Health benefits and consequences of the Eastern Orthodox fasting in monks of Mount Athos: a cross-sectional study.

BACKGROUND/OBJECTIVES: Greek Orthodox fasting (OF), which involves 180-200 days of fasting per year, is dictated by the Christian Orthodox religion. For the first time, this cross-sectional study examines the characteristics and the effects of OF on anthropometry, cardiometabolic markers and calcium homeostasis in Athonian monks (AMs). SUBJECTS/METHODS: Daily intakes of energy, macro- and micronutrients of a day during a weekend of Nativity Fast, defined as non-restrictive day (NRD), and a weekday during Great Lent, labeled as restrictive day (RD) were recorded. RESULTS: The daily energy intake of 70 AM (age=38.8±9.7 years) was low during both RD and NRD (1265.9±84.5 vs 1660±81 kcal, respectively, P<0.001). Paired samples t-test showed statistically significant difference between daily intakes in RD and NRD: carbohydrates (159.6±21.8 vs 294.3±23.4 g, P<0.0001) and saturated fat (12.7±0.0 vs 16.4±0.0 g, P<0.0001) were lower, whereas protein (89.2±1.3 vs 72.35±1.3 g, P<0.001) was higher during RD. A subsample of 50 monks (age=38.7±10.6 years) formed a study cohort for cardiometabolic and calcium homeostasis assessment. Body weight (74.3±12.9 kg) and body mass index (BMI; 23.8±4.1 kg/m2) were independent of level of physical activity. Optimal profiles for lipid and glucose parameters (total cholesterol: 183.4±41.7 mg/dl, LDL: 120.6±37.6 mg/dl, triglycerides: 72.2±31.3 mg/dl, HDL: 48.5±14.2 mg/dl and homeostasis model assessment of insulin resistance (HOMA-IR) 1.02±0.40) were found. Profound hypovitaminosis D (8.8±6.2 ng/ml), high parathyroid hormone (PTH): 115.5±48.0 pg/ml with normal serum calcium levels (8.9±3.2 mg/dl) was observed. CONCLUSIONS: Unaffected by variation in lifestyle factors, the results of this unique study offers clear evidence for the health benefits of the strict Athonian OF through optimal lipid and glucose homeostasis.

Heat treatment enhances the antimicrobial activity of (+)-Catechin when combined with copper sulphate.

UNLABELLED: The aim of the study was to compare the antimicrobial activities of freshly made, heat-treated (HT) and 14 day stored (+)-Catechin solutions with (+)-catechin flavanol isomers in the presence of copper sulphate. (+)-Catechin activity was investigated when combined with different ratios of Cu(2+) ; 100°C heat treatment; autoclaving; and 14 day storage against Staphylococcus aureus. Cu(2+) -(+)-Catechin complexation, isomer structure-activity relationships, and H2 O2 generation were also investigated. Freshly made, HT, and 14 day stored flavanols showed no activity. While combined Cu(2+) -autoclaved (+)-Catechin and -HT(+)-Catechin activities were similar, HT(+)-Catechin was more active than either freshly made (+)-catechin (generating more H2 O2 ) or (-)-Epicatechin (though it generated less H2 O2 ) or 14 day-(+)-Catechin (which had similar activity to Cu(2+) controls-although it generated more H2 O2 ). When combined with Cu(2+) , in terms of rates of activity, HT(+)-Catechin was lower than (-)-Epigallocatechin gallate and greater than freshly made (+)-Catechin. Freshly made and HT(+)-Catechin formed acidic complexes with Cu(2+) as indicated by pH and UV-vis measurements although pH changes did not account for antimicrobial activity. Freshly made and HT(+)-Catechin both formed Cu(2+) complexes. The HT(+)-Catechin complex generated more H2 O2 which could explain its higher antimicrobial activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Natural products attract considerable attention in the search for novel antimicrobials, prebiotics and antioxidants. Enhanced biological activity of natural products has been demonstrated with chemical and heat treatment. This article extends the few publications on heat treatments of plant products and combinations with adjuncts, to raise antimicrobial activity against pathogens such as Staphylococcus aureus. We demonstrated that heat treatment could increase the activity of (+)-Catechin, a weak antimicrobial flavanol found commonly in plants in the presence of copper sulphate. Heat treatment of readily available resources merits consideration in the development of more potent substances for use in clinical settings and agriculture.

