Greek Orthodox fasting rituals: a hidden characteristic of the Mediterranean diet of Crete

The longevity and excellent health status of the population of Crete has been attributed to its lifestyle and dietary habits. The impact of Greek Orthodox Christian Church fasting on these dietary habits has never been studied. One hundred and twenty Greek Orthodox Christians living in Crete participated in a 1-year prospective study. One half of the subjects, who fasted regularly (fasters), and sixty non-faster controls were followed longitudinally for the three main fasting periods over 1 year; Christmas (40 d), Lent (48 d) and the Assumption (15 d). Pre- and end-holy days measurements were performed in each fasting period including: 24 h dietary recall, blood collection and anthropometric measurements. Based on the 24 h recall, fasters as compared with controls had lower intakes of end-holy days dietary cholesterol, total fat, saturated fatty acids, trans-fatty acids and protein (P < 0.001). Fasters presented a decrease of 753 kJ (180 kcal) in end-holy days energy intake (P < 0.05) compared with an increase of 573 kJ (137 kcal) in the controls (P < 0.05). Fasters had a decrease in end-holy days Ca intake (P < 0.001) and an increase in end-holy days total dietary fibre (P < 0.001) and folate (P < 0.05), attributed to their higher consumption of fruit and vegetables in end-holy periods (P < 0.001). There were no differences for other vitamins or minerals between pre- and end-holy periods in both groups except for vitamin B2. The Orthodox Christian dietary regulations are an important component of the Mediterranean diet of Crete characterised by low levels of dietary saturated fatty acids, high levels of fibre and folate, and a high consumption of fruit, vegetables and legumes.     

'Designer' tumors in mice

We have developed and tested successfully a general method based on Cre-mediated recombination that can be used for ubiquitous or tissue-specific expression of protein products, including tumor-inducing oncoproteins. Depending on the specificity of a chosen promoter driving cre expression, tumors develop by design in bitransgenic mouse progeny derived by crossing Cre-producing mice with partners carrying a dormant oncogenic transgene (targeted into the 3' noncoding region of the cytoplasmic beta-actin locus) that becomes functional after excision of a 'floxed' DNA segment. To provide proof-of-principle, we have used as models transgenes encoding the polyomavirus middle T antigen (PVMT) and the T antigens of the SV40 early region (SVER). Cre-dependent activation of widespread SVER expression resulted in hyperplasias or invasive tumors affecting particular visceral smooth muscles, whereas Cre-dependent, mammary gland-specific expression of PVMT-induced adenocarcinomas, according to plan. Unexpectedly, we also encountered spontaneous (Cre-independent) oncogene expression occurring as a rare event, which simulates the initiation of sporadic tumors and leads to PVMT-induced hemangiomas and mammary carcinomas or SVER-induced disseminated sarcomas, thus, revealing particular tissue susceptibilities to the actions of these oncoproteins.     

Cytokines, nitric oxide, and cGMP modulate the permeability of an in vitro model of the human blood-brain barrier

The endothelial cells (EC) of the microvasculature in the brain form the anatomical basis of the blood-brain barrier (BBB). In the present study, the effects of agents that modify the permeability of a well-established in vitro model of the human BBB were studied. The monolayers formed by confluent human brain microvessel endothelial cell (HBMEC) cultures are impermeable to the macromolecule tracer horseradish peroxidase (HRP) and have high electrical resistance. Exposure of HBMEC to various cytokines including TNF-alpha, IL-1beta, interferon gamma (IFN-gamma), or lipopolysaccharide (LPS) decreased transendothelial electrical resistance (TEER) mainly by increasing the permeability of the tight junctions. Primary cultures of HBMEC express endothelial nitric oxide synthase (eNOS) and produce low levels of NO. Treatment with the NO donors sodium nitroprusside (SNP) and DETA NONOate or the cGMP agonist 8-Br-cGMP significantly increased monolayer resistance. Conversely, inhibition of soluble guanylyl cyclase with ODQ rapidly decreased the resistance, and pretreatment of HBMEC with Rp-8-CPT-cGMPS, an inhibitor of cGMP-dependent protein kinase, partially prevented the 8-Br-cGMP-induced increase in resistance. Furthermore, NO donors and 8-Br-cGMP could also reverse the increased permeability of the monolayers induced by IL-1beta, IFN-gamma, and LPS. These results indicate that NO can decrease the permeability of the human BBB through a mechanism at least partly dependent on cGMP production and cGMP-dependent protein kinase activation.     

