A phase I trial of thermal sensitization using induced oxidative stress in the context of HIPEC.

BACKGROUND: Inducing oxidative stress under hyperthermic conditions significantly decreases tumor cell growth in a murine model of human colon cancer carcinomatosis. This phase I study examines the safety and pharmacokinetics of induced oxidative stress by the addition of hydrogen peroxide (H2O2) to the perfusate in patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced abdominal-only malignancies. METHODS: Patients with advanced colon or appendiceal malignancies underwent maximal cytoreduction followed by HIPEC with mitomycin C (MMC). In addition, H2O2 was added to the perfusate at three concentrations (n = 3/level, 0.05, 0.075, 0.1 %). A control group consisted of patients perfused with MMC alone (n = 3). Perfusate, serum MMC, and H2O2 levels were measured, as were tissue levels of MMC. RESULTS: Twelve patients were enrolled onto this trial. The median (range) peritoneal carcinomatosis index was 13 (3-20) requiring a median operative time of 6.3 (4-8.5) h. The median postoperative length of stay was 9 (5-34) days, with six patients requiring readmission within 30 days. Similar complications were observed at all three H2O2 levels, as well as in the control group. One patient required reexploration for a colon perforation (control group), and three patients developed enterocutaneous fistulas (0.075 % H2O2, 0.1 % H2O2 and control group). There were no operative mortalities. CONCLUSIONS: Hyperthermic intraperitoneal chemotherapy with induced oxidative stress after maximal cytoreduction is well tolerated. On the basis of the encouraging toxicity profile after cytoreduction and HIPEC with induced oxidative stress, a phase II trial to verify activity is indicated.

Equivalent effects on fecal reactive oxygen species generation with oral supplementation of three iron compounds: ferrous sulfate, sodium iron EDTA and iron polymaltose.

BACKGROUND: In any context of iron supplementation in the prenatal prophylaxis or therapeutic dosage range, a large amount will remain unabsorbed and pass through the intestinal tract into the colonic digesta possibly causing increased oxidation. AIM: To compare the generation of fecal reactive oxygen species (ROS) in situ after daily consumption of 100 mg of elemental iron in three frequently used forms of iron supplements. METHODS: Ten healthy, iron-repleted adult males were investigated before and during supplementation with three oral iron compounds: 100 mg of oral iron were given as ferrous sulfate, Na Fe-EDTA and iron polymaltose for 6 days to each subject in an individually stratified sequence. Stool samples were collected and analyzed for iron content and the in situ generation of fecal ROS. RESULTS: Significant increases in fecal ROS generation were observed during oral iron supplementation. No statistical differences were seen in either residual concentrations of non-heme iron in stool or the level of fecal ROS generation between the three Fe compounds. There was, however, a significant association between the iron concentration in the stool and ROS generation. CONCLUSION: In spite of the differences in their chemical characteristics, none of the three distinct iron complexes reduced oxidative stress in the intestinal lumen.

Hormesis and synergy: pathways and mechanisms of quercetin in cancer prevention and management.

Quercetin is a unique dietary polyphenol because it can exert biphasic dose-responses on cells depending on its concentration. Cancer preventative effects of quercetin are observed at concentrations of approximately 1-40 microM and are likely mediated by quercetin's antioxidant properties. Pro-oxidant effects are present at cellular concentrations of 40-100 microM. However, at higher concentrations, many novel pathways in addition to ROS contribute to its effects. The potent bioactivity of quercetin has led to vigorous study of this compound and revealed numerous pathways that could interact synergistically to prevent or treat cancer. The effect of intake and concentration on emerging pathways and how they may interact are discussed in this review.

[The role of macro-elements in the human body]. / Az esszenciális makrofémionok szerepe az emberi szervezet muködésében.

The authors summarize the role of essential macro metal elements (Na, K, Ca, Mg) in human body: their homeostasis, absorption, transport, storage and excretion. Metabolism of macro-elements, daily requirements, cause of metal deficiencies and diseases caused by deficiencies are also discussed. Messenger and prooxidant effect of Ca2+-ions, indirect antioxidant effect of Mg2+-ions and the adjuvant application of magnesium are also reviewed.

The bleaching depth of a 35% hydrogen peroxide based in-office product: a study in vitro.

OBJECTIVES: The aim of the present study was to quantify the penetration of 35% hydrogen peroxide into enamel and dentine and to relate this to the resultant shade change of the tooth. METHOD: The crowns of 24 caries and developmental defect free human maxillary incisors were stained internally with a standardised tea solution. Twelve specimens were power bleached with light activated 35% hydrogen peroxide and 12 placed in water; both exposure times were 30min. Three different shade assessment methods (Vita shade guide [SG], shade vision system [SVS] and a chromometer) were employed prior to, after tea staining and after power bleaching/water treatments. Twelve specimens each from the bleach group and the water control water group were sectioned mesio-distally. An additional 12 specimens from the bleach and the control group were sectioned labio-palatally. The stain area for each specimen was measured using image analysis software. RESULTS: With tea staining, the mean changes in Vita shade guide units (SGU) ranged from 3.66 to 8.33. With the SVS system changes of 3.66-9 units were seen. Chromometer readings showed that following bleaching the L* values moved in the direction of black (3.8-6.7) and a* and b* values were in the red (0.3) and yellow (1.5) direction, respectively. Samples bleached and sectioned mesio-distally showed stain coverage of 28.6-39.4%, while palatal sections showed stain coverage of 58-72%. Control samples, whether sectioned mesio-distally or labio-palatally, showed staining throughout the dentine (97-100% coverage). CONCLUSION: A 35% hydrogen peroxide in-office bleaching gel demonstrated bleaching into dentine of uniform depth.