Dose-dependent benefits of quercetin on tumorigenesis in the C3(1)/SV40Tag transgenic mouse model of breast cancer.

Breast cancer is the leading cause of cancer related death in women. Quercetin is a flavonol shown to have anti-carcinogenic actions. However, few studies have investigated the dose-dependent effects of quercetin on tumorigenesis and none have used the C3(1)/SV40 Tag breast cancer mouse model. At 4 weeks of age female C3(1)/SV40 Tag mice were randomized to one of four dietary treatments (n = 15-16/group): control (no quercetin), low-dose quercetin (0.02% diet), moderate-dose quercetin (0.2% diet), or high-dose quercetin (2% diet). Tumor number and volume was assessed twice a week and at sacrifice (20 wks). Results showed an inverted 'U' dose-dependent effect of dietary quercetin on tumor number and volume; at sacrifice the moderate dose was most efficacious and reduced tumor number 20% and tumor volume 78% compared to control mice (C3-Con: 9.0 ± 0.9; C3-0.2%: 7.3 ± 0.9) and (C3-Con: 2061.8 ± 977.0 mm(3); and C3-0.2%: 462.9 ± 75.9 mm(3)). Tumor volume at sacrifice was also reduced by the moderate dose compared to the high and low doses (C3-2%: 1163.2 ± 305.9 mm(3); C3-0.02%: 1401.5 ± 555.6 mm(3)), as was tumor number (C3-2%: 10.7 ± 1.3 mm(3); C3-0.02%: 8.1 ± 1.1 mm(3)). Gene expression microarray analysis performed on mammary glands from C3-Con and C3-0.2% mice determined that 31 genes were down-regulated and 9 genes were up-regulated more than 2-fold (P < 0.05) by quercetin treatment. We report the novel finding that there is a distinct dose-dependent effect of quercetin on tumor number and volume in a transgenic mouse model of human breast cancer, which is associated with a specific gene expression signature related to quercetin treatment.

Topical application of a sandal wood oil and turmeric based cream prevents radiodermatitis in head and neck cancer patients undergoing external beam radiotherapy: a pilot study.

OBJECTIVE: The study objective was to assess the effectiveness of a turmeric- and sandal wood oil-containing cream [Vicco(®) turmeric cream (VTC); Vicco Laboratories, Parel, India] on radiodermatitis in patients with head and neck cancer undergoing radiotherapy. METHODS: A total of 50 patients with head and neck cancer requiring >60 Gy of curative radiotherapy/chemoradiotherapy were enrolled in the study. The volunteers were randomly divided into two groups of 25 patients. Group 1 was assigned to a topical application of Johnson's(®) baby oil (Johnson & Johnson Ltd, Baddi, India) and Group 2 for VTC. Prophylactic application of the cream was initiated on Day 1 and continued every day until 2 weeks after the end of treatment. Both agents were symmetrically applied within the irradiated field five times a day, and the acute skin reactions were assessed twice weekly in accordance with the Radiation Therapy Oncology Group scores by an investigator who was unaware of the details. RESULTS: The incidence of radiodermatitis increased with the exposure to radiation and was the highest in both groups at Week 7. However, a significant reduction in grades of dermatitis were seen in cohorts applying VTC at all time points, including 2 weeks post radiotherapy (p < 0.015 to p < 0.001). The occurrence of Grade 3 dermatitis was lower in the cohorts using VTC and was statistically significant (p < 0.01). Additionally, follow-up observations 2 weeks after the completion of radiotherapy also showed a reduced degree of radiodermatitis in cohorts applying VTC, which was significant (p = 0.015). CONCLUSION: VTC is shown to be effective in preventing radiodermatitis and needs to be validated in larger double-blind trials. ADVANCES IN KNOWLEDGE: For the first time, this study shows that the turmeric- and sandal oil-based cream was effective in preventing radiation-induced dermatitis.

Religiosity and depression in older people: evidence from underprivileged refugee and non-refugee communities in Lebanon.

