Obesity, vitamin D deficiency and old age a serious combination with respect to coronavirus disease-2019 severity and outcome.

PURPOSE OF REVIEW: Old age, obesity and vitamin D deficiency are considered as independent risk factors for severe courses of COVID-19. The aim of the review is to discuss common features of these risk factors and the impact of vitamin D. RECENT FINDINGS: The recently discovered relationship between vitamin D and the infection pathway of the virus via the renin--angiotensin system (RAS) and the adipokines leptin and adiponectin play an important role. The frequency of studies showing a relationship between a low vitamin D status in comorbidities and severe COVID-19 courses makes an impact of vitamin D effects likely. SUMMARY: There is a direct relationship between vitamin D, body fat and age in COVID-19 courses. With age, the ability of the skin to synthesize vitamin D decreases, and leads to vitamin D-deficits. If the skin is insufficiently exposed to sunlight, severe deficits can develop. As vitamin D plays an important role not only in the immune system but also in the RAS, and thus at the point where the virus attacks, a good vitamin D supply is an important basis for reducing the risk of severe COVID-19 processes. Treatment with vitamin D supplements should be based on severity of the vitamin D deficiency.

There's life in the old dog yet: vitamin C as a therapeutic option in endothelial dysfunction.

The use of vitamin C against different diseases has been controversially and emotionally discussed since Linus Pauling published his cancer studies. In vitro and animal studies showed promising results and explained the impact of vitamin C, particularly in cases with endothelial dysfunction. Indeed, studies (reviewed in this issue of Critical Care by Oudemans-van Straaten and colleagues) using high-dose vitamin C and the parenteral route of application seem to be more successful than oral vitamin C delivery.

Micronutrients supplementation and nutritional status in cognitively impaired elderly persons: a two-month open label pilot study.

BACKGROUND: Malnutrition is a widespread problem in elderly people and is associated with cognitive decline. However, interventional studies have produced ambiguous results. For this reason, we wanted to determine the effect of micronutrient supplementation on blood and tissue levels and on general nutritional status in persons with mild or moderate cognitive impairment. METHODS: We performed a 2-month, open-label trial, administering a daily micronutrient supplement to 42 memory clinic patients with mild cognitive deficits. Blood levels of antioxidants, zinc, and B vitamins were determined before and after supplementation. In addition, we assessed metabolic markers for B vitamins and intracellular (buccal mucosa cell [BMC]) antioxidant levels. Nutritional status was assessed by using the Mini Nutritional Assessment (MNA). RESULTS: Blood levels of B vitamins, folic acid, lutein, ß-carotene, α-carotene, and α-tocopherol increased significantly. Decreases in homocysteine levels and the thiamine pyrophosphate effect and an increase in holotranscobalamin were observed. We found no increase in intracellular antioxidant levels of BMC. The MNA score in subjects at risk for malnutrition increased significantly, mainly owing to better perception of nutritional and overall health status. CONCLUSIONS: Micronutrient supplementation improved serum micronutrient status, with improved metabolic markers for B vitamins but not for intracellular antioxidant status, and was associated with improved self-perception of general health status. Our data underline the necessity of determining micronutrient status and support the use of additional assessments for general health and quality of life in nutritional supplementation trials.

Bioactive compounds extracted from Indian wild legume seeds: antioxidant and type II diabetes-related enzyme inhibition properties.