Maternal vitamin D status during pregnancy: the Mediterranean reality.

Vitamin D status during pregnancy is linked to bone mineralization of developing fetus, which justifies targeting sufficient levels of vitamin D in pregnant women. Despite high level of sunshine in the Mediterranean regions, maternal hypovitaminosis D remain common in these countries. The aim of this narrative review was to provide potential explanations for this phenomenon in an effort to guide future public health policies and vitamin D intakes during pregnancy. We searched Medline for publications regarding hypovitaminosis D during pregnancy in the Mediterranean region. Available studies confirmed the high prevalence of hypovitaminosis D among pregnant women in the Mediterranean regions (50-65% in most studies), resulting in severe skeletal and nonskeletal health events among the offspring. Reasons for this may rely on maternal darker skin pigmentation, poor dietary vitamin D intake, veiled clothing and reduced sunshine exposure, health policies and increased prevalence of obesity. Public health organizations should be aware of this phenomenon and develop specific policies to prevent hypovitaminosis D and its adverse outcomes in maternal and neonatal health.

Self-admitted behavior and perceived use of performance-enhancing vs psychoactive drugs among competitive athletes.

The relationships between projected use, self-reported behavior and attitudes to performance-enhancing (PED) and recreational (RD) drugs were investigated among 82 competitive Hungarian athletes, with 14.6% admitting using PED and 31.7% using RD. Both the observed doping estimations (even those made by non-users) and self-admitted use were considerably higher than the average rate of positive doping tests (2% of all tests). The notable overestimation by PED users (34.6% vs 16.9%) was in keeping with the false consensus effect. A prediction model with attitude and projection to the likelihood of PED use suggested at least a 70% chance of self-involvement of athletes, with responses at or above the median scores (Performance Enhancement Attitude Scale ≥ 60 and estimation ≥ 50%) on the two independent measures. Users overestimated the prevalence of doping in their sport (P=0.007) but not RD use, with the converse holding for RD users' views of doping (P=0.029). PED users also showed a significantly more lenient attitude toward doping (P<0.001). This domain-specific characteristic adds new information to the ongoing research effort in understanding drug-doping co-morbidity. The reasons for elevated in-group projection are discussed, along with the potential application of this phenomenon in doping epidemiology studies.

Mission impossible? Regulatory and enforcement issues to ensure safety of dietary supplements.

Dietary supplements are widely used across all ages and user groups and constitute a considerable business sector in most developed countries. Hazards relating to concentration, composition, individual contaminants and supplement interactions present an increasing public health concern. The aim of this paper is to review the literature for reported supplement contaminations (occurs in ca 25% of supplements, with anabolic steroids being the most common) and complement these findings with notifications logged in the EU's Rapid Alert System for Food and Feed (RASFF) through imports or market surveillance, typically logged for poor quality control issues. Notifications in the RASFF have steadily increased by sixfold for supplements in the past 7 years with the USA and China being the major transgressors. Finland and Italy lead in detections, mainly notifying unpermitted substances and contaminants in sexual-enhancing or weight-loss supplements. This paper highlights the paucity of enforcement. Regulating supplements as a foodstuff and not a medicine, coupled with the fact that a significant proportion of the supplement market is distributed via the Internet (hence absent from routine border control and surveillance), make ensuring and enforcing safety a very challenging task. The need for better quality control, compliance and public awareness is evident.

Gate keepers of EU food safety: four states lead on notification patterns and effectiveness.

