Influence of the type of electrodes in the assessment of body composition by bioelectrical impedance analysis in the supine position.

BACKGROUND & AIMS: The main source of error in body composition assessment of bedridden patients by bioelectrical impedance analysis (BIA) is the electrode inadequacy and placement. As electrocardiogram (ECG) electrodes are often used for BIA measurements, this study aimed to compare three of them with a reference BIA electrode. METHODS: BIA was performed sequentially on 24 healthy subjects in the supine position, using 3 different ECG electrodes (3M® Red Dot® 2330; Ambu® BlueSensor 2300; Ambu® BlueSensor SU-00-C) and the reference electrode (Bianostic AT®) for the BIA device (Nutriguard-M®, Data Input, Germany). Resistance (R), reactance (Xc), phase angle (PhA), appendicular skeletal muscle index (ASMI), fat-free mass index (FFMI) and fat mass percentage (FM%) obtained with the different electrodes were compared using Bland-Altman plots, repeated measures one-way ANOVA and paired t-test. Patient characteristics potentially involved in BIA measurement differences were assessed using linear regression analysis. RESULTS: The study population consisted of 9 men and 15 women, 33% and 47% of whom were overweight, respectively. The measured R was within the physiological range for all men (428-561 Ω) and women (472-678 Ω), regardless of the type of electrodes used. Compared to the reference electrode, the 3M® Red Dot® 2330 and Ambu® BlueSensor SU-00-C electrodes gave significantly different Xc and PhA values, but only the Ambu® BlueSensor SU-00-C gave significantly different ASMI, FFMI and FM% at 50 kHz, with biases of -0.2 kg/m2, -0.3 kg/m2 and +1.4%, respectively. The higher the current frequency, the lower was the Xc and PhA measured by the Ambu® BlueSensor SU-00-C compared to the reference electrode. These measurement differences seemed mainly due to the too small gel area of the Ambu® BlueSensor SU-00-C (154 mm2) compared to the reference electrode (1311 mm2). CONCLUSIONS: The use of electrodes with small gel area affects BIA measurement in the supine position, especially when PhA is used as an indicator of the nutritional status. Therefore, it is essential to specify the type of electrodes and carry out comparative tests before changing consumables for body composition assessment, to ensure BIA measurement reliability in clinical and research settings.

Clinical evaluation of the new indirect calorimeter in canopy and face mask mode for energy expenditure measurement in spontaneously breathing patients.

BACKGROUND & AIMS: The new indirect calorimeter developed in the framework of the ICALIC project was first evaluated in ventilation mode. This second phase aimed to compare its ease of use and precision with another commonly used device in spontaneously breathing adult patients using a canopy hood or a face mask. METHODS: The time required to measure resting energy expenditure (REE) with Q-NRG® in canopy and face mask mode was compared with Quark RMR® in canopy mode by sequential measurements in 45 and 40 spontaneously breathing adult patients, respectively. Their precision was assessed at different time intervals, using coefficients of variation (CV%) and repeated measures one-way ANOVA. Agreement between the two devices was evaluated by correlation coefficients, Bland-Altman plots, and paired t-test. Patients' characteristics potentially affecting the measurement were assessed using linear regression analysis. RESULTS: REE measurement with Q-NRG® was faster than Quark RMR® (19.7 ± 2.9 min vs 24.5 ± 4.3 min, P < 0.001). In canopy mode, Q-NRG® gave values similar to Quark RMR®, with 73% of patients achieving a steady state (CV% <10%) within the 5-15 min interval. In face mask mode, Q-NRG® was less stable than Quark RMR® in canopy mode, and steady state was achieved in only 40% of the patients within the 5-15 min interval. Correlation between the two devices was stronger when Q-NRG® was used in canopy than in face mask mode, with Pearson coefficients of 0.96 and 0.86, respectively. Compared to Quark RMR® in canopy mode, systematic bias±1.96∗SD with Q-NRG® was -14 ± 236 kcal/day in canopy and 73 ± 484 kcal/day in face mask mode. Q-NRG® in face mask mode overestimated REE by 150 ± 51 kcal/day in men compared to Quark RMR® in canopy mode. CONCLUSIONS: Q-NRG® in canopy mode made it possible to save at least 5 min compared to Quark RMR® while maintaining the same measurement precision. However, its use in face mask mode could lead to REE overestimation in men and, therefore, should not be recommended in the clinical setting. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT03947294.