Religiosity is an important aspect of the life of older people, particularly in the Arab region where religiosity is an important part of daily social and political life. Studies have documented the relationship between religiosity and depression among older people, but none in the region. A total of 740 persons aged 60 + were interviewed in three poor urban areas of Lebanon, one of which was a Palestinian refugee camp. The questionnaire included five items on religiosity covering organizational and intrinsic religiosity. Depression was assessed using the 15-item Geriatric Depression Score (GDS-15). Depression was prevalent in 24% of the older persons interviewed with the highest proportion being from the Palestinian refugee camp (31%). Results suggest that only organizational religiosity was related to depression and this pattern was only significant among the refugee population. Religious practice is discussed as an indicator of social solidarity rather than an aspect of religiosity. Minority groups may rely on religious stratagems to cope with their distress more than other groups.

Warfarin dosage following prosthetic valve replacement: effect of smoking history.

Warfarin currently is the most widely used agent in the prevention of thrombosis and embolism after prosthetic cardiac valve replacement. Since smoking has been shown to increase the requirement for medications undergoing hepatic metabolism, this study was designed to determine if a correlation exists between smoking history and warfarin daily maintenance dose (DMD) in patients undergoing cardiac valve replacement. Of 200 charts retrospectively reviewed at the New England Medical Center, 174 satisfied the criteria for inclusion in the study (normal hepatic, renal, and hematologic function, and absence of complicating medications). The study population included aortic, mitral, and combined valve replacement. Study groups consisted of 117 nonsmokers (Group A), 23 light smokers (Group B), and 34 heavy smokers (Group C). Thirty-three percent of patients required a low DMD of warfarin (less than or equal to 2.5 mg), 43 percent required a moderate DMD (greater than 2.5-7.5 mg), and 24 percent required a high DMD (greater than 7.5 mg). Each of the subgroups followed a similar pattern. In Group A, there were 31 percent low, 44 percent moderate, and 25 percent high-dose requiring patients. In Group B, there were 48 percent low, 39 percent moderate, and 13 percent high-dose requiring patients and in Group C there were 29.5 percent low, 41 percent moderate, and 29.5 percent high-dose requiring patients. Chi-square analysis did not demonstrate any statistically significant difference between smokers and nonsmokers in regard to daily maintenance warfarin dose (p = 0.5). The study population followed a normal pattern of distribution in regard to warfarin dosage. On the basis of these data we conclude that smoking history does not affect warfarin dose requirement.

Comparative study of the thiourea carrier in erythrocytes.

A densimeter technique was used to measure the rate of exit of thiourea from erythrocytes of various species of mammals. The cells were first equilibrated with a 200 mM thiourea solution in 1% NaCl. An aliquot of these cells was added to 1% NaCl containing 4.6-23.1 mM thiourea. Facilitated diffusion was demonstrated in each case. Using exit times or initial rates, calculations of half-saturation constants (phi) in mM and maximum transport rates (K) in isotones per min were made by three different methods. The following values were obtained: human-phi=60, 42, 35; K=1.2, 2.9, 0.9; rabbit-phi=46, 33, 32; K=0.8, 2.1, 0.8; mouse-phi=46, 40, 30; K=3.4, 8.5, 3.2; rat-phi=65, 42, 23; K=6.1, 15.3, 3.7; ox-phi=107, 63, 88; K=0.6, 1.4, 0.4; sheep-phi=56, 38, 56; K=0.9, 2.2, 0.6; and pig-phi=110, 64, 49; K=1.6, 3.6, 1.1.

Measurements of exit rates to distinguish between facilitated and simple diffusion.

A modification of the method of Sen and Widdas (J. Physiol. London 160:392-403, 1962) was used to measure the rate of exit of several nonelectrolytes from erythrocytes of various species. In spite of additional errors introduced by the larger half-saturation values of the carriers (phi) and concentrations, it was possible to distinguish between systems with small values of phi, systems with relatively large values of phi, and systems involving only simple diffusion. Approximate values of phi in millimoles and of maximum transfer rate (K) in isotonic units per minute were obtained using times and initial slopes measured on experimental curves. The following values in the foregoing units were obtained: human glucose, phi = 1.8, 1.0, K = 0.8, 1.1; human glycerol, phi = 178, 94, K = 4.3, 3.3; sheep thiourea, phi = 56, 56, K = 0.9, 0.6; and rabbit glycerol, phi = 328, 64, K = 2.2, 1.0. Simple diffusion was demonstrated for the following systems: ox-ethylene glycol; ox-glycerol; sheep-ethylene glycol; and sheep glycerol.