Effect of maltose-containing sports drinks on exercise performance

This study examined the effect of maltose-containing sports drinks on exercise performance. Ten subjects completed 4 trials. Each trial consisted of a glycogen depletion protocol, followed by a 15-min refueling, after which subjects performed an 1-h performance test while consuming one of the experimental drinks (HGlu, glucose; HMal, maltose; MalMix, sucrose, maltose, and maltodextrin; Plac, placebo). Drinks provided 0.65 g/kg body weight carbohydrates during refueling and 0.2 g/kg every 15 min during the performance test. Although no significant differences were found in performance (HGlu: 67.2 +/- 2.0; HMal: 68.6 +/- 1.7; MalMix: 66.7 +/- 2.0; Plac: 69.4 +/- 3.0 min, P> 0.05), subjects completed the MalMix trial 3.9%; faster than the Plac. Carbohydrate drinks caused comparable plasma glucose values that were significantly higher during refueling and at the end of exercise, compared to Plac. The data suggest that although carbohydrate drinks help to maintain plasma glucose at a higher level, no differences in performance could be detected after glycogen-depleting exercise.     

Induction of aryl hydrocarbon receptor-mediated and estrogen receptor-mediated activities, and modulation of cell proliferation by dinaphthofurans

A group of heterocyclic aromatic compounds, dinaphthofurans (DNFs), recently have been identified as potentially significant contaminants in freshwater sediments. In the present study, a battery of in vitro assays was used for detection of toxic effects of DNFs that are potentially associated with endocrine disruption and tumor promotion. Dinaphthofurans were found to act as relatively potent inducers of aryl hydrocarbon receptor (AhR)-mediated activity in the chemical-activated luciferase reporter gene expression DR-CALUX assay. The relative AhR-inducing potencies of DNFs were similar or even higher than relative potencies of unsubstituted polycyclic aromatic hydrocarbons (PAHs), with dinaphtho[1,2-b;2'3'-d]furan being the most potent AhR agonist. Two compounds, dinaphtho[2,1-b;2'3'-d]furan and dinaphtho[1,2-b;1'2'-d]furan, induced estrogen receptor (ER)-mediated activity in the estrogen receptor-mediated CALUX (the ER-CALUX) assay. Two types of potential tumor-promoting effects of DNFs were investigated, using in vitro bioassays for detection of inhibition of gap-junctional intercellular communication and detection of a release from contact inhibition. Although the acute inhibition of gap-junctional intercellular communication was not observed, all six tested DNFs were able to release rat liver epithelial WB-F344 cells from contact inhibition at concentrations as low as 100 nM. In summary, the present study indicated that DNFs can exert multiple biological effects in vitro, including induction of the AhR-mediated activity, release of cells from contact inhibition, and induction of ER-mediated activity.     

Clinical review: severe asthma

Severe asthma, although difficult to define, includes all cases of difficult/therapy-resistant disease of all age groups and bears the largest part of morbidity and mortality from asthma. Acute, severe asthma, status asthmaticus, is the more or less rapid but severe asthmatic exacerbation that may not respond to the usual medical treatment. The narrowing of airways causes ventilation perfusion imbalance, lung hyperinflation, and increased work of breathing that may lead to ventilatory muscle fatigue and life-threatening respiratory failure. Treatment for acute, severe asthma includes the administration of oxygen, beta2-agonists (by continuous or repetitive nebulisation), and systemic corticosteroids. Subcutaneous administration of epinephrine or terbutaline should be considered in patients not responding adequately to continuous nebulisation, in those unable to cooperate, and in intubated patients not responding to inhaled therapy. The exact time to intubate a patient in status asthmaticus is based mainly on clinical judgment, but intubation should not be delayed once it is deemed necessary. Mechanical ventilation in status asthmaticus supports gas-exchange and unloads ventilatory muscles until aggressive medical treatment improves the functional status of the patient. Patients intubated and mechanically ventilated should be appropriately sedated, but paralytic agents should be avoided. Permissive hypercapnia, increase in expiratory time, and promotion of patient-ventilator synchronism are the mainstay in mechanical ventilation of status asthmaticus. Close monitoring of the patient's condition is necessary to obviate complications and to identify the appropriate time for weaning. Finally, after successful treatment and prior to discharge, a careful strategy for prevention of subsequent asthma attacks is imperative.