Precision and accuracy of bioelectrical impedance analysis devices in supine versus standing position with or without retractable handle in Caucasian subjects.

BACKGROUND & AIMS: Bioelectrical impedance analysis (BIA) could be facilitated in subjects who are able to stand by using scales without (BIAstd4) or with a retractable handle (BIAstd8), provided that they are as precise as BIA devices commonly used in the supine position in the hospital setting (BIAsup). This observational prospective cross-sectional study aimed to compare the precision and accuracy of BIAstd4, BIAstd8 and BIAsup in a Caucasian population. METHODS: Fat mass percentage (FM%) was measured in 160 healthy Caucasian subjects (80 men/80 women) aged 20-60 years, with a body mass index (BMI) ≥18.5 and < 30 kg/m2, using the HAGRID Body Fat Scales (Huawei Technologies Co., Ltd., China) in BIAstd4 or BIAstd8 mode, and the Nutriguard-M (Data Input GmbH, Germany) as BIAsup. Intra-unit and inter-unit precisions of each device were evaluated by calculating the coefficients of variation (CV%) of 3 measurements with 3 different units of each device. Inter-device precisions were evaluated with Pearson correlations, Bland-Altman plots, and repeated measures ANOVA followed by post-hoc Bonferroni tests. Accuracy of these BIA devices was estimated in a subgroup of 16 subjects, using comparison with dual-energy X-ray absorptiometry (DXA). RESULTS: The study population was 40 ± 12 years old, with a body height and weight of 171 ± 10 cm and 72.2 ± 11.5 Kg, respectively. All three devices were very precise with intra-unit CV% of 0.5%, 0.9%, and 0.3% and inter-unit CV% of 0.5%, 1.1%, and 0.4% for BIAstd4, BIAstd8 and BIAsup, respectively. Inter-device precision was ±2.1% for BIAstd4/BIAsup, ±1.9% for BIAstd8/BIAsup, and ±1.3% for BIAstd8/BIAstd4. Bland-Altman plots showed bias ±1.96 SD of 0.3 ± 5.2% for BIAstd4/BIAsup, -0.4 ± 4.5% for BIAstd8/BIAsup and -0.6 ± 3.1% for BIAstd8/BIAstd4. Compared to DXA, all three devices tended to underestimate FM% in men with low BMI, while only BIAstd4 and BIAstd8 tended to overestimate FM% in women with high BMI. FM% measurement accuracy was ±2.6% for BIAsup/DXA, ±3.3% for BIAstd4/DXA, and ±3.4% for BIAstd8/DXA. CONCLUSIONS: Both BIAstd4 and BIAstd8 show a good intra- and inter-unit precision close to BIAsup, making them suitable for rapid body composition assessment in non-bedridden subjects. However, all these three devices should not be used interchangeably, because BIAstd4 and BIAstd8 tend to accentuate FM% changes during body composition monitoring compared to BIAsup and DXA. TRIAL REGISTRATION: ClinicalTrial.gov no. NCT04504799.

The clinical evaluation of the new indirect calorimeter developed by the ICALIC project.