Seven different wild legume seeds (Acacia leucophloea, Bauhinia variegata, Canavalia gladiata, Entada scandens, Mucuna pruriens, Sesbania bispinosa and Tamarindus indica) from various parts of India were analyzed for total free phenolics, l-Dopa (l-3,4 dihydroxyphenylalanine), phytic acid and their antioxidant capacity (ferric-reducing antioxidant power [FRAP] and 2,2-diphenyl-1-picrylhydrazyl [DPPH] assay) and type II diabetes-related enzyme inhibition activitiy (α-amylase). S. bispinosa had the highest content in both total free phenolics and l-Dopa, and relatively low phytic acid when compared with other seeds. Phytic acid content, being highest in E. scandens, M. pruriens and T. indica, was highly predictive for FRAP (r = 0.47, p < 0.05) and DPPH (r = 0.66, p < 0.001) assays. The phenolic extract from T. indica and l-Dopa extract from E. scandens showed significantly higher FRAP values among others. All seed extracts demonstrated a remarkable reducing power (7-145 mM FeSO4 per mg extract), DPPH radical scavenging activity (16-95%) and α-amylase enzyme inhibition activity (28-40%).

Effect of certain indigenous processing methods on the bioactive compounds of ten different wild type legume grains.

In recent years, research efforts are under-way on the possibilities of utilization of natural source of bioactive compounds for the dietary management of certain chronic diseases such as diabetes, obesity, cardiovascular diseases, cancer etc. In this connection, seed materials of promising wild type under-utilized food legume grains such as Acacia nilotica (L.) Willd. Ex Delile, Bauhinia purpurea L., Canavalia ensiformis (L.) DC., Cassia hirsuta L., Caesalpinia bonducella F., Erythrina indica L., Mucuna gigantea (Willd.) DC., Pongamia pinnata (L.) Pierre, Sebania sesban (L.) Merr. and Xylia xylocarpa Roxb. Taub., collected from South India, were investigated for certain bioactive compounds. All the samples were found to constitute a viable source of total free phenolics (3.12-6.69 g/100 g DM), tannins (1.10-4.41 g/100 g DM), L-Dopa (1.34-5.45 g/100 g DM) and phytic acid (0.98-3.14 g/100 g DM). In general, the seed materials of X. xylocarpa recorded high levels of total free phenolics and tannins, whereas the maximum levels of L-Dopa and phytic acid were noticed in M. gigantea and S. sesban, respectively. Further, presently investigated all the bioactive compounds were drastically reduced during soaking in tamarind solution + cooking as well as soaking in alkaline solution + cooking, and thus these treatments were considered to be more aggressive practices. Open-pan roasting also demonstrated a significant reduction of total free phenolics, tannins and moderate loss of L-Dopa and phytic acid. Alternatively, sprouting + oil-frying showed significant level of increase of total free phenolics (9-27%) and tannins (12-28%), but diminishing effect on phytic acid and L-Dopa. Hence, among the presently employed treatments, sprouting + oil-frying could be recommended as a suitable treatment for the versatile utilization of these wild under-utilized legume grains for the dietary management of certain chronic diseases.

Vitamin D recommendations: beyond deficiency.

Vitamin D plays an important role in regular bone growth and in adequate function of the innate immune system, including barrier functions of mucous membranes. A sufficient supply during pregnancy and lactation protects the child from infectious diseases. Clinical symptoms of severe vitamin D deficiency (rickets) are well known and can be easily detected. Signs and symptoms beyond deficiency, however, remain to be elucidated. Based on clinical and observational data, the plasma level of 25(OH)D may serve as a 'marker' to detect or define a subclinical deficiency. Levels below 50 nmol/l might be insufficient to maintain the non-bone-related activities of vitamin D. Finally, it has to be considered that all of the nonbone activities of vitamin D are in concert with vitamin A (9-cis retinoic acid). Studies combining both vitamins in sufficient amounts (cod liver oil) demonstrated a beneficial effect on the prevention of respiratory tract infections. Consequently, it should be strongly recommended to increase the intake of vitamin D and to ensure a daily intake of vitamin A as counseled.

Flavonoid content in ethanolic extracts of selected raw and traditionally processed indigenous foods consumed by vulnerable groups of Kenya: antioxidant and type II diabetes-related functional properties.