The EU RASFF database has been used to provide information on trends in food notifications. The major focus of previous reports has been on either the health hazards arising from various contaminants found in foodstuff or producers of these faulty products. To complement these analyses, the aim of this paper is to examine the food notifications, recorded via the RASFF between 2000 and 2009, from the detectors' point of view and to compare and contrast detecting activities of those playing a key role in guarding food safety and security in the EU. Data were scrutinized using network analysis to capture underlying pattern in the EU context and detailed descriptive statistics to generate an in-depth view. The results revealed that 60% of the notifications were made by Italy, Germany, the UK and Spain, with the remaining 40% shared among 26 other countries and Commission Services. A distinct reporting pattern was observed between these key countries with the Netherlands showing vigilance above and beyond that expected based on its population, suggesting that countries with major ports might secure food safety in their own country as well as guarding the EU's food market. The ethnic composition may also influence the detection patterns.

Antimicrobial pomegranate rind extracts: enhancement by Cu(II) and vitamin C combinations against clinical isolates of Pseudomonas aeruginosa.

Recently, natural products have been further evaluated as sources of antimicrobial agents with efficacies against a variety of microorganisms. This study reports the antimicrobial activities of pomegranate rind extract (PRE) in combination with Fe(II) and Cu(II) salts against extended-spectrum multidrug-resistant Pseudomonas aeruginosa. Antimicrobial suspension assays were carried out using aqueous extract of pomegranate alone or in combination with metals salts against P. aeruginosa. The extract:metal salt combination was also enhanced with the addition of vitamin C. Marked activities were observed for the aqueous PRE/Cu(II) preparations, which were greatly enhanced by the addition of the reductant vitamin C. In contrast, the aqueous PRE/Fe(II) preparations were inactive, regardless of addition of vitamin C. The combination of PRE and Cu(II) salts and vitamin C showed the greatest activity against clinical isolates of P. aeruginosa. These results warrant further investigation of PRE as a potential source of new antimicrobial agents.

Popular drugs in sport: descriptive analysis of the enquiries made via the Drug Information Database (DID).

OBJECTIVE: To analyse enquiries made in the Drug Information Database (DID) to develop a better understanding of athletes' interests and concerns regarding the prohibited status of available substances. SETTING: Retrospective analyses of anonymous enquiries recorded in the DID in 2006 and 2007. PARTICIPANTS: Athletes and supporting personnel. RESULTS: The DID recorded 223 717 enquiries with 200 of the >6000 UK licensed pharmaceutical products receiving over 100 enquiries each. The majority (79.2%) of these enquiries were in the pharmaceutical product category, followed by recreational drugs (10.4%). A variety of common medications were subject to enquiry, with anti-inflammatory agents, decongestants and bronchodilators being most common; a trend in keeping with reported medication use by athletes. Of all enquiries, 42% were not found owing to misspelled words or enquiries about unregulated substances. The proportion of enquiries about substances not listed in the database is relatively high and has increased over the 24 month observation period. CONCLUSION: The DID is a well-used information resource with some 10 000 enquiries being made each month. Of the c. 60% of successful enquiries, the major focus was on pharmaceutical products. With some 73% of enquiries being made by the athletes themselves, further investigations are warranted to explore enquiry patterns in relation to specific sports. Of the unsuccessful enquiries, a large number were related to nutritional supplements, which warrants further investigation. The DID database appears to be a valid mirror of athletes' chemically assisted practices and may be successfully used to inform health professionals as well as antidoping prevention programmes.

Mercury, cadmium and lead contamination in seafood: a comparative study to evaluate the usefulness of Target Hazard Quotients.

