Carbogen breathing increases 5-fluorouracil uptake and cytotoxicity in hypoxic murine RIF-1 tumors: a magnetic resonance study in vivo

The purpose of this study was to examine the effect of carbogen gas (95% O2-5% CO2) on uptake and metabolism of 5-fluorouracil (5FU) in murine RIF-1 tumors and their growth in vivo. In addition, we have explored the mechanisms by which carbogen can transiently affect the physiology of RIF-1 tumors. After i.p. injection of 1 mmol/kg 5FU into C3H mice, the uptake and metabolism of the drug by s.c. RIF-1 tumors was followed for 2 h noninvasively using 19F-magnetic resonance spectroscopy (MRS). In all animals, irrespective of tumor size, carbogen caused a significant increase in the half-life (t(1/2)) of the elimination of 5FU by the tumor and a significant increase in growth inhibition. In 2-3-g tumors (group II), carbogen also caused increased 5FU uptake and metabolism to the cytotoxic 5-fluoronucleotides, whereas in 0.8-1.5-g tumors (group I), only the t(1/2) was slightly increased. These results suggested that tumor size was an important factor in the effect of carbogen on tumor physiology. Measurements of RIF-1 tumor vascular and necrotic volume showed no significant differences between group I and group II tumors. However, 1H-MR images of RIF-1 tumors showed that carbogen caused a transient decrease in signal intensity, which correlated positively (P = 0.02) with tumor size, suggesting that larger tumors responded to carbogen by transiently increasing O2 uptake from the blood. 19F-MRS was used to measure RIF-1 tumor retention of the fluorinated nitroimidazole SR-4554. These studies also showed a positive correlation (P = 0.001) with tumor size, implying greater hypoxia in larger tumors. We propose that carbogen may transiently open nonfunctional blood vessels in the tumor, allowing increased leakage of 5FU from the plasma into the extracellular space. 5FU transport is known to be pH dependent. Intra- and extracellular tumor pH was measured using 31P- and 19F-MRS, which showed that carbogen caused a significant decrease in the extracellular pH of 0.1 unit in group II tumors and a consequent increase in the negative pH gradient across the tumor plasma membrane, which can cause increased 5FU uptake. The pH gradient was unaffected in group I tumors. We conclude that carbogen breathing can increase tumor uptake of 5FU by two independent mechanisms involving changes in tumor blood flow and pH, which consequently cause increased formation of 5-fluoronucleotides and cytotoxicity. The effect seems more pronounced in hypoxic tumors, implying that carbogen would be a valuable aid in clinical chemotherapy.     

Antioxidant application for the correction of endogenic intoxication in patients with complex abdominal hernia

To say that enrolled nurse Liz Roberts is dedicated to her work with continuing care patients at Palmerston North Hospital is an understatement. Her care for them extends even to her days off.     

THE MECHANISMS OF TRANSPORT OF WATER AND N-PROPANOL THROUGH PULP AND PAPER

Measurements have been made of transport rates of water, n-propanol, and mixtures of the two through samples of kraft pulp and filter paper. Comparison of the rates for the two components and the measured effects of temperature and relative humidity provide insight into the rate-limiting mechanisms of transport within these materials. Results show that gas-phase transport within pores and interstices dominates the mass-transfer process. Condensed-phase transport also occurs for water at high moisture contents, more so for paper than for pulp. The lesser contribution of condensed-phase transport for pulp may reflect the substantially lower bulk density of pulp. The dominance of gas-phase transport for pulp is also borne out by results of a second experiment, wherein pressure drops for gas permeation through pulp were measured following step changes in the humidity of the permeating gas.     

Clinical studies with a low dose estrogen-progestogen combination

Clindamycin, tinidazole (a parent compound to metronidazole), and doxycycline were compared in vitro against 376 anaerobic bacteria isolated from clinical specimens. Bacteriostatic tests indicated that clindamycin was the most active drug, on a weight basis, against these strains except for Clostridium species. The three drugs were compared as therapies for anaerobic wound infections in cancer patients. In a randomized double-blind study, no statistically significant differences between clindamycin and tinidazole could be documented. Doxycycline was less active presumably because of the lack of clinical response in three out of four patients infected with doxycycline-resistant strains. No major untoward effects were observed. The bactericidal dilution of the serum was predictive of the clinical outcome.     

Food extrusion

Extrusion processing has become an important food process in the manufacture of pasta, ready‐to‐eat cereals, snacks, pet foods, and textured vegetable protein (TVP). An extruder consists of a tightly fitting screw rotating within a stationary barrel. Preground and conditioned ingredients enter the screw where they are conveyed, mixed, and heated by a variety of processes. The product exits the extruder through a die where it usually puffs and changes texture from the release of steam and normal forces. Mathematical models for extruder flow and torque have been found useful in describing extrusion operations. Scale‐up can be facilitated by the application of these models. A variety of food extruder designs have developed. The differences and similarity of design are discussed. Pertinent literature on the extrusion of cereal/snack products, full‐fat soy, TVP, pet foods (dry and semi‐moist), pasta, and beverage or other food bases are discussed. In many of these applications, the extruder is a high temperature, short time process which minimizes losses in vitamins and amino acids. Color, flavor, and product shape and texture are also affected by the extrusion process. Extrusion has been widely applied in the production of nutritious foods. Emphasis is placed on the use of extrusion to denature antinutritional factors and the improvement of protein quality and digestibility.