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Selected AbstractsModulation of plasma lipid levels affects benzo[a]pyrene-induced DNA damage in tissues of two hyperlipidemic mouse modelsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2003Daniëlle M.J. Curfs Abstract The role of plasma lipids in the uptake, transportation, and distribution of lipophilic carcinogens like benzo[a]pyrene (B[a]P) remains unclear. Therefore, we studied the effects of dietary-modulated plasma lipids on B[a]P-induced DNA damage in several organs of two hyperlipidemic mouse models. Male apolipoprotein E (ApoE)*3-Leiden (n = 22) and ApoE knockout (ApoE-KO) mice (n = 20) were fed a high-fat cholesterol (HFC) diet or low-fat cholesterol (LFC; standard mouse chow) diet for 3 weeks, after which the animals were exposed to a single oral dose of 5 mg/kg bw B[a]P or vehicle and killed 4 days later. Plasma lipids were determined and DNA adducts were measured in aorta, heart, lung, liver, brain, and stomach. Total cholesterol and low-density lipoprotein (LDL) cholesterol were increased in all animals on a HFC diet, whereas a decrease of triglycerides was seen only in the ApoE-KO mice. In ApoE-KO mice on a normal diet, DNA-adduct levels were highest in aorta (10.8 ± 1.4 adducts/108 nucleotides), followed by brain (7.8 ± 1.3), lung (3.3 ± 0.7), heart (3.1 ± 0.6), liver (1.5 ± 0.2) and stomach (1.2 ± 0.2). In the ApoE*3-Leiden mice, adduct levels were equally high in aorta, heart, and lung (4.6 ± 0.7, 5.0 ± 0.5 and 4.6 ± 0.4, respectively), followed by stomach (2.7 ± 0.4), brain (2.3 ± 0.2), and liver (1.7 ± 0.2). In the ApoE-KO mice, the HFC diet intervention resulted in lower adduct levels in lung (2.1 ± 0.2), heart (1.9 ± 0.2), and brain (2.9 ± 0.5), as compared with the LFC group. In contrast, a nonsignificant increase of adducts was found in aorta (13.1 ± 1.5). A similar but nonsignificant trend was observed in the ApoE*3-Leiden mice. Multiple regression analysis showed that in aorta, DNA adducts were inversely related to plasma triglycerides (P = 0.004) and were also modulated by the ApoE genotype (P < 0.001). The results of the present study support further investigation into the role of dietary modulation of plasma lipids, ApoE, and polycyclic aromatic hydrocarbon exposure on the formation of DNA adducts in chronic degenerative diseases. Environ. Mol. Mutagen. 42:243,249, 2003. © 2003 Wiley-Liss, Inc. [source] Role of Manual Compression Time and Bed Rest Duration on the Occurrence of Femoral Bleeding Complications After Sheath Retrieval Following 4Fr Left-Sided Cardiac CatheterizationJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 1 2001VÉRONIQUE THORÉ R.N. To shorten hospital stay or to allow ambulatory procedures, 4Fr catheters for left-sided cardiac catheterization can be used. These latter parameters may also be influenced by compression time and bed rest duration. The role of these parameters was assessed by prospectively including 130 consecutive patients who underwent 4Fr femoral diagnostic procedures. The patients were randomized into two groups: group 1 consisted of 70 patients undergoing 5-minute compression and group 2 consisted of 60 patients with 15-minute compression. In each group, a second randomization was applied to determine the bed rest duration (2,4 hours). More group 1 patients experienced immediate bleeding following manual compression than group 2 patients (12 [17%] vs 3 [5%], P < 0.03, respectively). Compared to group 2, a slight but nonsignificant increase in the total number of hematomas was observed in group 1 (31 vs 22%, NS). No difference existed in terms of local large hematomas at 24 hours (7% in each group) or in terms of benign 10 cm diffuse subcutaneous ecchymosis at 7-day follow-up (13 [19%] group 1 patients vs 8 [13%] group 2 patients, NS). However, persistence of diffuse subcutaneous ecchymosis at 7-day follow-up appeared to be related to the history of immediate bleeding following manual compression in both groups (group 1: 5/13 vs 7/57 patients [P < 0.04] and group 2: 3/8 vs 0/52 patients [P < 0.002]). In conclusion, 4Fr femoral left-sided cardiac catheterization is safe and could be performed as an ambulatory procedure. However, it requires 15-minute duration of manual compression associated with 2-hour bed rest to decrease local bleeding complications. (J Interven Cardiol 2001;14:7,10) [source] Genetic influences on heart rate variability at rest and during stressPSYCHOPHYSIOLOGY, Issue 3 2009Xiaoling Wang Abstract We tested whether the heritability of heart rate variability (HRV) under stress is different from rest and its dependency on ethnicity or gender. HRV indexed by root mean square of successive differences (RMSSD) and high-frequency (HF) power was measured at rest and during 3 stressors in 427 European and 308 African