BACKGROUND & AIMS: The ICALIC project was initiated for developing an accurate, reliable and user friendly indirect calorimeter (IC) and aimed at evaluating its ease of use and the feasibility of the EE measurements in intensive care unit (ICU). METHODS: This was a prospective unblinded, observational, multi-center study. Simultaneous IC measurements in mechanically ventilated ICU patients were performed using the new IC (Q-NRG®) and currently used devices. Time required to obtain EE was recorded to evaluate the ease of use of Q-NRG® versus currently used ICs and EE measurements were compared. Conventional descriptive statistics were used: data as mean ± SD. RESULTS: Six centers out of nine completed the required number of patients for the primary analysis. Mean differences in the time needed by Q-NRG® against currently used ICs were -32.3 ± 2.5 min in Geneva (vs. Deltatrac®; p < 0.01), -32.3 ± 3.1 in Lausanne (vs. Quark RMR®; p < 0.05), -33.7 ± 1.4 in Brussels (vs. V-Max Encore®; p < 0.05), -26.4 ± 7.8 in Tel Aviv (vs. Deltatrac®; p < 0.05), -28.5 ± 3.5 in Vienna (vs. Deltatrac®; p < 0.05), and 0.3 ± 1.2 in Chiba (vs. E-COVX®; p = 0.17). EE (kcal/day) measurements by the Q-NRG® were similar to the Deltatrac® in Geneva and Vienna (mean differences±SD: -63.1 ± 157.8 (p = 0.462) and -22.9 ± 328.2 (=0.650)), but significantly different in Tel Aviv (307.4 ± 324.5, p < 0.001). Significant differences were observed in Lausanne (Quark RMR®: -224.4 ± 514.9, p = 0.038) and in Brussels (V-max®: -449.6 ± 667.4, p < 0.001), but none was found in Chiba (E-COVX®; 55.0 ± 204.1, p = 0.165). CONCLUSION: The Q-NRG® required a much shorter time than most other ICs to determine EE in mechanically ventilated ICU patients. The Q-NRG® is the only commercially available IC tested against mass spectrometry to ensure gas accuracy, while being very easy-to use.

[Fasting during health and diseases]. / Le jeûne dans la santé et pendant la maladie.

Fasting, intermittent or continuous, religious or therapeutic, is knowing a growing craze. Despite few randomized controlled studies, therapeutic fasting is prescribed in various chronic diseases, as diabetes, hypertension and also cancer. Fasting is applied to lose weight in overweight and obese patients. However, weight loss is often associated with fat-free mass loss. Chronic caloric restriction has been associated with longevity in animal studies, while it has been poorly studied in humans to date. Good quality studies are needed to better understand the effects of fasting on health and diseases.

Le jeûne volontaire, intermittent ou continu, religieux ou thérapeutique, connaît un engouement grandissant. Malgré la rareté des études randomisées et contrôlées chez l'homme, le jeûne thérapeutique est souvent proposé dans certaines pathologies chroniques, telles que le diabète de type 2, l'hypertension artérielle et le cancer. Il est aussi pratiqué dans le but de maigrir chez les sujets en surpoids ou obèses. Sa pratique n'est pas sans risques. La perte de poids est souvent associée à une perte de masse maigre, facteur de mauvais pronostic. Enfin, alors que la restriction calorique est associée à la longévité dans certaines études animales, ses effets ont été peu étudiés chez l'homme. Des études cliniques de bonne qualité sont nécessaires pour une meilleure évaluation des effets du jeûne sur la santé et lors de maladies.

Interaction of ω-3 polyunsaturated fatty acids with radiation therapy in two different colorectal cancer cell lines.

BACKGROUND & AIMS: This study aims at evaluating if docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) increases the efficacy of radiation therapy (RT) on two human colorectal cancer cell lines with different radio-sensitivity. METHODS: LS174T and HT-29 cells were treated with 20 or 50 µmol/L EPA or DHA followed by single X-ray RT of 0, 2 or 4 Gy, to evaluate cell survival, apoptosis, peroxide and malondialdehyde productions. Inflammation- and apoptosis-related proteins were analyzed by Western Blot. ANOVAs were used for statistical analysis. RESULTS: LS174T was more sensitive to RT than HT-29. DHA and to a lesser extent EPA increased cell death, apoptosis and peroxide production after RT in LS174T and to a lesser extent in HT-29 (p < 0.05). This was associated with increased expression of heat shock protein 70, decreased expression of NF-kB p65, COX-2 and Bcl-2 proteins. CONCLUSIONS: The effect of RT combination with DHA and to a lesser extent EPA was synergistic in the radio-sensitive LS174T cells, but additive in the radio-resistant HT-29 cells. This enhanced cytotoxicity was provoked at least partly by lipid peroxidation, which consequently modulated inflammatory response and induced apoptosis.