The present study evaluated the flavonoid content, antioxidant as well as type II diabetes-related enzyme inhibition activities of ethanolic extract of certain raw and traditionally processed indigenous food ingredients including cereals, legumes, oil seeds, tubers, vegetables and leafy vegetables, which are commonly consumed by vulnerable groups in Kenya. The vegetables exhibited higher flavonoid content (50-703 mg/100 g) when compared with the grains (47-343 mg/100 g). The ethanolic extract of presently studied food ingredients revealed 33-93% DPPH radical scavenging capacity, 486-6,389 mmol Fe(II)/g reducing power, 19-43% α-amylase inhibition activity and 14-68% α-glucosidase inhibition activity. Among the different food-stuffs, the drumstick and amaranth leaves exhibited significantly higher flavonoid content with excellent functional properties. Roasting of grains and cooking of vegetables were found to be suitable processing methods in preserving the functional properties. Hence, such viable processing techniques for respective food samples will be considered in the formulation of functional supplementary foods for vulnerable groups in Kenya.

Antioxidant and type 2 diabetes related functional properties of phytic acid extract from Kenyan local food ingredients: effects of traditional processing methods.

Emerging scientific evidences reveal that phytic acid has several positive effects on human health. The antioxidant and type 2 diabetes related enzyme inhibition properties of phytic acid extract prepared from raw and traditionally processed local grains and vegetables collected from Kenya were evaluated. Phytic acid content of raw grains and vegetables ranged between 2.81-3.01 and 0.29-3.23 g/100 g DM, respectively. The phytic acid extract from raw samples revealed 59%-89% of DPPH radical scavenging capacity, 27-3,526 mmol Fe(II)/g extract of reducing power, 20%-72% of α-amylase inhibition activity and 8%-91% of α-glucosidase inhibition activity. Cooking and roasting improved the antioxidant and health relevant functionality of phytic acid extracts obtained from Kenyan local vegetables and grains, respectively.

Vitamin E requirements in parenteral nutrition.

Patients with parenteral nutrition depend on an adequate supply of micronutrients, in particular, antioxidant vitamins and cofactors such as selenium. In cases of oxidative stress (eg, chronic inflammation, sepsis, lung distress syndrome, and organ failure), there is a higher need for antioxidants. One of the most important antioxidant vitamins is vitamin E. For very low birth weight infants the plasma level is an indicator for adequate supply and for safety. Safe and effective blood levels are between 23 and 46 micromol/L, maintained with a dose of 2.8 IU/kg body weight (1-2 mg/day). For safety reasons a plasma level of 80 micromol/L should not be exceeded. For adults, 10 IU/day (9.1 mg/day) are recommended. Whether this dose is sufficient to ensure body stores and sufficient antioxidant activity is controversial. If parenteral lipid emulsions are supplied there is an additional need for vitamin E to protect the lipids (polyunsaturated fatty acids) from lipid peroxidation and to deliver additional vitamin E. Dietary guidelines for healthy adults recommend an intake of polyunsaturated fatty acids equal to 10% of total energy and an intake of alpha-tocopherol greater than 0.4 mg/g of polyunsaturated fatty acids. Randomized clinical trials are performed using special formulations of vitamin E solutions because vitamin E is available only in lipid emulsions to protect lipids, but not in an isolated solution for parenteral supply.

Beta-carotene is an important vitamin A source for humans.

Experts in the field of carotenoids met at the Hohenheim consensus conference in July 2009 to elucidate the current status of ß-carotene research and to summarize the current knowledge with respect to the chemical properties, physiological function, and intake of ß-carotene. The experts discussed 17 questions and reached an agreement formulated in a consensus answer in each case. These consensus answers are based on published valid data, which were carefully reviewed by the individual experts and are justified here by background statements. Ascertaining the impact of ß-carotene on the total dietary intake of vitamin A is complicated, because the efficiency of conversion of ß-carotene to retinol is not a single ratio and different conversion factors have been used in various surveys and following governmental recommendations within different countries. However, a role of ß-carotene in fulfilling the recommended intake for vitamin A is apparent from a variety of studies. Thus, besides elucidating the various functions, distribution, and uptake of ß-carotene, the consensus conference placed special emphasis on the provitamin A function of ß-carotene and the role of ß-carotene in the realization of the required/recommended total vitamin A intake in both developed and developing countries. There was consensus that ß-carotene is a safe source of vitamin A and that the provitamin A function of ß-carotene contributes to vitamin A intake.