American twins. No ethnic or gender differences were found for any measures. There was a nonsignificant increase in heritability of RMSSD (from 0.48 to 0.58) and HF (from 0.50 to 0.58) under stress. Up to 81% and 60% of the heritabilities of RMSSD and HF under stress could be attributed to genes influencing rest levels. The heritabilities due to genes expressed under stress were 0.11 for RMSSD and 0.23 for HF. The findings suggest that, independent of ethnicity and gender, HRV regulation at rest and under stress is largely influenced by the same genes with a small but significant contribution of stress-specific genetic effects. [source] Oral retinoic acid metabolism blocking agent RambazoleTM for plaque psoriasis: an immunohistochemical studyBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2007H.J. Bovenschen Summary Background, The novel systemic all- trans retinoic acid metabolism blocking agent (RAMBA) R115866 (RambazoleTM; Barrier Therapeutics, Geel, Belgium; further referred to as rambazole) increases intracellular levels of endogenous all- trans retinoic acid (RA). Well-known effects of RA are normalization of aberrant epithelial growth and differentiation. Hence, rambazole might be beneficial in the treatment of plaque psoriasis. Objectives, The dynamics of epidermal proliferation, keratinization, lesional T-cell subsets and cells expressing natural killer (NK)-receptors in plaque psoriasis were assessed during treatment with rambazole, as part of a phase IIa open-label clinical trial. Methods, Six patients were treated with rambazole, 1 mg, once daily, for 8 weeks. At weeks 0, 2 and 8, psoriatic plaque severity scores (SUM) and biopsies from a target lesion were assessed. Epidermal proliferation (Ki67), keratinization markers (K10, K13, K19), T-cell subsets (CD3, CD4+, CD8+, CD45RO+, CD45RA+, CD2+, CD25+, GITR+) and cells expressing NK-receptors (CD94, CD161) were immunohistochemically stained and quantified with image analysis. Results, At week 2 the mean SUM-score was virtually equal to baseline, which was accompanied immunohistochemically by equal epidermal hyperproliferation, a nonsignificant decrease in K10 positive epidermis and, overall, a nonsignificant increase in immunocyte subsets. At week 8, in contrast, plaque severity was reduced by 34% from baseline (P < 0·05). Improvements were also detected for epidermal proliferation (,63%; P < 0·01) and K10 expression (+29%; P < 0·01), compared with baseline. No induction of retinoid-specific keratinization (K13, K19) was observed. A nonsignificant reduction of all pathogenic T-cell subsets and cells expressing NK-receptors was observed at week 8 of treatment (P > 0·05). Conclusions, Clinical efficacy of rambazole is primarily the result of restoring proliferation (Ki67) and differentiation (K10) of epidermal keratinocytes. Secondly, relevant T-cell subsets and cells expressing NK-receptors showed nonsignificant reductions after 8 weeks of treatment with rambazole. [source] Influence of body mass index on outcomes and treatment-related toxicity in patients with colon carcinomaCANCER, Issue 3 2003Jeffrey A. Meyerhardt M.D., M.P.H. Abstract BACKGROUND Obesity is a risk factor for the development of colon carcinoma. The influence of body mass index (BMI) on long-term outcomes and treatment-related toxicity in patients with colon carcinoma has not been well characterized. METHODS This cohort study was conducted within a large, randomized adjuvant chemotherapy trial of 3759 men and women with high-risk, Stage II and Stage III colon carcinoma who were treated between 1988 and 1992 throughout the United States. With a median follow-up of 9.4 years, the authors examined the influence of BMI on disease recurrence, overall survival, and treatment-related toxicity. RESULTS Compared with women of normal weight (BMI, 21.0,24.9 kg/m2), obese women with colon carcinoma (BMI , 30.0 kg/m2) experienced significantly worse overall mortality (hazard ratio [HR], 1.34; 95% confidence interval [95% CI], 1.07,1.67) and a nonsignificant increase in the risk of disease recurrence (HR, 1.24; 95% CI, 0.98,1.59). The influence of BMI among women was not related to any differences in chemotherapy dose-intensity across categories of BMI. In contrast, BMI was not related significantly to long-term outcomes among male patients in this cohort. Among all study participants, obese patients had significantly lower rates of Grade 3,4 leukopenia and lower rates of any Grade , 3 toxicity compared with patients of normal weight. CONCLUSIONS Among women with Stage II,III colon carcinoma, obesity was associated with a significant increase in overall mortality as well as a borderline significant increase in disease recurrence. Nonetheless, obesity was not associated with any increase in chemotherapy-related toxicity. Cancer 2003;98:484,95. © 