Colon cancer cell chemosensitisation by fish oil emulsion involves apoptotic mitochondria pathway.

Adjuvant use of safe compounds with anti-tumour properties has been proposed to improve cancer chemotherapy outcome. We aimed to investigate the effects of fish oil emulsion (FOE) rich in n-3 PUFA with the standard chemotherapeutic agents 5-fluorouracil (5-FU), oxaliplatin (OX) or irinotecan (IRI) on two human colorectal adenocarcinoma cells with different genetic backgrounds. The HT-29 (Bax+/+) and LS174T (Bax-/-) cells were co-treated for 24-72 h with 1 µm-5-FU, 1 µm-OX or 10 µm-IRI and/or FOE dilution corresponding to 24 µm-EPA and 20·5 µm-DHA. Soyabean oil emulsion (SOE) was used as isoenergetic and isolipid control. Cell viability, apoptosis and nuclear morphological changes were evaluated by cytotoxic colorimetric assay, flow cytometry analysis with annexin V and 4',6'-diamidino-2-phenylindole staining, respectively. A cationic fluorescent probe was used to evaluate mitochondrial dysfunction, and protein expression involved in mitochondrial apoptosis was determined by Western blot. In contrast to SOE, co-treatment with FOE enhanced significantly the pro-apoptotic and cytotoxic effects of 5-FU, OX or IRI in HT-29 but not in LS174T cells (two-way ANOVA, P <0.01). These results were confirmed by the formation of apoptotic bodies in HT-29 cells. A significant increase in mitochondrial membrane depolarisation was observed after the combination of 5-FU or IRI with FOE in HT-29 but not in LS174T cells (P <0.05). Co-administration of FOE with the standard agents, 5-FU, OX and IRI, could be a good alternative to increase the efficacy of chemotherapeutic protocols through a Bax-dependent mitochondrial pathway.

Increase of [(18)F]FLT tumor uptake in vivo mediated by FdUrd: toward improving cell proliferation positron emission tomography.

PURPOSE: 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT), a cell proliferation positron emission tomography (PET) tracer, has been shown in numerous tumors to be more specific than 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) but less sensitive. We studied the capacity of a nontoxic concentration of 5-fluoro-2'-deoxyuridine (FdUrd), a thymidine synthesis inhibitor, to increase uptake of [(18)F]FLT in tumor xenografts. METHODS: The duration of the FdUrd effect in vivo on tumor cell cycling and thymidine analogue uptake was studied by varying FdUrd pretreatment timing and holding constant the timing of subsequent flow cytometry and 5-[(125)I]iodo-2'-deoxyuridine biodistribution measurements. In [(18)F]FLT studies, FdUrd pretreatment was generally performed 1 h before radiotracer injection. [(18)F]FLT biodistributions were measured 1 to 3 h after radiotracer injection of mice grafted with five different human tumors and pretreated or not with FdUrd and compared with [(18)F]FDG tumor uptake. Using microPET, the dynamic distribution of [(18)F]FLT was followed for 1.5 h in FdUrd pretreated mice. High-field T2-weighted magnetic resonance imaging (MRI) and histology were used comparatively in assessing tumor viability and proliferation. RESULTS: FdUrd induced an immediate increase in tumor uptake of 5-[(125)I]iodo-2'-deoxyuridine, that vanished after 6 h, as also confirmed by flow cytometry. Biodistribution measurements showed that FdUrd pretreatment increased [(18)F]FLT uptake in all tumors by factors of 3.2 to 7.8 compared with controls, while [(18)F]FDG tumor uptake was about fourfold and sixfold lower in breast cancers and lymphoma. Dynamic PET in FdUrd pretreated mice showed that [(18)F]FLT uptake in all tumors increased steadily up to 1.5 h. MRI showed a well-vascularized homogenous lymphoma with high [(18)F]FLT uptake, while in breast cancer, a central necrosis shown by MRI was inactive in PET, consistent with the histomorphological analysis. CONCLUSION: We showed a reliable and significant uptake increase of [(18)F]FLT in different tumor xenografts after low-dose FdUrd pretreatment. These results show promise for a clinical application of FdUrd aimed at increasing the sensitivity of [(18)F]FLT PET.