Climate Change Enhanced Carotenoid Pro-Vitamin A Levels of Selected Plantain Cultivars.

Diet diversification and the exploitation of traditional, micronutrient-rich germplasm of staple crops are generally regarded as sustainable and low-cost approaches to increase the micronutrient intake of resource-poor people. Sun's UV index was collected daily throughout the year. The study assessed the seasonality of provitamin A carotenoids in three plantain cultivars in response to climatic condition. Fruits were harvested at three maturities and freeze-dried before analysis. The results showed that there were high levels of the sun's UV-B radiations throughout the year with the highest occurring from November to May when the area experienced clear skies with minimal cloud cover. These high levels of the sun's UV-B index occurred between 9.00 h GMT and 17.00 h GMT. The study also showed that α-carotene content increased with maturity in "Apantu" during the rainy seasons ranging from 95 to 172 µg/100 g of dry pulp. Similar trends were observed during the dry season with a range of 28 to 489 µg/100 g. The α-carotene contents were very high in the periods of high sun's UV-B radiations compared to the periods of low sun's UV-B radiations. The α-carotene levels in the giant French plantains showed similar trends. Intermediate French "Oniaba" and False Horn "Apantu" plantain cultivar showed the highest content of ß-carotene during the dry season. The high provitamin A carotenoid levels in the cultivars coincided with the high levels of the sun's UV index.

Impact of reactive oxygen species on the expression of adhesion molecules in vivo.

Many non-surgical tumor treatments induce reactive oxygen species (ROS) which result in cell damage. This study investigated the impact of ROS induction on the expression of adhesion molecules and whether alpha-tocopherol pre-treatment could have a protective effect. Experimental rat DS-sarcomas were treated with a combination of localized 44 degrees C-hyperthermia, inspiratory hyperoxia and xanthine oxidase which together lead to a pronounced ROS induction. Further animals were pre-treated with alpha-tocopherol. The in vivo expression of E- and N-cadherin, alpha-catenin, integrins alpha v, beta 3 and beta 5 as well as of the integrin dimer alpha v beta 3 was assessed by flow cytometry. The expression of alpha v-, beta 3-integrin, of the alpha v beta 3-integrin dimer and of E-cadherin was significantly reduced by the ROS-inducing treatment. This effect was partially reversible by alpha-tocopherol, indicating that ROS play a role in this process. N-cadherin, alpha-catenin and beta 5-integrin expression were unaffected by ROS. These results indicate that the expression of several adhesion molecules is markedly reduced by ROS and may result in a decrease in the structural stability of tumor tissue. Further studies are needed to clarify the impact of ROS induction on the metastatic behavior of tumors.

Animal-based food taboos during pregnancy and the postpartum period of Southeast Asian women - A review of literature.

This paper gives an overview of the various taboos on animal products and the reasons behind such practices among women in the member countries of the Association of Southeast Asian Nations (ASEAN), while they are pregnant, during their postpartum period, and while breastfeeding. Three data search engines, Google® Scholar, PubMed and Scopus, were used one after the other, to generate the papers for this review. The online searches using the term food taboo, its synonyms, and truncations, in combination with the terms pregnancy, postpartum, and breastfeeding, and with the country name, were conducted from January to February 2017. In total, 28 papers were pooled and included in this review. The taboos and the justification for avoidance were collated and grouped per their occurrence, and according to the country where they are practiced. Nine papers provided information on the food taboos during pregnancy, 16 on postpartum food taboos, and six on breastfeeding. The food taboos included various river or seafood, meat from terrestrial animals, and derived products like fish paste, blood and internal organs. Healthcare providers should be aware of the food taboos being adhered to in the region to provide the right information and guidance to the women practicing them. There is a need to educate the public in general, and women, in particular, about the risk of malnutrition when food taboos are followed, and to support their nutritional requirements during pregnancy and the postpartum period by promoting dietary diversification. More research could be conducted to fill in the gap in information with regards to the food taboos and their impact in some of the ASEAN members. Culture-sensitive health interventions based on timely research work can contribute to the attainment of the sustainable development goal of reducing the maternal and under-five mortality ratios in Southeast Asia.