2003 American Cancer Society. DOI 10.1002/cncr.11544 [source] Outcomes with drug-eluting stents versus bare metal stents in acute ST-elevation myocardial infarction: Results from the Strategic Transcatheter Evaluation of New Therapies (STENT) Group,CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 7 2008Bruce R. Brodie MD Abstract Objectives: This study compares outcomes with drug-eluting stents (DES) versus bare metal stents (BMS) in patients with ST-elevation myocardial infarction (STEMI). Background: DESs have been effective in elective percutaneous coronary intervention (PCI), but their safety and efficacy in patients with STEMI have not been well studied. Methods: The STENT Registry is a multicenter United States registry evaluating outcomes of DES. Our study population includes patients with STEMI treated with either a DES or BMS who completed 9-month or 2-year follow-up. Outcomes were adjusted using propensity score analysis. Results: DES patients were younger, had less prior infarction and prior bypass surgery, but had smaller vessels and longer lesions. After adjusting for differences in baseline variables, there were no significant differences between DES and BMS in death, reinfarction, or major adverse cardiac events (MACE). DES had lower rates of stent thrombosis at 9 months (1.0% vs. 2.7%, HR 0.40 [0.17,0.95]) and lower rates of target vessel revascularization (TVR) at 9 months (4.0% vs. 7.5%, HR 0.55 [0.34,0.88]) and 2 years (8.0% vs. 11.3%, HR 0.57 [0.35,0.92]). There was a nonsignificant increase in stent thrombosis with DES versus BMS from 1 to 2 years (1.1% vs. 0.3%, P = 0.28). Conclusions: Our data suggest that DES used with primary PCI for STEMI are more effective than BMS in reducing TVR and are safe for up to 2 years. Whether DES are safe beyond 2 years and whether the reduction in TVR is enough to justify their use in STEMI will have to wait for the results of large randomized trials. 2008 Wiley-Liss, Inc. [source] Caries incidence in permanent first molars after discontinuation of a school-based chlorhexidine-thymol varnish programCOMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY, Issue 3 2003Pilar Baca Abstract , Objectives: To determine whether the cessation for 3 years of a 24-month program of chlorhexidine-thymol varnish applications would affect caries incidence in the first permanent molars of a population of schoolchildren of middle and lower-middle socioeconomic level. Methods: Two groups of 6,7-year-old schoolchildren, randomized by school-class, were followed up in a clinical trial. One group received applications of chlorhexidine-thymol varnish every 3 months and the other group acted as controls. The program ended after 24 months and its effects were evaluated. Three years later, 55.5% of the schoolchildren were re-examined and the caries increments were documented. Results: At the end of the 24-month program, the treated children had significantly fewer decayed and filled surfaces in permanent molars (lower DFS index) versus the controls. At 3 years after the discontinuation of the program, this difference had disappeared; there were no differences in the incidence of decayed, missing and filled surfaces (DMFS) index in permanent molars between the treated children and the controls. Conclusion: The cessation for 3 years of a 3-month program of chlorhexidine-thymol varnish applications resulted in a nonsignificant increase in the prevalence of dental caries in the permanent first molar. [source] Phenolic Acid Content and Composition in Leaves and Roots of Common Commercial Sweetpotato (Ipomea batatas L.) Cultivars in the United StatesJOURNAL OF FOOD SCIENCE, Issue 6 2007V.-D. Truong ABSTRACT:, Phenolic acids in commercially important sweet potato cultivars grown in the United States were analyzed using reversed-phase high-performance liquid chromatography (HPLC). Caffeic acid, chlorogenic acid, 4,5-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 3,4-di-O-caffeoylquinic acid were well separated with an isocratic elution in less than 25 min compared to about 120 min for analyzing and re-equilibrating the column with a gradient method. The isocratic elution order of these caffeoylquinic acid derivatives was confirmed by LC-MS/MS. Chlorogenic acid was the highest in root tissues, while 3,5-di-O-caffeoylquinic acid and/or 4,5-di-O-caffeoylquinic acid were predominant in the leaves. Steam cooking resulted in statistically nonsignificant increases in the concentration of total phenolics and all the individual phenolic acids identified. Sweetpotato leaves had the highest phenolic acid content followed by the peel, whole root, and flesh tissues. However, there was no significant difference in the total phenolic content and antioxidant activity between purees made from the whole and peeled sweet potatoes. [source] |