[Nutrition and physical activity: two targets for cancer prevention]. / Alimentation et activité physique: cibles d'action pour la prévention des cancers.

The links between nutrition and cancer onset are now well established by epidemiological studies. The scientific evidence is presented in a report of the World Cancer Research Foundation (WCRF). Protective factors towards overall cancer risk are fruit and vegetable consumption and physical activity. Overweight and obesity, intakes of alcoholic beverage, fat, salt, high temperature cooked and processed red meat, increase cancer risk. In addition, beta-carotene systematic supplementation could increase lung cancer risk in smokers. As optimal controlling of these risk factors can decrease cancer mortality by 25%, nutritional counselling must be integrated in the global strategy of primary and secondary prevention of cancers.

Angiogenesis as a potential target of pharmaconutrients in cancer therapy.

PURPOSE OF REVIEW: The aim of this review is to provide insight into tumor angiogenesis inhibition by pharmaconutrients through description of the most relevant and recent findings in cancer research. RECENT FINDINGS: Cancer growth needs oxygen and nutrients supplied through blood vessels to the tumor site. New vessel formation named angiogenesis can be prevented to avoid cancer invasion. Epidemiological studies suggested that specific food intakes could decrease incidence of many cancers. Recently, scientists were interested in the potential antitumor effects of nutrients because of their safety and general acceptance. Many excellent publications demonstrated that a large class of natural compounds including pharmaconutrients exhibits antitumoral activities in selected cancer types. This review focuses on the antiangiogenic role of natural products in cancer treatment, used alone or in combination with conventional chemotherapy. SUMMARY: There is strong evidence that natural diets influence cancer development by modulating signaling pathways. Our goal is to highlight the specific impact of specific nutrients in the modulation of vascular network leading to tumor angiogenesis inhibition.

Advancing from immunonutrition to a pharmaconutrition: a gigantic challenge.

PURPOSE OF REVIEW: This review presents some difficulties encountered to develop and translate immunonutrition into clinical practice, and suggests moving forward to a pharmaconutrition approach. RECENT FINDINGS: Immunonutrition suffers from inconclusive and contradictory data due to the design of many of experiments and clinical studies conducted so far. The concept of a single immunonutrient formula applicable to various types of patients has also contributed to leave the medical world in a state of uncertainty. We propose to move forward to the concept of pharmaconutrition where a disease-dedicated nutrition therapy is developed following a rigorous step-by-step procedure. Nutrients are selected according to their pharmacological properties and after an in-depth evaluation of their biological interactions when mixed together. The optimum administration schedule (i.e. dose, route, timing and duration) of the new formulae is then determined in well conducted projective clinical trials where it is administered apart from the standard nutrition to ensure full delivery of the expected doses. SUMMARY: This review suggests moving forward to a pharmaconutrition approach where a rigorous step-by-step procedure would allow overcoming of the difficulties encountered to translate immunonutrition into clinical practice.

Clinical relevance of parenteral nutrition prescription and administration in 200 hospitalized patients: a quality control study.

BACKGROUND & AIMS: Optimal implementation of parenteral nutrition (PN) is required to promote clinical outcome and costs control. This prospective quality control study examined if PN prescription was justified and PN administration was adequate to cover the nutritional needs of patients hospitalized in the Geneva University Hospital. METHODS: Two-hundred consecutive patients receiving PN were included from Medicine, Intensive Care or Surgery Units. PN prescription was considered justified if oral feeding or enteral nutrition were contraindicated or provided less than 40% of the energy target after 5 days. PN was considered adequate if it covered 90%-110% of the recommended need for energy (i.e., 110% of the Harris-Benedict formula) and proteins (i.e., 1.2 or 1.0 g protein/kg body weight/day for patients < or = or >65 years, respectively), and was supplemented with vitamins and trace elements. RESULTS: PN prescription was justified in all but 14 patients (7%). However, PN administration was frequently inadequate: overfeeding (62%) was more often observed than underfeeding (14%), particularly among thin, elderly and female patients (P<0.01). Moreover, PN was not supplemented with vitamins and/or trace elements in 47 patients (24%). CONCLUSION: PN prescription is generally justified but PN administration is often inadequate. Further teaching of medical teams and quality control surveys are warranted to optimize PN practices.