Validation of the CIMI-Ethiopia Program and Seasonal Variation in Maternal Nutrient Intake in Enset (False Banana) Growing Areas of Southern Ethiopia.

BACKGROUND: Tools for the rapid and accurate analysis of nutrient intakes from diets of individuals in Southern Ethiopia are lacking. The Calculator of Inadequate Micronutrient Intake program for Ethiopia (CIMI-Ethiopia) has been developed to overcome this problem. CIMI-Ethiopia also computes protein and energy intakes from the diet. The objectives of the current study were to validate CIMI-Ethiopia for the dietary pattern of Southern Ethiopia, and assess the nutrient intakes in postharvest dry and lean wet seasons. METHODS: 24-h dietary recall (24HR) data was collected from 578 women of a reproductive age in postharvest dry and lean wet seasons in 2017. For analysis, 24HR data was entered into NutriSurvey (NS), which was the reference nutrition software, and then into CIMI-Ethiopia. For validation, the mean and standard deviation (SD) of the difference between CIMI-Ethiopia and NS were computed. The percentage of participants with an inadequate intake was calculated. The correlation between CIMI-Ethiopia and NS results was determined. The nutrient intakes in postharvest dry and lean seasons were compared. RESULTS: Among the nutrients, pantothenic acid, vitamin B1, and protein showed a very high accuracy in CIMI-Ethiopia calculation (|difference (D)| < 5.0% of the NS result). Nutrients with a good accuracy (|D| = 5%-15%) were iron, zinc, magnesium, vitamin B12, vitamin B6, and energy. The accuracy for calcium, niacin, and vitamin A was moderate (|D| = 15%-30%). The intakes calculated by CIMI-Ethiopia and NS of iron, zinc, magnesium, calcium, B-complex vitamins, vitamin A, protein, and energy were highly correlated (r = 0.85-0.97, p < 0.001). NS analysis identified a significant reduction in the mean intake of iron; zinc; magnesium; pantothenic acid; vitamin B1, B12, and D; protein; and energy in the lean wet season; however, calcium and vitamin A intake increased. CONCLUSIONS: It has been found that CIMI-Ethiopia is a valid tool for estimating nutrient intakes at an individual level in Southern Ethiopia. The study demonstrated a decline in intakes of iron; zinc; magnesium; pantothenic acid; vitamin B1, B12, and D; protein; and energy in the lean wet season. This result provides some hint for fortification and supplementation programs that aim to combat maternal malnutrition in rural Southern Ethiopia.

Dietary Diversity and Anthropometric Status of Mother-Child Pairs from Enset (False Banana) Staple Areas: A Panel Evidence from Southern Ethiopia.