The aim of this paper is to explore the applicability of Target Hazard Quotient (THQ) estimations to inform on seafood hazards through metal contamination. The food recall data set was collated by the Laboratory of the Government Chemist (LGC, UK) over the period from January to November 2007. Pearson chi-square goodness of fit test, nonparametric correlation (Kendall tau) and Kruskal-Wallis test were used. Descriptive statistics and statistical analyses were computed by using Excel and SPSS 15.0. The vast majority of food alerts/recalls owing to metal contamination occur in seafood and during the summer months. Only swordfish and shark containing produce received over 10 recalls which were mainly for mercury contamination. Seafood produce originating from only 3 countries had over 10 recalls owing to metal contamination (Spain 50; France 11 and Indonesia 11). Based upon the food alert/recall system, the application of THQ estimations of risk in cases of metal contamination of seafood is questionable as THQ implies frequent if not daily exposure over a lifetime. Infrequent recalls owing to metal contamination and the absence of patterns make it highly unlikely that an individual would be subject to multiple exposures to significant levels of metal ions in seafood.

Metal ion chelating peptides with superoxide dismutase activity.

The superoxide dismutase activities of two novel synthetic chelating peptides are reported. The peptides comprise a polyaminocarboxylic acid chelator (EDTA) conjugated to tyrosine (ET(1)) and phenylalanine (EP(1)). Superoxide dismutase (SOD) activity was exhibited for Cu(II) but not the Fe(III) complexes. The mimetic activities were compared to bovine erythrocyte SOD (3730 U/mg) and exhibited activities of 1119 U/mg for ET(1)-Cu(II) and 551 U/mg for EP(1)-Cu(II). Thus, small alterations in structure can have significant effects on the enzymatic activity of metallopeptides. These synthetic chelators have dual potential anti-inflammatory activity by chelating deleterious non-protein bound metal ions and concomitantly affording anti-oxidant mimetic activity.

Novel peptoids for the detection and suppression of reactive oxygen and nitrogen species.

Novel peptoids useful for the detection and suppression of various components contributing to oxidative stress and for elucidation of the interplay between these species are presented. Oxidative stress involves redox-active metal ion activation/generation of RONS (reactive oxygen and nitrogen species). For detection of RONS, the peptoid probes consist of a conjugate designed to (1) complex redox-active and non-redox-active metal ions, and (2) differentiate between RONS based upon the reaction products following RONS attack on the probe. For suppression of RONS, subtle modifications in peptoid structure impart catalase and superoxide dismutase activities to the peptoids upon ferric or cupric ion complexation.

Vitamin C contributes to inflammation via radical generating mechanisms: a cautionary note.

Reactive oxygen and nitrogen species (RONS) have been ascribed an important role in oxidative stress contributing to the progression of inflammatory diseases such as Crohn's disease and rheumatoid arthritis. Redox-active metal ions such as Fe(II) and Cu(I) further activate RONS and thus perpetuate their damaging effects. High intake of ascorbic acid exerts a pro-oxidant effect by its interaction with metal ions via a number of established RONS generating systems. Caution should be exerted regarding surplus ascorbic acid intake for patients with chronic inflammatory diseases.

Hypoxia-induced upregulation of the glycolytic enzyme glucose-6-phosphate isomerase perpetuates rheumatoid arthritis.

Intra-articular hypoxia in the inflamed rheumatoid joint is associated with increased cell proliferation, enhanced metabolism and compromised vascular perfusion. Recent clinical studies using direct measurements of hypoxia in rheumatoid joints have delineated up to 20% of soft tissue pO(2) readings as below 10mm Hg. Increased markers for glycolysis exist in rheumatoid synovial fluid and upregulation of tissue glycolytic enzymes occurs in a rat model of synovitis. Recent reports show arthritis is provoked by linked T and B cell lymphocyte recognition of the glycolytic enzyme glucose-6-phosphate isomerase (GPI). This suggests an unusual physiological feature of rheumatoid joints leads to autoimmune destruction. In this report I suggest that hypoxia, within the rheumatoid joint, leads to upregulation of the glycolytic enzyme GPI which in turn perpetuates rheumatoid arthritis.