Oral nutritional supplements and taste preferences: 545 days of clinical testing in malnourished in-patients.

BACKGROUND & AIMS: Acceptability and intake of oral nutritional supplements are often suboptimal, partly because patients dislike flavour, texture or smell. We assessed the taste preferences about milk-based and fruit-juice typed supplements in malnourished in-patients. METHODS: One hundred and nine in-patients requiring oral nutritional support were assigned to consume four given supplements on four consecutive days, to answer a questionnaire based on a 10-point visual analogue scale (VAS) on acceptance/tolerance, and to choose their preferred product for the fifth day. RESULTS: Overall pleasantness was significantly better for milk-based supplements than for sweet and salty fruit-juice typed products (on VAS: 6.2+/-3.1 versus 4.4+/-3.9, p<0.01 and 3.5+/-3.4, p<0.0001, respectively, when 1 meant "not at all" and 10 "very much"), whereas digestive tolerance was comparable. When offered together on day 5, milk-based products were more frequently preferred (81.6%) than fruit-juice typed supplements (18.4%, p<0.001). Among milk-based products, vanilla, coffee and strawberry had comparable good results, whereas chocolate was less chosen and neutral never. For fruit-juice typed products, tomato obtained better results than orange or apple. CONCLUSIONS: Oral nutritional supplements are globally well-accepted and tolerated, but with variations according to categories and flavours that must be considered to improve compliance.

Effect of an immunonutrient mix on human colorectal adenocarcinoma cell growth and viability.

OBJECTIVE: L-Glutamine, L-arginine, RNA, and omega-3 polyunsaturated fatty acids (PUFAs) have been incorporated into nutritional formulas to improve immunity of patients with gastrointestinal cancer. We therefore examined the individual and net effects of these immunonutrients on four different human colorectal adenocarcinoma cell lines. METHODS: LS174T, HT-29, CO112, and Caco-2 cells were exposed to dilutions of 1:50, 1:100, and 1:1000 of a mix or individual components of a mix of 15 g/L of L-glutamine, 16.3 g/L of L-arginine, 1.6 g/L of RNA, and 2.7 g/L of omega-3 PUFAs. Cell growth kinetic was assessed using cell count with a flow cytometer. Cell cycle and apoptosis were evaluated with double fluorescence-activated cell sorter analyses using bromodeoxyuridine labeling index and annexin V staining, respectively. One-way analysis of variance and Student's t tests were used for comparison. RESULTS: Evaluation of the cell growth kinetic over an 18-d period showed that the immunonutrient mix stimulated cancer cell growth only when diluted > or =100 times. Individual component evaluation indicated that the cell growth stimulation was mainly due to the presence of L-glutamine and to a lesser extent RNA in the mix. L-Arginine had no effect. At a lower dilution of 1:50, omega-3 PUFA concentrations were sufficient to induce cell cycle arrest and massive cell death in part through apoptosis. CONCLUSION: These results suggest that cancer cell growth stimulation by current immunonutrient formulas is unlikely due to predominant cytotoxic effect of omega-3 PUFAs.

Colon cancer therapy: new perspectives of nutritional manipulations using polyunsaturated fatty acids.

PURPOSE OF REVIEW: Recent advances in the development of new therapeutic strategies combining conventional adjuvant radio/chemotherapy with nutritional manipulations with n-3 polyunsaturated fatty acids (PUFAs) are presented. RECENT FINDINGS: Studies in cell culture and tumour-bearing animals have reported the ability of long-chain n-3 PUFAs to enhance the cytotoxicity of several anticancer drugs. In colon cancer, combination of n-3 PUFAs with 5-fluorouracil resulted in an additive growth inhibitory effect on different cell lines. Moreover, recent findings suggest that eicosapentaenoic or docosahexaenoic acid may be used to enhance tumour radiosensitivity while reducing mucosal/epidermal radiotoxicity similar to radioprotective agents. The underlying mechanism is probably mediated through lipid peroxidation because the antitumour effect of n-3 PUFAs is shared with the n-6 PUFA, arachidonic acid, and abolished by vitamin E. In vivo, the use of n-3 PUFAs may provide an additional advantage compared with n-6 PUFAs. Downregulation of eicosanoid synthesis from cyclooxygenase II may reduce angiogenesis, inflammation and metastasis induction. SUMMARY: New insights suggest that n-3 PUFAs may play an important role not only in cancer prevention but also in cancer management. They may act synergistically with radio/chemotherapy to kill tumour cells by increasing oxidative stress while reducing angiogenesis, inflammation and metastasis induction.