BACKGROUND: A sizable cross-sectional studies demonstrated a low dietary diversity in Southern Ethiopia. However, its seasonal trend has not been well studied in areas where nutrient-poor enset (false banana (Ensete ventricosum)) foods are major staple. Moreover, there is scarcity of information on seasonal nature of anthropometric status of mother-child pairs (MCP) from the same areas in Southern Ethiopia. Therefore, the present study aimed to investigate the dietary diversity and anthropometric status of MCP in postharvest dry and lean wet seasons and identify factors associated with anthropometric status. METHODS: The dietary intake and anthropometric data were collected from 578 households (578 mothers and 578 children) January-June 2017. The study compared data of the two seasons using McNemar's test for dichotomous, Wilcoxon signed-rank test for non-normally distributed, and paired samples t-test for normally distributed continuous data. Logistic regression was conducted to identify risk factors for malnutrition. In addition, Spearman's Rho test was used to determine correlations between maternal and child variables. RESULTS: Over 94% of the mothers did not fulfil the minimum diet diversity score in both seasons. The meal frequency and pulses/legumes intake significantly declined in lean wet season; however, dark green leaves consumption increased. Meat, poultry, and fish consumption dropped to almost zero in the lean wet season. The dietary diversity and anthropometric status of the MCP were correlated. Weight-for-age (WAZ) and weight-for-height (WHZ) of children significantly declined in the lean wet season. In the same way, maternal mid upper arm circumference (MUAC), body weight, and body mass index (BMI) dropped (p < 0.001) in this season. Being pregnant and a lactating mother, poverty, and the ability to make decisions independently predicted maternal undernutrition (low MUAC). On the other hand, maternal undernutrition and education were associated with child underweight. CONCLUSIONS: The results demonstrated that the dietary diversity of MCP is low in both postharvest dry and lean wet seasons. This suggests the need for continuous nutrition intervention to improve the dietary diversity. In addition, the anthropometric status of MCP declines in lean wet season. This may provide some clue for policy targeting on improving nutritional status of mothers and children in rural Southern Ethiopia.

Vitamin A Supplementation by Endotracheal Application of a Nano-encapsulated Preparation Is Feasible in Ventilated Preterm Lambs.

BACKGROUND: Vitamin A (VA) is crucial for lung growth and development. In premature infants, inadequate VA levels are associated with an increased risk of bronchopulmonary dysplasia (BPD). Intramuscular VA supplementation has been shown to decrease the incidence of BPD, but is not widely used in the clinical setting due to concerns about feasibility and pain. We studied VA kinetics, distribution, and the induction of early genetic expression of retinoid homeostatic genes in the lung after endotracheal and intravenous application in a preterm lamb model. METHODS: Lambs were delivered prematurely after 85% of gestation, intubated, and ventilated for 3 hours. The animals were randomized to receive no VA ("control"), a bolus of VA intravenously ("i.v."), or VA endotracheally directly after administration of surfactant ("e.t."). RESULTS: Animals treated with VA endotracheally directly after administration of surfactant showed significant increases of VA in serum and lung compared to controls. Animals treated with a bolus of VA intravenously showed significant increases of VA in serum, lung, and liver; however, peak serum concentrations and mRNA levels of homeostatic genes raised concerns about toxicity in this group. CONCLUSIONS: Endotracheal VA supplementation in preterm lambs is feasible and might offer advantages in comparison to i.v. Further studies are warranted to explore biological effects in the context of BPD.

Inhibition of heme oxygenase-1 increases responsiveness of melanoma cells to ALA-based photodynamic therapy.

Based on the observation that 5-aminolevulinic acid (ALA) induces the expression of heme oxygenase-1 (HO-1) in cultured melanoma cells, the role of HO-1 on the effectiveness of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) was examined. Transcriptional activation of the HO-1 gene is considered to be an adaptive response to oxidative and cellular stress and confers a protective capacity against cell and tissue injury, which could affect the responsiveness to ALA-PDT. A time-dependent accumulation (0-16 h) of protoporphyrin IX (PPIX) within melanoma cells was seen after incubation with ALA (0.5 mM ALA). Over the same time interval, a significant increase (up to 25-fold) in HO-1 protein expression was observed. Thus, the production and degradation of PPIX (via heme by HO-1) were simultaneously enhanced, leading to a reduced intracellular concentration of the photodynamically active substance PPIX. Diminishing HO-1 activity by the HO-1 inhibitor tin protoporphyrin IX (SnPPIX) significantly enhanced the formation of PPIX up to 1.8 fold. A further strong increase in HO-1 protein expression (up to 128-fold) was seen after ALA-PDT treatment. Induction of HO-1 is an essential step in the 'rescue response' of tumor cells. The pharmacological inhibition of HO-1 activity by SnPPIX leads to a considerable increase in the sensitivity of tumor cells to ALA-PDT treatment. At low radiation doses (0.42 J/cm(2)), the percentages of death cells increased significantly from 7.3+/-1.3% to 43.7+/-6.4%. This effect could be further intensified by cellular depletion of HO-1 mRNA by siRNA. The combination of pharmacological inactivation of HO-1 with gene silencing led to an increase in the death rate of up to 54.1+/-8.6%. The results presented indicate that HO-1 can play a protective role against ALA-PDT mediated cytotoxicity so that a specific inhibition of HO-1 activity and/or expression might be used to increase the efficacy of ALA-based photodynamic therapy.