Drug targeting to hypoxic tissue using self-inactivating bioreductive delivery systems.

Hypoxia is a characteristic feature of a number of diseases including some cancers, rheumatoid arthritis and diabetes. Hypoxic tissue facilitates the use of bioreductive drug targeting systems as oxygen suppresses the release of the active drug. This review focuses on bioreductive delivery where accompanying intramolecular cyclisation negates adduct formation between the bioreductive and macromolecules such as DNA. To date, three systems have been reported. In the quinone lactonization system, reduction of the quinone facilitates through bond cyclisation and concomitant release of the drug. In the self-alkylating system, a nucleophile is built into the bioreductive structure to favour intramolecular cyclisation over nucleophilic attack from DNA moieties. The final system is based on vitamin E which undergoes redox mediated cyclisation between its oxidised (tocopherol quionone) and reduced (tocopherol) forms. Self-inactivating bioreductive delivery systems represent a powerful tool for extending bioreductive-based drug delivery to non-cancerous hypoxic tissues.

EDTA bis-(ethyl phenylalaninate): a novel transition metal-ion chelating hydroxyl radical scavenger with a potential anti-inflammatory role.

Conjugation of ethylenediaminetetraacetic acid (EDTA) to ethyl phenylalaninate generates a novel radical scavenging metal-ion chelator EDTA bis-(ethyl phenylalaninate) (EBEP). The oxidation products o-, m- and p-tyrosine were isolated from hydrolysed, aqueous and aerated solutions containing EBEP, Fe(II) and H(2)O(2). Data obtained demonstrate the potential of EBEP to act as a radical scavenging, iron-ion chelating antioxidant under physiologically relevant conditions.

Iron(III)-mediated intra-articular crystal deposition in arthritis: a therapeutic role for iron chelators.

Crystal deposition in arthritic diseases has attracted much interest. Many reports have established the presence of calcium pyrophosphate (CPPD), hydroxyapatite (HAP) and urate crystals throughout the range of arthritic diseases. In particular, HAP crystals have been detected in 30-60% of synovial fluid (SF) samples from patients suffering from osteoarthritis (OA) and 33% of those suffering from rheumatoid arthritis (RA). In OA, crystal deposition has been linked to greater joint deterioration. The mechanism of intra-articular calcification is unknown. Nucleation is required to transform a 'metastable' phosphate- and calcium-rich biofluid into one that generates crystals. Ferric ions have been demonstrated to induce crystallization of these stable supersaturated solutions via the process of nucleation. The inflamed arthritic joint is prone to iron loading. Microbleeding from compromised vasculature contributes to intra-articular iron loading in arthritic conditions. Low-molecular-mass redox-active iron complexes have been detected in SF in inflammatory joint diseases. These species are credited with mediating oxidative stress via interaction with peroxides and superoxide. In addition, adventitious low-molecular-mass iron complexes can cause nucleation leading to crystal growth within the joint. Decorporating agents capable of removing this misplaced iron from the arthritic joint would have the joint benefit of relieving oxidative stress and preventing crystal nucleation. Systemic side effects could be overcome by the targeting suitable chelators using bioreductive delivery systems that are activated in hypoxic inflamed synovial tissue.

2-nitroimidazol-5-ylmethyl as a potential bioreductively activated prodrug system: reductively triggered release of the PARP inhibitor 5-bromoisoquinolinone.

5-Chloromethyl-1-methyl-2-nitroimidazole reacted efficiently with the anion derived from 5-bromoisoquinolin-1-one to give 5-bromo-2-((1-methyl-2-nitroimidazol-5-yl)methyl)isoquinolin -1-one. Biomimetic reduction effected release of the 5-bromoisoquinolin-1-one. The 2-nitroimidazol-5-ylmethyl unit thus has potential for development as a general prodrug system for selective drug delivery to hypoxic tissues.