Auger radiation targeted into DNA: a therapy perspective.

BACKGROUND: Auger electron emitters that can be targeted into DNA of tumour cells represent an attractive systemic radiation therapy goal. In the situation of DNA-associated decay, the high linear energy transfer (LET) of Auger electrons gives a high relative biological efficacy similar to that of alpha particles. In contrast to alpha radiation, however, Auger radiation is of low toxicity when decaying outside the cell nucleus, as in cytoplasm or outside cells during blood transport. The challenge for such therapies is the requirement to target a high percentage of all cancer cells. An overview of Auger radiation therapy approaches of the past decade shows several research directions and various targeting vehicles. The latter include hormones, peptides, halogenated nucleotides, oligonucleotides and internalising antibodies. DISCUSSION: Here, we will discuss the basic principles of Auger electron therapy as compared with vector-guided alpha and beta radiation. We also review some radioprotection issues and briefly present the main advantages and disadvantages of the different targeting modalities that are under investigation.

Omega-3 polyunsaturated fatty acids and ionizing radiation: combined cytotoxicity on human colorectal adenocarcinoma cells.

OBJECTIVE: This study evaluated whether omega-3 polyunsaturated fatty acids (PUFAs) could enhance the radiosensitivity of three different human colorectal adenocarcinoma cell lines. To understand the underlying mechanisms, the effects of omega-3 PUFAs on the cell growth, survival, and apoptosis were evaluated alone or in combination with an antioxidant (vitamin E) and compared with the effects of omega-6 PUFAs. METHODS: LS174T, CO112, and Caco-2 cell survival was assessed by clonogenic assay after a 3-d pretreatment with omega-3/omega-6 PUFAs and/or vitamin E before a single X-ray exposure to 4 Gy. Cell growth and viability were measured by double fluorescence-activated cell sorter analyses using propidium iodide and fluorescein isothiocyanate-conjugated annexin V. Student's t test or multivariable linear regression analyses were used for comparison. RESULTS: Preincubation with 30 to 100 micromol/L of omega-3 PUFAs induced a dose-dependent additive decrease in cell survival after irradiation (P < 0.05). Evaluation of the underlying mechanisms indicated that omega-3 PUFAs mainly decreased the cell number via apoptosis induction. Moreover, formation of lipid peroxidation products and modulation of cyclooxygenase II activity seemed to be involved, because coincubation with 10 micromol/L vitamin E abolished the effect of 50 micromol/L of omega-3 PUFAs (P < 0.05), whereas omega-6 PUFAs could partly mimic omega-3 PUFA effects. CONCLUSION: These observations suggest that omega-3 PUFAs may be potential candidates as nutritional adjuvants to enhance the efficacy of human colorectal cancer radiotherapy.

Ergonomic and economic aspects of total parenteral nutrition.

PURPOSE OF REVIEW: Ergonomics in total parenteral nutrition include the work performed in the (hospital) pharmacy and on the medical ward. This article reviews the developments in total parenteral nutrition ergonomics and the related cost-savings. RECENT FINDINGS: Research focuses on the ergonomic advantages of multi-compartment total parenteral nutrition bags compared with the multi-bottle system, of multi versus single-layered total parenteral nutrition bags and of the presence of a nutritional team and training in clinical nutrition to improve regimen prescription and delivery. SUMMARY: Three-compartment bags are safe, economic and ergonomic. It is important, however, to keep the knowledge of pharmacies to compound total parenteral nutrition for children and (adult) patients with specific pathologies. Research is ongoing in the development of bags with more than three compartments, to include for instance vitamins. This necessitates improvements in bag materials and wrapping. Progress can be made regarding total parenteral nutrition prescription and delivery, as well as in the incidence of related infections by promoting training in clinical nutrition and the implementation of a multidisciplinary nutritional support team.

