polysulfone group membranes and polyamide group membranes were tested. The crossflow operation mode was adapted, because membrane fouling problems could be easily controlled by adjusting the linear velocity. Due to the high concentration of the raw water, polyamide group membranes were originally expected to achieve two times higher permeable fluxes. However, difference was only approximately $20l/m^2{\cdot}h$ at $3kgf/cm^2$. It might be resulted from the high concentration of organic materials in the effluent of the RBC process. For the quality of the treated water, polyamide group membranes were slightly less effective. It might be resulted from the fact that polysulfone group membranes had more adsorptive capacities for the organic materials. The effects of temperature on the permeable flux were found to be significant. Despite of the irregular injection of raw water, the quality of the treated water was kept stable.

• Radiation Oncology Journal
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• v.12 no.1
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• pp.17-25
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• 1994

We evaluated the effect of nicotinamide on cellular $O_{2}$ consumption and metabolic status i.e., adenylate phosphates and $NAD^{+}$in-vitro, and changes in blood flow in-vivo, to determine whether changes in cellular metabolism or increased oxygen availability, was responsible for increased tumor oxygenation. Thirty min, pre-incubation of cells with$\∼$4mM (= 500mg/kg) nicotinamide resulted in no change in cellular $O_{2}$ consumption. Similarly neither the adenylate Phosphates nor the cellular $NAD^{+}$levels were altered in the presence of $\∼$4mM nicontinamide. In-vivo, nicotinamide (500mg/kg) increased $O_{2}$ availability as estimated by changes in relative tumor blood flow (RBC flux). The changes in RBC flux measured by the laser Doppler method, were tumor volume dependent and increased from$\∼$35$ \% $ in$\∼$ 150$mm_{3}$tumors to$\∼$~75$ \% $ in$\∼$500$mm^{3}$ tumors. In conclusion, these observations indicate a reduction in local tissue $O_{2}$ consumption is not a mechanism of improved tumor oxygenation by nicotinamide in FSa II murine tumor model. The primary mechanism of increased $pO_{2}$ appears to be an increased local tumor blood flow.