Impact of therapeutically induced reactive oxygen species and radical scavenging by alpha-tocopherol on tumor cell adhesion.

Many tumor treatment modalities such as ionizing radiation or some chemotherapy induce reactive oxygen species (ROS) resulting in therapeutic cell damage. The aim of this study was to analyze whether such ROS induction may affect the mechanical stability of solid tumor tissue by degradation of the extracellular matrix proteins or by a loss of cell adhesion molecules. Additionally, the protective impact of alpha-tocopherol treatment on these processes was studied. Experimental DS-sarcomas in rats were treated with a combination of localized 44 degrees C hyperthermia, inspiratory hyperoxia and xanthine oxidase in order to induce pronounced oxidative stress. A second group of animals were pretreated with alpha-tocopherol. The in vivo expression of E- and N-cadherin, alpha-catenin, integrins alphav, beta3 and beta5 as well as the expression of the integrin dimer alphavbeta3 were assessed by flow cytometry. The activity of the matrix metalloproteinases MMP-2 and -9 and the activity of the urokinase-type plasminogen activator (uPA) were determined by zymography. The expression of E-cadherin, the alphav-, beta3-integrin and the alphavbeta3-integrin dimer was significantly reduced by ROS induction, an effect which was at least partially reversible by alpha-tocopherol. N-cadherin, alpha-catenin and the beta5-integrin expression was not affected by ROS. In addition, MMP-2, MMP-9 and uPA activities were markedly reduced immediately after hyperthermia. Whereas 24 h later the effects on MMP-2 and -9 were no longer evident, for uPA the impact of oxidative stress became even more pronounced at this time. These results show that several processes responsible for the structural stability of the tumor tissue are affected by therapeutic ROS generation. Changes in some of the markers assessed suggested a decrease in tissue stability upon ROS induction, whereas others indicated changes which could lead to a more stable tumor cell cluster. Depending on the individual tumor entity ROS may therefore influence the mechanical stability of solid tumors and by this affect metastatic behavior.

Multivitamin/mineral supplements: Rationale and safety - A systematic review.

Multivitamin/mineral supplements (MVM) are widely used in many populations. In particular, in pregnant women, MVM together with iron and folic acid are recommended to improve birth outcome and reduce low birth weight and rates of miscarriage. However, MVM use is common in the general population. This raises questions regarding the safety of long-term use of these supplements. To estimate the safety of MVM use, we performed a literature search for randomized, controlled studies for supplements with a combination of at least nine vitamins and three minerals at a maximum concentration of 100% of the recommended dietary allowance. We found nine studies evaluating the use and efficacy of MVM in pregnant women and healthy adults and six studies in the elderly where adverse effects were explicitly addressed. Only minor adverse effects (e.g., unspecific gastrointestinal symptoms) were reported in all studies. In particular, there were no significant differences between treatment and placebo groups. MVM use within the range of the dietary reference intake will not result in excess intake, even when including the impact of food and fortified food, and does not increase mortality. Taken together, these findings indicate that MVM can be safe for long-term use (more than 10 y).