Short fluorodeoxyuridine exposure of different human glioblastoma lines induces high-level accumulation of S-phase cells that avidly incorporate 125I-iododeoxyuridine.

PURPOSE: Radio-iododeoxyuridine (IdUrd) is a potential Auger radiation therapy agent incorporated into DNA during the synthesis phase. In this study we sought to optimise S-phase targeting by modulating cellular cycling and radio-IdUrd DNA incorporation using short non-toxic fluorodeoxyuridine (FdUrd) incubations. METHODS: Three human glioblastoma cell lines with different p53 expression were pre-treated with various FdUrd conditions. After different intervals, (125)I-IdUrd DNA incorporation was measured. Fluorescence-activated cell sorter cell cycle analysis was performed after identical intervals post FdUrd pre-treatment. RESULTS: The highest increase in (125)I-IdUrd DNA incorporation was induced by 1-h incubation with 1 muM FdUrd. Increase in radio-IdUrd DNA incorporation was greatest 16-24 h after FdUrd, reaching factors of >or=7.5 over baseline incorporation in the three cell lines. Furthermore, cell synchronisation in S phase was observed with a peak of >or=69.5% in the three cell lines at 16 and 24 h post FdUrd, corresponding to an increase of 2.5-4.1 over baseline. CONCLUSION: FdUrd-induced thymidine synthesis inhibition led to S-phase accumulation that was maximal after an interval of 16-24 h and time-correlated with the highest radio-IdUrd DNA incorporation. These observations might allow the rational design of an Auger radiation therapy targeting a maximal number of S-phase cells in single treatment cycles.

Assessment of ascorbic acid stability in different multilayered parenteral nutrition bags: critical influence of the bag wall material.

BACKGROUND: The recent development of multilayered bags has minimized ascorbic acid oxidation in parenteral nutrition (PN) admixtures. However, the gas-barrier property of multilayered bags depends on their plastic material. This study compared ascorbic acid stability in different multilayered bags under experimental conditions. METHODS: Oxygen permeability of a newly developed 6-layered bag (6-L) was compared with a highly mechanical-resistant 3-layered bag (3-L(R)) and a highly flexible 3-layered bag (3-L(F)) using gas chromatography. Ascorbic acid stability was assessed by iodine titration in bags filled with 2.5 L H(2)O and 40 g carbohydrates after setting residual O(2) content at < or =1 or > or =5 ppm. The effect of storage at 4 degrees C, 21 degrees C, and 40 degrees C on ascorbic acid stability was assessed over 48 hours in a complete PN admixture (ie, 330 g carbohydrates, 100 g lipids, 96 g amino acids and trace elements) using high-pressure liquid chromatography. RESULTS: Oxygen permeability was markedly reduced in 6-L bags (0.5 mL O(2) /m(2)/d) compared with 3-L(R) (150 mL O(2) /m(2)/d) and 3-L(R) (1500 mL O(2)/m(2)/d). Accordingly, ascorbic acid was more stable in 6-L bags (half-life [T(1/2)] = 16 days up to 40 degrees C) than in 3-L(R) (T(1/2) = 9 days at 4 degrees C, 47 hours at 21 degrees C and 29 hours at 40 degrees C) and 3-L(F) (T(1/2) = 15 hours at 4 degrees C, 10 hours at 21 degrees C, and 6 hours at 40 degrees C). During the first 6 hours after PN admixture compounding, an additive ascorbic acid loss of 4.6 +/- 0.5 mg/L/ppm O(2) occurred because of residual O(2) in the bag. CONCLUSIONS: The new combination of plastic layers and careful O(2) monitoring during the filling process allowed near to complete prevention of ascorbic acid degradation in multilayered PN bags during 48 hours, regardless of the storage temperature.